A 57-year-old nonsmoking woman complained of cough, shortness of breath, chest distress, dyspnea, thoracolumbar and back pain for nearly one month and presented to our center just after the end of the COVID-19 lockdowns in Wuhan. She denied a history of tuberculosis exposure and any other history of disease except for well-controlled hypertension. She was notable for apparent bilateral supraclavicular lymphadenectasis after a physical examination. A chest computed tomography (CT) scan revealed numerous uniform pulmonary nodules in the bilateral lungs in addition to a 38x45 mm mass at the dorsal segment of the lower lobe of the left lung, with bilateral hilar and mediastinal lymphadenopathy ( Figures 1A, B ), and multiple bone metastases (including thoracic spine, sternum, ribs and left scapula). The enhanced CT scans showed multiple liver (the largest nodule about 21x21mm) and adrenal metastases ( Figure 1C ). Magnetic resonance examination of the head revealed no obvious metastases ( Figure 1D ). Her laboratory results (complete blood cell count: WBC (white blood cell) 8.6x109/L, RBC (red blood cell) 4.08x109/L, PLT (platelet) 433x109/L, liver panel: ALT (alanine aminotransferase) 19U/L, AST (aspartate aminotransferase) 34U/L, kidney panel: creatinine 47mumol/L) were within normal limits, her respiratory etiology test results (including tuberculosis) were negative, but her tumor markers were elevated ( Figure 2 ).
A supraclavicular lymph node biopsy was performed. Immunohistochemical staining was positive for PCK, CK7, TTF-1, and Ki-67 at 70%; negative for P40, Napsin A, Syn, and CDX-2; PD-L1(=1%, Clone: 22C3, Dako, Agilent Technologies, Inc.); which is consistent with lung adenocarcinoma ( Figure 3 ). Genetic testing of paraffin section from supraclavicular lymph node was conducted in CLIA-certified lab using hybridization capture-based next-generation sequencing panels. Gene targets (MyGene, BGI-Shenzhen [Headquarters]: Shenzhen, 518083, China. Genomic alterations assessed included single nucleotide variations, insertions and deletions, copy number variations, and gene rearrangements in selected genes. The MyGene panels covered common lung cancer-related genes. The minimum coverage across sample was >=1000x. Actionability of genomic alterations and the level of evidence were determined based on the OncoKB data set and drug approval status in mainland China ] revealed no mutated genes as EGFR [Exon 18/19/20/21/T790), FGFR2, FGFR3, ROS1, TP53, RET, PIK3CA (Exon 10/12, coding exon 9/20), ALK, KRAS (Codon 12/13/61/146), NRAS (Codon 12/13/61), KIT (Exon 9/11), BRCA1, BRCA2, and ERBB2 (Exon 20/copy number amplification). She was diagnosed with lung adenocarcinoma cT4N3M1 stage IVb, EGFR-negative (According to the eighth edition TNM classification, innumerable nodules in the ipsilateral lobes are categorized as T4, and those in a contralateral lobe while multiple metastases in distant organ are M1, bilateral hilar and mediastinal lymphadenopathy are N3).
She was given a cycle of pemetrexed (day 1: 500mg/m2) and cisplatin (day 1-3: 25mg/m2 every day), but reexamination of her chest CT and abdominal CT showed no signs of a reduction in her pulmonary nodules ( Figures 1E, F ). Then, three cycles of sintilimab (PD-1 inhibitor, day 1: 200mg) plus pemetrexed (day 1: 500mg/m2) and cisplatin (day 1-3: 25mg/m2 every day) were administered, the patient suffered greatly thoracolumbar and back pain, fierce cough, wheezing, chest distress, and dyspnea. Although there were no other immune-related adverse events, the treatment was terminated because of persistent disease progression ( Figures 1G, H ). Then, the patient received two cycles of recombinant human endostatin (Endostar, day 1-14: 7.5mg/m2 every day) combined with docetaxel (day 1: 75mg/m2) and lobaplatin (day 1: 75mg/m2). Her white blood cells were normal, liver and kidney function tests were normal (WBC 5.4x109/L, RBC 3.53x109/L, PLT 313x109/L, ALT 25U/L, AST 33U/L, creatinine 39mumol/L). Her symptoms, including cough, shortness of breath, wheezing, chest distress, dyspnea, thoracolumbar and back pain, were significantly relieved. She had no drug-related symptoms other than mild itching on his skin during this treatment period. Fortunately, chest and abdomen CT scans revealed almost complete disappearance of all pulmonary nodules, as well as an accentuated decrease in the primary lung mass (32x32mm) and liver metastasis volume (the largest one about 16x15mm) after this two cycle's treatment ( Figures 1I-L ). The diagram of her specific treatment progress see  Figure 1 .