ACT-6 Clinical manifestations of the patients with relapsed glioblastoma after bevacizumab treatment

Abstract Introduction:The outcome of glioblastoma (GBM) is improving recently, but still only temozolomide and bevacizumab (BEV) are recognized as the effective agents that are reimbursed in Japan. On large clinical trials, BEV prolonged progression free survival (PFS) but the remaining survival period from the relapse after BEV is only 3–5 month. On this study, we retrospectively analyzed the data of GBM patients who were treated with BEV to explore the best usage of BEV.Methods:230 patients were diagnosed as GBM and received BEV from July 2013 to March 2021 in our institution. Among them, 104 patient, whose clinical courses were followed, were included in this study. (M:F=59:45, median age was 65.5) Results:The patients were divided into three groups by when they used BEV; upfront group at first line therapy, 1st relapse group at second line, and 2nd+ relapse group at more than third line. There were 42, 35, 27 patients in each group. The median overall survival (OS) was 17.6, 24.7, 46.1 month (p<0.0001), median PFS after BEV treatment (PFSpBEV) was 8.8, 5.1, 5.0 month (p=0.2532), and the median survival after BEV treatment (OSpBEV) was 15.0, 9.9, 9.2 month (p=0.4437), respectively. There were 64 patients (22, 25, 17 in each group) who reached progressive disease (PD) after BEV. The median survival after PD (OSpBEVpPD) was 4.5, 5.8, 4.3 month (p=0.1590), respectively.Discussion:At the first onset, we use BEV only when the patients have low PS. Our results showed that OS was significantly longer when BEV was used in the later stage, but there was no significant difference in OS or PFS after BEV treatment. Especially OSpBEVpPD was 4–6 month regardless of the timing of BEV. To improve the treatment outcome of GBM, breakthrough therapy is needed in addition to optimizing the usage of BEV.

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Efficacy of low-dose radiotherapy (2 Gy × 2) in the treatment of marginal zone and mucosa-associated lymphoid tissue lymphomas

British Journal of Radiology ◽

10.1259/bjr.20210012 ◽

2021 ◽

pp. 20210012

Author(s):

Marzia Cerrato ◽

Erika Orlandi ◽

Angelisa Vella ◽

Sara Bartoncini ◽

Giuseppe C Iorio ◽

...

Keyword(s):

Low Dose ◽

Progression Free Survival ◽

Stage I ◽

Curative Intent ◽

Free Survival ◽

Palliative Intent ◽

First Line Therapy ◽

Distant Relapse ◽

Low Dose Radiotherapy ◽

Significant Difference

Objectives: To investigate the efficacy of a schedule of low dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients. Methods: We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I–IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan Meier product-limit. Results: Among 45 consecutive <>enrolled patients with a median age of 68 years (range 22–86), 26 (58%) were female. Thirty-one patients (69%) with a stage I–II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93%, 92%, 76% and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect. Conclusions: LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years. Advances in knowledge: This study shows the efficacy of LDRT in the treatment of MALT and MZL.

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Prediction of the VeriStrat test in first-line therapy of pemetrexed-based regimens for advanced lung adenocarcinoma patients

10.21203/rs.3.rs-41000/v3 ◽

2020 ◽

Author(s):

Bo Jia ◽

Zhi Dong ◽

Di Wu ◽

Jun Zhao ◽

Meina Wu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Progression Free Survival ◽

Intrinsic Resistance ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Bevacizumab Treatment ◽

Nsclc Patients ◽

The Relationship ◽

Poor Efficacy

Abstract Background：Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods：This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results：Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P<0.001) than VS-P patients. In addition, the partial response (PR) rate was higher in the VS-G group than that in the VS-P group (46.7% vs 25.0%, P=0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G group than that in the VS-P group regardless of whether patients received chemotherapy alone or chemotherapy plus bevacizumab. Conclusions：Our study indicated that VS might be considered as a novel and valid method to predict the efficacy of pemetrexed-based therapy and identify a subset of advanced lung adenocarcinoma patients who had intrinsic resistance to pemetrexed based regimens. However, larger sample studies are still needed to further confirm this result.

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Prediction of veristrat test in first-line therapy of pemetrexed based regimen for advanced lung adenocarcinoma patients

10.21203/rs.3.rs-41000/v2 ◽

2020 ◽

Author(s):

Bo Jia ◽

Zhi Dong ◽

Di Wu ◽

Jun Zhao ◽

Meina Wu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Progression Free Survival ◽

Intrinsic Resistance ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Bevacizumab Treatment ◽

Nsclc Patients ◽

The Relationship ◽

Poor Efficacy

Abstract Background: Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcome on pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aim to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods: This study retrospectively analyzed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results: Plasma samples from these patients were analyzed using VS and classified as Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacuzumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression free survival (PFS) (Unreached vs. 4.2 months; P＜0.001) than VS-P patients. Besides, partial response (PR) rate was higher in VS-G than that in VS-P group (46.7% vs 25.0%, P=0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G than that in VS-P group no matter for patients received chemotherapy alone or chemotherapy plus bevacizumab.Conclusions: Our study indicates that VS could be considered as a novel and valid method to predicit efficacy of pemetrexed based therapy and identify a subset of advanced lung adenocarcinoma patients who have intrinsic resistance to pemetrexed based regimen.

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Prediction of the VeriStrat test in first-line therapy of pemetrexed-based regimens for advanced lung adenocarcinoma patients

Cancer Cell International ◽

10.1186/s12935-020-01662-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Bo Jia ◽

Zhi Dong ◽

Di Wu ◽

Jun Zhao ◽

Meina Wu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Progression Free Survival ◽

Intrinsic Resistance ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Bevacizumab Treatment ◽

Nsclc Patients ◽

The Relationship ◽

Poor Efficacy

Abstract Background Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P < 0.001) than VS-P patients. In addition, the partial response (PR) rate was higher in the VS-G group than that in the VS-P group (46.7% vs. 25.0%, P = 0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G group than that in the VS-P group regardless of whether patients received chemotherapy alone or chemotherapy plus bevacizumab. Conclusions Our study indicated that VS might be considered as a novel and valid method to predict the efficacy of pemetrexed-based therapy and identify a subset of advanced lung adenocarcinoma patients who had intrinsic resistance to pemetrexed based regimens. However, larger sample studies are still needed to further confirm this result.

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Everolimus (E) versus axitinib (A) as second-line therapy (2L) in metastatic renal cell carcinoma (mRCC): Retrospective experience at Gustave Roussy.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.527 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 527-527 ◽

Cited By ~ 1

Author(s):

Annalisa Guida ◽

Laurence Albiges ◽

Yohann Loriot ◽

Christophe Massard ◽

Karim Fizazi ◽

...

Keyword(s):

Progression Free Survival ◽

Patient Characteristics ◽

Outcome Data ◽

Rank Test ◽

First Line Therapy ◽

Line Therapy ◽

Kaplan Meier ◽

Significant Difference ◽

Large Center ◽

Third Line

527 Background: Currently both E and A are standard treatments for patients (pts) with mRCC after failure of first line therapy (1L)with VEGF-targeted therapy. There is no comparative study reported so far, and this study aims to evaluate these 2 drugs in a large center. Methods: Patient characteristics, safety and outcome data from all mRCC pts who received E or A as 2L at Gustave Roussy from April 2007 to May 2015 have been compared. Progression-free Survival (PFS) and Overall Survival (OS) were assessed by the Kaplan-Meier method and compared with the log-rank test. Results: 81 pts were treated with E and 45 pts with A. The table shows patient characteristics. The 2 groups were similar. The most common 1L was sunitinib (79% in E group and 82.2% in A group). Median follow up was 29 mo (95%CI 26 – 31), 26 mo for A and 33 mo for E (p=0.046). Median OS was 21.5 mo for E and 14.9 mo for A (p = 0.23). Median PFS was 5.3 and 7.7 mo for E and A respectively (p = 0.39). Disease control rate was 69% and 73% (p=0.31) and partial response was achieved in 4% and in 24% of pts (p=0.002), respectively in E and A cohort. At time of analysis E is ongoing in 3 pts (4%) and A in 9 pts (20%) (p=0.008). Third-line therapy (3L) was administrated in 62% of pts after E and in 33% after A (p=0.003). The most common 3L after E is A (48%) and vice versa the most common after A is E (71%). Median PFS of 3L after E is 9.1 mo (12.1 mo for A and 8 mo when 3L is not A (p=0.17)). Median PFS of 3L after A is 7.8 mo (95%CI 4-12). Conclusions: No statistically significant difference for PFS and OS were observed. Nevertheless, A showed more PR than E, while more pts received 3L after E. A remains very active in 3L. [Table: see text]

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A survival analysis of surgically treated incidental low-grade glioma patients

Scientific Reports ◽

10.1038/s41598-021-88023-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lingcheng Zeng ◽

Qi Mei ◽

Hua Li ◽

Changshu Ke ◽

Jiasheng Yu ◽

...

Keyword(s):

Progression Free Survival ◽

Low Grade Glioma ◽

Low Grade ◽

Total Resection ◽

Surgical Timing ◽

Asymptomatic Group ◽

Free Survival ◽

Symptomatic Group ◽

Significant Difference ◽

Asymptomatic Phase

AbstractTo evaluate the surgical effect on survival in patients with incidental low-grade glioma (LGG) through comparison between asymptomatic and symptomatic patients. The medical records of surgically treated adult cerebral incidental LGG (iLGG) patients in our department between January 2008 and December 2015 were retrospectively reviewed. The survival of patients was calculated starting from the initial imaging diagnosis. Factors related to progression-free survival (PFS), overall survival (OS) and malignant progression-free survival (MPFS) were statistically analyzed. Seventy-five iLGG patients underwent surgery: 49 in the asymptomatic group, who underwent surgery in the asymptomatic period, and 26 in the symptomatic group, who underwent surgery after the tumor had grown and the patients had developed tumor-related symptoms. Significantly more tumors were initially located adjacent to the functional area in the symptomatic group than in the asymptomatic group (P < 0.05), but there was no significant difference in the total resection rate between the two groups. The incidence of postoperative complications (15.4%) and postoperative epilepsy (23.1%) was higher in the symptomatic group than in the asymptomatic group (4.1% and 10.2%, respectively). Multivariate analysis showed that surgical timing, namely, surgery performed before or after symptom occurrence, had no significant effect on PFS, OS or MPFS, while total resection significantly prolonged PFS, OS and MPFS, and the pathology of oligodendroglioma was positively correlated with PFS and OS (P < 0.05). Surgical timing for iLGGs should facilitate total resection. If total resection can be achieved, even after symptom occurrence, patients can achieve comparable survival benefits to those treated with surgery in the asymptomatic phase.

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Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

Scientific Reports ◽

10.1038/s41598-021-96089-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Atsushi Hiraoka ◽

Takashi Kumada ◽

Toshifumi Tada ◽

Joji Tani ◽

Kazuya Kariyama ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Liver Disease ◽

Hazard Analysis ◽

Progression Free Survival ◽

Significant Prognostic Factor ◽

Disease Etiology ◽

Alcoholic Fatty Liver ◽

Free Survival ◽

Significant Difference

AbstractIt was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

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L-Asparaginase, Doxorubicin, Vincristine, and Prednisolone (LHOP) Chemotherapy as a First-Line Treatment for Dogs with Multicentric Lymphoma

Animals ◽

10.3390/ani11082199 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2199

Author(s):

Jih-Jong Lee ◽

Albert Taiching Liao ◽

Shang-Lin Wang

Keyword(s):

Clinical Stage ◽

Progression Free Survival ◽

Cell Phenotype ◽

Chop Chemotherapy ◽

First Line ◽

Canine Lymphoma ◽

Free Survival ◽

Significant Difference ◽

Multicentric Lymphoma ◽

First Line Treatment

Cyclophosphamide exhibits the weakest therapeutic effect compared with vincristine and doxorubicin in the CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisolone) chemotherapeutic protocol for the treatment of canine lymphoma. Twenty dogs with multicentric lymphoma were treated using the LHOP protocol, which used l-asparaginase in place of cyclophosphamide, and the outcomes were historically compared with those of dogs that received CHOP chemotherapy in the same institution. No significant differences were found in age (p = 0.107), body weight (p = 0.051), sex (p = 0.453), clinical stage V (p = 1), substage b (p = 0.573), T-cell phenotype (p = 0.340), overall response (p = 1), and hypercalcaemia status (p = 1) between the LHOP and CHOP groups. The adverse effects of l-asparaginase were well tolerated and self-limiting. The median PFS (progression-free survival) and median ST (survival time) in the LHOP group were 344 days (range: 28–940 days) and 344 days (range: 70–940 days), respectively. The median PFS and median ST in the CHOP group were 234 days (range: 49–1822 days) and 314 days (range: 50–1822 days), respectively. The dogs that received LHOP chemotherapy had a significantly longer PFS than the dogs that received CHOP chemotherapy (p = 0.001). No significant difference was observed in ST between the LHOP and CHOP groups (p = 0.131). Our study findings thus indicate that the LHOP protocol can be used as a first-line chemotherapeutic protocol in canine multicentric lymphoma.

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Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02964-x ◽

2021 ◽

Author(s):

Yang Wang ◽

Jun Nie ◽

Ling Dai ◽

Weiheng Hu ◽

Jie Zhang ◽

...

Keyword(s):

Overall Survival ◽

Advanced Nsclc ◽

Objective Response ◽

Progression Free Survival ◽

Meaningful Improvement ◽

Free Survival ◽

Significant Difference ◽

Grade 3 ◽

Doublet Chemotherapy ◽

Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

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Cetuximab versus bevacizumab following prior FOLFOXIRI and bevacizumab in postmenopausal women with advanced KRAS and BRAF wild-type colorectal cancer: a retrospective study

BMC Cancer ◽

10.1186/s12885-020-07770-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chunlong Huang ◽

Xiaoyuan Gu ◽

Xianshang Zeng ◽

Baomin Chen ◽

Weiguang Yu ◽

...

Keyword(s):

Postmenopausal Women ◽

Survival Benefit ◽

Progression Free Survival ◽

Wild Type ◽

Free Survival ◽

Primary Endpoints ◽

Significant Difference ◽

Inductive Treatment ◽

Advanced Colorectal Carcinoma

Abstract Background An upgraded understanding of factors (sex/estrogen) associated with survival benefit in advanced colorectal carcinoma (CRC) could improve personalised management and provide innovative insights into anti-tumour mechanisms. The aim of this study was to assess the efficacy and safety of cetuximab (CET) versus bevacizumab (BEV) following prior 12 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus BEV in postmenopausal women with advanced KRAS and BRAF wild-type (wt) CRC. Methods Prospectively maintained databases were reviewed from 2013 to 2017 to assess postmenopausal women with advanced KRAS and BRAF wt CRC who received up to 12 cycles of FOLFOXIRI plus BEV inductive treatment, followed by CET or BEV maintenance treatment. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rate. The secondary endpoint was the rate of adverse events (AEs). Results At a median follow-up of 27.0 months (IQR 25.1–29.2), significant difference was detected in median OS (17.7 months [95% confidence interval [CI], 16.2–18.6] for CET vs. 11.7 months [95% CI, 10.4–12.8] for BEV; hazard ratio [HR], 0.63; 95% CI, 0.44–0.89; p=0.007); Median PFS was 10.7 months (95% CI, 9.8–11.3) for CET vs. 8.4 months (95% CI, 7.2–9.6) for BEV (HR, 0.67; 95% CI 0.47–0.94; p=0.02). Dose reduction due to intolerable AEs occurred in 29 cases (24 [24.0%] for CET vs. 5 [4.8%] for BEV; p< 0.001). Conclusions CET tends to be superior survival benefit when compared with BEV, with tolerated AEs.

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