# Metachronous triple primary malignancies: a case report of NGS-guided multidisciplinary management and literature review

**Authors:** Xiangxue Li, Lihua Zhang, Xiaowei Wang, Jing Lv, Caiqi Liu, Siyi Zhang, Xiaoxuan Li, Jialin Song, Wensheng Qiu, Shufen Zhao

PMC · DOI: 10.3389/fonc.2026.1705144 · 2026-02-19

## TL;DR

A 72-year-old man with three cancers was successfully managed using next-generation sequencing and a multidisciplinary team approach.

## Contribution

This case highlights the role of NGS and MDT in managing complex triple primary malignancies.

## Key findings

- The patient received personalized treatment combining chemotherapy and targeted therapy.
- The patient maintained good quality of life with no recurrence of gastric or rectal cancer.
- Lung metastases showed a sustained partial response to ongoing targeted therapy.

## Abstract

Although the incidence of multiple primary malignancies (MPM) is increasing, triple primary malignancies (TPM) remain extremely rare. The pathogenesis of MPM is currently unclear, and there is a lack of optimal management strategies. Herein, we report a case of metachronous TPM involving both the respiratory tract and the digestive tract.

This report aims to analyze the clinical characteristics of the patient and emphasize the significant role of next-generation sequencing (NGS) and multidisciplinary team (MDT) in the management of MPM.

A 72-year-old male patient was diagnosed with a lung cancer and underwent surgical resection. Two years later, he was diagnosed with synchronous gastric cancer, rectal cancer, and bilateral pulmonary metastases. Guided by NGS and multiple MDT consultations, the patient received four cycles of individualized neoadjuvant chemotherapy combined with targeted therapy, followed by radical resection and postoperative adjuvant chemotherapy alongside targeted treatment. Currently, the patient’s pulmonary metastatic lesions are being managed with ongoing targeted therapy.

The patient currently maintains a good quality of life. During the follow-up period, no recurrence or metastasis of gastric or rectal cancer was observed, and the bilateral lung metastases showed a sustained partial response.

The management of TPM is considerable complex. MDT guided by NGS can be instrumental in formulating optimal, personalized treatment strategies for such patients, which may contribute to improved clinical outcomes and quality of life.

## Linked entities

- **Diseases:** lung cancer (MONDO:0005138), gastric cancer (MONDO:0001056), rectal cancer (MONDO:0006519)

## Full-text entities

- **Genes:** NAPSA (napsin A aspartic peptidase) [NCBI Gene 9476] {aka KAP, Kdap, NAP1, NAPA, NR1H2-AS1, SNAPA}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, TTF1 (transcription termination factor 1) [NCBI Gene 7270] {aka TTF-1, TTF-I}, NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893] {aka ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}
- **Diseases:** hereditary syndromes (MESH:D009386), breast and ovarian cancer (MESH:D061325), endometrial cancer (MESH:D016889), Carcinogens (MESH:D011230), thyroid cancer (MESH:D013964), gastric antral adenocarcinoma (MESH:D020252), leukemia (MESH:D007938), dysplasia (MESH:D015792), smoker (MESH:C000719328), colorectal cancer (MESH:D015179), inflammation (MESH:D007249), lung metastases (MESH:D009362), Defects in (MESH:D000013), toxicity (MESH:D064420), rectal lesion (MESH:D012002), cough (MESH:D003371), microsatellite instability (MESH:D053842), insulin resistance (MESH:D007333), gastric and rectal tumors (MESH:D012004), ulcer (MESH:D014456), infective (MESH:D007239), lung cancer (MESH:D008175), adenocarcinoma (MESH:D000230), Cancer (MESH:D009369), immune deficiency (MESH:D007154), lung lesion (MESH:D008171), gastrointestinal cancers (MESH:D005770), ovarian cancer (MESH:D010051), carcinogenesis (MESH:D063646), diarrhea (MESH:D003967), gastric and rectal lesions (MESH:D013272), breast cancer (MESH:D001943), obesity (MESH:D009765), lung adenocarcinoma (MESH:D000077192), lymph node metastasis (MESH:D008207), gastric adenocarcinoma (MESH:D013274), bladder cancer (MESH:D001749), head and neck squamous cell carcinoma (MESH:D000077195), LS (MESH:D003123), MPM (MESH:D001932), metabolic diseases (MESH:D008659), TPM (MESH:C536008), esophageal cancer (MESH:D004938)
- **Chemicals:** hematoxylin (MESH:D006416), MDT (-), platinum (MESH:D010984), HE (MESH:D006371), capecitabine (MESH:D000069287), ceftazidime (MESH:D002442), levofloxacin (MESH:D064704), fluconazole (MESH:D015725), XELOX (MESH:C519688), almonertinib (MESH:C000718108), methylprednisolone (MESH:D008775), oxaliplatin (MESH:D000077150), cyclophosphamide (MESH:D003520), eosin (MESH:D004801), alcohol (MESH:D000438)
- **Species:** Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097]
- **Mutations:** c.68-2A>C, p. D410N, p. R26C, p. D691N, p. D238Y, p. G12D, p. P441L, p. G243A, c.8418 + 2T>C, p. G720E, p. P140L, Q61K, c.74_241 + 56del, p.R544*, L858R, p. S33Y, p. E548K, p. P655L, p. R175H, p.N2875S, c.1893_1941 + 168del, p. N283S, p.R608*, p. V2054G

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961439/full.md

---
Source: https://tomesphere.com/paper/PMC12961439