scholarly journals Clinical Outcomes of Genotype-Matched Therapy for Recurrent Gynecological Cancers: A Single Institutional Experience

Healthcare ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1395
Author(s):  
Kiyoka Sawada ◽  
Kentaro Nakayama ◽  
Kohei Nakamura ◽  
Yuki Yoshimura ◽  
Sultana Razia ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Response Rate ◽  
Gynecological Cancers ◽  
Target Sequencing ◽  
Genome Medicine ◽  
Patients With Cancer ◽  
Institutional Experience ◽  
Therapy Target ◽  
Generation Sequencing ◽  
Resistance To Chemotherapy

Recent advances in next-generation sequencing and genome medicine have contributed to treatment decisions in patients with cancer. Most advanced gynecological cancers develop resistance to chemotherapy and have a poor prognosis. Therefore, we conducted genomic tests in gynecological tumors to examine the efficacy and clinical feasibility of genotype-matched therapy. Target sequencing was performed in 20 cases of gynecological cancers (cervical cancer, 6; endometrial cancer, 6; and ovarian cancer, 6). Both actionable and druggable genes were identified in 95% (19/20) of the cases. Among them, seven patients (35%) received genotype-matched therapy, which was effective in three patients. Of the three patients, one patient with a PTEN mutation received everolimus, another patient with a TSC2 mutation received everolimus and letrozole, and the patient with a BRIP1 mutation received olaparib. Subsequently, disease control in these three patients lasted for more than half a year. However, all patients relapsed between 9 and 13 months after the initiation of genotype-matched therapy. In this study, the response rate of genotype-matched therapy was 43% (3/7), which may have contributed to improved prognoses. Therefore, genotype-matched therapies may help patients with refractory gynecological cancers achieve better outcomes.

scholarly journals Clinical Outcomes of Genotype-Matched Therapy For Recurrent Gynecological Cancers

2021 ◽  
Author(s):  
Kiyoka Sawada ◽  
Kentaro Nakayama ◽  
Kohei Nakamura ◽  
Yuki Yoshimura ◽  
Sultana Razia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Poor Prognosis ◽  
Response Rate ◽  
Gynecological Cancers ◽  
Gynecological Tumors ◽  
Target Sequencing ◽  
Genome Medicine ◽  
Patients With Cancer ◽  
Generation Sequencing ◽  
Resistance To Chemotherapy

Abstract Background: Recent advances in next-generation sequencing and genome medicine has contributed to treatment decisions in patients with cancer. Most advanced gynecological cancers develop resistance to chemotherapy and have a poor prognosis. Therefore, we conducted genomic tests in gynecological tumors to examine the efficacy and clinical feasibility of genotype-matched therapy. Methods: Target sequencing was performed in 20 cases of gynecological cancers (cervical cancer, 6; endometrial cancer, 6; and ovarian cancer, 6).Results: Both actionable and druggable genes were identified in 95% (19/20) of the cases. Among them, seven patients (35%) received genotype-matched therapy, which was effective in three patients. Of the three patients, one patient with a PTEN mutation received everolimus, another patient with a TSC2 mutation received everolimus and letrozole, and the patient with a BRIP1 mutation received olaparib. Subsequently, disease control in these three patients lasted for more than half a year. However, all patients relapsed between 9 and 13 months after the initiation of genotype-matched therapy. In this study, the response rate of genotype-matched therapy was 43% (3/7), which may have contributed to improved prognoses.Conclusions: Therefore, genotype-matched therapies may help patients with refractory gynecological cancers achieve better outcomes.

474 Multiple combinational strategies of immunotherapy for esophageal squamous cell carcinoma: one institutional experience in Taiwan since 2016

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A505-A505
Author(s):  
Jo-Pai Chen ◽  
Wei-Chen Lu ◽  
Ruey-Long Hong
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clinical Benefit ◽  
Response Rate ◽  
University Hospital ◽  
List Type ◽  
Duration Of Response ◽  
Institutional Experience

BackgroundEsophageal squamous cell carcinoma is still a health burden in Taiwan. In R/M setting, the prognosis becomes worse. ESCC is still an immunogenic cancer. In randomized 2nd line ATTRACTION-3 study(nivolumab vs taxane after PF failure), median OS improved from 8.4 months in chemotherapy to 10.9 months in nivolumab(HR, 0.77; 95% CI, 0.62–0.96; p =0.019). The median duration of response was 3.9 months and 6.9 months. Nivolumab is a new 2nd line option for ESCC.MethodsFrom early 2016 to early 2020, 15 advanced ESCC patients had ever received immunotherapy-containing regimens in Yun-lin Branch of National Taiwan University Hospital and were analyzed.ResultsThe overall response to immunotherapy-containing regimens was 60%(9/15) and clinical benefit was 80%(12/15). 2nd line nivolumab was given in 3 cases; response rate was33% and clinical benefit was 67%. 2nd line afatinib combined with anti-PD1 was given in 9 case; response rate was 67% and clinical benefit was 78%. The response rate of 2nd line afatinib & pembrolizumab was 75%(3/4); however, Gr. III pneumonitis & Gr. II hepatitis were noted in the patient with progression. The response rate of 2nd line afatinib & nivolumab was 60%(3/5) and clinical benefit was 80%(4/5); skin rash and diarrhea were often found. 1st line afatinib combined with anti-PD1 was given in 3 patients; response rate was 67% and clinical benefit was 100%. The response rate of 1st line afatinib & nivolumab was 100%(2/2).ConclusionsEGFR TKIs have multiple immuno-modulatory effects and may increase immunotherapy benefits in ESCC. Anti-PD1 and anti-CTLA4, another possible rationale, could bring more benefits maybe in 1st line CheckMate649 study.AcknowledgementsNilTrial RegistrationN/AEthics ApprovalN/AConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferencesNil

Institutional experience with nab-sirolimus in patients with malignancies harboring TSC1 or TSC2 mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3111-3111
Author(s):  
Mark Andrew Dickson ◽  
Vinod Ravi ◽  
Kristen N. Ganjoo ◽  
Gopa Iyer
Keyword(s):  
Response Rate ◽  
Xenograft Model ◽  
Low Frequency ◽  
Mtor Pathway ◽  
Serious Adverse Events ◽  
Improved Outcomes ◽  
S 100 ◽  
Institutional Experience ◽  
Tumor Accumulation ◽  
Tumor Types

3111 Background: TSC1/ TSC2 genes are tumor suppressors in the mTOR pathway; mutated at low frequency across tumor types (̃1–2%). Retrospective analyses of patients (pts) with mTOR pathway mutations treated with everolimus did not show improved outcomes vs the wild type (Voss et al. Clin Cancer Res 2019. PMID 30327302). In NCT02201212, pts with TSC1/TSC2 mutations treated with everolimus had a 7% (2/30) response rate. In the AMPECT study, pts with advanced PEComa treated with a novel mTOR inhibitor (mTORi), nab-sirolimus ( nab-S, ABI-009), the subset of pts with TSC1/TSC2 mutations had a response rate of 64% (9/14) (Wagner et al. CTOS 2020. #3463014). In a xenograft model, nab-S showed significantly higher tumor accumulation, target suppression (pS6) and antitumor activity vs everolimus or sirolimus (Hou et al. AACR 2019. #348). In an expanded access program (NCT03817515), pts with advanced tumors bearing TSC1/ TSC2 mutations were treated with nab-S and outcomes in pts with malignancies other than PEComa are reported herein. Methods: Eligible pts (ECOG 0–2) received nab-S 100 mg/m2 IV, once weekly for 2 of every 3 weeks at 3 US sites between 7/2019 and 11/2020. Results: 7 pts with TSC1/ TSC2 mutations have been consecutively enrolled and are reported here. 6/7 pts had multiple prior therapies including 2 pts previously progressing on an mTORi. 4/7 pts had partial response (PR), all in mTORi naïve pts. 2/7 pts had stable disease (SD). In 2 pts previously treated with an mTORi, 1 had SD and 1 came off treatment after 1 cycle (CA125 ↑) with no follow-up scan. Treatment-related serious adverse events (SAEs; hyperglycemia and infection) and dose reduction were reported in 1 pt with metastatic angiosarcoma; SAEs resolved and the pt continued Rx. No other SAE or dose limiting event was reported Conclusions: Patients with various malignancies bearing TSC1 or TSC2 mutations, most with progression on multiple prior therapies, showed evidence of response and manageable toxicities during treatment with nab-S. A basket trial of nab-S in malignancies with TSC1/ TSC2 mutations is planned. Clinical trial information: NCT03817515. [Table: see text]

scholarly journals Patients’ understanding of clinical research: An Italian cancer patient survey

2018 ◽  
Vol 105 (1) ◽  
pp. 31-37
Author(s):  
Britt Rudnas ◽  
Emanuela Montanari ◽  
Monia Dall’Agata ◽  
Elisabetta Petracci ◽  
Oriana Nanni
Keyword(s):  
Clinical Research ◽  
Response Rate ◽  
Medical Oncology ◽  
Patient Survey ◽  
Research Knowledge ◽  
Patients With Cancer ◽  
Trial Experience ◽  
Clinical Trial Experience ◽  
Previous Clinical Trial ◽  
Level Of Knowledge

Introduction: Patients’ awareness of clinical research and their involvement in clinical trials is of great importance, but it is difficult to estimate the extent of knowledge on the research being undertaken. Methods: We evaluated the level of knowledge about clinical research using a self-reporting survey distributed to 967 adult patients with cancer attending the Departments of Medical Oncology and Onco-Haematology Units of IRST IRCCS and 4 hospitals in the region of Emilia-Romagna, Italy. The questionnaire was composed of 10 specific items on research knowledge. Patients responding correctly to at least 8 of the 10 items were considered to have a good understanding of clinical research. Results: The questionnaire was completed by 769 patients (response rate 79.5%). Only 19% of patients were found to have a good understanding of clinical research. Patients with higher education and those who had previous clinical trial experience showed a significantly better understanding. Fifty-three percent of patients said that they would be willing to participate in a trial studying a new drug and 75% expressed an interest in taking part in informative meetings/events about clinical studies. Conclusions: Our results show that patients’ understanding of clinical research is limited and highlight an interest in learning more.

scholarly journals Perspectives on Immunotherapy of Metastatic Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yongjiu Dai ◽  
Wenhu Zhao ◽  
Lei Yue ◽  
Xinzheng Dai ◽  
Dawei Rong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Liver Metastasis ◽  
Experimental Design ◽  
Poor Prognosis ◽  
Response Rate ◽  
Traditional Treatment ◽  
The Poor ◽  
New Thinking ◽  
New Treatment

Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future.

scholarly journals Next generation sequencing demonstrates association between tumor suppressor gene aberrations and poor outcome in patients with cancer

Cell Cycle ◽  
2015 ◽  
Vol 14 (11) ◽  
pp. 1730-1737 ◽  
Author(s):  
Maria Schwaederle ◽  
Gregory A Daniels ◽  
David E Piccioni ◽  
Santosh Kesari ◽  
Paul T Fanta ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Next Generation ◽  
Patients With Cancer ◽  
Poor Outcome ◽  
Generation Sequencing

Intraspinal Sparganosis Diagnosed by Metagenomics Next Generation Sequencing：An Uncommon Infection

2021 ◽  
Author(s):  
Rongming Wang ◽  
Bobin Hu ◽  
Jianning Jiang ◽  
Minghua Su
Keyword(s):  
Surgical Treatment ◽  
High Risk ◽  
Lower Limb ◽  
Poor Prognosis ◽  
High Dose ◽  
Next Generation ◽  
Praziquantel Treatment ◽  
Long Course ◽  
Generation Sequencing ◽  
Complex Lesions

Abstract In this paper, we report a case of lumbago with lower limb fatigue. After a series of biochemical, immunological, imaging, and pathological examinations, the patient was diagnosed with intraspinal sparganosis based on metagenomics next generation sequencing. Due to the length of infection, the presence of multiple complex lesions, and the high risk of surgical treatment with poor prognosis, we did not advocate surgical treatment, but chose to administer a high dose and long course of praziquantel treatment for this case.

scholarly journals Recent Findings in the Posttranslational Modifications of PD-L1

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Shu-Man Li ◽  
Jie Zhou ◽  
Yun Wang ◽  
Run-Cong Nie ◽  
Jie-Wei Chen ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Immune Checkpoint ◽  
Protein Modification ◽  
Immune Cell ◽  
Response Rate ◽  
Malignant Tumors ◽  
Objective Response ◽  
Cell Activity ◽  
Patients With Cancer ◽  
L1 Protein

Immune checkpoint therapy, such as the reactivation of T-cell activity by targeting programmed cell death 1 (PD-1) and its ligand PD-L1 (also called B7-H1 and CD274) has been found pivotal in changing the historically dim prognoses of malignant tumors by causing durable objective responses. However, the response rate of immune checkpoint therapy required huge improvements. It has been shown that the expression of PD-L1 on cancer cells and immune cell membranes is correlated with a more durable objective response rate to PD-L1 antibodies, which highlights the importance of deeply understanding how this protein is regulated. Posttranslational modifications such as phosphorylation, N-glycosylation, and ubiquitination of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In this review, we summarized the latest findings of PD-L1 protein modification and their clinical applications.

scholarly journals Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1588 ◽  
Author(s):  
Sabrina Weber ◽  
Benjamin Spiegl ◽  
Samantha O. Perakis ◽  
Christine M. Ulz ◽  
Peter M. Abuja ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Reference Materials ◽  
Test Performance ◽  
Liquid Biopsy ◽  
Attractive Alternative ◽  
Routine Practice ◽  
Patients With Cancer ◽  
Technical Evaluation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Molecular profiling from liquid biopsy, in particular cell-free DNA (cfDNA), represents an attractive alternative to tissue biopsies for the detection of actionable targets and tumor monitoring. In addition to PCR-based assays, Next Generation Sequencing (NGS)-based cfDNA assays are now commercially available and are being increasingly adopted in clinical practice. However, the validity of these products as well as the clinical utility of cfDNA in the management of patients with cancer has yet to be proven. Within framework of the Innovative Medicines Initiative (IMI) program CANCER-ID we evaluated the use of commercially available reference materials designed for ctDNA testing and cfDNA derived from Diagnostic Leukaphereses (DLA) for inter- and intra-assay as well as intra- and inter-laboratory comparisons. In three experimental setups, a broad range of assays including ddPCR, MassARRAY and various NGS-based assays were tested. We demonstrate that both reference materials with predetermined VAFs and DLA samples are extremely useful for the performance assessment of mutation analysis platforms. Moreover, our data indicate a substantial variability of NGS assays with respect to sensitivity and specificity highlighting the importance of extensive validation of the test performance before offering these tests in clinical routine practice.

scholarly journals Oncologists’ Use of Genomic Sequencing Data to Inform Clinical Management

2018 ◽  
pp. 1-13
Author(s):  
Michele C. Gornick ◽  
Erin Cobain ◽  
Lan Q. Le ◽  
Natalie Bartnik ◽  
Elena Stoffel ◽  
...  
Keyword(s):  
Medical Record ◽  
Medical Records ◽  
Clinical Management ◽  
Response Rate ◽  
Sequencing Data ◽  
Prospective Survey ◽  
Actual Change ◽  
Tumor Sequencing ◽  
Survey Responses ◽  
Generation Sequencing

Purpose To determine whether oncologists intended to change treatment as a result of tumor sequencing, and subsequently, whether patients experienced an alteration of clinical management or derived clinical benefit. Patients and Methods A prospective survey of oncologists referring adult patients with rare, advanced, or refractory cancer to the Michigan Oncology Sequencing program was conducted from June 2014 to March 2015 to assess the use of and intent to disclose sequencing findings. Oncologists’ responses were compared with the referred patients’ self-reported survey responses, and a content analysis of disclosure documented in the medical record was performed. Medical records were reviewed retrospectively to determine if clinical management was informed or changed by sequencing results. Results Oncologists (response rate, 93%) referring 112 consecutive patients were surveyed. Medical records of patients were reviewed for changes in clinical management on the basis of sequencing findings. Oncologists intended to change the treatment of 22% of patients (n = 24) on the basis of sequencing findings. Of these patients, 37.5% (n = 9) had an actual change in clinical management. Thirty-four patients with postsequencing survey data reported that a results disclosure discussion did not occur, despite documentation of disclosure by the physician in the medical record. Conclusions Findings demonstrate that many oncologists view next-generation sequencing results to be potentially valuable in directing subsequent therapy for their patients; however, barriers in communicating results to patients and implementing them in clinical management remain.

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