Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A retrospective multicenter study

Background Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG80 and analyzed retrospectively. The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG80 was detected in 84% of HCC patients. There was no correlation between hPG80 and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG80 compared to AFP, especially at early stages. Patients with high hPG80 (hPG80+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG80 (hPG80−) levels (12.4 months versus not reached respectively, p < 0.0001). Further stratification by combining hPG80 and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG80−/AFP+ and hPG80−/AFP−, 13.4 months versus not reached respectively, p < 0.0001 and hPG80+/AFP+ and hPG80+/AFP−, 5.7 versus 26 months respectively, p < 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC.

Feline and Canine Cutaneous Lymphocytosis: Reactive Process or Indolent Neoplastic Disease?

Cutaneous lymphocytosis (CL) is an uncommon and controversial lymphoproliferative disorder described in dogs and cats. CL is generally characterized by a heterogeneous clinical presentation and histological features that may overlap with epitheliotropic lymphoma. Therefore, its neoplastic or reactive nature is still debated. Here, we describe clinicopathological, immunohistochemical, and clonality features of a retrospective case series of 19 cats and 10 dogs with lesions histologically compatible with CL. In both species, alopecia, erythema, and scales were the most frequent clinical signs. Histologically, a dermal infiltrate of small to medium-sized lymphocytes, occasionally extending to the subcutis, was always identified. Conversely, when present, epitheliotropism was generally mild. In cats, the infiltrate was consistently CD3+; in dogs, a mixture of CD3+ and CD20+ lymphocytes was observed only in 4 cases. The infiltrate was polyclonal in all cats, while BCR and TCR clonal rearrangements were identified in dogs. Overall, cats had a long-term survival (median overall survival = 1080 days) regardless of the treatment received, while dogs showed a shorter and variable clinical course, with no evident associations with clinicopathological features. In conclusion, our results support a reactive nature of the disease in cats, associated with prolonged survival; despite a similar histological picture, canine CL is associated with a more heterogeneous lymphocytic infiltrate, clonality results, and response to treatment, implying a more challenging discrimination between CL and CEL in this species. A complete diagnostic workup and detailed follow-up information on a higher number of cases is warrant for dogs.

Anlotinib Combined with Temozolomide Therapy for Recurrent Glioblastoma (IDH-wt and TERTp-mut) After Standard Treatment

Purpose IDH1-wt glioblastoma patients with TERTp-mut had the worst prognosis, and no effective management strategy was established after tumor recurrence. The median overall survival (OS) of recurrent GBM patients who only received supportive therapy was approximately 1.0 month. We reported survival outcomes of recurrent glioblastoma (rGBM) treated with anlotinib combined with temozolomide therapy (ACTT), and to explore the management strategy of rGBM. Methods The clinical data of 14 rGBM patients treated with ACTT was collected. Therapeutic efficacy and adverse effects were evaluated in every 2 months of treatment. We also included 16 patients treated with bevacizumab (Bev), 22 with TMZ, 28 with re-operation, 21 with re-irradiation, and 75 with supportive care to make comparison. Kaplan-Meier analysis was used to compare the survival of ACTT group versus other treatment groups. Results Fourteen rGBM patients treated with ACTT were enrolled. After 2-month of ACTT, the overall response and disease control rate were 50.0% and 92.9%, respectively. The 6-months PFS rate was 78.6%, and the 1-year survival rate was 50.0%. The median PFS and OS in ACTT group were 11.0 and 13.0 months, respectively. The median PFS and OS in Bev-group was 4.0 and 8.0 months. The patients treated with ACTT had better PFS than that in Bev-group. And compared to all the others treatment groups, ACTT could prolong survival. Conclusion The treatment regimen of ACTT maybe reliable, safe, and effective for rGBM. The patients can gain survival benefits from ACTT, and prolonged survival were observed compared with other treatment regimens.

Recurrence and Prognosis in Intrahepatic Cholangiocarcinoma Patients with Different Etiology After Radical Resection: A Multi-Institutional Study

Objective We aimed to evaluate the prognosis and adjuvant chemotherapy (ACT) in intrahepatic cholangiocarcinoma (ICC) patients with different etiology after radical resection. Methods A total of 448 patients with ICC who underwent radical resection between 2010 and 2018 at ten Chinese tertiary hospitals were analyzed in the study. These patients were divided into conventional ICC (Con-ICC, n=261, 58.2%), hepatitis B virus ICC (HBV-ICC, n=102, 22.8%) and hepatolithiasis (Stone-ICC, n=85,19.0%) subtypes according to different etiology. Propensity score matching (PSM) was conducted to mitigate the baseline differences between related two subtypes. Results Univariate and multivariate analysis showed that different etiology was a prognostic factor for overall survival and relapse-free survival, and different etiology was an independent risk factor for overall survival in ICC patients, respectively (P<0.05). In addition, there was a statistical difference for overall survival in early recurrence patients among the three etiological subtypes (P<0.05). After PSM, the overall survival of patients with Stone-ICC was worse than those of Con-ICC and HBV-ICC subtypes (P<0.05), while the relapse-free survival of patients with Stone-ICC was equivalent to patients with Con-ICC and HBV-ICC (P>0.05). In Stone-ICC patients, the median overall survival was 16.0 months and 29.7 months, and the median relapse-free survival was 9.0 months and 20.0 months for non-ACT and ACT patients, respectively (P<0.05). Conclusion The prognosis of Stone-ICC patients was significantly worse than those of Con-ICC and HBV-ICC patients. Interestingly, postoperative adjuvant chemotherapy can improve the prognosis of Stone-ICC patients effectively.

Daratumumab Monotherapy for Heavily Pre-treated and Refractory Myeloma: Results from a UK Multicentre Real World Cohort

Daratumumab is the first anti-CD38 targeting monoclonal antibody approved as monotherapy in multiply relapsed myeloma patients who progressed following prior treatment with proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). We present real world data on the efficacy of single agent daratumumab in a cohort of 55 multiply relapsed patients treated in the UK. The median age was 72 years, the majority (96%) received ≥ 3 previous lines of treatment; 54.5% were PI-refractory, 76.4% were IMiD-refractory and 47.2% were double refractory; 20% of patients had high-risk (HR) disease. The overall response rate was 49%. After a median follow up of 9.2 months, the median progression-free survival (PFS) for the total cohort was 5.1 months. Patients who achieved a partial response or better (≥PR) demonstrated a significantly longer PFS compared to those with <PR; 9.8 versus 2.7 months, p < 0.001. Double-refractory patients had an inferior PFS compared to single-refractory patients; 2.7 versus 7.4 months, p = 0.084. High-risk disease was associated with significantly shorter PFS compared to standard-risk (SR); 2.3 versus 6.7 months, p = 0.001. The median overall survival (OS) was 15.9 months. Despite a relatively short PFS seen in the double-refractory and high-risk patients; a favourable median overall survival of 12.9 months was achieved in these groups. Patients who achieved ≥PR, those with a previous objective response to PIs or IMiDs and those with SR disease, all benefited from a significantly longer OS which was not reached. A clear benefit in survival is encouraging in this setting of unmet clinical need and limited treatment options.

TACE Plus Lenvatinib Versus TACE Plus Sorafenib for Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Prospective Cohort Study

Background and ObjectivesThis study aimed to compare the efficacy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S) to TACE plus lenvatinib (TACE-L) for the treatment of HCC with portal vein tumor thrombus (PVTT).MethodsThis cohort study recruited patients from September 2017 to September 2020. A total of 59 and 57 consecutive patients were treated with TACE-L and TACE-S, respectively.ResultsBefore propensity score matching (PSM), comparing TACE-L to TACE-S, the median overall survival (OS) time was 16.4 months and 12.7 months, respectively [hazard ratio (HR) 1.34; 95% confidence interval (CI): 0.81–2.20; p = 0.25]. The median progression-free survival (PFS) time was 8.4 months and 7.43 months, respectively (HR 1.54; 95% CI: 0.98–2.41; p = 0.081). After PSM, the median OS time was 18.97 months and 10.77 months, respectively (HR 2.21; 95% CI: 1.12–4.38; p = 0.022); the median PFS time was 10.6 months (95% CI: 6.6–18.0 months) and 5.4 months (95% CI: 4.2–8.1 months), respectively (HR 2.62; 95% CI: 1.43–4.80; p = 0.002). After PSM, the overall response rate (ORR) was 66.8% vs. 33.3% [odds ratio (OR) 0.85; 1.05–6.90; p = 0.037].ConclusionBoth TACE-L and TACE-S are safe, well-tolerated treatments for HCC with PVTT. In HCC with PVTT, TACE-L was significantly superior to TACE-S with respect to OS, PFS, and ORR. A larger-scale randomized clinical trial is needed.

Local and Systemic Therapy in Breast Cancer Patients with Central Nervous System Metastases

Purpose As survival of patients with central nervous system (CNS) metastases from breast cancer is poor and incidence rates are increasing, there is a growing need for better treatment strategies. In the current study, the efficacy of local and systemic therapies was analyzed in breast cancer patients with CNS metastases.Methods Medical records from patients with breast cancer and brain and/or leptomeningeal metastases treated at a tertiary referral center and a teaching hospital between 2010 and 2020 were retrospectively studied. Main outcomes of interest were overall survival and CNS progression free survival. Analyses were performed for the different systemic and local therapies for CNS metastases, and subgroups based on breast cancer subtypes and brain metastases vs leptomeningeal metastases were tested.Results We identified 155 patients, 44 HER2-positive, 68 hormone receptor positive/HER2-negative and 43 triple negative. Median overall survival was 5.9 months for all 155 analyzed patients. Survival differed significantly between breast cancer subtypes (HER2-positive 22.8 months, hormone receptor positive/HER2-negative 2.4 months, triple negative 4.2 months, P<0.001). Patients receiving a combination of local and systemic therapy demonstrated prolonged median overall survival (18.5 months) as compared to local therapy only (5.7 months) or systemic therapy only (4.3 months, P<0.001). No significant difference in overall survival was observed between different systemic treatment regimens.Conclusion Breast cancer patients with CNS metastases show longest median overall survival when the subtype is HER2-positive and when they are treated with both local and systemic therapy.

Brain Metastases from Adult Sarcomas: A Retrospective Cohort Study from the Hellenic Group of Sarcomas and Rare Cancers (HGSRC)

Brain metastases are rare events in patients with sarcoma and the available information is relatively limited. We retrospectively reviewed medical records of patients with sarcoma who developed brain metastases between April 2010 and April 2020 in six centers. Thirty-four adult patients were included with a median age at brain metastases diagnosis of 55.5 years (range, 18–75). The primary sarcomas originated either from soft tissue (n = 27) or bone (n = 7) and the most common subtypes were leiomyosarcoma (n = 8), Ewing sarcoma/peripheral neuroectodermal tumor (PNET) (n = 7) and osteosarcoma (n = 3). Most primary tumors were of high grade and located mainly in the extremities (n = 18). The vast majority of patients at the time of brain metastasis diagnosis already had extracranial metastatic disease (n = 26). The median time from sarcoma diagnosis to cerebral metastasis diagnosis was 16 months (range, 1–136). Treatment modalities for brain metastatic disease included whole-brain radiation therapy (WBRT) (n = 22), chemotherapy (n = 17), exclusive palliative care (n = 5), surgery (n = 9), targeted therapy (n = 6) or stereotactic radiosurgery (n = 2). Most patients experienced a progression of brain metastases (n = 11). The median overall survival from brain metastasis diagnosis was 3 months (range, 0–80). OS was significantly influenced by time-to-brain metastases (p = 0.041), WBRT (p = 0.018), surgery (p = 0.002) and chemotherapy (p = 0.006). In a multivariate analysis, only the localization of the primary (p = 0.047) and WBRT (p = 0.038) were associated with survival with statistical significance. Patients with sarcoma brain metastases have a particularly poor prognosis and an appropriate therapeutic approach is yet to be defined.

TAS-102 Monotherapy and Combination Therapy with Bevacizumab for Metastatic Colorectal Cancer

Objective. To evaluate the effectiveness and safety of TAS-102 monotherapy and combination therapy with bevacizumab in the treatment of metastatic colorectal cancer. Methods. The PubMed, Web of Science, MEDLINE, and Cochrane Library databases were searched for the literature on TAS-102 treatment of metastatic colorectal cancer. Extracted data include median overall survival (mOS), median progression-free survival (mPFS), and the incidence of adverse events for meta-analysis. Results. Our study found that the mOS of patients treated with TAS-102 monotherapy was 6.95 (95% CI: 6.26-7.72) months and the mPFS was 2.53 (95% CI: 2.31-2.78) months. The mOS in patients treated by TAS-102 combined with bevacizumab was 10.41 (95% CI: 8.40-12.89) months, and the mPFS is 4.35 (95% CI: 3.05-6.20) months. In the control experiment, the patients’ mOS and mPFS were improved. TAS-102+B vs. TAS-102 ( OR = 0.41 , 95% CI: 0.18-0.93; OR = 0.72 , 95% CI: 0.63-0.83) and TAS-102 vs. placebo ( OR = 0.44 , 95% CI: 0.29-0.67; OR = 0.51 , 95% CI: 0.42-0.62) were studied to actively prevent the occurrence of neutropenia, leukopenia, febrile neutropenia, anemia, and vomiting. Conclusion. TAS-102 monotherapy and combination therapy with bevacizumab can significantly improve the survival of patients and prevent specific adverse events from happening.