To evaluate the consistency of drug efficacy between the clinical systemic treatment anddrug sensitive test based on patient-derived organoid in R/M SGC patients, using aprospective and multicenter observational study to increase the generalizability andreliability of research conclusion.
Salivary gland cancer (SGC) is one type of head and neck cancer, accounting for about 5%
of all head and neck tumors and less than 0.5% of all cancers, making it relatively rare.
SGC originates from the salivary glands and can involve the three major salivary glands
(parotid, submandibular, and sublingual glands) as well as the minor salivary glands
distributed throughout the oral cavity. For early to mid-stage SGC, surgery ±
radiotherapy is the main treatment; for recurrent or metastatic (R/M) SGC, palliative
treatment is required, symptomatic or rapidly progressive disease should take systemic
therapy into account. R/M SGC is highly heterogeneous, however, high-quality
evidence-based evidence related to drug treatment is still insufficient. Individualized
drug treatment needs to determine the specific treatment plan according to the
characteristics of the patient and the tumor. In addition to NGS sequencing,
high-throughput models for in vitro drug sensitive tests are an effective means to
improve clinical efficacy.
Organoids are in vitro cultured micro-organs with 3D structures, capable of spontaneous
self-renewal, self-organization, and differentiation to form complex structures similar
to real tissues, partially simulating the physiological functions of the source tissue or
organ. Compared with other in vitro and in vivo models such as cell lines and
patient-derived xenograft models, organoid models have unique advantages: they can more
vividly retain the phenotypic, genetic, and functional characteristics of the original
tissue, and have a short modeling cycle, high cost-performance ratio, and can achieve
high throughput drug sensitive test. In 2018, a study showed that ex vivo drug
sensitivity testing based on gastrointestinal tumor organoids has a very high predictive
value for clinical efficacy, with a sensitivity of 100%, specificity of 93%, and positive
and negative predictive values of 88% and 100%, respectively. In addition, cancer
organoids have been developed from many other cancer types and its feasibility in guiding
precision medicine is investigated. The aim of present study is to evaluate the
consistency of drug efficacy between the clinical systemic treatment and drug sensitive
test based on patient-derived organoid in R/M SGC patients. A prospective and multicenter
observational study is planned to increase the generalizability and reliability of
research conclusion.
The patients with R/M SGC would receive drug treatment according to the clinical
guideline or doctor's experience, at the same time, tumor biopsy samples would be
collected to establish PDO for drug sensitive test. Fifteen different drug regimens
sensitive test would be performed, including the actual drug regimens that the patients
clinically receive, and the corresponding ex vivo tumor inhibition rate would be
recorded. After the patients received the clinical treatment, they would be followed up
to collect the objective response rate (ORR), disease control rate (DCR),
progression-free survival time (PFS), and overall survival time (OS). Finally, the
consistency of drug efficacy would be evaluated between clinical systemic treatment and
drug sensitive test based on patient-derived organoid.
Other: No Intervention: Observational Cohort
The patients with R/M SGC would receive drug treatment according to the clinical
guideline or doctor's experience, at the same time, tumor biopsy samples would be
collected to establish PDO for drug sensitive test. But no intervention would be used
based on the PDO drug sensitive test.
Inclusion Criteria:
- Pathologically confirmed R/M SGC patients
- Tumor tissues available for organoid culture
- ECOG score: 0-2 points
- Life expectancy > 3 months
- Normal major organ function, tolerable to chemotherapy, targeted therapy,
immunotherapy: a. Hematology examination criteria must meet: WBC≥4.0×109/L,
ANC≥1.5×109/L, PLT≥80×109/L, Hb≥90 g/L (no blood transfusion or blood products
within 14 days, no use of G-CSF or other hematopoietic growth factors); b.
Biochemical examination must meet the following criteria: serum albumin≥3.0 g/dL (30
g/L), TBIL≤1.5×ULN, ALT, AST≤2.5×ULN, BUN and CRE≤1.5×ULN or endogenous creatinine
clearance≥60 ml/min (Cockcroft-Gault formula); c. Good coagulation function: defined
as International Normalized Ratio (INR) or Prothrombin Time (PT)≤1.5 times ULN; if
the study participant is on anticoagulant therapy, as long as PT is within the
intended range of the anticoagulant medication
- Able to understand the content of informed consent form, sign the informed consent
form, and willing to cooperate with the follow-up
Exclusion Criteria:
- Metastatic tumors in the head and neck region, or non-salivary gland cancer tumors
such as sarcoma, squamous cell carcinoma, nasopharyngeal carcinoma, etc.
- Known allergy to the study drugs or their active ingredients or any excipients; or
had a severe allergic reaction to other monoclonal antibodies
- Pregnant or breastfeeding female patients; or women of childbearing age with
positive pregnancy test results (serum or urine) within 7 days before enrollment, or
negative results but refusing to use effective contraception during the study period
and 2 months after the last administration of study medication; or male patients
with partners of childbearing age, refusing to use effective contraception during
the study period and 2 months after the last administration of study medication
- Severe liver diseases (such as cirrhosis), kidney diseases, respiratory system
diseases, hematopoietic system diseases, or endocrine system diseases, uncontrolled
diseases
- Infected with HIV, active hepatitis B (HBV-DNA≥104 copies/ml) or hepatitis C
(hepatitis C antibody positive, and HCR-RNA above the lower limit of detection of
the analytical method), uncontrolled diseases
- Within 6 months before enrollment, the following conditions occurred: myocardial
infarction, severe/unstable angina, NYHA class 2 or above heart failure, clinically
significant supraventricular or ventricular arrhythmias, and symptomatic congestive
heart failure, uncontrolled diseases
- Patients with mental illness or known history of psychiatric drug abuse or drug
addiction
- Unable to give consent, unable to obtain the required amount of tumor tissue for the
study
- Other serious physical or mental diseases or laboratory test abnormalities that may
increase the risk of participating in the study or interfere with the study results;
or any other situation that the researchers deem unsuitable for participation in
this study
Huashan Hospital, Fudan University
Shanghai, Shanghai, China
Lai-ping Zhong, MD, PhD, Principal Investigator
Huashan Hospital