Registry to Collect Data on Patients Undergoing Segmental Mandibular Defect Reconstruction Following Oral Squamous Cell Carcinoma Resection

• ClinicalTrials.gov Identifier: NCT04098146
• Recruitment Status: Recruiting
• First Posted: September 23, 2019
• Last Update Posted: December 15, 2023
• Sponsor: AO Innovation Translation Center
• Information provided by (Responsible Party): AO Innovation Translation Center

Study Description

Brief Summary:

Prospective will be collected in a minimum of 300 patients presenting with an acquired segmental mandibular defect ≥ 4 cm secondary to OSSC removal and who require mandibular reconstruction.

Condition or disease	Intervention/treatment
Mandibular Reconstruction; Segmental Mandibular Defects	Procedure: Surgical Resection and Reconstruction

Detailed Description:

Prospective data will be collected in a minimum of 300 patients presenting with an acquired segmental mandibular defect ≥ 4 cm secondary to OSSC removal and who require mandibular reconstruction.

The follow up (FU) will consist of standard of care (routine) procedures and data collection will be done at 3, 6, 12, 18 and up to 24 months after resection and/or reconstruction. The maximum FU for each patient within the registry will be 2 years after mandibular resection.

Data collection will include confounding baseline data, tumor characteristics, neurological function, patient reported outcomes, quality of life as well as anticipated procedure-related adverse events (AEs). Available images will be collected and evaluated centrally to determine the location, positioning, osseointegration, bone quantity and quality of the transplants.

Depending on the volume and quality of the collected data, different statistical analyses will be performed. Exploratory analyses will be conducted to find relationships between the different treatment modalities and their outcomes.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 300 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Target Follow-Up Duration: 2 Years
• Official Title: International, Multicenter, Prospective Registry to Collect Data on Patients Undergoing Segmental Mandibular Defect Reconstruction (SMDR) Following Oral Squamous Cell Carcinoma (OSSC) Resection
• Actual Study Start Date: September 12, 2022
• Estimated Primary Completion Date: January 31, 2027
• Estimated Study Completion Date: December 31, 2028

Groups and Cohorts

Group/Cohort

Intervention/treatment

Mandibular Reconstruction; Patients undergoing segmental mandibular defect reconstruction. The decision of one stage or two stage reconstruction is done according to the patient and treating surgeon preferences following the local standard of care

Procedure: Surgical Resection and Reconstruction; One stage reconstruction: Osseous reconstruction is performed in the same surgery of the tumor/mandibular resection. It is also known as immediate or primary reconstruction. Second stage reconstruction: Osseous reconstruction is performed after the tumor/mandibular resection surgery as an independent surgery. After the mandibular resection a temporary alloplastic bridging might be put in place. It is also known as delayed or secondary reconstruction.

Outcome Measures

Primary Outcome Measures :

1. Demographics [ Time Frame: Baseline until resection surgery approximately 4 weeks ]
   Demographics (year of birth, height in cm and weight in kilogram, race)
2. Comorbidities [ Time Frame: Baseline until resection surgery approximately 4 weeks ]
   Comorbidities assessed by Charlson Comorbidity Index (this score assesses the comorbidity level by considering both the number and severity of predefined comorbidity conditions. It provides a weighted score of a patient's comorbidities which can be used to predict mortality rates
3. Nicotine consumption [ Time Frame: Baseline until resection surgery approximately 4 weeks ]

   Current and previous nicotine use will be collected:

   • Number of years
   • Time (years) since stopped using (if applicable)
   • Amount of cigarettes/day
4. Patient reported outcome: Oral Health Impact Profile (OHIP) [ Time Frame: Baseline/ 3months/ 6 months/ 12 months/ 18 months/ 24 months ]

   Change in the OHIP over the follow-up period.

   The Oral Health Impact Profile is providing a comprehensive measure of self-reported dysfunction, discomfort and disability attributed to oral conditions. The OHIP is concerned with impairment and three functional status dimensions (social, psychological, and physical). Respondents are asked to indicate on a five-point Likert scale how frequently they experienced each problem. Response categories for the five-point scale are: "Very often", "Fairly often", "Occasionally", "Hardly ever" and "Never". The OHIP consists of 14 questions in which higher scores indicate worse outcomes.

5. Difference of tumor locations of the oral squamous cell cancer [ Time Frame: Baseline until resection surgery ( approximately 4 weeks) ]

   Oral squamous cell carcinoma locations acoording to follwoing regions:

   • Anterior compartment which includes lower lip, buccal mucosa, anterior vestibule, anterior ridge and anterior floor mouth
   • Lateral compartment which includes posterior vestibule, posterior alveolar ridge, posterior (lateral) floor of mouth
   • Retromolar compartment which includes alveolar ridge posterior to last molar, region of wisdom teeth, retromolar triangle ie buccal cheek, soft palate (arch), tonsillar regions
   • Tongue which includes ventral tongue (undersurface of tongue), lateral rim of tongue, base of tongue
6. Difference of tumor staging according to the TNM system [ Time Frame: Baseline until resection surgery ( approximately 4 weeks) ]

   Oral squamous cell carcinoma staging according to TNM (Tumor, Node, Metastasis) system.

   In the TNM system the "T" refers to the size and extent of the main tumor likert from T0 to T4 whereas T0 is the smallest and T4 the biggest size.

   The main tumor is usually called the primary tumor. The "N" refers to the number of nearby lymph nodes that have cancer likert for N0 to N3 whereas N0 is the single nearby lymphnode and N3 multiple lymphnodes. The "M" refers to whether the cancer has metastasized likert from M0 to M1 whereas M0 is no distant metastasis and M1 is distant metastasis.

7. Difference of surgical duration and hospital stay if resection and reconstruction was performed in one or two stages [ Time Frame: Day of resection surgery until day of reconstruction surgery up to 18 months ]
   • Duration of surgery (skin to skin) in minutes
   • Length of hospital stay in days
   • Date of osseous reconstruction (if different from resection surgery) in days
8. Difference of surgical procedures of osseous reconstruction [ Time Frame: Day of resection surgery until day of reconstruction surgery up to 18 months ]
   • Numers of Bone and soft tissue flaps to reconstruct the mandible: ie number of pieces in which the donor bone(s) is cut to shape the reconstructed mandible
   • Type of bone donor/ bone transfer site(s): Vascularized bone flap(s) or composite flaps (ie bone and adjacent soft tissue harvested within the same flap) and type(s)
9. Different surgical parameters of tumor and segmental mandibular resection if VSP planning was used [ Time Frame: Day of resection surgery until day of reconstruction surgery up to 18 months ]
   • Use of virtual surgical planning (VSP) for resection: Yes/No.
   • Only virtual planning and simulation of resection (no 3D printing):Yes/No.
   • 3D-printed biomodels: Yes/No

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Sampling Method: Probability Sample

Study Population

Patients presenting with an acquired segmental mandibular defect secondary to oral squamous cell carcinoma removal and who require mandibular reconstruction.

Criteria

Inclusion Criteria:

• Age 18 years and older
• Initial pathologically confirmed diagnosis of primary oral squamous cell carcinoma located in mucosa and/or mandible
• Undergoing primary curative treatment with segmental resection of the mandible ≥4 cm
• Intention to undergo mandibular reconstruction with autologous bone using a primary (one stage) or secondary (two stage) approach

• Informed consent obtained, ie:

  • Ability to understand the content of the patient information/ICF
  • Willingness and ability to participate in the clinical investigation according to the registry plan (RP)
  • Signed and dated IRB/EC approved informed consent (ICF) OR
  • Written consent provided according to the IRB/EC defined and approved procedures for patients who are not able to provide to provide independent written informed consent

Exclusion Criteria:

• Tumors affecting the condyle
• Distant OSCC metastasis
• Any other active concomitant malignancy within the last 5 years
• Patients who require neoadjuvant therapy
• Patients under palliative care
• Previous extensive mandibular surgeries (including reconstructions)

Intraoperative exclusion criteria:

• Nonsegmental mandibular defect (eg. box resection/partial resection)
• Segmental mandibular defect of less than 4 cm
• Mandibular defects extending beyond the sigmoid notch into the condyles

Additional exclusion criterion:

• No osseous reconstruction with autologous bone performed within 18 months from resection

Contacts and Locations

Contacts

Contact: Felix Thomas, PhD; + 41 79 671 47 98; felix.thomas@aofoundation.org

Contact: Alix Frischknecht, M.sc.; alix.frischknecht@aofoundation.org

Locations

United States, Florida

University of Florida College of Medicine; Recruiting

Jacksonville, Florida, United States, 32209

Contact: Rui Fernandes, Prof 904-244-3901 Rui.Fernandes@jax.ufl.edu

United States, Texas

John Peter Smith Health Network; Not yet recruiting

Fort Worth, Texas, United States, 76104

Contact: Roderick Kim, MD 817-702-6979 roderickykim@gmail.com

Germany

Universitätsklinikum Tübingen; Not yet recruiting

Tübingen, Baden-Württemberg, Germany, 72076

Contact: Andreas Naros, MD +49 7071 2986174 andreas.naros@med.uni-tuebingen.de

University Hospital RWTH Aachen; Recruiting

Aachen, Germany, 52074

Contact: Ali Modabber, Prof +49 241 80 88258 Amodabber@ukaachen.de

University Hospital Charité; Recruiting

Berlin, Germany, 13353

Contact: Max Heiland, Prof +49 450 655 270 Max.Heiland@charite.de

Hannover Medical School; Recruiting

Hannover, Germany, 30625

Contact: Philippe Korn, PD, MD +49 511 532 4879 korn.philippe@mh-hannover.de

Universitätsklinikum Heidelberg; Recruiting

Heidelberg, Germany, 69120

Contact: Christian Freudlsperger, Prof +49 6221 56 34444 Christian.Freudlsperger@med.uni-heidelberg.de

University Hospital Leipzig; Recruiting

Leipzig, Germany, 04103

Contact: Tabea Pankow, PD, MD + 49 3419721863 tabea.pankow@medizin.uni-leipzig.de

Klinikum der LMU München; Recruiting

Munich, Germany, 80337

Contact: Wenko Smolka, PD, MD +49 440054458 Wenko.Smolka@med.lmu.de

Netherlands

Erasmus University Medical Centre; Not yet recruiting

Rotterdam, Netherlands, 3015 GD

Contact: Eppo Wolvius, Prof +31 6 22 48 77 81 E.Wolvius@erasmusmc.nl

Spain

12 de Octubre; Recruiting

Madrid, Spain, 28041

Contact: Maria Mejía Nieto, MD +34 687 083 530 Mmejianieto@hotmail.com

Sweden

Uppsala University Hospital; Not yet recruiting

Uppsala, Sweden, 75185

Contact: Andreas Thor, Prof +46 18 6116450 Andreas.Thor@akademiska.se

Switzerland

University Hospital Basel; Not yet recruiting

Basel, Switzerland, 4031

Contact: Florian Thieringer, MD +41 612 657 344 Florian.Thieringer@usb.ch

Sponsors and Collaborators

AO Innovation Translation Center

Investigators

• Principal Investigator: Rüdiger Zimmerer, PD, MD; University of Leipzig

More Information

• Responsible Party: AO Innovation Translation Center
• ClinicalTrials.gov Identifier: NCT04098146
• Other Study ID Numbers: SMDR Registry
• First Posted: September 23, 2019
• Last Update Posted: December 15, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AO Innovation Translation Center:

Mandibular osteotomy; Free bone flap; Reconstructive surgical procedure; Adjuvant Irradiation / Chemotherapy

Additional relevant MeSH terms:

Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site