About Dr. Li Jin
Dr. Li Jin is a senior oncologist at Fudan University Shanghai Cancer Center, specializing in lung cancer diagnosis and targeted therapy. She has extensive experience in molecular profiling-guided treatment planning and multidisciplinary tumor boards. Dr. Li is known for her patient-centered approach to complex oncology cases.
Case Overview
A 58-year-old female non-smoker presented with a two-month history of dry cough, left-sided chest pain, and one week of progressive headache and nausea. Imaging revealed a 3.5 cm left upper lobe lung mass with mediastinal lymph node involvement and a solitary symptomatic right frontal brain metastasis. NGS confirmed a rare EGFR Exon 20 insertion mutation (A763_Y764insFQEA) — insensitive to conventional first- and second-generation EGFR-TKIs. Under the leadership of Dr. Li Jin at Fudan University Shanghai Cancer Center, the patient underwent stereotactic radiosurgery (SRS) for the brain lesion followed by mobocertinib (160 mg QD) as first-line systemic therapy. At 11 months, disease progression with MET amplification-driven resistance prompted enrollment in a Phase II clinical trial of a novel EGFR/c-MET bispecific antibody, followed by platinum-based chemotherapy with bevacizumab and durvalumab maintenance. Overall survival exceeds 30 months; the patient remains ambulatory and fully self-caring.
Patient Background
- Age / Sex: 58-year-old female
- Occupation: Middle school teacher
- Smoking History: Never-smoker
- Family History: Mother with breast cancer (cured)
- ECOG Performance Status: 1 at diagnosis
- Chief Complaint: Dry cough with left-sided chest and back pain for 2 months; progressive headache and nausea for 1 week
- Physical Exam: Slightly reduced breath sounds over the left lung; no palpable lymphadenopathy
Diagnostic Workup
Imaging
- Chest CT (Enhanced): Irregular lobulated mass in the left upper lobe, 3.5 cm x 2.8 cm, with pleural traction; enlarged mediastinal lymph nodes (stations 4L and 5)
- Brain MRI: Single 1.5 cm right frontal lobe lesion with significant surrounding edema — consistent with brain metastasis
- Whole-body PET-CT: Left upper lobe hypermetabolic mass (SUVmax 12.5); mediastinal lymph node and right frontal metastatic foci hypermetabolic; no additional distant metastases identified
Pathology (CT-Guided Lung Biopsy)
- Histology: Lung adenocarcinoma
- IHC: TTF-1 (+), Napsin A (+), CK7 (+), P40 (-), Syn (-)
- Ki-67: 40%
Molecular Profiling
Next-Generation Sequencing (NGS — 520-Gene Large Panel)
- Driver Mutation: EGFR Exon 20 insertion — A763_Y764insFQEA (variant allele frequency 45%)
- Co-mutations: TP53 mutation (VAF 42%); RB1 inactivation
- Negative Results: EGFR Exon 19 deletion, L858R, T790M, ALK fusion, ROS1 fusion, RET fusion, KRAS G12C, MET Exon 14 skipping, HER2, BRAF V600E — all negative
- PD-L1 (TPS): 5% (low expression)
- TMB: 4.2 mut/Mb (low tumor mutational burden)
Dr. Li Jin's MDT commentary: "If this patient had been tested only by PCR — which covers only common mutations — the Exon 20 insertion would have been missed entirely. NGS large-panel testing should be the standard of care at initial diagnosis of lung adenocarcinoma."
Clinical Decision Making & Treatment
Phase 1 — First-Line Therapy (Targeted-First Strategy)
MDT Discussion (chaired by Dr. Li Jin): The patient presented with the classic profile of an Asian, female, never-smoker with adenocarcinoma — a population with high rates of EGFR-driven disease. However, the identified Exon 20 insertion mutation (A763_Y764insFQEA) is inherently resistant to first- and second-generation EGFR-TKIs (e.g., gefitinib, osimertinib). Based on FDA and NMPA approvals and data from the FURTHER study, mobocertinib (160 mg QD) was selected as first-line targeted therapy.
Local Intervention for Brain Metastasis: Given the symptomatic 1.5 cm right frontal lesion with significant edema, stereotactic radiosurgery (SRS / Gamma Knife) was performed prior to systemic therapy initiation to rapidly relieve intracranial hypertension and prevent cerebral herniation.
Treatment Response (2-Month Assessment)
- Primary lung lesion: 35% reduction in size — Partial Response (PR)
- Brain metastasis: marked reduction; surrounding edema resolved
- Headache resolved; ECOG PS improved to 0
- Adverse Events: Grade 2 diarrhea (CTCAE); no rash
Dr. Li Jin's ward round note: "In targeted therapy, we must look beyond PFS. Grade 2 diarrhea requires timely intervention — loperamide and dietary counseling were initiated. No dose reduction at this stage; reassess in one week."
Phase 2 — Disease Progression & Resistance Management (Month 11)
Repeat CT demonstrated enlargement of the primary left lung lesion (Progressive Disease) and new hepatic metastases.
Resistance Mechanism Workup
- Liquid Biopsy (ctDNA): No T790M or C797S detected; MET gene amplification identified (increased copy number)
- Re-biopsy (Hepatic Metastasis): Pathology confirmed persistent adenocarcinoma histology; no small cell transformation (RB1 inactivation present but no phenotypic conversion)
MDT Second Discussion: MET amplification is a recognized bypass resistance mechanism in EGFR-mutant NSCLC. Dr. Li Jin proposed a targeted combination strategy — mobocertinib plus savolitinib (MET inhibitor) — or enrollment in a clinical trial targeting Exon 20 insertion with a novel bispecific antibody. Per the patient's preference for oral therapy and avoidance of chemotherapy, enrollment in a Phase II trial of a novel EGFR/c-MET bispecific antibody was pursued.
Phase 3 — Second-Line Therapy & Maintenance
- Clinical Trial (Phase II): Novel EGFR/c-MET bispecific antibody — disease stabilization (SD) maintained for 5 months
- Subsequent Therapy: Following slow progression, Dr. Li Jin's team transitioned to platinum-based doublet chemotherapy (pemetrexed + carboplatin) combined with bevacizumab, with durvalumab (Imfinzi) maintenance — selected cautiously given low PD-L1 expression and low TMB
- Overall Survival: Exceeds 30 months; patient remains under active follow-up and fully self-caring
Expert Commentary — Dr. Li Jin
1. Precision Molecular Testing Is the Foundation
This case illustrates precisely why NGS large-panel testing must replace PCR-based single-gene testing as the standard at initial diagnosis of lung adenocarcinoma. A PCR panel covering only common mutations — Exon 19 deletion, L858R — would have returned a false-negative result for this patient. She would have been classified as EGFR-negative and denied targeted therapy entirely. The Exon 20 insertion was the key that unlocked her entire treatment strategy. Without it, we are not practicing precision oncology — we are practicing guesswork.
2. Comprehensive Management of Brain Metastasis
For symptomatic oligometastatic brain disease, the sequencing of local and systemic therapy is critical. In this case, SRS was performed first to control intracranial hypertension and eliminate the immediate risk of cerebral herniation. Systemic targeted therapy then controlled the primary tumor and remaining disease burden. The result was durable disease control that would not have been achievable with either modality alone. Local and systemic therapy are not competing strategies; they are complementary tools that must be deployed in the right order.
3. Patient-Centered Toxicity Management
Mobocertinib carries a significant gastrointestinal toxicity burden. A physician who prescribes the drug and does not manage the side effects has not completed the job. In our team, the Nurse Navigator — our individual case manager — plays a central role in this phase: telephone follow-up, dietary guidance, loperamide titration, and early identification of patients at risk of treatment discontinuation due to adverse events. Keeping a patient on an effective drug is as important as selecting the right drug in the first place.
4. Dynamic Monitoring After Resistance
Resistance to targeted therapy is inevitable. The question is not whether it will occur, but what mechanism drives it and what the next step should be. Liquid biopsy — ctDNA analysis — is the non-invasive tool that allows us to monitor resistance mutations in real time without subjecting the patient to repeat tissue biopsy. In this case, the identification of MET amplification by liquid biopsy directly informed the decision to pursue a MET-targeted combination strategy and ultimately clinical trial enrollment. Dynamic molecular monitoring is not optional in the management of advanced NSCLC — it is the standard of care.
How CMCS Shanghai Coordinated This Case
China Medical Concierge Shanghai (CMCS) supported this patient's care pathway from initial overseas inquiry through ongoing follow-up. Our coordination included:
- Pre-arrival CT and pathology report review and specialist referral to Dr. Li Jin's oncology team at Fudan University Shanghai Cancer Center
- Arrangement of NGS large-panel molecular profiling (520-gene panel) and PD-L1 / TMB testing
- Bilingual interpretation during MDT discussion, including detailed explanation of the Exon 20 insertion mutation, treatment options, and clinical trial eligibility
- Coordination of SRS (Gamma Knife) scheduling and pre-treatment brain MRI at the Cancer Center
- Surgical and treatment admission logistics, including hospital registration and accommodation support for accompanying family
- On-site medical interpretation throughout the hospitalization and treatment initiation period
- Nurse Navigator liaison for toxicity monitoring — facilitating telephone follow-up between the patient and Dr. Li Jin's case management team during mobocertinib therapy
- Post-progression coordination of liquid biopsy (ctDNA), re-biopsy logistics, and clinical trial enrollment documentation
- Ongoing follow-up coordination including imaging surveillance, chemotherapy scheduling, and durvalumab maintenance monitoring
For international patients facing a complex lung cancer diagnosis — particularly one involving a rare mutation, brain metastasis, and evolving resistance — the clinical and logistical demands are immense. CMCS exists to manage that complexity: ensuring patients access Shanghai's leading oncology expertise with every molecular result explained, every treatment decision supported, and every step of the care pathway coordinated from first contact through long-term follow-up.
This case report is de-identified and published for educational purposes. All clinical details have been anonymized in accordance with patient privacy standards. CMCS Shanghai is a medical concierge service and does not provide direct medical care.
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