Please select the eligibility criteria that correspond to the clinical trial below.
Title: Canadian Optically Guided Approach for Oral Lesions Surgical Trial - COOLS
Brief Summary: Oral squamous cell carcinoma (SCC) is a global disease responsible for \~300,000 new cancer cases each year. Local recurrence (\~30% of cases) and formation of second primary malignancy are common.2, 3 Cosmetic and/or functional compromise associated with treatment of disease stage is often significant. These statistics underscore the urgent need to develop a better approach in order to control this deadly disease.

It is becoming increasingly apparent that oral cancers develop within wide fields of diseased tissue characterized by genetically altered cells that are widespread across the oral cavity and present in clinically and histologically normal oral mucosa. Complete removal of these lesions is difficult because high-risk changes frequently go beyond clinically visible tumor. In recognition of this, current 'best practice' is to remove SCC with a significant width (usually 10 mm) of surrounding normal-looking oral mucosa. However, since occult disease varies in size such approach often results in over-cutting (causing severe cosmetic and functional morbidity) or under removal of disease tissue, as evidenced by frequent positive surgical margins and high local and regional recurrence - a failure of the 'best practice.

There is a wealth of literature that supports the use of tissue autofluorescence in the screening and diagnosis of precancers in the lung, uterine cervix, skin and oral cavity. This approach is already in clinical use in the lung and the mechanism of action of tissue autofluorescence has been well described in the cervix. Changes in fluorescence reflect a complex interplay of alterations to fluorophores in the tissue and structural changes in tissue morphology, each associated with progression of the disease.

As one of the internationally leading teams in applying tissue fluorescence technology, we have shown that direct fluorescence visualization (FV) tools can identify clinically visible or occult premalignant and malignant lesions that are associated with lesions at risk, with high-grade histology and high-risk molecular change. In a recently small scaled, retrospective study, we have shown that FV helped surgeons in the operating room to determine the extent of the high-risk FV field surrounding the cancer and resulted in remarkably lower 2-year recurrence rates (0% for FV-guided vs. 25% for those without FV-guided approach). There is need to design a larger scale prospective, randomized controlled (Phase III) trial to gather strong evidence in proving the efficacy of the surgery approach using this adjunct tool.

To establish the evidence supporting the change in clinical practice using FV-guided surgery. There are 3 objectives.

2.1. Objective 1 (Clinical evidence): To assess the effect of FV-guided surgery on the recurrence-free survival of histologically confirmed disease within the context of a randomized controlled trial (efficacy). Hypothesis: FV-guided surgery will increase the recurrence-free survival.

2.2. Objective 2 (Quality of Life evidence): To establish the cost per recurrence prevented for this approach and assess quality of life issues. Hypothesis: FV-guided surgery can be delivered in a cost effective manner and improve the quality of life of patients 2.3 Objective 3 (Scientific/Molecular evidence): To assess the presence of previously validated molecular markers (microsatellite analysis, LOH) and histological change (quantitative pathology) in surgical margins in a nested case-control study involving a tumor bank created within this project. Hypothesis: FV-guided surgery will spare normal tissue at the same time improving capture of high-risk tissue.


Options:
A: Inclusion Criteria:

* age 18 or older
* willing to provide informed consent
* ECOG performance status 0-2
* Histologically confirmed squamous cell carcinoma primary rumour site in the oropharynx (includes tonsil, soft palate, base of tongue, walls of oropharynx)
* Tumour stage:T1 or T2, with likely negative resections at surgery
* Nodal stage: N0, N1, or N2 (less than or equal to 4 cm in maximum dimension in any plane, on either side of the neck), without extranodal extension on pre-randomization imaging.
* Patient assessed at head and neck multidisciplinary clinic (with assessment by radiation oncologist and surgeon) and presented at multidisciplinary tumour board prior to randomization.

Exclusion Criteria:

* Serious medical comorbidities or other contraindications to radiotherapy, chemotherapy or surgery
* Prior history of head and neck cancer within 5 years
* Prior head and neck radiation at any time
* Metastatic disease
* Inability to attend full course of radiotherapy or follow-up visits
* Neck disease with unknown primary site
* Prior invasive malignant disease unless disease-free for at least 5 years or more, with the exception of non-melanoma skin cancer
* unable or unwilling to complete QoL questionnaires
B: Inclusion Criteria:

1. Histologically proven T1 or T2 N0 M0 (clinical) squamous cell carcinoma of the buccal mucosa, lower alveolus, oral tongue and floor of mouth.
2. Surgery is the preferred treatment and the primary tumor can be excised with clear margins via the per-oral route.
3. No history of a prior malignancy in the head and neck region.
4. No prior malignancy outside the head and neck region in the preceding 5 years.
5. Patient will be reliable for follow-up
6. Age\> 18 years and \< 75 years.
7. No significant co-morbid conditions - ASA grade II and I.
8. Understands the protocol and is able to give informed consent.

Exclusion Criteria:

1. Prior radiotherapy or surgery for malignancy in the head and neck region.
2. Non squamous cell carcinomas of the oral cavity.
3. Upper alveolus and palatal lesions where there is a possibility of retropharyngeal node involvement.
4. Per-oral excision of tumor will compromise margins in the opinion of the treating surgeon.
5. Significant co-existing pre-malignant conditions like erytho-leucoplakia and oral sub mucous fibrosis that in the opinion of the clinician would interfere in the planned treatment management of the patient.
C: Inclusion Criteria:

* Histologically proven SCC of the oropharynx; T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0, with only amendable to transoral resection)
* Primary tumor must be resectable through transoral approach
* p16 immunohistochemitry by local pathology or FFPE tissue must be available for central HPV diagnostic
* Written and signed informed consent
* Briefing through surgeon and radiation oncologist
* ECOG PS ≥2, Karnofsky PS ≥ 60 %
* Age ≥ 18
* Curative treatment intent
* Adequate bone marrow function: leucocytes \> 3.0 x 109/L, neutrophils \> 1.5 x 109/L, platelets \> 80 x 109/L, hemoglobin \> 9.5 g/dL
* Adequate liver function: Bilirubin \< 2.0 g/dL, SGOT, SGPT, \< 3 x ULN
* If of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing.
* dental examination and appropriate dental therapy if needed prior to Confidential TopROC 2017_03_24 Version 1.0 Seite 15 von 124 beginning of radiotherapy
* Nutritional evaluation prior to initiation of therapy and optional prophylactic gastrostomy (PEG) tube placement

Exclusion Criteria:

* Prior invasive malignancy except controlled skin cancer or carcinoma in situ of cervix
* Unknown primary (CUP), nasopharynx, hypopharynx, laryngeal or salivary gland cancer
* Metastatic disease
* Serious co-morbidity, e.g. high-grade carotid artery stenosis, congestive heart failure NYHA grade 3 and 4, liver cirrhosis CHILD C
* Hemoglobin level \<9.5g/dl within 4 weeks before randomization
* Pregnancy or lactation
* Women of child-bearing potential with unclear contraception
* Previous treatment with chemotherapy, radiotherapy, EGFR-targeting agents or surgery exceeding biopsy in head and neck
* Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening
* Social situations that limit compliance with study requirements or patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol
* Patients institutionalized by official means or court order
* Deficient
D: Inclusion Criteria:

* Patients diagnosed with severe dysplasia, carcinoma in situ, invasive squamous cell carcinoma (T1 or T2) of the oral cavity (ICO-D site codes: C02.0-C06.9) who will be undergoing curative resection (primary disease).

Exclusion Criteria:

* Patients with a non-oral malignancy diagnosed (not including non-melanoma skin cancer and lymphoma outside of head and neck region) within the past 3 years.
* Patients with evidence of distant metastasis (as determined by CAT and X-ray) at the time of recruitment.

Answer: D