This study is for patients who have been diagnosed with locoregionally advanced squamous cell carcinoma. The purpose of this study is to compare two usual treatment approaches to head and neck cancer: high-dose cisplatin given every 3 weeks with radiation to low-dose cisplatin given weekly with radiation. The usual approach for patients who are not in this study is treatment with radiation therapy combined with the chemotherapy drug cisplatin. Cisplatin is a drug approved by the Food and Drug Administration (FDA) to treat your head and neck cancer. Cisplatin can be given at different doses and at different times during radiation, but the most common way to give cisplatin is either as a high-dose every 3 weeks or a low-dose weekly during radiation. Participants can expect to be on this study for up to 7 weeks and then followed annually until disease progression.

This study is for patients that have been diagnosed with Oropharyngeal Squamous Cell Carcinoma. The purpose of this research study is to determine if lower doses of radiation therapy are as effective as the standard higher doses. Participants will have tests and procedures that would be performed as part of regular care. Participants will be assigned to one of three study groups based on your risk for cancer recurrence. Depending on the group assigned, participants receive either standard dose of radiation therapy (RT), a moderately reduced dose of RT, or an extremely reduced dose of RT. During the RT treatment, participants will also receive chemotherapy. Chemotherapy will be given at the same dose used in routine care for everybody in the study. Participants will be in the study for up to 5 years.

In this study, the participants will take pembrolizumab for 24 months or get pembrolizumab plus a course of radiation therapy for 24 months until the cancer progresses. After the study treatment is finished, the study doctor will continue to follow the participants condition for a total of 3 years. Some risks in this study is that pembrolizumab with radiation may not be as good as the usual approach for cancer shirking or stabilizing. Some risks associated with pembrolizumab and radiation which are reduction in blood counts, mouth or throat pain and difficulty swallowing. The potential benefit of this study is that radiation and chemotherapy/pembrolizumab can be effective at shrinking or stabilizing the cancer. The purpose of this study is to compare using pembrolizumab with radiation to pembrolizumab without radiation.

This study will evaluate possible new treatments for advanced stage head and neck cancer. Patients who have undergone surgery to remove their tumor may qualify if the tissue is positive for a specific type of squamous cell cancer. The purpose of this study is to compare the current standard treatment, radiation therapy along with chemotherapy with a drug called cisplatin, to two other treatments. One experimental treatment is radiation therapy along with two chemotherapy agents, docetaxel and cetuximab, and the other experimental treatment is the standard treatment currently used along with the addition of an immunotherapy drug atezolizumab. Patients who qualify for participation will be randomly assigned to one of the 3 treatment groups (done with a computerized system). In the current standard treatment group, participants will receive radiation therapy 5 days per week for 6 weeks, and cisplatin once a week through a vein for the 6-week treatment period. The group receiving doxetaxel and cetuximab (both FDA approved medications for the treatment of certain cancers) will receive the same 6 weeks of radiation along with cetuximab through a vein 1 week prior to the start of radiation therapy, and then once a week for the 6 weeks of radiation and the doxetaxel will also be given through a vein once a week for the 6 weeks of radiation therapy. The final group will get the current standard treatment with 6 weeks of radiation and 6 weeks of cisplatin, along with atezolizumab through a vein 1 week prior to your starting radiation and then every 3 weeks for a total of 8 doses, There will be twice as many patients in this last group than the other two groups.

Follow-up will be at Month 1 & 3 and then every 3 months for 2 years, and then every 6 months for 3 more years, and then annually for as long as a participant is willing and able. There will be blood tests and CT scans that will occur throughout the study, however they are standard for the type of cancer being treated and how each individual responds to the treatment. The benefit of participation is there may be improved outcomes in this group of patients however the risks involved with receiving new treatments may be more than with the usual standard treatment. Some of the most common side effects that the study doctors know about are infection, nausea, vomiting, diarrhea, pain, tiredness, kidney problems, numbness/tingling in hands and feet. There may be some risks that the study doctors are not aware of at the moment. There will be a total of up to 480 participants across all sites and approximately 24 participants at MUSC.

This study is to treat cutaneous squamous cell cancer that cannot be removed with surgery and is relatively large or has spread beyond its original location with the combination of radiation therapy and cemiplimab. Cemiplimab is FDA approved for this head and neck cancer, but the combination of cemiplimab and radiation is investigational. This treatment consist of 17 weeks of cemiplimab followed by 7 weeks of cemiplimab + radiation followed by 28 weeks of cemiplimab alone. There will be 3 clinic visits during treatment so the study doctor can check on the participant's health and see if they are having any side effects. Some of the most common risk and side effects that the study doctors know about are lack of energy or feeling tired (fatigue), loose or watery stools (diarrhea), rash, allergic reaction to study drug, and possible effects on liver, kidney, heart, and blood. Treatment will last a year with a follow-up call at the end of year 2.

This study is designed to learn more about how swallowing function works after completing reduced dose radiation after surgery. If decided to take part in this study, participants will go through a screening period, treatment period, and follow-up period. During the screening period following signing of consent form participants will be evaluated for screening criteria and the initiation of radiotherapy within 28 days of signing the consent form. During treatment period some participants will receive reduced-dose radiotherapy and others will receive standard of care radiotherapy. In the follow up period participants will have visits every 3-6 months. Participation in this study may last up to two years. The swallowing function will be quantified using the MD Anderson Dysphagia index composite score 1 year after surgery. Some serious risk related to this study is that the reduced amount of radiation may not be as effective at curing this cancer compared to the standard dose. The most common risks and discomforts expected in this study are pain and swelling at the site of blood draw that may last several days. The main risk of this study is the increased risk of relapse. There may not a benefit from joining the study. The head and neck cancer may improve while on this study but it may not, and it may even get worse. It will also help inform how well this reduced dose works at curing this type of cancer. The study results may be used to help others in the future.