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Head and neck dermatofibrosarcoma protuberans (HNDFSP) is extremely rare and not entirely understood.To investigate the clinicopathological features of HNDFSP and identify the expression of its clinically relevant indicators, with the expectation of improving the existing treatment strategies.A long-term follow-up of patients with HNDFSP who received treatment between 2000 and 2021 at Shanghai Ninth People's Hospital was conducted. The clinical, histological, and immunohistochemical data of the patients were retrieved and analyzed. The endpoint of the study was the incidence of significant disease-related clinical events (recurrences or metastasis).A total of 49 patients with HNDFSP were included in the study, with males (92.7%) predominating than females (7.3%). Eighteen patients developed recurrent disease (36.8%) after surgery, and the median time of recurrence was 48 months (interquartile, 20-74 months). Metastasis occurred in two cases (4.1%). Two patients died during follow-up, both with local recurrence, and one of them with intestinal metastasis. Post-operation radiotherapy was administered to eight patients (16.3%) and the effect in local control was remarkable. Age, tumor size, and negative margins with sufficient safety width were the main independent factors affecting the disease-free survival. Several potential targeted therapeutic indicators, including EZH2 (80.0%), EGFR (91.4%), PDGF (97.1%), PD-L1 (77.1%), and VEGF (77.1%), were positively expressed in most tumor samples.HNDFSP is rare, significantly challenging to control locally, and has a worse prognosis with current treatment strategies. Wide local excision and long-term follow-up are needed. Radiotherapy could improve the prognosis of patients with HNDFSP.

Head and neck squamous cell carcinoma (HNSCC) is a common and frequently lethal cancer with few therapeutic options. In particular, there are few effective targeted therapies. Development of highly effective therapeutic strategies tailored to patients with HNSCC remains a pressing challenge. To address this, we present a pharmacogenomic study to facilitate precision treatments for patients with HNSCC. We established a large collection of 56 HNSCC patient-derived cells (PDCs), which recapitulated the molecular features of the original tumors. Pharmacological assessment of HNSCCs was conducted using a three-tiered high-throughput drug screening using 2248 compounds across these PDC models and an additional 18 immortalized cell lines. We integrated genomic, transcriptomic, and pharmacological analysis to predict biomarkers, gene-drug associations, and validated biomarkers. These results supported drug repurposing for multiple HNSCC subtypes, including the JAK2 inhibitor fedratinib, for low KRT18 –expressing HNSCC cases, and the topoisomerase inhibitor mitoxantrone, for IL6R -activated HNSCC cases. Our results demonstrated concordance between susceptibility predictions from the PDCs and the matched patients’ responses to standard clinical medication. Moreover, we identified and experimentally confirmed that high expression of ITGB1 elicited therapeutic resistance to docetaxel and high SOD1 expression conferred resistance to afatinib. We further validated ITGB1 as a predictive biomarker for the efficacy of docetaxel therapy in a phase 2 clinical trial. In summary, our study shows that this HNSCC cell resource, as well as the resulting pharmacogenomic profiles, is effective for biomarker discovery and for guiding precision oncology therapies in HNSCCs.

Objective Controversy still exists regarding the volume of radiation for head and neck cancer of unknown primary (HNCUP). Theoretically, elective mucosal irradiation (EMI) should achieve a balance between survival and toxicity. This prospective study was conducted to evaluate the long‐term benefit of EMI in Chinese HNCUP patients. Methods A phase II, single‐arm trial was performed at two centers in China. HNCUP patients with pathologically confirmed metastatic squamous cell carcinoma or poorly differentiated carcinoma were enrolled. Patients with metastatic lymph nodes limited to level IV and/or the supraclavicular fossa were excluded. The EMI approach was specifically customized to Chinese patients by differentiating HNCUP as putative nasopharyngeal carcinoma (NPC) or non‐putative NPC. The primary endpoint was 3‐year mucosal recurrence‐free survival (MRFS). Results A total of 48 patients were enrolled between 02/02/2010 and 08/01/2018; 46 patients were analyzed, including 24 putative NPC and 22 non‐putative NPC patients. No primary recurrence was observed during a median follow‐up period of 70 months, and only 1 patient experienced out of field recurrence in the contralateral neck. The 3‐year MRFS was 90.6% (95%CI: 76.4%‐96.4%). The 5‐year MRFS, regional‐recurrence free survival (RRFS) and overall survival (OS) were 90.6% (95%CI: 76.4%‐96.4%), 86.0% (95%CI: 71.1%‐93.7%), and 90.6% (95%CI: 76.4%‐96.4%), respectively. No grade 4 acute or late toxicities occurred, and the most frequent grade 3 acute toxicity was oral mucositis (45.7%). Conclusion To the best of our knowledge, this is the first prospective study to evaluate the long‐term outcomes of EMI in Chinese HNCUP patients. Excellent MRFS and OS rates were observed. Further randomized studies are warranted., This is the first prospective clinical study focused on the clinical efficacy and toxicity of EMI in Chinese HNCUP patients. The encouraging results of this EMICUP study showed a 3‐year MRFS of 90.6%. Long‐term clinical benefit was demonstrated with a 5‐year MRFS rate of 90.6%, a 5‐year DFS rate of 86.1%, a 5‐year OS rate of 90.6%, and acceptable acute and late toxicities. The EMI approach was safe and feasible and seemed to balance tumor control and toxicity. In addition, this study also emphasized that putative NPC and non‐putative NPC should be defined and treated differently, as HNCUP includes a heterogeneous group of patients.

6060 Background: Immune checkpoint inhibitor combined with antiangiogenic agent has been investigated in many solid tumors, including advanced head and neck squamous cell carcinoma (HNSCC; NCT02501096), but the evidence is limited. This study was conducted to investigate the efficacy and safety of anti-programmed cell death-1 antibody camrelizumab plus antiangiogenic agent apatinib as induction therapy in patients with locally advanced HNSCC. Methods: In this single-center phase II trial (NCT04440917), patients with untreated locally advanced HNSCC who had inoperable lesions, could not tolerate surgery, or refused surgery were enrolled. Patients received camrelizumab 200 mg once every 2 weeks and apatinib 250 mg once daily for two 28-day cycles, followed by local treatment based on the re-examination results. The primary endpoint was objective response rate (ORR) after induction therapy, as assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. Simon’s two-stage design was adopted for this study. Results: Between December 2019 and July 2021, 18 patients were enrolled in the first stage. Eight (44%) patients had oropharyngeal carcinoma, nine (50%) had oral carcinoma, and one (6%) had hypopharyngeal carcinoma. There were six (33%), three (17%), and nine (50%) patients with stage III, IVA, and IVB disease, respectively. After induction therapy, six patients achieved complete response, nine achieved partial response, and three had stable disease, with an ORR of 83%. The study proceeded to the second stage and the enrollment for another 14 patients is ongoing. Two (11%) patients with partial response received surgery and adjuvant radiotherapy, and 16 (89%) received radical radiotherapy. With a median follow-up duration of 18 months (range, 9-26), only one disease recurrence and no deaths occurred. The most common adverse events during induction therapy were hypertension (ten [56%]), oral pain (nine [50%]), and increased aspartate aminotransferase (five [28%]). Only one [6%] grade 3 hypertension and one [6%] grade 3 proteinuria were observed, and no grade 4 or 5 adverse events occurred. Conclusions: Camrelizumab plus apatinib showed promising antitumor activity as induction therapy in patients with locally advanced HNSCC, with acceptable safety profile. Clinical trial information: NCT04440917.

e18067 Background: In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), major pathological response (MPR) to neoadjuvant therapy may translate into improved survival. The combination of anti-PD-1 and chemotherapy as neoadjuvant protocol has not been well reported in OSCC. Methods: The prospective single arm trial (NCT04473716) was performed to evaluate the neoadjuvant therapy with anti-PD-1 (Toripalimab) and chemotherapy (albumin paclitaxel/cisplatin) in OSCC patients at clinical stage III and IVA (AJCC 2018). The patients received two cycles (21 days each) of intravenous albumin paclitaxel (260mg/m2), cisplatin (75mg/m2) and Toripalimab (240mg) on day 1 and day 22. Radical surgery was performed within two weeks after neoadjuvant therapy. Post-operative radiotherapy/chemoradiotherapy was performed within 1.5 months after surgery. The primary endpoints were MPR and safety. Primary tumors were assessed for the percentage of residual viable tumor cells on HE staining, and tumor with no more than 10% viable tumor cell was considered as MPR. Results: From Nov. 2020 to Apr. 2021, 20 patients were enrolled, including 16 males and 4 females, at clinical stage III (16) and IVA (4). They aged from 19 to 75 (median 54) years . The primary tumor site was eight tongue, six mouth floor, three gingiva, two retromolar trigone and one buccal mucosa. The neoadjuvant therapy was well-tolerated with low incidence of grade 3-4 adverse events (AEs) including 5% grade 4 neutropenia, 10% grade 3 leukopenia, 5% grade 3 neutropenia, hypokalemia, vomiting, and rash each. Common grade 1-2 AEs included baldness/rash/itch/pain/fatigue, AST/ALT/uric acid elevation, nausea/vomiting/diarrhea, hyperbilirubinemia, proteinuria, neutropenia/leukopenia. All AEs were relieved after expectant treatment, the subsequent standard treatment was not delayed. According to pathological evaluation, the MPR rate was 60% (12/20), including 30% (6/20) pCR. According to RECIST 1.1, radiological evaluation on neoadjuvant therapy showed two CR, ten PR, seven SD and one PD. It was significantly consistent between pathological and radiological evaluation in linear regression analysis ( P＜0.0001). Combined positive score (CPS) of PD-L1 expression in biopsy was evaluated in 19 patients, MPR was archived in all 4 patients with CPS≥10, in 6 out of 8 patients (75%) with CPS≥1, and in 5 out of 11 patients (45.5%) with CPS < 1. Conclusions: Neoadjuvant therapy with combination of Toripalimab, albumin paclitaxel, and cisplatin in resectable OSCC patients is safe and well-tolerated, with high MPR rate. Clinical trial information: NCT04473716.

6066 Background: For elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the role of postoperative concurrent chemotherapy was controversial since the intolerable toxicities and increased acute mortality, thus, radiotherapy alone was recommended. Aimed to seek out a feasible regimen for concurrent treatment, we evaluated the feasibility and quality of life of postoperative concurrent radiotherapy and toripalimab (anti-PD-1 antibody) in elderly HNSCC patients. Methods: The IMPORT trial was an investigator-initiated, multicentre, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at 3 hospitals in China. We randomly assigned (1:1) patients aged＞65 years, with ECOG Performance Status(PS) of 0–2, and with postoperative Stage III-IV (AJCC 8th Staging system) HNSCC to concurrent radiotherapy (60-66Gy) and toripalimab (240mg on D0, D21 and D42)(RT+PD-1 group) or radiotherapy alone(RT group). Following stratification by PS(0-1 vs 2) and pathological adverse features (extranodal extension or positive margin vs others), patients were randomly assigned using a computer-generated randomization list. Acute toxicities were reported. Quality of life were evaluated by EORTC QLQ-C30 and QLQ-H&N35 at baseline, week3, week6 and 1 month after radiotherapy, and the standard scores were compared between groups by linear mixed-effects models. Results: Between September 2020 and December 2021, 38 patients randomly assigned(19 per group). The median age were 70 years (range 66-81) for the RT+PD-1 group and 73 years (range 67-78 years) for RT group. 16 (84.2%) patients in the RT+PD-1 group and 15 (78.9%) patients in the RT group complete the planed radiation dose. In the RT+PD-1 group, 13 (68.4%) patients completed 3 cycles of toripalimab, 3 (15.8%) patients completed 2 cycles due to adverse events and 3 (15.8%) patients declined toripalimab; The most common adverse events of grade 3-5 was oral mucositis (55.6% vs 58.8%) and lymphocyte count decreased(61.1% and 41.2%) in RT+PD-1 group and RT group. In the RT+PD-1 group, only 1 patients experienced grade 3 immune-related enteritis. As to the quality of life scores evaluated by QLQ-C30, no difference was found in standard score of global health status, as well as in most functional scales including: physical, emotion, cognitive and social, except for role functioning (p = 0.045). As to the symptom scale scores evaluated by QLQ-H&N35, no difference was found in standard score of pain, swallowing, dry mouth, opening mouth, and stick saliva, except for speech problem (p = 0.032). Conclusions: For elderly patients with locally advanced HNSCC, postoperative concurrent radiotherapy and toripalimab was safe and feasible. Concurrent toripalimab did not worsen quality of life scores in the majority of cases. Clinical trial information: NCT04523883.

Supplemental material, sj-pdf-2-tam-10.1177_17588359211013626 for Apatinib in patients with recurrent or metastatic adenoid cystic carcinoma of the head and neck: a single-arm, phase II prospective study by Guopei Zhu, Lin Zhang, Shengjin Dou, Rongrong Li, Jiang Li, Lulu Ye, Wen Jiang, Minjun Dong, Min Ruan, Wenjun Yang and Chenping Zhang in Therapeutic Advances in Medical Oncology

Supplemental material, sj-pdf-1-tam-10.1177_17588359211013626 for Apatinib in patients with recurrent or metastatic adenoid cystic carcinoma of the head and neck: a single-arm, phase II prospective study by Guopei Zhu, Lin Zhang, Shengjin Dou, Rongrong Li, Jiang Li, Lulu Ye, Wen Jiang, Minjun Dong, Min Ruan, Wenjun Yang and Chenping Zhang in Therapeutic Advances in Medical Oncology

Background: Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various cancer types. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN. Methods: In this phase II single-arm, prospective study, patients aged 15–75 years with incurable R/MACCHN received apatinib at a 500 mg dose once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate based on RECIST version 1.1. The secondary endpoints included response rate, overall survival (OS), and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment. Results: Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25.8 months. The 6-month, 12-month, and 24-month PFS rates were 92.3% [95% confidence interval (CI): 83–97.5%], 75.2% (95% CI: 61.5–84.0%) and 44.7% (95% CI: 32.3–57.5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46.2% (95% CI: 33.7–59.0%) and 98.5% (95% CI: 91.7–100.0%), respectively. The median duration of response was 17.7 months [interquartile range (IQR) 14.0–20.9]. The 12-month and 24-month OS rates were 92.3% (95% CI: 83.0–97.5%) and 82.3% (95% CI: 70–90.4%), respectively. The most common adverse events of grades 3–4 were hypertension (5.9%), proteinuria (9.2%), and hemorrhage (5.9%). One patient developed a fatal hemorrhage. Conclusion: An encouraging PFS, a high ORR, and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation. This study was prospectively registered in ClinicalTrials.gov (NCT02775370; date of registration: 17 May 2016; date of first patient enrollment: 25 May 2016)

Novel systemic agents and effective treatment strategies for recurrence adenoid cystic carcinoma (ACC) of the head and neck are still worthy of further exploration. Here, we analyzed the mutations and expression profiles of 75 Chinese ACC patients, characterized the prognostic value of the immune signature for recurrence or distant metastasis, and explored the potential of immunotherapeutic biomarkers in ACC. In general, MYB fusion and somatic mutations accounted for a high proportion, which was 46.7% (35/75). ACCs displayed an overall low mutation burden and lack of programmed cell death ligand-1 (PD-L1) expression. The antigen-presenting machinery (APM) expression score and immune infiltration score (IIS) were the lowest among ACC patients, compared with other cancer types. For 61 primary cases, the locoregional recurrence-free survival (LRRFS) was statistically significantly correlated with the IIS [univariate analysis; hazard ratio (HR) = 0.32; 95% CI, 0.11–0.92; p = 0.035] and T-cell infiltration score (TIS) (univariate analysis; HR = 0.33; 95% CI, 0.12–0.94; p = 0.037]. Patients with lower IIS (log-rank p = 0.0079) or TIS (log-rank p = 0.0079) had shorter LRRFS. Additionally, solid pattern was also a prognostic factor related to locoregional recurrence, whereas postoperative radiotherapy (PORT) exerted its beneficial effects. We further evaluated the pretreatment immune profile of five ACC patients treated with PD-1 inhibitors. Patients who responded to camrelizumab or pembrolizumab observed elevated APM and TIS, compared with patients with progressive disease. Our study highlights the immune infiltration pattern and messenger RNA (mRNA) signatures of Chinese ACC patients, which has the potential value for prognosis and immunotherapy.

Background: Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various types of cancer. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. The high VEGFR expression in R/MACCHN makes antiangiogenesis a potential effective treatment in patients with R/MACCHN. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN. Methods: In this phase II single-arm, prospective study, patients aged 15-75 years with incurable R/MACCHN received apatinib at a dose of 500 mg once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate, which was based on RECIST version 1·1. The secondary endpoints included response rate, overall survival (OS) and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment. Findings: Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25·8 months. The 6-month, 12-month and 24-month PFS rates were 92·3% (95% confidence interval [CI]: 83–97·5%), 75·2% (95% CI: 61·5-84·0%) and 44·7% (95% CI: 32·3-57·5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46·2% (95% CI: 33·7–59·0%) and 98·5% (95% CI: 91·7–100·0%), respectively. The median duration of response was 17·7 months (interquartile range [IQR], 14·0-20·9). The 12-month and 24-month OS rates were 92·3% (95% CI: 83·0-97·5%) and 82·3% (95% CI: 70-90·4%), respectively. The most common adverse events of grades 3–4 were hypertension (5·9%), proteinuria (9·2%) and hemorrhage (5·9%). One patient developed a fatal hemorrhage. Interpretation: An encouraging PFS, a high ORR and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation. Trial Registration: Registered under http://www.clinicaltrials.gov (NCT02775370) Funding Statement: This work was supported by Shanghai Municipal Commission of Health and Family Planning (grant number 201640158)；the Clinical Research Program of 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine and the Shanghai Shenkang Hospital Development Center Refractory Diseases Project (project number 16CR2004A); Clinical Research Program of 9th People's Hospital, Shanghai Jiao Tong University School of Medicine (program number JYLJ201825). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This investigator-initiated phase II study was approved by the ethics committee of Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, and performed according to Good Clinical Practice Guidelines. All patients provided written informed consent before enrollment.

Purpose To evaluate the efficacy and safety of postoperative concurrent chemoradiation therapy using weekly docetaxel in patients with high-risk oral squamous cell carcinoma (OSCC). Methods and Materials This is a prospective single-arm study from a single institute in Shanghai Ninth People's Hospital, Shanghai, China. Patients with locally stage III to IV OSCC who underwent radical surgery with at least 1 high-risk feature were enrolled for the study. High-risk features evaluated included (1) pathologically confirmed positive or close margins in the primary site or extracapsular nodal extension; (2) histologic involvement of ≥2 regional lymph nodes; and (3) locoregional recurrent OSCC (after initial surgery alone) treated with salvage surgery with curative intent. Docetaxel was administered at a dose of 20 mg/m2 concurrently with postoperative radiation therapy (total dose 60-66 Gy). The primary outcome was 2-year disease-free survival (DFS). Secondary endpoints included 2-year locoregional progress-free survival, 2-year overall survival (OS), and toxicities. Results From March 2016 to February 2018, 91 patients (59 males, 32 females) were recruited. Median age was 59 years (range, 26-70). All patients were included in final analysis. Fifty-eight patients (63.7%) completed the 6 planned cycles of docetaxel, and all patients completed postoperative radiation therapy. With a median follow-up of 24 months, the 2-year DFS and OS were 75.3% (95% confidence interval, 65.7%-84.2%) and 82.4% (95% confidence interval, 73.0%-89.6%), respectively. Patterns of failure were 13 local recurrences, 2 regional lymph nodes recurrences, and 8 distant failures. Seven patients (7.7%) were recorded as having grade 3 oral cavity mucositis. Two patients had grade 3 hypersensitivity reaction. No other grade 3 or higher adverse events, including hematologic toxicities, were observed. Conclusions The addition of low-dose weekly docetaxel with concurrent radiation therapy is a tolerable regimen with favorable DFS and OS in patients with high-risk, resected OSCC.

e18003 Background: Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Anti-PD1/PD-L1 checkpoint inhibitors have shown survival benefit for the treatment on HNSCC, and are better tolerated than chemotherapy. Unfortunately, the response rate of immunotherapy is low for advanced HNSCC. Therefore, the identification of predictive biomarkers of response to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit from immunotherapy. Methods: The present study included 44 patients with advanced HNSCC who received anti-PD-1 immunotherapy. Follow-up was available for them. Primary tumor tissues and matched blood samples were collected. Genome profiles were analyzed using a designed 543-gene panel based on NGS, and were available on 39 of 44 patients. Profiles of infiltrating immune cells were available for 44 patients. The infiltrating intensity of PD-1, PD-L1, CD8, CD68 and CD57 positive cells were assessed by multiplex immunohistochemistry. Results: The most frequently mutated genes were TP53 (79%), CDKN2A (33%), NOTCH1 (21%), CASP8 (13%) and PIK3CA (10%). Patients with mutations in the PI3K pathway showed a trend of longer OS (P = 0.06). Moreover, the TMB-high group showed significant superior OS than the TMB-low group (p = 0.0018). PD-L1 expression was positively correlated with CD8 expression within stroma, and PD-1 expression correlated significantly with PD-L1 and CD8 expression within both tumor and stroma areas. In addition, tumor/stromal PD-L1 and PD-1 expression were both associated with better OS (P < 0.05). Prolonged OS was also observed in patients with more tumor and stromal infiltration of CD8+ cells, CD8+PD-L1+ cells, CD68+ macrophages, or nature killer (NK, CD57+) cells. Conclusions: Higher TMB, PD-L1 expression, as well as the infiltration of immune cells within both tumor and stromal area might serve as favorable prognostic markers in advanced HNSCC patients treated with anti-PD-1 immunotherapy.

6052 Background: In patients with locally advanced oral squamous cell carcinoma (LAOSCC), major pathologic response (MPR) to induction therapy may translate into improved survival. The induction therapy using chemo-free drugs, such as the combination of anti-PD1 and anti-VEGFR drugs, has not been well issued in LAOSCC. Methods: A prospective single arm trial (NCT04393506) has been performed to evaluate the induction therapy of anti-PD1 and anti-VEGFR protocol in LAOSCC patients at clinical stage III and IVA. The patients received three cycles of intravenous Camrelizumab (PD-1 antibody, 200mg) on d1, d15, d29; and oral Apatinib (anti-VEGFR inhibitor, 250mg) daily, initiating on d1, ending on the 5th day before surgery. Radical surgery was planned on d42-d45. Post-operative radiotherapy was planned within 1.5 months after surgery, based on clinical and pathological stage. The primary endpoints were MPR and safety; primary tumors were assessed for the percentage of residual viable tumor that was identified on HE staining, and tumors with no more than 10% viable tumor cells were considered as MPR. This study has been approved by institutional ethics committee at Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Results: From April to December 2020, 21 patients were enrolled in this trial, and one patient withdraw from the trial at the beginning of treatment. The induction therapy was well-tolerated with no grade 3-4 toxicity or serve induction therapy-related AEs. One patient required surgery delay for 7 days due to unexplainable cTnI elevation. One patient put off Camrelizumab for 14 days due to grade 2 thrombocytopenia. One patient suspended Apatinib for 21 days due to grade 2 Hyperbilirubinemia. The induction therapy did not effect on the subsequent standard treatment. MPR rate was 40% (8/20), including 5% (1/20) pCR. Radiological evaluation of response to induction therapy showed 3 PR, 10 SD, 5 PD and 2 NA. Weak correlation was found between pathologic and radiological evaluation on induction therapy. Combined positive score (CPS) of PD-L1 expression in biopsy was evaluated in 19 patients; all 4 patients with CPS≥ 20 had MPR, 3 out of 11 patients with 1≤CPS < 20 had MPR, and 1 out of 4 patients with CPS < 1 had MPR. Conclusions: The chemo-free protocol of induction therapy using Camrelizumab and Apatinib is safe and well-tolerated for the patients with LAOSCC. The MPR rate is much higher using the anti-PD1 and anti-VEGFR protocol than the traditional induction chemotherapy protocol in LAOSCC. Clinical trial information: NCT04393506.

6039 Background: The predominant pattern of failure for Head and Neck Squamous Cell Carcinoma (HNSCC) is locoregional disease. Salvage surgery remains the standard of care for operable disease. Re-irradiation after previous full course radiotherapy generally has been considered contraindicated. Since anti-PD-1 antibodies were efficacious and safety in recurrent/metastatic HNSCC, this study aimed to evaluate the efficacy and safety of adjuvant toripalimab (anti-PD-1 antibody) in recurrent, previously irradiated HNSCC treated with salvage surgery. Methods: This study was a single-arm, phase II study. Patients with HNSCC occurring in an area of previously irradiated and with at least one high risk factors after salvage surgery (1- positive margin; 2- extranodal extension; 3- rStaging T3-4/N2-3/T2N1) were enrolled. In the Stage I of 12 patients, patients received toripalimab 240mg once every 3 weeks until confirmed disease progression or unacceptable toxicity, for 12 months. In the stage II of 8 patients with PD-L1 CPS≥1, patients received toripalimab combined with S-1, which was given orally at 25 mg/m2, twice daily, on day 1 to 14, repeated every 21 days for 4-6 cycles. The primary endpoint was 1-year progression-free survival (PFS). We hypothesized a 1-year PFS of at least 56% and assumed a null hypothesis of 34%. A retrospective cohort of 16 patients was compared. Results: Between May 2019 and December 2020, 20 patients were enrolled. High-risk factors included ENE (35%), positive margin (25%), T3-4(30%) and T2N+(10%). Seventeen patients have PD-L1 CPS≥1 and 3 patients have CPS＜1. With a median follow-up of 11.2 months, estimated 1-year PFS and overall survival was 57.0% (95% confidence interval, 32%– 77%) and 79.2% (51%–91%). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. When compared to the retrospective cohort, the PFS was significantly better(p=0.001)，even for Stage I patients(Median PFS: 5.1 vs 3.7 months, p=0.03 ). Stage II patients resulted a better PFS and OS compare to stage I (p=0.02 and p=0.002). For patients with CPS≥1, 1-year PFS and OS was 79.1% (95% confidence interval, 51%–91%) and 91.7%(68%–99%), which were significantly better than patients with CPS＜1 (p=0.001 and p=0.05). Adjuvant Toripalimab or combine with S-1 was well-tolerated with no grade 3-4 toxicity and dose interruption as a result of treatment-related adverse event only occurred in 2 patients. Flow cytometry revealed that patients with short PFS had fewer baseline overall count of B cells(p=0.09). Conclusions: Adjuvant Toripalimab or combined with S-1 after salvage surgery is efficacious and safety in recurrent, previously irradiated HNSCC, and a better PFS was observed in patients treated with combined therapy and with CPS≥1. Further randomized trials are warranted. Clinical trial information: NCT04126460.

e18010 Background: PDL-1 and tumor mutation burden are only useful to select a small portion of patients with head and neck squamous cell carcinoma for immunotherapy, more biomarkers are in an urgent need for the majority. Methods: Ninety-nine recurrent/metastatic patients were analyzed. PD-1 cohort including 78 patients; Non-PD-1(NPD-1) cohort including 28 patients received anti-EGFR antibody and harbored at least one of EGFR amplification/mutation, CCND1 amplification, FGF3/4/19 amplification, or CDKN2A/B mutations (including 7 patients received with both treatment). Patients were evaluated as no clinical benefit (NCB) if experiencing progressive disease or stable disease lasting < 6 months and were discontinued from immunotherapy within 3 months; otherwise, patients were evaluated as clinical benefit (CB). Tumor genomic DNA was isolated from formalin-fixed paraffin-embedded tissue for the targeted sequencing by a 769-gene panel. R package was used for fisher test to evaluate the variants. p < 0.05 was set as significant. Results: With median age of 57 years old, this study included 75 (75.8%) oral squamous cell carcinoma patients,17 (17.2%) oropharyngeal carcinoma patients and 7 others. Sixty-nine (69.7%) patients have PD-L1 CPS≥1, 27 (27.3%) patients have CPS＜1 and 3 (3.0%) have an unknown CPS. The estimated 10-month progression-free survival of the NPD-1 cohort and PD-1cohort were 60.0%and 47.6% (p = 0.06) respectively. In NPD-1 cohort, 23 patients were evaluated as CB (78.3%), and in PD-1 cohort, 41 were evaluated as CB (52.6%) (p = 0.00682), indicating EGFR amplification/mutation, CCND1 amplification, FGF3/4/19 amplification, or CDKN2A/B mutations may be negatively correlated with immunotherapies. There were 14 patients who harbored either EGFR amplification or SNV mutation. Of the 8 patients who received NPD-1 treatment, 7 were CB (87.5%); Of the 8 patients who received PD-1 treatment, 2 were CB (25%) Statistically, the difference between NPD-1 treatment group and PD-1 treatment group was significant with a p value of 0.04056. There were 16 patients who harbored CCND1 amplification, or FGF3/4/19 amplification. Of the 12 patients who received NPD-1 treatment, 10 were evaluated as CB (83.3%); Of the 7 patients who received PD-1 treatment, 1 was evaluated as CB (14.3%). The difference was significant with a p value of 0.00627. There were 44 patients who obtained CDKN2A/B mutations. Of the 12 patients who received NPD-1 treatment, 11 acquired CB (81.7%); Of the 33 patients who received PD-1 treatment, 18 acquired CB (54.5%). The difference was significant with a p value of 0.03325. Conclusions: We for the first time showed that genetic-altered EGFR, FGF3/4/19, CCND1 and CDKN2A/B were negatively correlated with anti-PD-1 therapy in clinical cohorts retrospectively and these genetic aberrations may serve as novel immune-negative biomarkers for immunotherapies.

6026 Background: There is no standard treatment for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). Moreover, MYB and/or NOTCH1 mutation can lead to worse prognosis. Currently, anti-angiogenic targeted therapy is a relatively effective treatment option, but the accompanied toxicities may hinder the continuous medication. All-trans retinoic acid (ATRA) induces differentiation and promotes apoptosis, enhancing the cytotoxicity of anti-tumor agents; on the other hand, inhibits c-MYB and/or NOTCH1 expression. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2. We reported the preliminary results of the efficacy and safety of ATRA combined with low-dose apatinib in patients with R/M ACC. Methods: In this exploratory study, patients with pathologically or histologically confirmed advanced, R/M ACC with measurable disease were screened. Patients who previously received anti-angiogenic therapy then withdrew due to toxicities could be recruited. ATRA was administered orally at a dose of 20 mg twice a day, and apatinib was administered orally at a dose of 250 mg once a day. The primary endpoint was objective response rate (ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors v1.1. Results: Between March 2019 and April 2020, a total of 16 patients were enrolled. The median age was 53 years (range: 35-69), and 7 (44%) patients were male. Four (25%) patients received ATRA plus apatinib as the third-line therapy, while 12 (75%) received as the second-line therapy. Of 16 patients, 3 (19%) achieved partial response and 13 (81%) achieved stable disease (SD), with ORR of 19% and disease control rate of 100%, respectively. Among patients with SD, 12 (75%) showed tumor shrinkage (3%-28%) and 1 (6%) showed minor tumor enlargement (2%). The median follow-up time was 14.5 months (range: 8.1-22.1). Throughout the period, 5 (42%) patients developed disease progression. The 6-month and 12-month progression-free survival rates were 100% and 80%, respectively. Grade 3 adverse events included hand-foot syndrome (1 [6%]) and proteinuria (1 [6%]). No grade ≥4 adverse events occurred. Conclusions: ATRA combined with low-dose anti-angiogenic drug apatinib could be a potential treatment option for patients with R/M ACC, including those with pretreated advanced ACC after progression on or intolerance to other therapies. These encouraging results were worth further investigations, and a randomized phase 2 trial in ongoing (the Aplus study, NCT04433169).

// Shengjin Dou 1 , Wei Qian 1 , Qinghai Ji 2 , Zhuoying Wang 2 , Guopei Zhu 3 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China 2 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China 3 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China Correspondence to: Guopei Zhu, email: antica@gmail.com Zhuoying Wang, email: wangzhuoying@shca.org.cn Keywords: unknown primary carcinoma, cervical lymph node metastasis, multimodality therapy, treatment decision, head and neck cancer Received: October 22, 2015 Accepted: May 05, 2016 Published: May 20, 2016 ABSTRACT Background: There is no consensus on the treatment of head-and-neck cancer of unknown primary (HNCUP). The objective of this study is to report our single institution’s experience of a tailored multimodality therapy guided by a two-step decision making process. Materials and Methods: From January 2007 to November 2013, 92 consecutive patients of HNCUP were treated. 77 patients were treated according the process above, 24 were treated by radiotherapy to the nasopharyngeal site, 7 received neck dissection and radiotherapy to other putative mucosal site, 30 were treated by neck dissection alone, and 16 received neck dissection followed by radiotherapy to the neck. SPSS 20.0 software was used for statistical analysis. Results: After a median follow-up of 34 months, the 3-year overall survival rate was 84.5%. The 3-year mucosal control rate, neck control rate, distant metastasis-free survival rate and disease-free survival rate were 80.9%, 76.2%, and 92.0%, respectively. Of the 24 patients treated as putative nasopharyngeal carcinoma, no primary emerged from any site. Primary tumor emerged in 14 patients, and no primary emerged in the 31 patients treated with putative site radiation (3-year mucosal control rate: 100% vs. 67.9%, p = 0.010). Of the 46 patients treated with neck dissection with/without postoperative radiation, 14 developed neck recurrence, and patients without postoperative radiation suffered more ipsilateral neck recurrence. Conclusions: The two-step decision-making process seem to be reasonable in treating Chinese HNCUP patients. However, this results need to be prospectively validated.

6523 Background: Based on an individual patient data (IPD) network meta-analysis (NMA) of 20 randomized trials and 5,144 patients (pts), the MAC-NPC collaborative group has shown that the addition of adjuvant chemotherapy (AC) to chemo-radiotherapy (CRT) achieved the highest survival benefit in nasopharyngeal carcinoma (NPC; Ribassin-Majed JCO 2017). Here, we updated the meta-analysis with the addition of 8 trials. Methods: Trials of Radiotherapy (RT) with or without chemotherapy (CT) in patients with non-metastatic NPC were identified and updated IPD obtained. Both Western and Chinese medical literatures were searched. Overall Survival (OS) was the main endpoint. Fixed and random-effects frequentist NMA models were applied, network heterogeneity and consistency were evaluated. P-score was used to rank the treatments. R software - netmeta package was used to perform the analyses. Treatments were grouped in the following categories: RT alone (RT), induction chemotherapy followed by RT (IC-RT), induction chemotherapy without taxanes followed by concomitant chemoradiotherapy (ICtax(-)-CRT), induction chemotherapy with taxanes followed by concomitant chemoradiotherapy (ICtax(+)-CRT), concomitant chemoradiotherapy (CRT), concomitant chemoradiotherapy followed by adjuvant chemotherapy (CRT-AC) and RT followed by adjuvant chemotherapy (RT-AC). Results: Overall 28 trials and 8,214 pts were included. Median follow-up was 7.2 years. There was no heterogeneity in the NMA. There was inconsistency in the main analysis, which disappeared after the exclusion of 2 outlier trials. ICtax(+)-CRT ranked the best treatment for OS with a P-Score of 91%. Hazard ratio [HR, 95% Confidence Interval] for ICtax(+)-CRT was 0.75 [0.59-0.96] compared to CRT and 0.92 [0.69-1.24] compared to CRT-AC (second best treatment in raking with a P-Score of 85%; see league table below). When the 2 types of IC were merged, CRT-AC ranked the first followed by IC-CRT with P-Scores of 93% and 86% respectively, with a HR of 0.97 [0.84-1.14] for CRT-AC vs. IC-CRT. Conclusions: This IPD NMA of the treatment of locally advanced NPC demonstrates that the addition of IC or AC to CRT improves disease control probability and survival over CRT alone. Data on progression-free survival, locoregional and distant control will be presented at the meeting. [Table: see text]

e15191 Background: Here, we profiled genetic hallmarks of Chinese adenoid cystic carcinoma (ACC) patients and immune cells infiltration levels by gene expression-based computational methods to investigate the correlation with immunotherapy. Methods: 54 patients with pathologically confirmed ACC admitted from January 2016 to October 2019 were included. Mutation and expression profiles were obtained by whole-exome sequencing (WES) and RNA-seq, respectively. A nomogram that integrated clinicopathological features with the immune signature to predict recurrence or distant metastasis probability was constructed by multivariate Cox regression. Results: As expected, we observed MYB fusion and somatic mutations in our cohort (57%, 31/54), strengthening the role of these aberrations as critical events in ACC. Mutations in NOTCH1 were also found in our cohort (19%, 10/54). Median tumour mutational burden (TMB) of these patients is 0.85 Muts/Mbp (0-11 Muts/Mbp). Analysis of WES data showed that all patients were microsatellite instability (MSI)-negative, and 17 of them were confirmed by conventional MSI-PCR testing. Lack of PD-L1 expression is 96.0% (n = 46/48) at a tumour proportion score 0% and 22.9% (11/48) of cases showed more than 10% CD8+ prevalence. We compared cancer types using an immune infiltration score (IIS) and an antigen presenting machinery expression (APM) score and find that ACC is among the lowest for both scores. Statistically significant correlations were found between IIS and distant metastasis-free survival (univariate analysis, HR = 2.64, 95% confidence interval [CI], 1.134 to 6.145, p = 0.023). Patients with higher IIS had shorter distant metastasis-free survival time (log-rank p = 0.020), and patients with higher T cell infiltration score (TIS) had shorter locoregional recurrence-free survival time (log-rank p = 0.050). In addition, we investigated the pretreatment immune profile of five ACC patients treated with PD-1 checkpoint inhibitors, and found that both TIS and APM were elevated in responding patient (with a partial response to camrelizumab) whereas they were in the lowest for patients with progressive disease on camrelizumab or pembrolizumab. Conclusions: Our study highlights the immune infiltration patterns and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ACC.

Objectives: The objectives of this study were to prospectively compare individualized dietary counseling with or without oral nutritional supplements (ONSs) in nasopharyngeal carcinoma (NPC) patients undergoing concurrent chemoradiotherapy (CCRT) in a Phase II, randomized trial. Materials and Methods: Between June 2014 and August 2016, Stage II–IVb NPC patients were randomly enrolled. The primary endpoint was change in body weight between during CCRT, and the secondary endpoints were change in body mass index (BMI) and fat-free mass index (FFMI). Results: Fifty-two patients were randomized; 19 patients in the control group and 23 in the ONS group were eligible for analysis. Weight, BMI, and body composition parameters significantly decreased from baseline to week 6. FFMI was significantly better in patients with ONS intake >2/3 planed than the control group (P = 0.028). Weight and BMI maintenance was slightly better in patients with total intake >2/3 planed (P = 0.170 and P= 0.229, respectively). The mean Patient-Generated Subjective Global Assessment score was also better in the ONS group at the end of CCRT (P = 0.053). Conclusions: ONSs with individualized dietary counseling may be beneficial in patients with enough intake, and further prospective studies with large groups of patients are warranted.

Background: Apatinib has shown promising antitumour activities and tolerable toxicities in advanced gastric cancer and is being evaluated for many other cancers. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) is linked to a poor prognosis and limited treatment options. This was a single-arm study (NCT02775370) conducted to determine prolonged progression-free survival (PFS) associated with apatinib administered in patients with R/MACCHN. Methods: In this phase II, single-arm trial, patients with R/MACCHN received apatinib 500 mg once daily until unacceptable toxicity, disease progression, or death. Patients with pathologically confirmed R/MACCHN who showed evidence of disease progression within 3 months or in whom at least one line of systemic chemotherapy failed were eligible. The primary end point was the 6-month PFS. The secondary end points included response rate, duration of response, overall survival (OS), and safety. Findings: Sixty-eight patients with R/MACCHN were evaluable (median follow-up, 13 months). The 6-month PFS rate was 87·9% (95% CI: 76·6%-99·1%), and the 12-month PFS rate was 50·7% (95% CI: 21·8%-79·7%) in the per-protocol population. The 12-month OS rate was 96·3% (95% CI: 91·3%-101·3%). Moreover, the best objective response rate and disease control rate were 46·2% (95% CI: 33·7-58·6%) and 98.5% (95% CI: 95·4-101·5), respectively. The median duration of response was 12·5 months (95% CI: 10·5-16·6 months). Common adverse events of grades 3-4 were hypertension (39·7%), hand-foot syndrome (27·9%), and proteinuria (19·1%). One patient developed a fatal haemorrhage of grade 5. Interpretation: Apatinib showed clinical activity with a manageable safety profile in patients with R/MACCHN. The findings suggested that apatinib is a meaningful therapeutic advance for this incurable disease. However, careful selection of patients is mandatory to minimise the risk of severe bleeding in future use. Clinical Trial Registration Number: This study is registered with ClinicalTrials.gov, number NCT02775370. Funding Statement: This work was supported by Shanghai Municipal Commission of Health and Family Planning (grant number 201640158) and Shanghai Shenkang Hospital Development Center Refractory Diseases Project (Project number 16CR2004A). Declaration of Interests: The authors declare that they have no competing interests Ethics Approval Statement: This investigator-initiated phase II study was approved by the ethics committee of Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine and performed according to the guidelines of Good Clinical Practice Guidelines as defined by the International Conference on Harmonization and the Declaration of Helsinki. All patients gave written informed consent before enrollment.

To evaluate the clinical efficacies and toxicities of induction chemotherapy followed by concomitant cisplatin-chemoradiotherapy (CRT) or cetuximab-radiotherapy (ERT) in locally advanced nasopharyngeal carcinoma (NPC).Previously untreated patients with stage III-IVb NPC were eligible. They were randomized to CRT arm: intensity modulated radiation therapy (IMRT) with weekly cisplatin (30 mg/m(2)/w) or ERT arm: IMRT with weekly cetuximab (loading dose of 400 mg/m(2) followed by weekly doses of 250 mg/m(2)). Two cycles of induction chemotherapy (docetaxel 75 mg/m(2) d1 and cisplatin 80 mg/m(2) d1) were administered to both arms. Endpoints were survivals, toxicities and quality of life (QoL).Because of the unexpectedly high rates of grade 3/4 mucositis observed in the ERT arm, the study was closed ahead of schedule. A total of 44 patients (23 in CRT arm and 21 in ERT arm) were enrolled. All patients completed the scheduled induction chemotherapy and radical radiotherapy. The results showed better compliance (P0.001) with more oral mucositis, acneiform rash and dysphagia (P0.05) of cetuximab. The 3-year disease-free survival (DFS) were achieved as 78.3% and 85.7% (P=0.547) in CRT and ERT arm, respectively. In the analysis of QoL, the addition of cetuximab to radiotherapy temporarily increased the adverse symptoms but did not result in long-term dysfunction.ERT was not more efficacious than CRT but was more likely to cause acute adverse events in LA NPC. The recommended treatment modality was still concurrent cisplatin-IMRT. The combination of TP induction chemotherapy and concurrent cetuximab-radiotherapy should only be used in selected patients.

Summary Objective To determine whether concurrent chemoradiotherapy (CCRT) can improve survival rates compared to the neoadjuvant chemotherapy (NACT) regimen in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. Materials and methods A total of 338 patients with biopsy-proven NPC were randomly assigned to receive NACT followed by radical radiotherapy (RT) then adjuvant chemotherapy (AC) or CCRT followed by AC. Results With a median follow-up of 60 months, the 5-year overall survival (OS) rate did not differ significantly between two groups (75.5% vs 79.4% in CCRT and NACT group respectively, P = 0.47, HR = 0.84, 95%CI 0.53–1.33). Metastasis-free survival (MFS) rate was significantly improved by the CCRT (79.0% vs 86.9%, P = 0.05, HR = 0.59, 95%CI 0.35–1.00). Subgroup analysis indicated that the benefit of CCRT was derived from N0/N1 tumors (78.0% vs 93.5%, P = 0.05, HR = 0.35, 95%CI 0.12–0.99). Higher rates of mucositis (52.4% vs. 35.9% P = 0.02) and vomiting (13.7% vs. 4.7% P = 0.00) were noted in the CCRT arm. Late toxicities were similar in two groups. Conclusions The updated results demonstrated no significant survival benefit of CCRT over NACT in patients with locoregionally advanced NPC. CCRT only showed significant MFS efficacy in T3-4N0-1 populations.

Background: Our objective was to evaluate progression-free survival (PFS) and distant metastasis–free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs). Methods: Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R2 between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS. Results: PFS was strongly correlated with OS at the individual level (ρ = 0.93, 95% confidence interval [CI] = 0.93 to 0.94) and at the trial level (R2 = 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (ρ = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R2 = 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (ρ = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R2 = 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (ρ = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R2 = 0.78, 95% CI = 0.33 to 1.00). Conclusions: PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier.

Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs [95% CIs]) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.