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

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.

scholarly journals High Dose Rate Brachytherapy as a Treatment Option in Endobronchial Tumors

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Ali Hosni ◽  
Andrea Bezjak ◽  
Alexandra Rink ◽  
Kasia Czarnecka ◽  
Andrew McPartlin ◽  
...  
Keyword(s):  
Dose Rate ◽  
External Beam Radiotherapy ◽  
Late Toxicity ◽  
Complete Response ◽  
High Dose Rate ◽  
High Dose ◽  
Subjective Response ◽  
Short Term ◽  
Curative Intent ◽  
Promising Treatment

Purpose. To report our experience with high dose rate endobronchial brachytherapy (HDR-EBBT) and to assess its efficacy and tolerability with possibility of its use in selected cases with curative intent. Method. Retrospective review of patients with endobronchial tumors treated at our institution in 2007–2013 with HDR-EBBT. Subjective response and treatment related toxicity were extracted from patients’ records. Clinical response was evaluated by chest CT +/− bronchoscopy 2-3 months after treatment. Local control (LC) and overall survival (OS) were analyzed. Results. Overall 23 patients were identified. Ten patients were treated with curative intent, in 8 of them HDR-EBBT was combined with external beam radiotherapy. Short term palliation was as follows: dyspnea (13/15), cough (12/14), and hemoptysis (3/3). Seventeen patients were evaluated, of whom 9 (53%) showed complete response. Four patients developed local failure (only 1 of them treated with curative intent) and were salvaged with HDR-EBBT (n=1), chemotherapy (n=2), and laser (n=1). Among patients treated with curative intent, the 2-year LC and OS were 89% and 67%, respectively, and 2 out of 4 deaths were cancer-related. Late toxicity included bronchial stenosis (n=1). Only 1 patient had fatal hemoptysis and postmortem examination indicated local recurrence. Conclusion. HDR-EBBT is promising treatment with tolerable complication if used in properly selected patients.

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

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.

scholarly journals Mode of progression after radioembolization in patients with colorectal cancer liver metastases

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Caren van Roekel ◽  
Jennifer M. J. Jongen ◽  
Maarten L. J. Smits ◽  
Sjoerd G. Elias ◽  
Miriam Koopman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Progressive Disease ◽  
Complete Response ◽  
Extrahepatic Disease ◽  
Colorectal Cancer Liver Metastases ◽  
Dominant Disease ◽  
Baseline Characteristics ◽  
Extrahepatic Metastases ◽  
Colorectal Cancer Patients ◽  
The Impact

Abstract Background Radioembolization is an established treatment modality in colorectal cancer patients with liver-dominant disease in a salvage setting. Selection of patients who will benefit most is of vital importance. The aim of this study was to assess response (and mode of progression) at 3 months after radioembolization and the impact of baseline characteristics. Methods Three months after radioembolization with either yttrium-90 resin/glass or holmium-166, anatomic response, according to RECIST 1.1, was evaluated in 90 patients. Correlations between baseline characteristics and efficacy were evaluated. For more detailed analysis of progressive disease as a dismal clinical entity, distinction was made between intra- and extrahepatic progression, and between progression of existing metastases and new metastases. Results Forty-two patients (47%) had extrahepatic disease (up to five ≥ 1 cm lung nodules, and ≤ 2 cm lymph nodes) at baseline. No patients showed complete response, 5 (5.5%) patients had partial response, 16 (17.8%) had stable disease, and 69 (76.7%) had progressive disease. Most progressive patients (67/69; 97%) had new metastases (intra-hepatic N = 11, extrahepatic N = 32; or both N = 24). Significantly fewer patients had progressive disease in the group of patients presenting without extrahepatic metastases at baseline (63% versus 93%; p = 0.0016). Median overall survival in patients with extrahepatic disease was 6.5 months, versus 10 months in patients without extrahepatic disease at baseline (hazard ratio 1.79, 95%CI 1.24–2.57). Conclusions Response at 3-month follow-up and survival were heavily influenced by new metastases. Patients with extrahepatic disease at baseline had a worse outcome compared to patients without.

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

2020 ◽  
Vol 192 (09) ◽  
pp. 862-869
Author(s):  
Johannes Haubold ◽  
Markus P. Reinboldt ◽  
Axel Wetter ◽  
Yan Li ◽  
Johannes Maximilian Ludwig ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Tumor Response ◽  
Serum Bilirubin ◽  
Evaluation Criteria ◽  
Complete Response ◽  
Meld Score ◽  
Treatment Alternative ◽  
Degradable Starch Microspheres ◽  
Key Points ◽  
Promising Treatment

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

scholarly journals Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany

2021 ◽  
Vol 9 (2) ◽  
pp. e001701
Author(s):  
Julia Maria Ressler ◽  
Matthias Karasek ◽  
Lukas Koch ◽  
Rita Silmbrod ◽  
Joanna Mangana ◽  
...  
Keyword(s):  
Chart Review ◽  
Progressive Disease ◽  
Overall Response Rate ◽  
Real Life ◽  
Retrospective Chart Review ◽  
Distant Metastases ◽  
Complete Response ◽  
Talimogene Laherparepvec ◽  
Metastatic Lesions ◽  
Melanoma Patients

BackgroundTalimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%.ObjectivesThe aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting.MethodsBased on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36–95 years) treated with T-VEC during the period from May 2016 to January 2020.Results88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1–65), an average of 11 doses (range: 1–36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%).ConclusionThis real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs.

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

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.

S133 – Boron Neutron Capture Therapy for Melanoma in Nasal Cavity

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P121-P121
Author(s):  
Norimasa Morita ◽  
Aihara Teruhito ◽  
Msako Uno ◽  
Koji Ono ◽  
Tamotsu Harada
Keyword(s):  
Nasal Cavity ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Research Reactor ◽  
Ethics Committees ◽  
Lethal Effect ◽  
Complete Response ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture ◽  
Promising Treatment

Objectives Boron neutron capture therapy (BNCT) is one of the radiation therapies known to have a selective lethal effect on tumor cells. Thermal neutrons are captured by the 10B atom, resulting in the emission of linear recoiling Alfa particles and 7Li nuclei, with traveling ranges of ∼9 and ∼5 micrometers respectively. These particles are high linear energy transfer (LET) radiation and lethally damage DNA. BNCT for cutaneous melanoma, using 10B-para-boronophe-nylalanine (BPA) as the boron delivery agent, was developed and successful BNCT treatment of 18 melanoma patients has been reported by Mishima et al. Methods Based on their treatment regimen and with the approval of the Nuclear Safety Bureau of the Japanese government and the Medical Ethics Committees of Kawasaki Medical School and Kyoto University, we have conducted BNCT clinical trials on patients with mucosal melanomas in head-and-neck at the Kyoto University Research Reactor (KUR) and the Japan Research Reactor No. 4 (JRR-4) since 2005. Results To date, we have treated 6 patients with mucosal melanomas in the nasal cavity with BNCT. 4 patients showed a complete response (CR) by 6 months and 2 patients showed a partial response (PR) 3 months after BNCT. None of the patients showed any serious damage in normal tissue surrounding tumor site. One patient from this study died due to distant metastasis. However, no local recurrence of melanoma has been observed in all CR patients and no regrowth of melanoma in all PR patients. Conclusions BNCT thus is a promising treatment for achieving local control of mucosal melanomas.

Association of total neoadjuvant therapy with favorable clinical outcomes in patients with locally advanced esophageal and gastroesophageal junction adenocarcinomas (LA-GEJ CA).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 231-231
Author(s):  
Lauren Jurkowski ◽  
Aditya Varnam Shreenivas ◽  
Sakti Chakrabarti ◽  
Mandana Kamgar ◽  
James P. Thomas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Clinical Outcomes ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Metabolic Imaging ◽  
R0 Resection ◽  
Curative Intent

231 Background: Both peri-operative chemotherapy and neoadjuvant chemoradiation have been shown to improve outcomes in patients (pts) with LA-GEJ CA compared to surgery alone. Rates of post-operative chemotherapy delivery remain suboptimal. Total neo-adjuvant therapy (TNT) in LA-GEJ CA - induction chemotherapy (IC) followed by concurrent chemoradiation (CRT) - may improve systematic delivery of neoadjuvant therapy and result in favorable clinical outcomes. Methods: We retrospectively reviewed medical records of 135 pts with LA-GEJ CA at our institution between 2/2007 and 11/2019; pertinent clinical data were abstracted with Institutional Review Board approval. Patients treated with IC and curative-intent CRT with ≥40 Gy dose of radiation for adenocarcinoma were included in this analysis (N = 59). Doublet or triplet IC regimens utilizing 5-Flurouracil(5-FU), Cisplatin/Oxaliplatin and Docetaxel were commonly administered while combinations of Carboplatin +Paclitaxel or 5-FU + Oxaliplatin were used in CRT. Clinical complete response (CCR) was defined as metabolic imaging and endoscopic biopsies negative for residual malignancy after completion of TNT. Patients were followed from diagnosis to recurrence and overall survival. Survival probabilities were estimated using the Kaplan-Meier method and compared between groups using a log-rank test. Results: Out of 59 evaluable pts, 69% were clinical stage T3, 71% were node positive. 37 pts (63%) underwent surgery, R0 resection rate was 89% (33/37), pathologic complete response (pCR) rate was 19% (7/37). Among the pts who did not undergo surgery, 41% (9/22) opted to forego surgery since they attained a CCR. For the entire cohort, median Disease-Free Survival (mDFS), median Overall Survival (mOS), and 3-yr OS were 2.4 yrs, 4.7 yrs, and 67% respectively. Pts who did not undergo surgery had a mDFS, mOS, and 3-yr OS of 1.5 yrs, 4.2 yrs, and 59% respectively. Median DFS, mOS, and 3-yr OS of patients who underwent surgery were 3.5 yrs, 5.8 yrs and 72% respectively. Patients who achieved a CCR and opted to forego surgery (N = 9) had a 3 -yr DFS of 42% vs 83% for pts (N = 7) who demonstrated a pCR after curative intent tri-modality therapy. (P = 0.0099) Interestingly, the same group that achieved CCR and opted out of surgery had 3yr OS of 89% vs 83% of those who demonstrated a pCR (p = 0.0042). Conclusions: TNT for pts with LA-GEJ CA is associated with high rates of R0 resection as well as excellent DFS and OS compared to historical controls, warranting prospective evaluation. The remarkable DFS and OS in patients who opted to forego surgery due to achieving CCR is reflective of the local and systemic control rendered by this approach. Careful characterization and close longitudinal follow-up of patients who achieve CCR may help identify a subgroup of LA-GEJ CA pts who may benefit from surgery sparing approaches.

NIMG-48. TLR7/8-AGONIST-LOADED NANOPARTICLES REPROGRAM TUMOR-ASSOCIATED MYELOID CELLS FOR EFFECTIVE IMMUNOTHERAPY OF EXPERIMENTAL GLIOMA AND MRI-BASED TREATMENT MONITORING

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi139-vi140
Author(s):  
Kira Pfleiderer ◽  
Verena Turco ◽  
Natalie K Horvat ◽  
Jessica Hunger ◽  
Kianush Karimian-Jazi ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Progressive Disease ◽  
Tumor Regression ◽  
Myeloid Cells ◽  
Complete Response ◽  
New Approach ◽  
Splenic Macrophages ◽  
Selective Depletion ◽  
Immunosuppressive Tumor Microenvironment

Abstract Drivers of glioblastoma progression include the immunosuppressive tumor microenvironment (TME), dominated by tumor-associated myeloid cells. Therefore, we investigated a new approach targeting the myeloid compartment to reprogram myeloid cells in the TME using a β-cyclodextrin nanoparticle (CDNP) formulation encapsulating the toll-like receptor 7 and 8 (TLR7/8) agonist R848. Biodistribution confirmed specific targeting of CDNP-R848 to tumor-associated macrophages (TAMs) (labeling efficiency: 34.0% ± 22.2%), whereas tumor microglia (5.4% ± 4.4%) and splenic macrophages (13.2% ± 0.7%) revealed less uptake. Interestingly, intravenous application of CDNP-R848 induced strong tumor regression with an overall response rate of 80% (2.5% complete response, 52.5% partial response and 25% stable disease, n=40 mice) in Gl261 syngeneic experimental gliomas, while CDNP vehicle treated animals showed exponential tumor growth (100% progressive disease, n=12 mice). As advanced imaging is essential to monitor intracranial disease and possibly predict response and resistance, we performed high resolution magnetic resonance imaging using ultrasmall iron oxide nanoparticles (USPIO) for macrophage tracking. Increased levels of USPIO uptake in vehicle treated animals compared to CDNP-R848 treated animals were found as an early marker of responding mice (ΔT2*: -11.7 ± 4.2 vs -4.0 ± 2.8 ms, p=0.01). This correlated with an increased influx of myeloid cells into the TME of vehicle treated animals and showed a strong correlation of macrophage recruitment and USPIO uptake (R2: 0.78, p=0.004). Mechanistically, phenotyping of macrophages (CD45high/CD11b+) indicated a pro-inflammatory shift of TAMs with an increased infiltration of pro-inflammatory F4/80+/MHCII+ macrophages during CDNP-R848 treatment. Surprisingly, the anti-tumor effect of CDNP-R848 was independent of CD8+ T cells, CD4+ T cells or NK cells during selective depletion experiments. In summary, this work demonstrates the ability of myeloid-targeted therapies to re-shape the tumor microenvironment for an effective immunotherapy of glioma.

Repeat sequential oxaliplatin-based chemotherapy (FLOX) and nivolumab versus FLOX alone as first-line treatment of microsatellite-stable (MSS) metastatic colorectal cancer (mCRC): Initial results from the randomized METIMMOX study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3556-3556
Author(s):  
Anne Hansen Ree ◽  
Hanne Hamre ◽  
Christian Kersten ◽  
Eva Hofsli ◽  
Marianne Grønlie Guren ◽  
...  
Keyword(s):  
Adverse Events ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Complete Response ◽  
Immune Checkpoint Blockade ◽  
Curative Intent ◽  
Study Program ◽  
Mutational Status ◽  
Short Course ◽  
Grade 3

3556 Background: Immune checkpoint blockade (ICB) has revolutionized patient outcome for the small mCRC subgroup with highly immunogenic disease. The majority of mCRC cases, however, are MSS without innate ICB susceptibility. In our ongoing METIMMOX study, we hypothesize that MSS mCRC can be transformed into an immunogenic condition by short-course oxaliplatin-based therapy (FLOX), enabling patients with unresectable, previously untreated metastases to obtain durable disease control when adding ICB therapy. Here we present the protocol-planned interim analysis. Methods: Eligibility criteria include infradiaphragmatic metastasis and C-reactive protein < 60 mg/L. At analysis 15 January 2021, 54 patients stratified according to primary tumor sidedness and mutational status and evaluable for the primary end point (progression-free survival; PFS) had been randomly assigned to a standard-of-care schedule of 8 FLOX cycles Q2W (control arm) or repeat sequential 2 FLOX cycles and 2 nivolumab cycles (240 mg Q2W) to a total of 8 cycles (experimental arm), for both arms before treatment break until disease progression and reintroduction of a new treatment sequence. Radiologic response assessment is every 8 weeks. Safety, tolerability, objective response rate, and duration of response are among secondary end points. Results: At median follow-up of 6.4 (range, 0.5-20) months, patients were well balanced between the treatment arms with regard to the predefined strata and single-organ or multiple-organ metastases. Median PFS for the entire groups of control and experimental arm patients was 5.6 (range, 0.5-15; n = 26) and 6.6 (range, 0.5-20; n = 28) months, respectively. The number of FLOX-related CTCAE grade 3 or higher adverse events, including 2 deaths after initial FLOX administration, was comparable in the two arms. Twelve immune-related grade 3-4 adverse events (no new safety signals) were recorded. In the experimental arm, 4 (16%) patients, all RAS/BRAF-mutant cases, had experienced complete response and 9 (32%) patients had ongoing objective response at 8 months. The control arm cases had 0 with complete response and 6 (23%) with ongoing objective response at 8 months, 1 of whom had proceeded to curative-intent liver surgery. Conclusions: MSS mCRC patients may hold the opportunity of ICB responsiveness evoked by short-course oxaliplatin-based chemotherapy. The search for predictive biomarkers of ICB responsiveness is ongoing in the specifically designed METIMMOX correlative study program. Clinical trial information: NCT03388190.

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