Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

All Conditions

Neoplasms

Mouth and Tooth Diseases

Rare Diseases

Laryngeal Diseases

Hypopharyngeal Neoplasms

Laryngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Laryngeal Cancer

Hypopharyngeal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Immunomodulating Agents

In the surgical group, patients will undergo curative surgery for laryngeal/hypopharyngeal cancer along with cervical lymph node dissection. Organ preservation surgery is recommended, and the specific surgical approach will be chosen based on individual case characteristics and the treatment protocols followed at our center. Depending on postoperative pathology results, adjuvant radiotherapy or concurrent radiochemotherapy may be administered as deemed necessary. If postoperative pathology indicates extracapsular invasion of lymph nodes or positive surgical margins, concurrent radiochemotherapy based on cisplatin is recommended. Starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.

In the concurrent radiochemotherapy group, patients will undergo target delineation based on the scope before induction chemotherapy. Radiotherapy will be administered at a total dose of 70 Gy over 35 fractions, and concurrent chemotherapy will involve weekly administration of cisplatin. Starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.

In the surgical group, patients will undergo curative surgery for laryngeal/hypopharyngeal cancer along with cervical lymph node dissection. Organ preservation surgery is recommended.

Surgery

In the surgical group, depending on postoperative pathology results, adjuvant radiotherapy or concurrent radiochemotherapy may be administered as deemed necessary. If postoperative pathology indicates extracapsular invasion of lymph nodes or positive surgical margins, concurrent radiochemotherapy based on cisplatin is recommended.

In the concurrent radiochemotherapy group, patients will undergo target delineation based on the scope before induction chemotherapy. Radiotherapy will be administered at a total dose of 70 Gy over 35 fractions, and concurrent chemotherapy will involve weekly administration of cisplatin at a dosage of 30 mg/m².

Radiation

In the both groups, starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.

Toripalimab

Yu Wang, M.D.

Xiaomin Ou, M.D.

Yu Wang

In the global landscape of cancer, head and neck malignancies are highly prevalent, with 878,000 new cases and 444,000 deaths recorded in 2020. Notably, laryngeal and hypopharyngeal cancers contribute to around 30% of these instances. More than 50% of patients are diagnosed with locally advanced disease, necessitating intensive treatments that significantly impact their quality of life. Despite these efforts, the prognosis for laryngeal and hypopharyngeal cancers remains grim, with a 5-year survival rate of 30% to 50%.

Past approaches focused on preserving laryngeal function and patient well-being, including minimally invasive surgery, advanced radiotherapy, and induction chemotherapy. Our prior research highlighted the effectiveness of combining toripalimab-based induction therapy and chemotherapy, followed by concurrent chemoradiotherapy or surgery. Positive short-term outcomes and manageable side effects were observed, with encouraging larynx preservation rates after one year.

Against this backdrop, the current study aims to explore neoadjuvant immunotherapy combined with chemotherapy for patients with locally advanced laryngeal and hypopharyngeal cancer. It seeks to compare the therapeutic efficacy and quality of life impacts of concurrent radiochemotherapy and organ-preserving surgery. The ultimate goal is to identify optimal strategies for future interventions.

Head and neck cancer stands as one of the most prevalent forms of malignancy on a global scale. Among these, head and neck squamous cell carcinoma (HNSCC) takes precedence as the predominant histological subtype, encompassing around 90% of the total caseload. Notably, laryngeal and hypopharyngeal cancer contribute to approximately 30% of these instances. Upon initial diagnosis, a striking majority-over 50% of patients find themselves grappling with locally advanced disease, necessitating an assertive therapeutic approach that significantly impacts their overall quality of life. Despite the rigor of these treatments, the prognosis for laryngeal and hypopharyngeal cancer remains discouraging, characterized by a 5-year overall survival rate ranging between 30% and 50%.

Past endeavors have been dedicated to preserving laryngeal function and enhancing the well-being of patients, spanning from the adoption of minimally invasive and organ-conserving surgical techniques to advancements in radiotherapy and the advent of induction chemotherapy. Recent strides in immunotherapy, particularly the integration of programmed cell death protein-1 (PD-1) inhibitors, have brought about a remarkable paradigm shift in how recurrent/metastatic HNSCC is managed. Our previous investigation underscored the efficacy of the strategy involving the combination of toripalimab-based induction therapy and chemotherapy, followed by concurrent chemoradiotherapy or surgical intervention, showcasing favorable short-term outcomes and manageable adverse effects. The data further revealed highly promising larynx preservation rates at the one-year mark.

Given this backdrop, the present study seeks to delve into patients experiencing partial relief through neoadjuvant immunotherapy combined with chemotherapy in cases of locally advanced laryngeal and hypopharyngeal cancer. The study aims to compare the therapeutic efficacy and discrepancies in quality of life resulting from concurrent radiochemotherapy and organ-preserving surgical treatment. The overarching goal is to delineate optimal strategies for subsequent interventions.

Neoadjuvant Chemoimmunotherapy Followed By Radiation Or Organ Preservation Surgery In Laryngeal/Hypopharyngeal Cancer

Neoadjuvant Immunotherapy And Chemotherapy Followed By Concurrent Chemoradiation Or Organ Preservation Surgery In Locally Advanced Laryngeal Cancer And Hypopharyngeal Cancer

The sharing of inviduual participant data will be decided after the pubilcation of this research and the approvement of IRB of Fudan Univerisity Shanghai Cancer Center

Progression-free survival is defined as the time interval from the commencement of randomization until the first documented occurrence of objective tumor progression or death due to any cause, whichever comes first.

Larynx-preservation is considered to have failed on the date of total laryngectomy, or evidence of local recurrence on primary site.

Overall survival is measured as the time from the initiation of randomization to the occurrence of death due to any cause.

Spots Global Cancer Trial Database for larynx presrvation surgery