scholarly journals What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?

Liver Cancer ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 115-125
Author(s):  
Atsushi Hiraoka ◽  
Takashi Kumada ◽  
Toshifumi Tada ◽  
Kazuya Kariyama ◽  
Joji Tani ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Group Performance ◽  
Therapeutic Option ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Clinical Role ◽  
Hepatic Reserve ◽  
Significant Difference ◽  
Ecog Ps

Background/Aim: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). Methods: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. Results: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001). Conclusion: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

2017 ◽  
Vol 36 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Christian Labenz ◽  
Vera Prenosil ◽  
Sandra Koch ◽  
Yvonne Huber ◽  
Jens U. Marquardt ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hepatocellular Carcinoma ◽  
Metabolic Syndrome ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The Metabolic Syndrome ◽  
The Impact

Background/Aim: Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. Methods: Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. Results: The presence of overweight/obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and of the MS itself did not impair the median OS. Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status ≥1 (hazards ratio [HR] 2.03), presence of macrovascular invasion (HR 1.71), Child-Pugh score B/C (HR 2.19), tumor grading G3 (HR 2.17), no prior HCC treatment (HR 2.34), and the presence of 2 or more out of 5 individual components of the MS (HR 0.65) were independent prognostic factors regarding the median OS. Conclusions: Our investigations do not confirm a negative prognostic role of individual components of the MS or the MS itself for patients with advanced HCC treated with sorafenib.

Pancreatic cancer outcomes in Nova Scotia: Searching for small windows of opportunity.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16219-e16219
Author(s):  
Peiran Sun ◽  
Ravi Ramjeesingh
Keyword(s):  
Older Adults ◽  
Pancreatic Cancer ◽  
Multivariate Analysis ◽  
Nova Scotia ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Healthcare Delivery ◽  
Wait Times ◽  
Significant Difference

e16219 Background: While pancreatic cancer (PC) globally has poor outcomes, there are still regional variation in PC outcomes in Canada. Nova Scotia (NS) has been documented to have some of the worst outcomes in PC but the details and barriers to the care of PC in NS have never been analyzed. Methods: A retrospective chart review was performed on PC patients (pts) diagnosed in NS from 2013 to 2017 for patient characteristics, referral pattern, treatments and wait times. Cox proportional hazards methods were used to analyze overall survival (OS) with Age, Stage, Eastern Cooperative Oncology Group Performance Status (PS), Charleston Comorbidity Index (CCI), receiving ERCP and receiving chemotherapy as covariates in the multivariate analysis. Results: 667 consecutive pts were identified, which included 357 males and 310 females with a median age of 71 at diagnosis. 42 (6.25%) lived beyond 2 years, while 163 (24.4%) survived for under 30 days and 260 (39%) survived for under 60 days. Patients with a limited survival (under 30 days) when compared to pts who survived > 60 days are older (mean 75 vs 71, P < 0.05), had a higher proportion of ECOG > 2 (81.6% vs 20.3%, P < 0.01), and a higher proportion of stage 4 disease (73.9% vs 41.2%, P < 0.01). There was no significant difference in any measure of wait times. Pts with limited survival were less likely to be seen by Medical Oncology (MO) (20.9% vs 70.9%, P < 0.001), and less likely to receive chemotherapy (1.2% vs 45%, P < 0.001) or ERCP (27% vs 53.8%, P < 0.01). Multivariate analysis showed that receiving ERCP (P = 0.027) and chemotherapy(P < 0.001) are independent predictors of survival, even when accounting for PS, CCI, stage, and age. Conclusions: Analysis of PC outcomes in NS demonstrates a large proportion of pts dying within 30 days of diagnosis. Those pts are older and present with higher stage and worse PS but did not have any significant difference in diagnostic and referral wait times. Those pts receive fewer referrals to Oncology services, fewer potentially life prolonging treatments and we uniquely discovered ERCP as an independent predictor of survival in our population. While further work is needed, this study characterized some of the unique challenges of PC care in NS as a province with a higher proportional of older adults and highlights potential opportunities to improve early healthcare delivery in older adults with limited windows for care.

Radioembolization in Advanced Hepatocellular Carcinoma

2018 ◽  
Vol 36 (19) ◽  
pp. 1898-1901 ◽  
Author(s):  
Ahsun Riaz ◽  
Robert Lewandowski ◽  
Riad Salem
Keyword(s):  
Hepatocellular Carcinoma ◽  
Portal Vein ◽  
Group Performance ◽  
Performance Status ◽  
Relevant Literature ◽  
Eastern Cooperative Oncology Group ◽  
Distant Metastases ◽  
Advanced Hepatocellular Carcinoma ◽  
Vein Thrombosis ◽  
Management Approaches

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old man with a remote history of alcohol abuse presented with vague abdominal pain. A review of systems suggested the patient had an Eastern Cooperative Oncology Group performance status 1 (restriction of strenuous physical activity). There were no physical examination findings of note. Laboratory studies disclosed Child-Pugh A liver status (no ascites; no encephalopathy; total bilirubin, 1 mg/dL; albumin, 3.5 g/dL; and international normalized rato, 1.2). The alpha-fetoprotein was mildly elevated (19.5 ng/mL). Magnetic resonance imaging with contrast disclosed an infiltrative mass with extensive malignant right and left portal vein thrombosis ( Fig 1A ) with cavernous transformation of the portal vein. The infiltrative mass ( Fig 2A ) was biopsied, revealing hepatocellular carcinoma. No distant metastases were found on a bone scintigraphy or computerized tomography scan. Given these features, this patient was classified as Barcelona Clinic for Liver Cancer stage C. The patient was referred for management of advanced hepatocellular carcinoma.

Complications following symptom-limited thoracentesis using suction

2020 ◽  
Vol 56 (5) ◽  
pp. 1902356 ◽  
Author(s):  
Ala Eddin S. Sagar ◽  
Maria F. Landaeta ◽  
Andres M. Adrianza ◽  
Grecia L. Aldana ◽  
Leonardo Pozo ◽  
...  
Keyword(s):  
Pleural Fluid ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Chest Discomfort ◽  
Mediastinal Shift ◽  
Increased Risk ◽  
Procedural Complications ◽  
Ecog Ps ◽  
Current Guidelines

BackgroundThoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO.MethodsA retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included.ResultsPleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04–0.54%; 95% CI 0.13–2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (p<0.01).ConclusionsSymptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.

QTc interval in advanced cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20658-e20658
Author(s):  
D. Trivanovic ◽  
R. Dobrila-Dintinjana ◽  
Z. Mavric ◽  
D. Stimac ◽  
M. Petkovic
Keyword(s):  
Prognostic Factors ◽  
Advanced Cancer ◽  
Median Survival ◽  
Cardiac Disease ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Solid Cancer ◽  
Qtc Interval ◽  
One Year

e20658 Background: The purpose is to identify prognostic factors that may have impact on survival in patients with advanced cancer. Methods: We retrospectively reviewed the data of patients who had biopsy proven advanced solid cancer disease in stage IV and no history or evidence of any prior cardiac disease. Univariate and multivariate stepwise Cox proportional hazard regression analysis were performed to identify independent predictors of one year survival. Results: Between 1/01 and 9/05, 143 patients (83 male and 60 female) with advanced cancers were evaluated in our institution. The primary site of disease was lung (28%), pancreas (19%), colon (15%), rectum (13%), breast (12%), and other (13%). The median follow-up was 12,5 months, median overall survival (OS) was 8.1 months, and 1-year OS rate was 62%. Median age was 65 years. OS was significantly related to the following pre-treatment prognostic factors: Age ≥65 (years), anaemia (hemoglobin level <13.2 g/dl), Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, and prolonged QTc interval in electrocardiogram (ECG). However, multivariate analysis revealed only prolonged QTc as independent prognostic parameter with 1-y survival status. Using 440 ms as the cut off value, the QTc interval was prolonged in 32 patients (22%) with median survival of 45 days and normal in 111 patients (78%) with median survival of 280 days. During the one-year 25 patients (78%) died in group with prolonged QTc interval while in group with normal QTc interval died 63 patients (57%). Conclusions: The results of our study indicate that a prolonged QTc interval (> 440 ms) is an adverse prognostic sign in patients with advanced cancer and without cardiac disease which correlates with increased mortality rates within one year after the diagnosis. Our findings suggest that QTc prolongation may be a good adjunct in risk stratification of patients with advanced cancer who are being considered for aggressive treatment regimens. [Table: see text] No significant financial relationships to disclose.

Real world eligibility of treatment-refractory stage IV colorectal cancer patients for palliative intent regorafenib monotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15007-e15007 ◽  
Author(s):  
Arkhjamil Angeles ◽  
Wayne Hung ◽  
Winson Y. Cheung
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Real World ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Stage Iv ◽  
Correct Trial ◽  
Eligibility Criteria ◽  
Ecog Ps

e15007 Background: The CORRECT trial demonstrated overall survival benefits of regorafenib monotherapy in patients with metastatic colorectal cancer (CRC) who were refractory to prior chemotherapy and biological therapy. However, stringent criteria used to determine treatment eligibility in the trial setting may limit its external validity in the real world. We aimed to examine treatment attrition rates and eligibility of regorafenib in routine clinical practice. Methods: All patients diagnosed with metastatic CRC between 2009 and 2014 who received 2 or more lines of systemic therapy at the British Columbia Cancer Agency were identified. During the study timeframe, cetuximab (cmab) and panitumumab (pmab) were only used in the chemo-refractory setting. Data on clinical factors, pathological variables and outcomes were ascertained and analyzed. Eligibility was defined based on criteria outlined in the CORRECT trial. Results: A total of 391 patients were included among whom only 39% were considered eligible for regorafenib. Median age was 61 (range 22-84) years. 247 (63%) were men, 305 (78%) were Caucasian, and 237 (60%) had a colonic primary. The disease burden at diagnosis was high: 267 (81%) had lymph node involvement, and 225 (59%) had distant metastases. In patients previously treated with cmab, main reasons for regorafenib ineligiblity were Eastern Cooperative Oncology Group performance status (ECOG PS) > 1 (26.9%), aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) (6.5%), and arterio-venous thrombotic or embolic events in the preceding 6 months (6.5%). In the group treated with pmab previously, main reasons for ineligibility were ECOG PS > 1 (46.6%), total bilirubin > 1.5 x ULN (14.1%), and thrombotic or embolic events in the past 6 months (5.7%). Additional analyses showed that regorafenib-eligible patients had increased median overall survival compared to ineligible patients (44.0 vs 37.1 months, P= 0.028). Conclusions: The strict trial eligibility criteria disqualified the majority of real world patients with metastatic CRC for regorfenib. As ineligibility predicts poorer outcomes, trials aimed at serving protocol-ineligible patients are warranted.

Influence of tumor size and Eastern Cooperative Oncology Group performance status (ECOG PS) at baseline on patient (pt) outcomes in lenvatinib-treated radioiodine-refractory differentiated thyroid cancer (RR-DTC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6081-6081 ◽  
Author(s):  
Lori J. Wirth ◽  
Sophie Leboulleux ◽  
Naomi Kiyota ◽  
Makoto Tahara ◽  
Kei Muro ◽  
...  
Keyword(s):  
Tumor Size ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Disease Characteristics ◽  
Kaplan Meier ◽  
Ecog Ps ◽  
Post Hoc

6081 Background: In SELECT, lenvatinib significantly improved progression-free survival (PFS) of pts with RR-DTC versus placebo (18.3 v 3.6 months; hazard ratio [HR]: 0.21 [99% CI: 0.14, 0.31]; P<0.001). Here we examine the treatment of RR-DTC with lenvatinib in relation to tumor size (sum of all targeted lesions) and ECOG PS. Methods: In this post hoc analysis of SELECT with pts randomized to receive lenvatinib, Kaplan-Meier estimates of time to ECOG PS ≥2 were calculated for subgroups of pts according to baseline ECOG PS or tumor size. Objective response rate (ORR) and Kaplan-Meier estimates of overall survival (OS) and PFS according to ECOG PS (0 or 1) at baseline were calculated. Correlations between ECOG PS at baseline (0 or 1) and maximum tumor shrinkage were calculated using one-way analysis of variance. Results: Pts with ECOG PS 0 or 1 at baseline had similar demographic and disease characteristics. ORR was 78.5% and 51.0% for pts with ECOG PS 0 and 1 at baseline, respectively (odds ratio [95% CI]: 3.508 [2.018, 6.097]). Mean maximum percent decrease in tumor size was significantly greater in pts with baseline ECOG PS 0 (-46.13%) versus pts with ECOG PS 1 (-37.16%; P=0.0017). For pts with ECOG PS 1 at baseline, time to ECOG PS ≥2 was numerically shorter with tumor size >60 mm versus tumor size ≤60 mm (HR [95% CI]: 1.450 [0.708, 2.967]). Additional results are summarized in the table. Conclusions: Among pts with RR-DTC, PFS, OS, ORR, and time to ECOG ≥2 were generally better for patients with lower ECOG PS or smaller tumor size at baseline. These results may indicate that it is beneficial to start lenvatinib in pts with RR-DTC early, before ECOG PS worsens and tumor size increases. Clinical trial information: NCT01321554. [Table: see text]

scholarly journals Digital Detection of Sarcopenia in Pancreatic Cancer: Additional Utilization to Plan Patient Management

2021 ◽  
Author(s):  
Mustafa Jalal ◽  
Jennifer A Campbell ◽  
Jonathan Wadsley ◽  
Andrew D Hopper
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Skeletal Muscle Index ◽  
Ecog Ps ◽  
Cancer Network

Abstract Purpose: The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting ‘digital sarcopenia’ is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC).Methods: Patients diagnosed with LAPC referred for endoscopic ultrasound guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) was noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. Results: In total 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received BSC only. The prevalence of sarcopenia (p=0.0003), age ≥ 75 years old (p=0.03) and ECOG-PS 2-3 (p=0.01) were significantly higher in the patents receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. Conclusion: Our study has shown that digital skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

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