Neoplasms

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Mouth Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Squamous Cell Carcinoma

Oral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Fluorouracil

Cisplatin

The patients in the experimental group received the TPF induction chemotherapy for 2 cycles followed by radical surgery and post-operative radiotherapy.

docetaxel:75mg/m2 cisplatin:75 mg/m2 5-Fu:750 mg/m2/day

Radical resection of the primary lesion and full neck,radiotherapy was arranged 4 to 6 weeks after surgery

TPF induction chemotherapy: 2 cycles; docetaxel(75mg/m\^2), cisplatin(75 mg/m\^2), 5-Fu(750 mg/m\^2/day) for 5 days; 16 days later, the 2nd cycle.

TPF induction chemotherapy

Radical resection of the primary lesion and full neck dissection(functional or radical) with proper reconstruction(pedicle or free flap) were performed.

surgery group

Radiotherapy was arranged 4 to 6 weeks after surgery. Routine external beam radiotherapy, such as conformal or intensity modulated radiotherapy was performed and the dose was 1.8-2 Gy/day, 5 days/week for 6 weeks, and totally 54-60 Gy.

Post-operative radiotherapy

Lai-ping Zhong, MD, PhD

The purpose of this study is to confirm the predictive value of GDF15 expression for TPF induction in T3/T4cN0M0 patients with OSCC

Induction chemotherapy is regarded as an effective way to reduce or downgrade the locally advanced or aggressive cancers, and to improve the chance of eradication of the locoregional lesions by radical surgery and/or radiotherapy. However, there are still debates on the clinical value of induction chemotherapy for patients with advanced and resectable oral squamous cell carcinoma. A prospective, open label, parallel, interventional, randomized control trial on TPF induction chemotherapy indicate there is no difference in overall survival, disease free survival, local regional recurrence free survival and metastasis free survival between experimental group and control group, however, the subgroup analysis proves that the induction chemotherapy of TPF protocol could benefit the patients with GDF15 high expression and cN0 locally advanced oral squamous cell carcinoma. (Yang et al, GDF15 is a potential predictive biomarker for TPF induction chemotherapy and promotes tumorigenesis and progression in oral squamous cell carcinoma, Ann Oncol, 2014) This prospective, interventional, randomized control trial was to prove that this predictive biomarker for T3/T4cN0M0 patients with high GDF15 expression benefitting from TPF induction chemotherapy.

The patients would receive TPF induction chemotherapy followed by radical surgery and post-operative radiotherapy (the experimental group) or radical surgery and post-operative radiotherapy (the control group). The study had a power of 80% on the basis of an assumed 5-year survival rate of 85% in the experiment group and 66% in the control group, with use of a two-sided log-rank test at a level of significance of 0.05. The recruitment period would be 2 years, and the follow-up period would be 5 years, and 15% of patients would drop out early or be lost to follow-up. A maximum of 36 patients per group were to be recruited with stplan 4.5 software calculation. （Department of Biostatics, MD Anderson Cancer Center, University of Texas，USA）The patients in the experimental group received the TPF induction chemotherapy for 2 cycles followed by radical surgery and post-operative radiotherapy. The palpable edges of the primary lesion (both the longest and shortest axis) were marked before induction chemotherapy by at least four points, which were 0.5cm away. The patients in the control group received the radical surgery and post-operative radiotherapy.

Induction chemotherapy: For the patients who were randomly assigned to receive TPF induction chemotherapy, peripherally inserted central catheter was firstly inserted before intravenous infusion, docetaxel(at a dose of 75mg/m2 of body surface area) was administered as a 2-hour intravenous infusion, followed by intravenous cisplatin(75 mg/m2), administered during a period of 2 to 3 hours. Then, 5-Fu (750 mg/m2/day) was administered as a 120-hour continuous intravenous infusion for 5 days. Induction chemotherapy was given every 3 weeks for 2 cycles, unless there was disease progression, unacceptable toxic effects, or withdrawal of consent by the patients. Dexamethasone was given before docetaxel infusion to prevent docetaxel-related hypersensitivity reactions, skin toxic effects, and fluid retention; prophylactic antibiotics were also given starting on day 5 of each cycle for 3 days. Hydration with diuretic and antiemetic treatment was also performed. Primary prophylaxis with recombinant granulocyte colony-stimulating factor was not suggested. Chemotherapy dose reductions were allowed for grade 3/4 toxicities occurring after cycle 1: 25% and 50% dose reductions of the three chemotherapy agents were suggested for grade 3 and grade 4 hematologic toxicities or gastrointestinal toxicities, respectively; 25% and 50% cisplatin dose reductions were suggested for grade 3 and grade 4 renal toxicities, respectively. Surgery was performed at least 2 weeks after completion of induction chemotherapy.

Surgery: Radical resection of the primary lesion and full neck dissection(functional or radical) with proper reconstruction(pedicle or free flap) were performed. The safety margins of the primary lesion were 1.0-1.5cm far away from the palpable margins of the lesion; for patients who received induction chemotherapy, the safety margins were 1.0cm away from the marks that were placed before induction chemotherapy, to ensure the same extent surgery in both arms. Frozen sections during surgery were performed to confirm adequate margins.

Post-operative radiotherapy: Radiotherapy was arranged 4 to 6 weeks after surgery. Routine external beam radiotherapy, such as conformal or intensity modulated radiotherapy was performed, and the dose was 1.8-2 Gy(Gray)/day, 5 days/week for 6 weeks, and totally 54-60 Gy, in the patient with high risk features, such as positive surgical margin, extra capsular nodal spread, vascular embolism, concurrent chemotherapy with cisplatin 80mg/m2 was suggested.

A complete medical history was obtained and tumor assessment was performed at baseline. Clinical tumor response was assessed by clinical evaluation and imaging study and was characterized according to the criteria of response evaluation criteria in solid tumors (version 1.1) before surgery. Post-operative pathologic response was assessed by post-operative pathologic examination as good and bad response. A good response was defined as absence of any tumor cells (pathologic complete response) or presence of scattered foci of a few tumor cells (minimal residual disease with \<10% viable tumor cells); otherwise, a bad pathologic response was defined. Toxic effects were assessed weekly during and after completion of induction chemotherapy and radiotherapy according to the common terminology criteria for adverse events (version 3.0).

Overall survival was calculated from the date of randomization to the date of death; disease free survival was calculated from the date of randomization to tumor recurrence or distant metastasis or death from any cause; locoregional recurrence/distant metastasis free survival was calculated from the date of randomization to locoregional recurrence/distant metastasis of tumor or death from any cause. Time to locoregional recurrence/distant metastasis was calculated from the date of finishing treatment to tumor locoregional recurrence/distant metastasis. Patients were monitored by every three months in the first two years, every six months in the next 2 years, and once a year thereafter until death or data censoring.

GDF15 Based TPF Induction Chemotherapy for OSCC Patients

GDF15 (Growth Differentiation Factor 15) Based TPF Induction Chemotherapy for Oral Squamous Cell Carcinoma Patients at T3/T4cN0M0 Stage: a Phase II Randomized Controlled Trial

2-year overall survival rate as a measure by the numbers of living patients

2-year disease free survival as a measure by the number of patients without recurrence or death

2-year local recurrence free survival as a measure by the number of patients without recurrence

2-year distant metastasis free survival as a measure by the number of patients without metastasis

Shanghai Jiao Tong University School of Medicine

associate professor,PHD,DDS,MD

Squamous Cell Carcinoma of Head and Neck

Antibodies

Cetuximab

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

TPF version 1 (standard)

1. Induction chemotherapy:

   Docetaxel 75 mg/m2 d 1 Cis-platinum 75 mg/m2 d 1 5-FU 750 mg/m2/d c.i. d 1-4 every 21 days for 3 cycles
2. Antibody therapy with:

   cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX
3. RTX: HART (72 Gy), IMRT or 3D-conformal techniques

TPF version 2 (experimental)

1. Induction chemotherapy:

   Docetaxel 40 mg/m2 d 1+8 Cis-platinum 40 mg/m2 d 1+8 5-FU 1500 mg/m2/24h c.i. d 1+8 every 21 day for 3 cycles
2. Antibody therapy with:

   cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX
3. RTX: HART (72 Gy), IMRT or 3D-conformal techniques

Standard RCT:

1. HART (72 Gy), IMRT or 3D-conformal techniques
2. with concurrent chemotherapy: Cis-platinum 30 mg/m2 once weekly d 1, 8, 15, 22, 29, 36 5-FU 600mg/m² /24h c.i. d 1-5

Docetaxel 75 mg/m2 d 1 Cis-platinum 75 mg/m2 d 1 5-FU 750 mg/m2/d c.i. d 1-4 Cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX

Docetaxel 40 mg/m2 d 1+8 Cis-platinum 40 mg/m2 d 1+8 5-FU 1500 mg/m2/24h c.i. d 1+8 every 21 day for 3 cycles 2. Antibody therapy with: cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX

TPF experimental

Hyperfractionated accelerated radiotherapy with concurrent Cisplatin and 5-Fluorouracil chemotherapy

Standard Radiochemotherapy (HART)

Volker Budach, MD, PhD

This is an open-label, randomized, Phase II-study to evaluate the efficacy of a standard-TPF induction chemotherapy (IC) and an alternative TPF induction chemotherapy followed by radio-antibody-therapy, in patients with unresectable LA-SCC of the HN region (oro-hypopharynx carcinoma, cancer of the oral cavity).

The primary objective of the study is to assess the feasibility of an experimental 'fractionated' TPF regimen compared to a current standard TPF regimen.

Composite endpoint of compliance and feasibility in terms of

* response (RECIST1.1) and
* hematological acute toxicity (CTCAE v.4.02)
* on time application of RAT following an experimental or standard TPF IC.

Secondary endpoints are

* Treatment intensity achieved
* Toxicity (according to CTCAE v.4.02)
* Response rates after completion of induction chemotherapy and after completion of entire protocol treatment (RECIST1.1)
* Survival (progression-free, metastasis-free, recurrence-free, overall) 1 year after randomisation
* Quality of life according to EORTC QoL C30 \& HN35

The study will be conducted at 5-6 investigational sites in Germany recruiting 90 patients in total. Eligible patients will have a diagnosis of histologically confirmed SSC of the HN. Patients will receive one of 2 different regimens of TPF IC followed by cetuximab together with radiotherapy (RAT) or a standard radiochemotherapy(RCT) regimen.

InductionChemo-Radio-Antibody-Treatment

Randomized Phase II Study of Two Different Regimens of TPF Induction Chemotherapy Regimen Followed by Radiation Therapy Plus Cetuximab (TPF-CET-HART) vs. HART and Cis-platinum, 5-FU (PF-HART) in Patients With Locally Advanced Unresectable Squamous Cell Carcinomas of the Head and Neck

All adequate items illustrating acute toxicity and late morbidity, in particular by hematological measures until one year after treatment (according to NCI-CTCAE v.4.02) Survival (progression-free, metastases-free, recurrence-free, Overall survival) after 1 year Response rates after TPF IC (RECIST1.1) Response rates after completion of multimodal treatment (see follow-up for scheduling RECIST1.1) Efficacy in relation to HPV status (p16 IHC) Quality of life according to EORTC QLC-30 \& HN35

Charite University, Berlin, Germany

Prof. Dr. Volker Budach

Induction chemotherapy before surgery: docetaxel, cisplatin, and 5-fluorouracil.

Docetaxel (at a dose of 75mg/m2 of body surface area) was administered as a 2-hour intravenous infusion, followed by intravenous cisplatin (75 mg/m2), administered during a period of 2 to 3 hours. After completion of the cisplatin infusion, 5-Fu (750 mg/m2/day) was administered during a period at least 8 hours for 5 days. Induction chemotherapy was given every 3 weeks for 2 cycles, unless there was disease progression, unacceptable toxic effects, or withdrawal of consent by the patient.

Zhi-yuan Zhang, MD, PhD

Induction chemotherapy is regarded as an effective way to reduce or downgrade the locally advanced or aggressive cancers, and to improve the chance of eradication of the locoregional lesions by radical surgery and/or radiotherapy. However, there are still debates on the clinical value of induction chemotherapy for patients with advanced and resectable oral squamous cell carcinoma. The hypothesis of this study is that the induction chemotherapy of TPF (docetaxel, cisplatin, and 5-fluorouracil) protocol could benefit the patients with locally advanced oral squamous cell carcinoma. The endpoints of this study are the survival rate, local control, and safety.

The primary endpoint of this study is the survival rate (2, 3, 5 years) after induction chemotherapy followed by surgery and radiotherapy. The second endpoint of this study is locoregional control rates (1, 2 years), and the safety.

TPF Induction Chemotherapy for Locally Advanced and Resectable Oral Squamous Cell Carcinoma

Study of TPF (Docetaxel, Cisplatin, 5-fluorouracil) Induction Chemotherapy Followed by Surgery and Radiotherapy in Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma

To evaluate the survival rate after TPF induction chemotherapy followed by surgery and radiotherapy.

To evaluate the 1, 2, 3, 5-year local and regional control rate and distant metastasis rate after TPF indcution chemotherapy followed by surgery and radiotherapy

All adverse events, including serious adverse events, exposure of all study drugs and radiation.

Ninth People's Hospital, School of Medicine

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

The participants will receive 3 doses of neoadjuvant PD-1 blockade. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.

The participants will receive 3 doses of PD-1 blockade and 2 courses of TPF induction chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.

The participants will receive camrelizumab (200 mg) intravenous infusion each 2-week cycle for 3 cycles prior to surgery.

Camrelizumab

The participants will receive camrelizumab (200 mg) through intravenous infusion each 2-week cycle, and docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2, 5-Fluorouracil (F) 750 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.

Camrelizumanb plus TPF

Gang Chen, MD

The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced oral squamous cell carcinoma.

The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced OSCC. And on this basis, we will explore the changes of the profiles and functions of immune cells within tumors, lymph nodes and peripheral blood after the experimental interventions, as well as their correlation with the patients' response and prognosis.

Neoadjuvant PD-1 Blockade in Resectable Oral Squamous Cell Carcinoma

A Randomized Phase II Study of Neoadjuvant PD-1 Blockade Alone or Plus TPF Induction Chemotherapy for Resectable Local Advanced Oral Squamous Cell Carcinoma

The level of circulating exosomal PD-L1 at serial time points pre- and on-treatment, as detected by enzyme-linked immunosorbent assay (ELISA).

Pathologic response of resected tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy. Hematoxylin and eosin (H\&E)-stained slides of entire tumor and all sampled lymph nodes were scanned and assessed by two independent pathologists. The entire tumor bed and all sampled lymph nodes were examined histologically in patients who had pathological complete response (pCR), which was defined as the absence of viable tumor in all slides. MPR was defined as the presence of 10% or less viable residual tumor in the resected tumor specimens. Pathological partial response (pPR) was defined as presence of more than 10% and less than 50% viable residual tumor and pathological non-response (pNR) was defined as presence of more than 50% viable residual tumor in the resected tumor specimens. Pathologic response was defined as sum of pCR and MPR.

Radiographic response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy were evaluated by enhanced computed tomography examinations and defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete Response (CR) was defined as disappearance of all target lesions. Partial Response (PR) was defined as \>=30% decrease in the sum of the longest diameter of target lesions. Stable disease (SD) was defined as \<20% increase and \<30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) was defined as \>=20% increase in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.

EFS is the time from the date of randomization to the date of first record of disease progression as defined by RECIST 1.1.

OS is the time from randomization to death due to any cause.

Number of participants experiencing any sign, symptom, disease, or worsening of preexisting conditions temporally associated with the experimental interventions or irrespective of the experimental interventions.

Jiangsu HengRui Medicine Co., Ltd.

Hospital of Stomatology, Wuhan University

Chief physician, Professor

The participants will receive 3 doses of neoadjuvant PD-1 blockade. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.

Camrelizumab: The participants will receive camrelizumab (200 mg) intravenous infusion each 2-week cycle for 3 cycles prior to surgery.

Neoadjuvant PD-1 Blockade Alone

The participants will receive 3 doses of PD-1 blockade and 2 courses of TPF induction chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.

Camrelizumanb plus TPF: The participants will receive camrelizumab (200 mg) through intravenous infusion each 2-week cycle, and docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2, 5-Fluorouracil (F) 750 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.

Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

China

Region of Enrollment

Tumor site

Smoking history

Alcohol use history

Classification of patients of oral squamous cell carcinoma based on T stage

Clinical T-stage

Classification of patients of oral squamous cell carcinoma based on N stage

Clinical N-stage

The expression of programmed cell death-ligand 1 (PD-L1) in patients was carried out using immunohistochemical staining. Combined positive score (CPS) of PD-L1 was defined as the total number of PD-L1-stained cells (including tumor cells, tumor-associated lymphocytes, and macrophages) divided by the total number of viable tumor cells, multiplied by 100. The range was from 0-100. PD-L1\>1 was considered as cut-off value for derermine positive expression of PD-L1 in oral squamous cell carcinoma.

PD-L1 combined positive score

Pathologic Response.

Radiographic Response.

Event-free Survival (EFS) Rate on Each Treatment Arm.

Overall Survival (OS) on Each Treatment Arm.

Adverse Events (AEs).

Changes in the Level of Circualting Exosomal PD-L1.

Overall Study

The patients in the experimental group received the TPF induction chemotherapy for 2 cycles followed with surgery and radiotherapy/chemoradiotherapy.

docetaxel:75mg/m2 cisplatin：75 mg/m2 5-Fu：750 mg/m2/day

The patients in the control group received the radical surgery and radiotherapy/chemoradiotherapy.

TPF induction chemotherapy: 2 cycles; docetaxel(75mg/m\^2), cisplatin(75 mg/m\^2), 5-Fu(750 mg/m\^2/day) for 5 days; 16 days later, the 2nd cycle. 2 weeks later, surgery.

Surgery: radical resection and full neck dissection with reconstruction. Radiotherapy: 4-6 weeks after surgery, 1.8-2Gy/day, 5 days/week for 6 weeks, and totally 54-60Gy

In the TPF group,surgery was performed at least 2 weeks after completion of induction chemotherapy.Surgery group includes radical resection of the primary lesion and full neck dissection(functional or radical) with proper reconstruction(pedicle or free flap) were performed.

surgery

Radiotherapy was arranged 4 to 6 weeks after surgery.Routine external beam radiotherapy, such as conformal or intensity modulated radiotherapy was performed, and the dose was 1.8-2 Gy(gray)/day, 5 days/week for 6 weeks, and totally 54-60 Gy.

radiotherapy

To confirm the subgroup result from TPF (docetaxel, cisplatin and 5-fluorouracil ) trial (NCT01542931) that cN2 OSCC patients could benefit from TPF induction chemotherapy compared to the standard treatment.

Induction chemotherapy is regarded as an effective way to reduce or downgrade the locally advanced or aggressive cancers, and to improve the chance of eradication of the locoregional lesions by radical surgery and/or radiotherapy. However, there are still debates on the clinical value of induction chemotherapy for patients with advanced and resectable oral squamous cell carcinoma(OSCC). A prospective, open label, parallel, interventional, randomized control trial on TPF induction chemotherapy indicate there is no difference in overall survival, disease free survival, local regional recurrence free survival and metastasis free survival between experimental group and control group,（Zhong et al, Randomized Phase III Trial of Induction Chemotherapy With Docetaxel, Cisplatin, and Fluorouracil Followed by Surgery Versus Up-Front Surgery in Locally Advanced Resectable Oral Squamous Cell Carcinoma, J Clin Oncol 2013） however, the meta analysis proves that the induction chemotherapy of TPF protocol could benefit the patients with cN2 locally advanced oral squamous cell carcinoma. The previous study was registered at ClinicalTrials.gov website with NCT01542931 identification number.

This prospective, interventional, randomized control trial was to evaluate the TPF induction chemotherapy have a better effects in the cN2 patients with locally advanced and resectable OSCC. The patients would receive TPF induction chemotherapy followed by radical surgery and post-operative radiotherapy (the experimental group) or radical surgery and post-operative radiotherapy (the control group).

The study had a power of 80% on the basis of an assumed 2-year survival rate of 62.4% in the experiment group and 36.9% in the control group, with use of a two-sided log-rank test at a level of significance of 0.05. The recruitment period would be 2 years, and the follow-up period would be 2 years, and 15% of patients would drop out early or be lost to follow-up. A total number of 101 patients were to be recruited with stplan 4.5 software calculation. （Department of Biostatics, MD Anderson Cancer Center, University of Texas，USA） The patients in the experimental group received the TPF induction chemotherapy for 2 cycles followed by radical surgery and post-operative radiotherapy. The palpable edges of the primary lesion (both the longest and shortest axis) were marked before induction chemotherapy by at least four points, which were 0.5cm away. The patients in the control group received the radical surgery and post-operative radiotherapy/chemoradiotherapy.

Induction chemotherapy: For the patients who were randomly assigned to receive TPF induction chemotherapy, peripherally inserted central catheter was firstly inserted before intravenous infusion, docetaxel(at a dose of 75mg/m2 of body surface area) was administered as a 2-hour intravenous infusion, followed by intravenous cisplatin(75 mg/m2), administered during a period of 2 to 3 hours. Then, 5-Fu(750 mg/m2/day) was administered as a 120-hour continuous intravenous infusion for 5 days. Induction chemotherapy was given every 3 weeks for 2 cycles, unless there was disease progression, unacceptable toxic effects, or withdrawal of consent by the patients. Dexamethasone was given before docetaxel infusion to prevent docetaxel-related hypersensitivity reactions, skin toxic effects, and fluid retention; prophylactic antibiotics were also given starting on day 5 of each cycle for 3 days. Hydration with diuretic and antiemetic treatment was also performed. Primary prophylaxis with recombinant granulocyte colony-stimulating factor was not suggested. Chemotherapy dose reductions were allowed for grade 3/4 toxicities occurring after cycle 1: 25% and 50% dose reductions of the three chemotherapy agents were suggested for grade 3 and grade 4 hematologic toxicities or gastrointestinal toxicities, respectively; 25% and 50% cisplatin dose reductions were suggested for grade 3 and grade 4 renal toxicities, respectively. Surgery was performed at least 2 weeks after completion of induction chemotherapy.

Surgery: Radical resection of the primary lesion and full neck dissection(functional or radical) with proper reconstruction(pedicle or free flap) were performed. The safety margins of the primary lesion were 1.0-1.5cm far away from the palpable margins of the lesion; for patients who received induction chemotherapy, the safety margins were 1.0cm away from the marks that were placed before induction chemotherapy, to ensure the same extent surgery in both arms. Frozen sections during surgery were performed to confirm adequate margins.

Post-operative radiotherapy: Radiotherapy was arranged 4 to 6 weeks after surgery. Routine external beam radiotherapy, such as conformal or intensity modulated radiotherapy was performed, and the dose was 1.8-2 Gy/day, 5 days/week for 6 weeks, and totally 54-60 Gy, in the patient with high risk features, such as positive surgical margin, extra capsular nodal spread, vascular embolism, concurrent chemotherapy with cisplatin 80mg/m2 was suggested.

A complete medical history was obtained and tumor assessment was performed at baseline. Clinical tumor response was assessed by clinical evaluation and imaging study and was characterized according to the criteria of response evaluation criteria in solid tumors (version 1.1) before surgery. Post-operative pathologic response was assessed by post-operative pathologic examination as good and bad response. A good response was defined as absence of any tumor cells (pathologic complete response) or presence of scattered foci of a few tumor cells (minimal residual disease with \<10% viable tumor cells); otherwise, a bad pathologic response was defined. Toxic effects were assessed weekly during and after completion of induction chemotherapy and radiotherapy according to the common terminology criteria for adverse events (version 3.0).

Overall survival was calculated from the date of randomization to the date of death; disease free survival was calculated from the date of randomization to tumor recurrence or distant metastasis or death from any cause; locoregional recurrence/distant metastasis free survival was calculated from the date of randomization to locoregional recurrence/distant metastasis of tumor or death from any cause. Time to locoregional recurrence/distant metastasis was calculated from the date of finishing treatment to tumor locoregional recurrence/distant metastasis. Patients were monitored by every three months in the first two years, every six months in the next 2 years, and once a year thereafter until death or data censoring.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
GDF15 Based TPF Induction Chemotherapy for OSCC Patients	NCT02285530	Mouth Neoplasms Carcinoma, Squa...	TPF induction c... surgery group Post-operative ...	18 Years - 75 Years	Shanghai Jiao Tong University School of Medicine
InductionChemo-Radio-Antibody-Treatment	NCT01181401	Squamous Cell C... Squamous Cell C...	TPF induction c... TPF experimenta... Standard Radioc...	18 Years -	Charite University, Berlin, Germany
InductionChemo-Radio-Antibody-Treatment	NCT01181401	Squamous Cell C... Squamous Cell C...	TPF induction c... TPF experimenta... Standard Radioc...	18 Years -	Charite University, Berlin, Germany
TPF Induction Chemotherapy for Locally Advanced and Resectable Oral Squamous Cell Carcinoma	NCT01542931	Stage III Oral ... Stage IVA Oral ...	TPF induction c...	18 Years - 75 Years	Shanghai Jiao Tong University School of Medicine
Neoadjuvant PD-1 Blockade in Resectable Oral Squamous Cell Carcinoma	NCT04649476	Oral Squamous C...	Camrelizumab Camrelizumanb p...	18 Years - 70 Years	Hospital of Stomatology, Wuhan University
InductionChemo-Radio-Antibody-Treatment	NCT01181401	Squamous Cell C... Squamous Cell C...	TPF induction c... TPF experimenta... Standard Radioc...	18 Years -	Charite University, Berlin, Germany
A Phase II Trial of TPF Induction Chemotherapy in cN2 OSCC Patients	NCT02285543	Mouth Neoplasms Carcinoma, Squa...	TPF induction c... surgery radiotherapy	18 Years - 75 Years	Shanghai Jiao Tong University School of Medicine
A Phase II Trial of TPF Induction Chemotherapy in cN2 OSCC Patients	NCT02285543	Mouth Neoplasms Carcinoma, Squa...	TPF induction c... surgery radiotherapy	18 Years - 75 Years	Shanghai Jiao Tong University School of Medicine

Spots Global Cancer Trial Database for tpf induction chemotherapy