Nedaplatin

As described previously (16 (link)), DEB-BACE procedures were performed under local anesthesia via a femoral artery approach. A 5-French pigtail catheter (PIG Impress; Merit Medical Systems, Inc., USA) was initially used for aortic arch angiography to detect the origins of tumor-feeding arteries. Then, a 5-French cobra (CB 1 Impress; Merit Medical Systems, Inc., USA) or left gastric catheter (Radifocus; Terumo Corporation, Japan) was used to select the bronchial arteries or non-bronchial systemic arteries. Super-selective catheterization with a 1.98-French microcatheter (Masters PARKWAY SOFT; Asahi Intec Co., Japan) was inserted coaxially. The chemotherapeutic regimen of paclitaxel (100–200 mg; Keaili, CSPC Pharmaceutical Group Co., China) was administered during BAI for patients who had already received systemic platinum-based chemotherapy, while nedaplatin (80–100 mg; Lubei, Qilu Pharmaceutical Co., China) was administered for patients who had not received systemic platinum-based chemotherapy. Gemcitabine (200–1,000 mg; Zefei, Hansoh Pharmaceutical Group Co., China) or endostatin (60-120 mg; Endu, Simcere Pharmaceutical Group, China) was infused on demand. BAI was followed by DEB-BACE, which was performed using 100–300 μm or 300–500 μm or 500–700 μm CalliSpheres microspheres (Jiangsu Hengrui Medical Co., China) loaded with gemcitabine (800 mg; Hansoh, China) or pirarubicin (30 mg; Adriamycin, Shenzhen Main Luck Pharmaceutical Inc., China). The CalliSpheres microspheres were first mixed with gemcitabine or pirarubicin at a temperature of 23°C–28°C for 30 min and vibrated every 5 min. Then, iodixanol (100 ml:65.2 g/32 g iodine; Hengrui, China) was added at a 1:1 ratio. The DEB-BACE was performed slowly and carefully in tumor-feeding arteries under fluoroscopic monitoring to avoid reflux into nontarget vessels. The technical endpoint of embolization was the absence of additional tumor staining or stasis/near stasis of the tumor-feeding arteries. For patients who received combination therapy, DEB-BACE was performed 2–45 days after MWA, followed by repeated DEB-BACE/BAI on demand. For the patients who received a repeated DEB-BACE/BAI, DEB-BACE was performed if abundant tumor staining was revealed in angiography, while BAI alone was performed for those patients without.

Eligibility criteria were as follows: the presence of untreated, pathologically confirmed primary OPSCC without distant metastases (M0), advanced clinical AJCC stage (stage III, IVA or IVB), age ≥18 years, and CCRT as a principal treatment with curative intent. Locoregional response to CCRT was determined by clinical and radiological (CT, magnetic resonance imaging, or PET-CT) examination as well as surgical biopsy in cases where local recurrence was strongly suspected.
A representative treatment scheme is shown in Fig. 1. The details of CCRT were obtained from medical charts and radiotherapy records. All patients had CT-assisted 3-dimensional radiation treatment planning in the treatment position with mask immobilization. The oropharynx and upper neck were treated through bilaterally opposed fields. The bilateral lower neck down to the supraclavicular fossa was treated with separate anteroposterior-posteroanterior portals that allowed shielding of the larynx and spinal cord. The primary lesion and whole neck including bilateral neck lymph nodes were irradiated with 1.8 Gy per day, up to 50.4 Gy. The primary site and metastatic lymph nodes were subsequently boosted with a further 16.2 Gy in 9 fractions. The accumulated dose to the gross primary tumor and metastatic neck lymph nodes was 66.6 Gy at 1.8 Gy/day, 5 times a week, in 37 fractions (once daily fractionation).
Several chemotherapy regimens were employed in this study. A summary of chemotherapy regimens is shown in Table I. The main chemotherapy regimen was a combination of nedaplatin (CDGP) and 5-fluorouracil (5-FU) (FN regimen). In the FN regimen, CDGP was administered at a dose of 90 mg/m² on day 1 and 5-FU was administered continuously at a dose of 800 mg/m² on days 2–6; the regimen was, in principle, given twice with a 4-week interval. The combination of docetaxel, CDGP, and 5-FU (TPF regimen) consisted of continuous administration of 5-FU (600 mg/m²) on days 1–4 and administration of CDGP (60 mg/m²) and docetaxel (60 mg/m²) on day 2; the weekly docetaxel regimen (weekly TXT) consisted of administration of docetaxel 10 mg, 5 times. The chemotherapy regimen administered was determined according to the patient’s general condition and any complications and at the discretion of the radiologist and surgeon.
The radiological response of the primary lesion was determined at 39.6 Gy by CT, according to the new Response Evaluation Criteria in Solid Tumours (revised RECIST guidelines, version 1.1) (23 (link)). If the primary lesion showed a partial response (≥30% reduction in size), CCRT continued as per the protocol. When the primary tumor failed to show a partial response regardless of the neck lymph node response, patients underwent curative surgery for the primary lesion combined with neck dissection. Patients who had N2 and N3 lesions were planned to receive neck dissection 2–3 months after CCRT (PND). The decision to perform comprehensive or selective neck dissection was made by the surgeon.
Every lymph node and extranodal deposit at PND was classified pathologically as either having no disease, treated disease with no viable cells, or residual viable cells. A pathologic CR in the neck was defined as the absence of viable tumor in any of the cervical lymph nodes or cervical soft tissues. Primary site response to CCRT was assessed with a combination of clinical and imaging examinations. All patients underwent a pan-endoscopy of the head and neck region at each visit during the observation period. In addition, biopsy of the primary site and fine needle aspiration of the neck lymph node were used in patients with suspected recurrence.

Before treatment, all NPC patients underwent Nasopharyngoscope and biopsy, as well as MRI scans of the nasopharynx and neck (both plain and enhanced), chest CT, abdominal CT or ultrasound, and bone ECT to determine the TNM staging. Patients with stage I or II were primarily treated with intensity-modulated radiotherapy alone, while those with stage III or IVa received combined treatment with radiotherapy and chemotherapy. The radiotherapy regimen consisted of intensity-modulated radiotherapy using 6-MV X-rays, with a total dose of 68–71.04 Gy/30–32 F for the planning target volume (PTVnx) of the gross tumor volume (GTVnx) of the nasopharynx, 64–68 Gy/30–32 F for the PTV of the neck lymph nodes (PTVnd), 60–62 Gy/30–32 F for PTV1, and 54–56 Gy/30–32 F for PTV2. Radiotherapy was administered once daily for five consecutive days per week. For neoadjuvant chemotherapy, the TP regimen (docetaxel or paclitaxel plus cisplatin or nedaplatin or lobaplatin) or PF regimen (cisplatin or nedaplatin or lobaplatin plus 5-fluorouracil) was mainly used. Concurrent chemotherapy primarily consisted of a single agent platinum-based regimen (cisplatin or nedaplatin or lobaplatin) or the PF regimen. Chemotherapy was administered once every 3 weeks. Follow-up evaluations typically occurred one month after the completion of radiotherapy, with subsequent evaluations conducted every three months within the first 2 years after treatment, every six months between years 3 and 5, and annually after 5 years. The latest follow-up was conducted on June 10, 2023.

In the observation group, the neoadjuvant immune combination chemotherapy regimen was paclitaxel(200 mg) + cisplatin(100 mg/m²)/nedaplatin(100 mg/m²)/carboplatin(400 mg/m²) + sintilimab(200 mg) in one or two days. One cycle is 21 days, and patients were treated symptomatically in case of adverse reactions.