Long-Term Survival of PD-1 Inhibitor Combined with Antiangiogenic Agents in a Patient with Pulmonary Sarcomatoid Carcinoma Complicated with Esophageal Cancer: A Case Resport and Literature Review

Abstract Pulmonary sarcomatoid carcinoma (PSC) is a highly aggressive rare subtype of non-small cell lung cancer (NSCLC). PSC is known for its poor prognosis and low sensitivity to conventional treatments such as chemotherapy, radiation, and adjuvant therapies. In recent years, the application of targeted therapy and immunotherapy in this field has made progress. Although programmed cell death 1 (PD-1) inhibitors have been reported to show favorable antitumor effects in PSC patients with high programmed death-ligand 1 (PD-L1) expression, the efficacy of PD-1 inhibitors in combination with antiangiogenic drugs has not been investigated. Here, we report for the first time a case of dual-source cancer with low expression of PD-L1 and microsatellite stability (MSS) which showed continuous response to sintilimab combined with anlotinib as first-line treatment and achieved a long progression free survival (PFS) of 24 months with no serious adverse reactions. This case presents a new therapeutic prospect for PSC and a potential to enhance its prognosis and treatment strategies.

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Metastatic Colorectal Cancer Patient With Microsatellite Stability and BRAFV600E Mutation Showed a Complete Metabolic Response to PD-1 Blockade and Bevacizumab: A Case Report

Frontiers in Oncology ◽

10.3389/fonc.2021.652394 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chongkai Fang ◽

Jietao Lin ◽

Tao Zhang ◽

Jiajun Luo ◽

Duorui Nie ◽

...

Keyword(s):

Colorectal Cancer ◽

Case Report ◽

Metastatic Colorectal Cancer ◽

Metabolic Response ◽

Colorectal Cancer Patient ◽

Combined Treatment ◽

Treatment Strategies ◽

Progression Free Survival ◽

Angiogenic Therapy ◽

Microsatellite Stability

A vast majority of colorectal cancer (CRC) patients with microsatellite stability (MSS) or proficient mismatch repair (pMMR) are refractory to immunotherapeutic strategies. The current research focusses on the combined treatment strategies for identification and optimization in order to improve the efficacy of immunotherapy among patients with microsatellite stability (MSS), who account for the majority of metastatic colorectal cancer (mCRC) cases. mCRC patients harboring MSS and the BRAFV600E mutation show a worse prognosis and barely benefit from immunotherapy. In this report, we discuss the case of a mCRC patient with MSS and BRAFV600E mutation, who exhibited significant response to the combined treatment with nivolumab and bevacizumab, and has been exhibiting a progression-free survival (PFS) of more than 17 months. Our findings indicate that combined anti-angiogenic therapy can improve the efficacy of immunotherapy, which results in the prolong survival of the patient. This is a case report on MSS and BRAFV600E colorectal cancer which presents with a response to immunotherapy and anti-angiogenic therapy.

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Validation of CIP2A as a Biomarker of Subsequent Disease Progression and Treatment Failure in Chronic Myeloid Leukaemia

Cancers ◽

10.3390/cancers13092155 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2155

Author(s):

Richard E. Clark ◽

Ammar A. Basabrain ◽

Gemma M. Austin ◽

Alison K. Holcroft ◽

Sandra Loaiza ◽

...

Keyword(s):

Chronic Myeloid Leukaemia ◽

Treatment Failure ◽

Myeloid Leukaemia ◽

Disease Progression ◽

Treatment Strategies ◽

Progression Free Survival ◽

Prognostic Indicator ◽

Molecular Response ◽

Term Survival ◽

Protein Levels

Background: It would be clinically useful to prospectively identify the risk of disease progression in chronic myeloid leukaemia (CML). Overexpression of cancerous inhibitor of protein phosphatase 2A (PP2A) (CIP2A) protein is an adverse prognostic indicator in many cancers. Methods: We examined CIP2A protein levels in diagnostic samples from the SPIRIT2 trial in 172 unselected patients, of whom 90 received imatinib and 82 dasatinib as first-line treatment. Results: High CIP2A levels correlated with inferior progression-free survival (p = 0.04) and with worse freedom from progression (p = 0.03), and these effects were confined to dasatinib recipients. High CIP2A levels were associated with a six-fold higher five-year treatment failure rate than low CIP2A levels (41% vs. 7.5%; p = 0.0002), in both imatinib (45% vs. 11%; p = 0.02) and dasatinib recipients (36% vs. 4%; p = 0.007). Imatinib recipients with low CIP2A levels had a greater risk of treatment failure (p = 0.0008). CIP2A levels were independent of Sokal, Hasford, EUTOS (EUropean Treatment and Outcome Study), or EUTOS long-term survival scores (ELTS) or the presence of major route cytogenetic abnormalities. No association was seen between CIP2A levels and time to molecular response or the levels of the CIP2A-related proteins PP2A, SET, SET binding protein 1 (SETBP1), or AKT. Conclusions: These data confirm that high diagnostic CIP2A levels correlate with subsequent disease progression and treatment failure. CIP2A is a simple diagnostic biomarker that may be useful in planning treatment strategies.

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Targeting the PI3K/AKT/mTOR Signaling Pathway in Primary Central Nervous System Lymphoma: Current Status and Future Prospects

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200517112252 ◽

2020 ◽

Vol 19 (3) ◽

pp. 165-173

Author(s):

Xiaowei Zhang ◽

Yuanbo Liu

Keyword(s):

Central Nervous System ◽

Nervous System ◽

B Cell ◽

Signaling Pathway ◽

Central Nervous System Lymphoma ◽

B Cell Lymphoma ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Antitumor Effects ◽

Term Survival

Primary Central Nervous System Lymphoma (PCNSL) is a rare invasive extranodal non- Hodgkin lymphoma, a vast majority of which is Diffuse Large B-Cell Lymphoma (DLBCL). Although high-dose methotrexate-based immunochemotherapy achieves a high remission rate, the risk of relapse and related death remains a crucial obstruction to long-term survival. Novel agents for the treatment of lymphatic malignancies have significantly broadened the horizons of therapeutic options for PCNSL. The PI3K/AKT/mTOR signaling pathway is one of the most important pathways for Bcell malignancy growth and survival. Novel therapies that target key components of this pathway have shown antitumor effects in many B-cell malignancies, including DLBCL. This review will discuss the aberrant status of the PI3K/AKT/mTOR signaling pathways in PCNSL and the application prospects of inhibitors in hopes of providing alternative clinical therapeutic strategies and improving prognosis.

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The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-021-84117-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hiroaki Kanzaki ◽

Tetsuhiro Chiba ◽

Junjie Ao ◽

Keisuke Koroki ◽

Kengo Kanayama ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Kinase Inhibitors ◽

Progression Free Survival ◽

Erk Signaling ◽

Enzyme Linked Immunosorbent Assay ◽

Antitumor Effects ◽

The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

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Identification of the Response-Related Biomarker of Bimonthly Hepatic Arterial Infusion Chemotherapy

Journal of Clinical Medicine ◽

10.3390/jcm10040629 ◽

2021 ◽

Vol 10 (4) ◽

pp. 629

Author(s):

Kei Moriya ◽

Tadashi Namisaki ◽

Hiroaki Takaya ◽

Kosuke Kaji ◽

Hideto Kawaratani ◽

...

Keyword(s):

Hepatic Arterial Infusion ◽

Progression Free Survival ◽

Serum Levels ◽

Hepatic Arterial Infusion Chemotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Term Survival ◽

Arterial Infusion Chemotherapy ◽

Infusion Chemotherapy ◽

Molecularly Targeted Agents

Despite the availability of molecularly targeted agents for advanced hepatocellular carcinoma (aHCC), these are limited to compensated cirrhotic patients, and concerns about decreased hepatic functional reserve (HFR) and unknown adverse events, which may affect long-term survival, remain unaddressed. In this study, we enrolled 96 aHCC patients treated with bimonthly hepatic arterial infusion chemotherapy (B-HAIC) with cisplatin or sorafenib monotherapy (oral sorafenib 400 mg twice daily) not only to demonstrate its efficacy and significance but also to indicate preferable candidates by setting a response-related biomarker. Differences in treatment had no significant effect on overall survival (OS). The response rate in patients treated with B-HAIC was relatively higher than those treated with sorafenib. HFR was well maintained over the treatment course with B-HAIC, while it was significantly impaired with sorafenib. By employing multivariate analysis, we found negative trends between progression-free survival (PFS) periods and serum levels of alpha fetoprotein as well as des-gamma-carboxy prothrombin (DCP). In addition, a logistic regression analysis of the relationship between serum DCP levels and PFS periods over 420 days (14 months) showed that the PFS periods of patients with higher DCP was significantly shorter than those of patients with lower DCP (p = 0.02). Subsequently, the present study demonstrated the efficacy and safety of B-HAIC and identified a predictor of unpreferable patients. Based on these results, B-HAIC might be an alternative treatment after the implementation of new molecularly targeted therapies.

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Recent advances in the management of pulmonary sarcomatoid carcinoma

Expert Review of Respiratory Medicine ◽

10.1586/17476348.2016.1157475 ◽

2016 ◽

Vol 10 (4) ◽

pp. 407-416 ◽

Cited By ~ 7

Author(s):

Elaine Shum ◽

Matthew Stuart ◽

Alain Borczuk ◽

Feng Wang ◽

Haiying Cheng ◽

...

Keyword(s):

Sarcomatoid Carcinoma ◽

Recent Advances ◽

Pulmonary Sarcomatoid Carcinoma

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Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone

British Journal of Cancer ◽

10.1038/s41416-021-01477-9 ◽

2021 ◽

Author(s):

Sanne ten Hoorn ◽

Dirkje W. Sommeijer ◽

Faye Elliott ◽

David Fisher ◽

Tim R. de Back ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Subtype ◽

Primary Tumour ◽

Treatment Strategies ◽

Specific Treatment ◽

Progression Free Survival ◽

First Line ◽

Free Survival ◽

Tumour Location ◽

Selection For

Abstract Background Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location. Methods Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively. Results When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75, P = 0.003 and HR 0.12, 95% CI 0.04–0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96, P = 0.034). Conclusions The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.

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P35.01 Genomic Origin and Immune-related Status of Pulmonary Sarcomatoid Carcinoma

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2021.01.702 ◽

2021 ◽

Vol 16 (3) ◽

pp. S419

Author(s):

X. Liu ◽

F. Wang ◽

X. Chen ◽

X. Hou ◽

Q. Li ◽

...

Keyword(s):

Sarcomatoid Carcinoma ◽

Pulmonary Sarcomatoid Carcinoma

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Real-world data (RWD) reveals benefit for adjuvant chemotherapy with docetaxel, oxaliplatin and fluorouracil/leucovorin (FLOT) is limited to those with tumour regression grade (TRG) ≥3 in oesophago-gastric cancer (OGC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4039 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4039-4039

Author(s):

Brindley Sonal Hapuarachi ◽

Rebecca Lee ◽

Adeel Khan ◽

Laura Woodhouse ◽

Valentinos Kounnis ◽

...

Keyword(s):

Performance Status ◽

Laboratory Data ◽

Progression Free Survival ◽

Tumour Regression ◽

Real World Data ◽

Curative Surgery ◽

Term Survival ◽

Tumour Regression Grade ◽

High Relapse Rate ◽

Kaplan Meier

4039 Background: Despite potentially curative surgery, long-term survival from OGC remains poor due to high relapse rate. Neoadjuvant (naFLOT) and adjuvant (aFLOT) FLOT is currently standard treatment for resectable OGC based on data from the FLOT-4 trial. We explored whether TRG was associated with FLOT-outcome using RWD. Methods: Pts with OGC treated with naFLOT +/- aFLOT at a tertiary UK centre were identified following institutional board approval. Clinical and laboratory data were extracted from the patient record. TRG was evaluated by a histopathologist. Median overall survival (OS) and median progression-free survival (PFS) were evaluated using Kaplan-Meier and Log-rank tests; time taken from start of naFLOT, and associations between factors with Fisher’s exact (FE) test. Results: 171 pts were identified, median FU 30 mths. 144 (84%) male; median age 66 (32-84); oesophagus 66 (38%), junctional (GOJ) 73 (43%), gastric 32 (19%); stage IB 3 (2%), stage IIB 26 (15%), stage III 91 (53%), stage IVA 47 (28%) and unknown 4 (2%). Pts had median of 2 comorbidities (range 0-6); performance status (PS) 0: 95 (56%), PS 1: 71 (41%), PS 2: 3 (2%) and PS unknown 2 (1%). 132/171 pts completed 4 cycles of naFLOT and this was significantly associated with undergoing surgery (p = 0.02). Those who had surgery (140/171) had significantly improved PFS (not reached (NR) vs. 6 mths; 95% CI 2-10; p < 0.001) and OS (NR vs. 12 mths; 95% CI 6-18; p < 0.001). TRG was reported for 126/140 patients who underwent surgery. TRG 1/2 (42/126) vs. TRG ≥3 was significantly associated with improved PFS (NR vs. 35 mths; 95% CI NR; p < 0.001) and OS (median NR either group; p < 0.001). Pts with TRG 1/2 who commenced aFLOT (≥1 cycle; n = 31/42) or completed 4 cycles of aFLOT (17/31) did not have improved PFS or OS vs. those who did not. Those with TRG ≥3 who commenced aFLOT (≥1 cycle; n = 62/85) had improved PFS (median NR vs. 22 mths; 95% CI 13-31 p = 0.006) and OS (median NR vs. 25 mths; 95% CI 18-32 p = 0.019). Those with TRG ≥3 who completed 4 cycles of aFLOT (n = 38/62) had significantly improved PFS (median NR vs. 25 mths; 95% CI 14-36 p = 0.016) and OS (median NR vs. 36 mths; 95% CI 16-55 p = 0.012). There was no difference in PFS or OS in pts with TRG ≥3 who had a dose reduction at any time during aFLOT. Conclusions: TRG is a predictor of outcome following naFLOT + surgery with superior outcomes in those with TRG 1/2. Our analyses suggest that only pts with TRG >3 following naFLOT + surgery benefit from adjuvant FLOT. Prospective randomised studies are required to confirm whether pts with TRG 1/2 require treatment with aFLOT.

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