DSM-TACE of HCC: Evaluation of Tumor Response in Patients Ineligible for Other Systemic or Loco-Regional Therapies

Purpose To analyze tumor response, survival and safety in patients with non-resectable hepatocellular carcinoma (HCC) treated with transarterial hepatic chemoembolization using degradable starch microspheres (DSM-TACE) combined with doxorubicin who had no local interventional or systemic therapy alternative according to an interdisciplinary conference. Materials and Methods In this retrospective study, 28 patients (23 male, 5 female, median age 67 years) with unresectable HCC, serum bilirubin levels < 3 mg/dl and contraindications to Sorafenib, RFA, SIRT or cTACE were included. DSM-TACE was performed using Embocept® S (15 ml) and doxorubicin (50 mg/25 ml) three times every 4–6 weeks. Patients were initially staged using the Barcelona Clinic Liver Cancer System (BCLC). Basic liver function was evaluated with the MELD-score. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results DSM-TACE could be technically successfully performed in all 28 patients. At control imaging after three treatments, the overall rates of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were 14.3 %, 25 %, 39.3 % and 21.4 %, respectively, according to mRECIST. With regard to BCLC stages, the results were as follows (CR, PR, PD): BCLC A (n = 8): 7.1 %, 7.1 %, 10.7 %, 1.2 %; BCLC B (n = 12): 0 %, 10.7 %, 17.9 %, 14.3 %; BCLC C (n = 5): 0 %, 3.6 %, 10.7 %, 3.6 %; BCLC D (n = 3): 3.6 %, 3.6 %, 0 %, 3.6 %. According to this, DSM-TACE showed an overall good median survival of 682 days, although the patients’ survival was strictly dependent on BCLC stage. Conclusion DSM-TACE is a safe and promising treatment alternative for patients with unresectable HCC who are ineligible for other loco-regional therapies. Key Points: Citation Format

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Assessing solid tumor response with and without RECIST.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.504 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 504-504

Author(s):

Aileen Deng ◽

Benjamin E Leiby ◽

Russell J. Schilder ◽

William Kevin Kelly ◽

Sandeep Deshmukh ◽

...

Keyword(s):

Solid Tumors ◽

Progressive Disease ◽

Tumor Response ◽

Evaluation Criteria ◽

Kappa Statistic ◽

Response Assessment ◽

Complete Response ◽

Response Evaluation ◽

Academic Center ◽

Standard Report

504 Background: Response Evaluation Criteria in Solid Tumors (RECIST) has become widely accepted as gold standard for response evaluation in clinical trials. It remains underutilized in routine clinical practice. We compared tumor response assessment made with and without RECIST. Methods: This study included patients with solid tumors who underwent imaging from January 2013 to December 2014 at a single academic center. Tumor response was assessed by a radiologist using RECIST and by an oncologist (Onc) and resident (Res) without using RECIST (standard report). Tumor response was classified as progressive disease (PD), stable disease (SD), partial response (PR) and complete response (CR). Agreement in assessment between RECIST and standard report was determined by percent agreement and Kappa statistic. Results: 292 imaging studies were included. Concordance between RECIST and Onc-interpreted standard report is presented in Table 1. Overall agreement between RECIST and Onc-interpreted standard report was 56% (95% CI: 46-65%) and Kappa was 0.31 (95% CI: 0.19-0.44). Similar results were seen between RECIST and Res-interpreted standard report (Table 1). Overall agreement between RECIST and Res-interpreted report was 54% (95% CI: 44%-63%) and Kappa was 0.26 (95% CI: 0.13-0.40). Conclusions: Our study found variability in tumor response assessment between clinicians and radiologists. RECIST-classified PD was often interpreted as SD and vice versa, a distinction that affect treatment decisions. Our study highlights the need to standardize tumor response assessment. [Table: see text]

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Imaging Assessment of Tumor Response in the Era of Immunotherapy

Diagnostics ◽

10.3390/diagnostics11061041 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1041

Author(s):

Jun Nakata ◽

Kayako Isohashi ◽

Yoshihiro Oka ◽

Hiroko Nakajima ◽

Soyoko Morimoto ◽

...

Keyword(s):

Positron Emission Tomography ◽

Solid Tumors ◽

False Positive ◽

Progressive Disease ◽

Tumor Response ◽

Metabolic Response ◽

Evaluation Criteria ◽

Emission Tomography ◽

Response Criteria ◽

Positron Emission

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.

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Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001752 ◽

2021 ◽

Vol 9 (4) ◽

pp. e001752

Author(s):

Rivka R Colen ◽

Christian Rolfo ◽

Murat Ak ◽

Mira Ayoub ◽

Sara Ahmed ◽

...

Keyword(s):

Partial Response ◽

Stable Disease ◽

Progressive Disease ◽

Tumor Response ◽

Complete Response ◽

Classification Model ◽

P Value ◽

Rare Cancer ◽

Rare Cancers ◽

Contrast Enhanced Ct

BackgroundWe present a radiomics-based model for predicting response to pembrolizumab in patients with advanced rare cancers.MethodsThe study included 57 patients with advanced rare cancers who were enrolled in our phase II clinical trial of pembrolizumab. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST). Patients were categorized as 20 “controlled disease” (stable disease, partial response, or complete response) or 37 progressive disease). We used 3D-slicer to segment target lesions on standard-of-care, pretreatment contrast enhanced CT scans. We extracted 610 features (10 histogram-based features and 600 second-order texture features) from each volume of interest. Least absolute shrinkage and selection operator logistic regression was used to detect the most discriminatory features. Selected features were used to create a classification model, using XGBoost, for the prediction of tumor response to pembrolizumab. Leave-one-out cross-validation was performed to assess model performance.FindingsThe 10 most relevant radiomics features were selected; XGBoost-based classification successfully differentiated between controlled disease (complete response, partial response, stable disease) and progressive disease with high accuracy, sensitivity, and specificity in patients assessed by RECIST (94.7%, 97.3%, and 90%, respectively; p<0.001) and in patients assessed by irRECIST (94.7%, 93.9%, and 95.8%, respectively; p<0.001). Additionally, the common features of the RECIST and irRECIST groups also highly predicted pembrolizumab response with accuracy, sensitivity, specificity, and p value of 94.7%, 97%, 90%, p<0.001% and 96%, 96%, 95%, p<0.001, respectively.ConclusionOur radiomics-based signature identified imaging differences that predicted pembrolizumab response in patients with advanced rare cancer.InterpretationOur radiomics-based signature identified imaging differences that predicted pembrolizumab response in patients with advanced rare cancer.

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Radiomics to predict response to pembrolizumab in patients with advanced rare cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.5_suppl.66 ◽

2020 ◽

Vol 38 (5_suppl) ◽

pp. 66-66 ◽

Cited By ~ 1

Author(s):

Rivka R. Colen ◽

Sara Ahmed ◽

Nabil Elshafeey ◽

Daniel D. Karp ◽

Shubham Pant ◽

...

Keyword(s):

Tumor Response ◽

Evaluation Criteria ◽

Area Under The Curve ◽

Texture Features ◽

Complete Response ◽

Target Lesion ◽

Classification Model ◽

Unknown Primary ◽

Rare Cancers ◽

Contrast Enhanced Ct

66 Background: To predict responders versus non-responders to Pembrolizumab, an anti PD-1 monoclonal antibody, in patients with advanced rare cancers. Methods: The study included 58 patients with advanced rare cancers (eg. squamous cell carcinoma of the skin, adrenocortical carcinoma, carcinoma of unknown primary, and paraganglioma) who were enrolled in a phase 2 trial of Pembrolizumab. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients were categorized into: 21 responders (stable disease, partial response, and complete response) and 37 non-Responders (progressive disease). Target lesion(s) obtain from standard-of-care, pre-treatment contrast enhanced CT scans were segmented using 3D slicer v4.8.1. A total of 610 features (10 histogram-based and 600 second-order texture features) were calculated from each extracted volume of interest (VOI). Radiomic features were obtained using a feature selection approach based on Least Absolute Shrinkage and Selection Operator (LASSO). Selected features were used to build a classification model, using XGboost, for prediction of tumor response to Pembrolizumab. To evaluate the robustness of the estimates, Leave-One-Out Cross-Validation (LOOCV) was performed. Results: A total of 10 radiomic features were selected; the XGboost-based classification robustly differentiated between responders vs non-responders (area under the curve, sensitivity and specificity were 99%, 100%, and 95%, respectively [p<0.0001]). Conclusions: Our radiomic derived features were able to identify imaging differences that can evaluate patients’ response to Pembrolizumab treatment.

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Does the Degree of Hepatocellular Carcinoma Tumor Necrosis following Transarterial Chemoembolization Impact Patient Survival?

Journal of Oncology ◽

10.1155/2016/4692139 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Nathan Haywood ◽

Kyle Gennaro ◽

John Obert ◽

Paul F. Sauer ◽

David T. Redden ◽

...

Keyword(s):

Transarterial Chemoembolization ◽

Tumor Necrosis ◽

Progressive Disease ◽

Patient Survival ◽

Multivariable Analysis ◽

Evaluation Criteria ◽

Complete Response ◽

Tumor Diameter ◽

Main Driver ◽

Pugh Class

Purpose. The association between transarterial chemoembolization- (TACE-) induced HCC tumor necrosis measured by the modified Response Evaluation Criteria In Solid Tumors (mRECIST) and patient survival is poorly defined. We hypothesize that survival will be superior in HCC patients with increased TACE-induced tumor necrosis.Materials and Methods. TACE interventions were retrospectively reviewed. Tumor response was quantified via dichotomized (responders and nonresponders) and the four defined mRECIST categories.Results. Median survival following TACE was significantly greater in responders compared to nonresponders (20.8 months versus 14.9 months,p=0.011). Survival outcomes also significantly varied among the four mRECIST categories (p=0.0003): complete, 21.4 months; partial, 20.8; stable, 16.8; and progressive, 7.73. Only progressive disease demonstrated significantly worse survival when compared to complete response. Multivariable analysis showed that progressive disease, increasing total tumor diameter, and non-Child-Pugh class A were independent predictors of post-TACE mortality.Conclusions. Both dichotomized (responders and nonresponders) and the four defined mRECIST responses to TACE in patients with HCC were predictive of survival. The main driver of the survival analysis was poor survival in the progressive disease group. Surprisingly, there was small nonsignificant survival benefit between complete, partial, and stable disease groups. These findings may inform HCC treatment decisions following first TACE.

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Bevacizumab plus FOLFOX7 as first line treatment in patients with advanced colorectal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15092 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15092-e15092

Author(s):

M. Oukkal ◽

F. Kara ◽

S. Difi ◽

D. Bouzidi ◽

K. Bentabak ◽

...

Keyword(s):

Colorectal Cancer ◽

Progressive Disease ◽

Advanced Colorectal Cancer ◽

Complete Response ◽

Severe Toxicity ◽

Vascular Endothelial ◽

Significant Survival ◽

Promising Treatment ◽

Ecog Ps ◽

Endothelial Growth Factor

e15092 Background: Bevacizumab a monoclonal antibody against vascular endothelial growth factor (VEGF) has shown in combination with chemotherapy a significant survival improvement in pts with advanced colorectal cancer (F. Kabbinavar JCO 2005 and H. Hurwitz NEJM 2004). In this study we investigated the safety and the efficacy of the addition of bevacizumab to FOLFOX7 regimen in pts with metastatic colorectal cancer. Methods: Inclusion criteria: Histological proven colorectal carcinoma, measurable disease at time of inclusion, no prior chemotherapy (adjuvant chemotherapy allowed), no CNS metastasis, no peripheral neuropathy, no other serious concomitant illness, ECOG PS ≤ 2, Urine dipstick of proteinuria <2+, adequate renal and liver function, good bone marrow reserve and informed consent. Pts received bimonthly Oxaliplatin 130 mg/m2 D1, Folinic acid 400 mg/m2 D1, Fluorouracil 2400 mg/m2 46 hours continuous infusion and Bevacizumab 5mg/kg D3 Results: From April 2005 to June 2007, 47 pts (M/F = 28/19, colon/rectum = 28/19) were enrolled in the study. Median age is 52,7 years old (32–74). They received 452 cycles, median=7 range (1–18). All pts were evaluable for toxicity and survival and 46 for responses. Complete response (CR) was achieved in 3 pts (6.6%), partial response (PR) in 28 pts (60.8%), stable disease in 4 pts (8.7%) and progressive disease in 11 pts (24%). The overall response rate (ORR=CR+PR) is 67.3%. Severe toxicity (CTC/NCI ¾ Grade) related to chemotherapy was neuropathy 5.3%, neutropenia 8.4%, anaemia 3.3%, thrombocytopenia 1.8%, vomiting 8.2%, diarrhoea 2.9%, stomatis 4.9% and allergy 0.7%. Toxicity related to Bevacizumab was bleeding CTCNCI grade 1 and 2 in 40.8%, hypertension grade 1 qnd 2 in 3.7% qnd grqde 3 in 0.2. proteinuria grade and 2 in 13.7%. 1 case of phlebitis and 1 case of Bevacizumab allergy Conclusions: Bevacizumab and FOLFOX7 combination is a promising treatment with high efficacy and safety profile for pts with advanced colorectal cancer No significant financial relationships to disclose.

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Expression of ABCG2 Associated with Tumor Response in Metastatic Colorectal Cancer Patients Receiving First-line FOLFOX Therapy – Preliminary Evidence

The International Journal of Biological Markers ◽

10.5301/jbm.5000004 ◽

2013 ◽

Vol 28 (2) ◽

pp. 182-186 ◽

Cited By ~ 7

Author(s):

Pei-Ching Lin ◽

Hung-Hsin Lin ◽

Jen-Kou Lin ◽

Chun-Chi Lin ◽

Shung-Haur Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Tumor Response ◽

Evaluation Criteria ◽

Complete Response ◽

Preliminary Evidence ◽

First Line ◽

Selective Marker ◽

Primary Tumors ◽

Colorectal Cancer Patients

Purpose We retrospectively analyzed ABCG2 expression levels in patients with metastatic colorectal cancer (CRC) to investigate the interaction between ABCG2 expression and the tumor response to oxaliplatin and 5-fluorouracil (FOLFOX). Methods Forty-three patients with CRC with liver metastasis who received first-line FOLFOX treatment at our institution between 2008 and 2010 were enrolled. ABCG2 expression was assessed by immunohistochemistry. Tumor response was determined using the modified Response Evaluation Criteria in Solid Tumors criteria. Results At least 50% tumor shrinkage was observed in 16/43 patients (37.2%), including a complete response in 1 patient. According to the intensity of ABCG2 expression and the percentage of tumor cells expressing ABCG2, 21 tumors displayed high ABCG2 expression. Among these tumors, only 2 (9.5%) exhibited partial responses to FOLFOX; conversely, 63.6% of tumors with low ABCG2 expression (14/22) responded to FOLFOX. Primary and corresponding metastatic samples were available for 15 patients, and 13 of the metastatic tumors had higher ABCG2 expression than the corresponding primary tumors, but only 1 of these tumors responded to FOLFOX (7.7%). Conclusions ABCG2 expression is associated with the tumor response to FOLFOX in patients with metastatic CRC. ABCG2 may be a selective marker for the efficacy of FOLFOX in treating CRC.

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Outcomes of Hepatic Epithelioid Hemangioendothelioma with Different Managements: Retrospective Investigation of 50 Patients

10.21203/rs.3.rs-123213/v1 ◽

2020 ◽

Author(s):

Xiaolei Liu ◽

Zhiying Yang

Keyword(s):

Progressive Disease ◽

Complete Response ◽

Epithelioid Hemangioendothelioma ◽

Interferon Α ◽

Curative Intent ◽

Radiological Images ◽

Promising Treatment ◽

Extrahepatic Metastases ◽

High Chance ◽

Retrospective Investigation

Abstract Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor and no standard treatment has been established. This study was aimed to retrospectively investigate the outcomes of different managements for HEHE patients Methods: From March 2017 to November 2019, a retrospective investigation was performed among 50 HEHE patients to summarize the outcomes of different managements. Their medical records were collected and the outcome of each management was evaluated based on radiological images. Results: For all the 50 HEHE patients, 80% were asymptomatic and 94% had multiple intrahepatic lesions. Extrahepatic metastases were detected in 54% patients and 82% patients were radiologically misdiagnosed. For 18 patients with initial observation, 16 (88.9%) of them had progressive disease (PD). For 12 patients with curative intent surgery or radiofrequency ablation (RF), 10 (83.3%) of them had recurrence. Six patients with interferon-α had results of 4 partial response (PR), one complete response (CR) and one stable disease (SD). For 6 patients with thalidomide, 4 patients had PD and 2 patients had SD. Four patients with chemotherapy had 3 PD and one SD. Five patients with targeted therapy had 2 PR (both with apatinib), 2 PD and one SD. Conclusions: HEHE patients had a high chance of PD during observation. The risk of recurrence after surgery or RF was high. Interferon-α and apatinib were the managements with tumor response (PR or CR). The encouraging result of interferon-α makes it a promising treatment for HEHE.

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Palliative treatment with electrochemotherapy in recurrent or metastatic vaginal cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001471 ◽

2020 ◽

Vol 30 (7) ◽

pp. 939-946 ◽

Cited By ~ 1

Author(s):

Anna Myriam Perrone ◽

Martina Ferioli ◽

Andrea Galuppi ◽

Manuela Coe ◽

Francesca De Terlizzi ◽

...

Keyword(s):

Overall Survival ◽

Partial Response ◽

Stable Disease ◽

Palliative Treatment ◽

Progressive Disease ◽

Evaluation Criteria ◽

Complete Response ◽

Vaginal Cancer ◽

Response Evaluation ◽

Response Evaluation Criteria

ObjectiveVaginal metastases are very rare events with a poor prognosis. To improve the quality of life, local treatments should be considered. The aim of this study was to evaluate the role of electrochemotherapy as palliative treatment in vaginal cancer not amenable to standard treatments due to poor performance status, previous treatments, or advanced disease.MethodsThis is a prospective observational study on patients diagnosed with vaginal cancer and treated from January 2017 to December 2018 with palliative electrochemotherapy. We collected data on patients with vaginal cancer treated by electrochemotherapy with the aim of local control. Data regarding electrochemotherapy, hospital stay, adverse events, and patient outcomes were analyzed. Intravenous bleomycin was injected as a bolus in 2–3 min at a dose of 15 000 UI/m2 and electrical pulses started 8 min after chemotherapy. Electrochemotherapy response was defined according to the Response Evaluation Criteria in Solid Tumors.ResultsFive patients with vaginal recurrence (two squamous, two melanomas, and one leiomyosarcoma) and one with vaginal metastasis from intestinal adenocarcinoma received one treatment and two patients were re-treated. Imaging reported nodal metastasis (inguinal or pelvic) in two patients, distant metastases in two, and both node and distant metastasis in two patients, respectively. Response Evaluation Criteria in Solid Tumors showed a complete response in one patient, partial response in three patients, stable disease in one patient, and progressive disease in one patient, with an overall response rate of 67% and a clinical benefit rate (complete response, partial response, stable disease) of 83%. Two patients were re-treated and had a new response (partial response and stable disease, respectively). At last follow-up, two patients had died of the disease, two were alive with stable disease, one was alive with progressive disease, and one was alive without disease. Median post-electrochemotherapy overall survival was 12.9 months (range 1.6–26.9) and 1-year overall survival was 66.7%.ConclusionsThis preliminary experience showed a tumor response or stabilization in 83% of patients requiring palliative management for vaginal cancer. Further studies are needed to evaluate treatment outcome in larger and prospective series.

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Prognostic Significance of 99mTc Hynic-rh-Annexin V Scintigraphy During Platinum-Based Chemotherapy in Advanced Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.10.1337 ◽

2007 ◽

Vol 25 (18) ◽

pp. 2534-2539 ◽

Cited By ~ 59

Author(s):

Marina Kartachova ◽

Nico van Zandwijk ◽

Sjaak Burgers ◽

Harm van Tinteren ◽

Marcel Verheij ◽

...

Keyword(s):

Lung Cancer ◽

Progressive Disease ◽

Tumor Response ◽

Prognostic Significance ◽

Evaluation Criteria ◽

Annexin V ◽

Advanced Lung Cancer ◽

Response Evaluation ◽

Platinum Based Chemotherapy ◽

Induced Changes

Purpose The purpose of this study was to evaluate if sequential 99mTc Hynic-rh- annexin V scintigraphy (TAS) can predict outcome in patients with advanced lung cancer, shortly after the start of platinum-based chemotherapy. Patients and Methods In 16 consecutive chemotherapy-naive patients with advanced stage non–small-cell lung cancer scheduled for platinum-based chemotherapy, TAS was performed before and within 48 hours after the start of therapy. Chemotherapy-induced changes in tumor annexin V uptake, calculated as maximum count per pixel and expressed as percentage to baseline value, were compared with treatment response determined according to Response Evaluation Criteria in Solid Tumors. Results A significant correlation (r2 = 0.86; P = .0001) was found between annexin V metabolic changes and treatment outcome. All patients with notably increased annexin V tumor uptake showed complete or partial response. Less prominently increased or decreased uptake correlated with stable or progressive disease. Conclusion TAS is a promising test to predict tumor response in patients with advanced lung cancer early in the course of platinum-based chemotherapy.

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