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On June 10, 2015, a 41-year-old man came to our hospital with a complaint of a 2-year history of enlarged right inguinal nodules after a melanoma surgery on his right planta pedis 4 years ago. The pathology diagnosis indicated MM with immunophenotype: HMB45 (++), S-100 (+), Vim (++), EMA (+), SMA (+), Ki-67 (+50%), and Melan-A (+++). Except for multiple nodules in the right inguinal region, other metastases were ruled out by ultrasound, computed tomography (CT) scan, and MRI. Since being evaluated as a stable disease (SD), after two cycles of chemotherapy (Table 1), he went through a lymph node dissection in a local hospital.

(To view a larger version of Table 1, click here.)

Unfortunately, no further treatment was taken after surgery due to patient’s personal reasons. Three months after the surgery, chest CT scan showed multiple metastatic nodules in both lungs. Thus, a second-line chemotherapy of paclitaxel and carboplatin was then performed (Table 1). Because the patient complained of pelvic pain, early reexamination of CT and MRI was then performed 1 month after the first administration of the second-line chemotherapy. The results showed multiple metastases in both lungs, hilar lymph nodes, liver, and bones (including vertebra, sternum, and iliac bone; Figure 1A and B), and it was considered to be a progressive disease (PD).

(To view a larger version of Figure 1, click here.)

At this time, the patient progressed rapidly and was then refractory to traditional chemotherapy. Anti-PD-1 agents were unavailable, and the patient refused expensive targeted therapies and further clinical trials on MM in other hospitals. In the meantime, there is a medical products–donating project for apatinib that patients can get support since they pay for apatinib for the first 3 months. So after getting a written informed consent from the patient, a combination of apatinib and TMZ along with zoledronic acid was performed immediately (Table 1). After 2 months of treatment, the lesions in lung and liver were significantly reduced in size, which was considered to be a partial response (PR) based on the CT scan (Figure 1C and D). The following reviews of CT and MRI 3 months later showed no progression (Figure 1E and F). The patient continued to use apatinib and TMZ as a maintenance therapy. A progression-free survival (PFS) time of >1 year has been achieved.

The main toxicities the patient experienced were grade II hand-foot syndrome and grade II–III aphthous stomatitis. No other toxicities were complained and detected.

Next-generation sequencing (NGS; also known as high-throughput sequencing) analysis for the patient’s blood sample after 11 months of this new treatment revealed KIT mutation in exon 11, but didn’t show other genomic mutations, such as BRAFNRASPTEN, or CDKN2A. The protein expressions of CD117 and VEGFR3 were high (Figure 2). As the patient experienced multiple drugs treatment that might change gene mutation, we further tested the inguinal lymph node tissue samples before the treatment. The result also revealed only KIT mutation in exon 11.

(To view a larger version of Figure 2, click here.)