Transoral Robotic Surgery and Tailored Radiotherapy in Unknown Primary and Small Squamous Cell Head and Neck Cancer

Head and Neck Squamous Cell Carcinoma Clinical Trial

— FIND  

Official title:

A Pilot Study Integrating Transoral Robotic Surgery, Histopathologic Localization, and Tailored De-Intensification of Radiotherapy for Unknown Primary and Small Oropharyngeal Head and Neck Squamous Cell Carcinoma(FIND Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03281499
• Other study ID #: FIND Trial
• Status: Completed
• Phase: N/A
• Start date: August 15, 2017
• Est. completion date: July 19, 2022

Study information

• Verified date: July 2023
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the use of Transoral Robotic Surgery (TORS) to identify small oropharyngeal carcinomas. Findings from this study will be used to better determine which patients may be suitable for more targeted radiotherapy that would lead to a reduction in the total amount of radiotherapy needed as part of their treatment. Reducing the amount of radiotherapy received has been found to reduce the risk of late complications and toxicity to the patient.The pathologic findings will then be used to determine patients who may be candidates for de-intensification of radiotherapy.

Description:

Patients who present with carcinomas of unknown primary site (CUP) of the head and neck represent a challenging problem for clinicians both from a diagnostic and therapeutic perspective. Traditional techniques for identification of primary tumors involved a Positron Emission Tomography scan (PET)/ computerized tomography scan(CT) followed by examination under anesthesia with biopsies of the nasopharynx, tongue base, piriform sinuses in conjunction with a tonsillectomy may identify as many as 44% of primary tumors, the remaining unidentified tumors are treated with mucosal irradiation to all high risk mucosal sites. The addition of a lingual tonsillectomy with Transoral Robotic Surgery (TORS) may identify almost 70% of primary tumours that have otherwise escaped initial identification at this timepoint,. Historically, for those whose primary would not be discovered at the PET/CT, the discovery would have been made later during follow up visits.

The investigators propose to integrate Transoral Robotic Surgery into the diagnostic evaluation of participants presenting with metastatic squamous cell carcinoma to the neck of unknown primary origin. The investigators will localize small hidden oropharyngeal carcinomas, determine their laterality, and based on the laterality of the tumour, laterality of neck nodes, and completeness of resection, will offer reduced radiotherapy to the primary site and/or to the neck (de-intensification)to the participant. The investigators hypothesize that this approach to unknown primary carcinomas will be both safe and effective.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: July 19, 2022
• Est. primary completion date: July 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18

• Metastatic squamous cell carcinoma (T0,N1-3,M0) to at least one regional lymph node of the neck (includes N1-N3) based on fine needle aspiration (FNA) biopsy, core biopsy, excisional biopsy, or neck dissection

• Ability to understand and willing to sign a written informed consent document

• Women of child-producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication.

Exclusion Criteria:

• Evidence of a nasopharyngeal carcinoma by one or more of the following methods:

endoscopic examination, imaging, positive nasopharyngeal biopsy or core lymph node biopsy staining for Epstein Barr Encoded RNA (EBER) by In Situ Hybridization.

• Prior non-cutaneous head and neck squamous cell carcinoma

• Prior head and neck radiotherapy

• History of neck dissection - contralateral to the side of the nodal disease

• Presence of lymphadenopathy on CT unlikely to originate from a primary oropharyngeal carcinoma (i.e., parotid, isolated low (level IV/low level V)

• Radiologically abnormal/enlarged retropharyngeal adenopathy.

• Poor performance status (ECOG status 3 - 5)

• Severe comorbidity or uncontrolled inter-current illness (i.e., unstable angina or heart failure in last 6 months, myocardial infarction in last 6 months, chronic obstructive pulmonary disease with exacerbations necessitating hospitalization or emergency room visit in the past 3 months, history of pneumonia in the past 3 months, use of home oxygen, uncorrectable coagulopathy)

• Not a surgical candidate

• Pregnancy

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Other:
• da Vinci Surgical System Model IS4000
tailored radiotherapy regimen following transoral robotic surgery

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (11)

Abuzeid WM, Bradford CR, Divi V. Transoral robotic biopsy of the tongue base: A novel paradigm in the evaluation of unknown primary tumors of the head and neck. Head Neck. 2013 Apr;35(4):E126-30. doi: 10.1002/hed.21968. Epub 2011 Dec 16. — View Citation

Ali AN, Switchenko JM, Kim S, Kowalski J, El-Deiry MW, Beitler JJ. A model and nomogram to predict tumor site origin for squamous cell cancer confined to cervical lymph nodes. Cancer. 2014 Nov 15;120(22):3469-76. doi: 10.1002/cncr.28901. Epub 2014 Jul 24. — View Citation

Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F, Gillison ML. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013 Dec 20;31(36):4550-9. doi: 10.1200/JCO.2013.50.3870. Epub 2013 Nov 18. — View Citation

Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011 Nov 10;29(32):4294-301. doi: 10.1200/JCO.2011.36.4596. Epub 2011 Oct 3. — View Citation

Cianchetti M, Mancuso AA, Amdur RJ, Werning JW, Kirwan J, Morris CG, Mendenhall WM. Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Laryngoscope. 2009 Dec;119(12):2348-54. doi: 10.1002/lary.20638. — View Citation

D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56. doi: 10.1056/NEJMoa065497. — View Citation

Jones AS, Cook JA, Phillips DE, Roland NR. Squamous carcinoma presenting as an enlarged cervical lymph node. Cancer. 1993 Sep 1;72(5):1756-61. doi: 10.1002/1097-0142(19930901)72:53.0.co;2-5. — View Citation

Kostakoglu L, Fardanesh R, Posner M, Som P, Rao S, Park E, Doucette J, Stein EG, Gupta V, Misiukiewicz K, Genden E. Early detection of recurrent disease by FDG-PET/CT leads to management changes in patients with squamous cell cancer of the head and neck. Oncologist. 2013;18(10):1108-17. doi: 10.1634/theoncologist.2013-0068. Epub 2013 Sep 13. — View Citation

Rodel RM, Matthias C, Blomeyer BD, Wolff HA, Jung K, Christiansen H. Impact of distant metastasis in patients with cervical lymph node metastases from cancer of an unknown primary site. Ann Otol Rhinol Laryngol. 2009 Sep;118(9):662-9. doi: 10.1177/000348940911800911. — View Citation

Strojan P, Ferlito A, Medina JE, Woolgar JA, Rinaldo A, Robbins KT, Fagan JJ, Mendenhall WM, Paleri V, Silver CE, Olsen KD, Corry J, Suarez C, Rodrigo JP, Langendijk JA, Devaney KO, Kowalski LP, Hartl DM, Haigentz M Jr, Werner JA, Pellitteri PK, de Bree R, Wolf GT, Takes RP, Genden EM, Hinni ML, Mondin V, Shaha AR, Barnes L. Contemporary management of lymph node metastases from an unknown primary to the neck: I. A review of diagnostic approaches. Head Neck. 2013 Jan;35(1):123-32. doi: 10.1002/hed.21898. Epub 2011 Oct 27. — View Citation

Waltonen JD, Ozer E, Hall NC, Schuller DE, Agrawal A. Metastatic carcinoma of the neck of unknown primary origin: evolution and efficacy of the modern workup. Arch Otolaryngol Head Neck Surg. 2009 Oct;135(10):1024-9. doi: 10.1001/archoto.2009.145. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the rate of out-of-field failures following treatment	The primary outcome for the study is to determine the rate of out-of-field failures following treatment as determined by use of morphologic imaging (contrast enhanced CT or MRI of the head) and confirmed by biopsy.	2 years
Secondary	Adverse Events (AE) monitoring	To determine the profile of TORS related complications and Surgical Adverse Events within 30 days of surgery using National Cancer Institute Common Terminology Criteria (CTC) for Adverse Events (NCI CTC-AE v 4.0)	2 years
Secondary	Determination of proportions of occult oropharyngeal cancers identified	To determine the proportion of patients with occult oropharyngeal cancers identified	2 years
Secondary	Location of primary tumours identified through enumeration of patients in each identified site group	To determine the location of primary tumours identified through enumeration of patients in each identified site group. The study data will be sorted by location of primary tumour and the proportions for each location calculated	2 years
Secondary	Determination of the proportion of patients with completely resected primary tumours	To determine the location of primary tumours identified, the proportion of patients with primary oropharyngeal carcinomas completely resected (with negative margins), and the proportion of patients amenable to de-intensification treatment (ie, patients who receive no radiotherapy to the primary site and/or unilateral neck radiotherapy).	2 years
Secondary	Determination of the proportion of patients patients amenable to de-intensification treatment	Determination of the proportion of patients patients amenable to de-intensification treatment	2 years
Secondary	Exploration of expert rated swallowing impairment	To explore expert rated swallowing impairment on video fluoroscopic swallow studies (VFSS) using the Modified Barium Swallow Impairment (MBS-Imp)instrument tool 2 years	2 years
Secondary	Exploration of patient reported swallowing related quality of life	To explore patient reported swallowing related quality of life using the MD Anderson Dysphagia Inventory (MDADI)	2 years
Secondary	Exploration of speech and swallowing performance status	To explore observer rated speech and swallowing using the Performance Status Scale for Head and Neck (PSS-HN) instrument	2 years
Secondary	Exploration of patient reported neck impairment	To explore patient reported neck impairment using the Neck Dissection Impairment Index (NDII) instrument	2 years
Secondary	Determination of patterns of failure by location	To determine patterns of failure by location (local, regional, distant) as determined by CT/MRI of the Head and Neck and/or biopsy.	2 years
Secondary	Rates of survival after treatment	To determine rates of survival at 2 years	2 years