CTRI

Inoperable oral cavity malignancies represent a very advanced cancer of tongue or buccal mucosa which carries very high symptom burden and morbidity in patients. Without surgery these patients end up with a miserable few months of life before they succumb to the illness. In our clinical practice we found that there is a subset of patients who do well when aggressive alternate treatment with chemotherapy and radiation therapy is offered instead of the standard palliative approach. However, since this aggressive alternate treatment is expensive, involves longer stay at or near hospital and possible higher morbidity, the patients must be really motivated to undergo this despite them knowing that their condition is eventually fatal. We propose to manage inoperable oral cavity malignancies in a systematic design where we will offer radical therapy to motivated patients in a choice driven manner. At every decision-making point, we provide a cafeteria approach for the patient to either choose radical or palliative therapy. Based on their choice at each time point and their response to therapy, the patients will be divided in to 5 cohorts. Overall, the survival between these cohorts will be compared to test whether the approach is beneficial to patients. Additionally, their quality of life, symptom burden and cost â€“ utility analysis calculated with QALY (Quality adjusted life year) will be compared to evaluate if this approach stays relevant and useful to the patient, apart from extending survival, if it does.

Aim:

1. To test if a patient-choice driven radical approach improves survival in Inoperable oral cavity cancers
2. To assess the overall benefit of offering radical approach of therapy in motivated patients with inoperable oral cavity malignancies.

Objectives:
1. Primary: Comparison of overall survival between radical cohort vs palliative cohort in advanced oral cavity malignancies.
2. Secondary: To compare the symptom score, quality of life, cost â€“ utility analysis with QALY (Quality adjusted life year) between the radical and palliative cohorts.

Method:
Specific Aim 1- This is an observational study. Pragmatic patient choice driven cohort study will ascertain staged radical approach in marginally operable and inoperable oral cavity squamous cell carcinoma. Patients advised palliation as per multidisciplinary tumour board meeting will be included in the study. Patient and care givers will be explained in detail and an information sheet will be provided regarding the pros and cons of radical intent approach or upfront palliation. The patient is enrolled as per their choice and further treatment is carried out based on it. Patients choosing to go ahead with palliation {Cohort UPA (Upfront Palliation)} can opt for palliative radiation therapy, palliative chemotherapy, metronomic chemotherapy, best supportive care or any combination of these. Patients opting for upfront radical treatment {Cohort URAD (Upfront RADical)}, shall have a baseline planning CT. Target volume shall be contoured and defined. URAD cohort of patients shall be administered three cycles (2 to 4) of systemic chemotherapy with one of the three standard arms (decided based on patientsâ€™ performance status, comorbidities) followed by disease assessment; clinically and with contrast enhanced CT head and neck 3 to 4 weeks after the last chemotherapy Based on the response, the patients shall be categorized into two groups, Responders and Non-Responders.
Responders are defined as patients with â‰¥25% reduction in the volume of the disease and no new lesions, nodes, or distant metastasis. Non-Responders are defined as patients with â‰¤ 25% reduction in the volume of the disease or appearance of new lesions or nodes or distant metastasis. The Responders are explained regarding the better outlook with continuation of radical treatment, but still experimental. The Non- Responders are counselled that the outlook may be poor with radical approach, but still radical treatment can be continued. The patient chooses the treatment whether to continue with radical approach or switch over to palliation. Responders opting for further radical treatment {Cohort RRAD (Responder RADical)} shall proceed with radical radiation therapy with or without concurrent chemotherapy (based on performance status and comorbidities). Responders opting for palliative treatment {Cohort RPA (Responders PAlliative)} shall proceed with treatment as in Cohort UPA.

Non-Responders opting for radical treatment {(Cohort NRAD (Non-Responders RADical)} shall proceed with treatment as in the Cohort RRAD cohort. Non-Responders choosing palliation {(Cohort NPA (Non- Responders Palliation) shall proceed with treatment as in the Cohort UPA cohort.

Specific Aim 2- We plan to compare the overall survival of Cohort UPA vs URAD. Comparison of Cohort NPA vs NRAD and RPA vs RRAD in terms of progression free survival and overall survival, and 2-year survival shall be done to determine the benefits of induction chemotherapy and radiation therapy with radical intent.

The Quality of Life shall be assessed periodically with University of Washington Version 4. Duration of survival and the quality of survival will be quantified in each cohort and compared.
The cost â€“ utility analysis will be assessed with QALY (Quality adjusted life year) .