Stereotactic Post-operative Radiotherapy for Intraparotid Metastatic Cutaneous Squamous Cell Carcinoma

NCT07337161 | Recruiting DMC

• 2 other identifiers: 520115521
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the effectiveness and side effects of stereotactic radiotherapy (5 sessions) against conventional (standard) radiotherapy (20-30 sessions) for the treatment of skin cancer involving the head and neck after surgical resection. Stereotactic radiotherapy works in the same way that conventional (standard) radiotherapy does to kill cancer cells by damaging their genetic material and stopping the cancer cells from making copies of themselves. This study will help the study doctors find out if this different approach is the same, better, or worse than the standard of care for your cancer.

Conditions

Cutaneous; Head and Neck Cancer Squamous Cell Carcinoma

Keywords

skin; head and neck; radiation; SBRT; SABR

Outcome Measures

Primary Outcomes (1)

• Tumor control

  Tumor control within the irradiated field at 2 years following adjuvant radiation completion defined as absence of clinical, radiographic or biopsy-proven recurrence within the irradiated field

  2 years

Secondary Outcomes (7)

• Regional recurrence

  2 years

• Disease-free survival (DFS)

  2 years

• Overall survival

  2 years

• Rate of salvage surgery

  2 years

• Radiation-associated toxicity

  Baseline, during treatment, 2 weeks post treatment, 4 weeks post treatment, 3, 12, 18, 24 months post treatment, and yearly from years 2-5 after the end of radiation.

Study Arms (2)

Arm 1: Control

ACTIVE COMPARATOR

Patients in Arm 1 will receive daily conventional fractionation radiation over 4 or 6-6.5 weeks based on the treating oncologist's discretion. The below dose levels are recommended in the following clinical scenarios but may be modified per institutional standards: 20-fraction regimen or 30 to 33-fraction regimen

Radiation: Standard Radiation

Arm 2: SBRT arm

EXPERIMENTAL

Patients in Arm 2 will receive ultra-hypofractionated stereotactic radiation over 5 treatments delivered every other weekday or twice weekly as follows: * 40 to 42.5 Gy in 5 fractions: any areas of gross residual disease, or gross PNI on imaging * 32.5 to 35 Gy in 5 fractions: microscopic areas at risk including positive margin and/or ENE * 30 Gy in 5 fractions: entire operative bed including areas of primary tumor and involved nodes and dissected cervical nodal levels * 27.5 to 30 Gy 5 fractions: at risk undissected cervical nodal levels adjacent to pathologically involved nodal levels, based on the discretion of the treating oncologist

Radiation: SBRT

Interventions

SBRT RADIATION

Patients will receive ultra-hypofractionated stereotactic radiation over 5 treatments delivered every other weekday or twice weekly as follows: * 40 to 42.5 Gy in 5 fractions: any areas of gross residual disease, or gross PNI on imaging * 32.5 to 35 Gy in 5 fractions: microscopic areas at risk including positive margin and/or ENE * 30 Gy in 5 fractions: entire operative bed including areas of primary tumor and involved nodes and dissected cervical nodal levels * 27.5 to 30 Gy 5 fractions: at risk undissected cervical nodal levels adjacent to pathologically involved nodal levels, based on the discretion of the treating oncologist

Arm 2: SBRT arm

Standard Radiation RADIATION

Patients will receive daily conventional fractionation radiation over 4 or 6-6.5 weeks based on the treating oncologist's discretion. The below dose levels are recommended in the following clinical scenarios but may be modified per institutional standards: 20-fraction regimen or 30 to 33-fraction regimen

Arm 1: Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Patient able to provide informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient is a candidate for curative intent treatment
• Patient is able to comprehend English adequately to complete patient reported outcome questionnaires
• Biopsy-confirmed cutaneous SCC
• Definitive resection of a primary cutaneous tumor within the head and neck
• Tumor stage T1-T4 (AJCC 8th edition); or tumor stage unknown (T0/Tx) with a positive intraparotid, peri-parotid or cervical node that is assumed to be from a head and neck cutaneous SCC by the treating oncologist
• Nodal stage N1-N3 (AJCC 8th edition)
• At least 1 indication for adjuvant radiation, including:
• T3 or T4 tumor stage
• Lymphovascular invasion (LVI)
• Perineural invasion (PNI)
• Positive or close (≤ 3 mm) margin
• ≥ 1 positive intraparotid, peri-parotid or cervical lymph node

You may not qualify if:

• Definite metastatic disease at diagnosis
• Pregnant or breastfeeding women
• Significant health conditions or contraindications to receiving surgery and radiation
• History of previous head and neck cancer within 5 years, except for localized skin cancers (i.e. no nodal or distant spread)
• Prior head and neck radiation involving the ipsilateral parotid or neck. However, prior radiation to the index skin cancer that has led to the parotid nodal disease being treated on this trial is allowed, as long as there is no overlap, or inconsequential overlap, in the judgement of the treating oncologist.
• Indications for contralateral neck radiation (i.e. contralateral or bilateral lymph nodes)
• Previous invasive malignancy within 5 years, unless controlled with no evidence of disease

Sponsors & Collaborators

• David Palma: lead

Study Sites (1)

Verspeeten Family Cancer Centre

London, Ontario, N6A 5W9, Canada

RECRUITING

Related Publications (38)

• Culbert M, Bidermann G, Wallace AS. Decisional preferences and satisfaction with short-course radiation for breast cancer. JCO. 2018;36(30_suppl):193-193. doi:10.1200/JCO.2018.36.30_suppl.193

  BACKGROUND

• National Comprehensive Cancer Network Squamous Cell Skin Cancer (version 1.2024). https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed 24 August 2024.

  BACKGROUND

• National Cancer Institute-Common Toxicity Criteria Adverse Events Version 5. Published 2017. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refer ence_8.5x11.pdf. Accessed 25 August 2024.

  BACKGROUND

• Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.

  PMID: 18929686 BACKGROUND

• Hatswell A, Freemantle N, Baio G, Lesaffre E, van Rosmalen J. Summarising salient information on historical controls: A structured assessment of validity and comparability across studies. Clin Trials. 2020 Dec;17(6):607-616. doi: 10.1177/1740774520944855. Epub 2020 Sep 21.

  PMID: 32957804 BACKGROUND

• Pocock SJ. The combination of randomized and historical controls in clinical trials. J Chronic Dis. 1976 Mar;29(3):175-88. doi: 10.1016/0021-9681(76)90044-8. No abstract available.

  PMID: 770493 BACKGROUND

• Ringash J, O'Sullivan B, Bezjak A, Redelmeier DA. Interpreting clinically significant changes in patient-reported outcomes. Cancer. 2007 Jul 1;110(1):196-202. doi: 10.1002/cncr.22799.

  PMID: 17546575 BACKGROUND

• Yao JJ, Zhou GQ, Jin YN, Zhang WJ, Lin L, Yu XL, Shao JY, Ma J, Sun Y. Predictors of Mastoiditis after Intensity-Modulated Radiotherapy in Nasopharyngeal Carcinoma: A Dose-Volume Analysis. J Cancer. 2016 Jan 8;7(3):276-82. doi: 10.7150/jca.13183. eCollection 2016.

  PMID: 26918040 BACKGROUND

• Diao K, Nguyen TP, Moreno AC, Reddy JP, Garden AS, Wang CH, Tung S, Wang C, Wang XA, Rosenthal DI, Fuller CD, Gunn GB, Frank SJ, Morrison WH, Shah SJ, Lee A, Spiotto MT, Su SY, Ferrarotto R, Phan J. Stereotactic body ablative radiotherapy for reirradiation of small volume head and neck cancers is associated with prolonged survival: Large, single-institution, modern cohort study. Head Neck. 2021 Nov;43(11):3331-3344. doi: 10.1002/hed.26820. Epub 2021 Jul 16.

  PMID: 34269492 BACKGROUND

• Grimm J, Vargo JA, Mavroidis P, Moiseenko V, Emami B, Jain S, Caudell JJ, Clump DA, Ling DC, Das S, Moros EG, Vinogradskiy Y, Xue J, Heron DE. Initial Data Pooling for Radiation Dose-Volume Tolerance for Carotid Artery Blowout and Other Bleeding Events in Hypofractionated Head and Neck Retreatments. Int J Radiat Oncol Biol Phys. 2021 May 1;110(1):147-159. doi: 10.1016/j.ijrobp.2020.12.037. Epub 2021 Feb 11.

  PMID: 33583641 BACKGROUND

• Hanna GG, Murray L, Patel R, Jain S, Aitken KL, Franks KN, van As N, Tree A, Hatfield P, Harrow S, McDonald F, Ahmed M, Saran FH, Webster GJ, Khoo V, Landau D, Eaton DJ, Hawkins MA. UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Clin Oncol (R Coll Radiol). 2018 Jan;30(1):5-14. doi: 10.1016/j.clon.2017.09.007. Epub 2017 Oct 13.

  PMID: 29033164 BACKGROUND

• Ng SP, Wang H, Pollard C 3rd, Nguyen T, Bahig H, Fuller CD, Gunn GB, Garden AS, Reddy JP, Morrison WH, Shah S, Rosenthal DI, Frank SJ, Guha-Thakurta N, Ferrarotto R, Hanna EY, Su SY, Phan J. Patient Outcomes after Reirradiation of Small Skull Base Tumors using Stereotactic Body Radiotherapy, Intensity Modulated Radiotherapy, or Proton Therapy. J Neurol Surg B Skull Base. 2020 Dec;81(6):638-644. doi: 10.1055/s-0039-1694052. Epub 2019 Jul 31.

  PMID: 33381367 BACKGROUND

• Gerhard SG, Palma DA, Arifin AJ, Louie AV, Li GJ, Al-Shafa F, Cheung P, Rodrigues GB, Bassim CW, Corkum MT. Organ at Risk Dose Constraints in SABR: A Systematic Review of Active Clinical Trials. Pract Radiat Oncol. 2021 Jul-Aug;11(4):e355-e365. doi: 10.1016/j.prro.2021.03.005.

  PMID: 34217495 BACKGROUND

• Nichols AC, Lang P, Prisman E, Berthelet E, Tran E, Hamilton S, Wu J, Fung K, de Almeida JR, Bayley A, Goldstein DP, Eskander A, Husain Z, Bahig H, Christopoulous A, Hier M, Sultanem K, Richardson K, Mlynarek A, Krishnan S, Le H, Yoo J, MacNeil SD, Mendez A, Winquist E, Read N, Venkatesan V, Kuruvilla S, Warner A, Mitchell S, Corsten M, Rajaraman M, Johnson-Obaseki S, Eapen L, Odell M, Chandarana S, Banerjee R, Dort J, Matthews TW, Hart R, Kerr P, Dowthwaite S, Gupta M, Zhang H, Wright J, Parker C, Wehrli B, Kwan K, Theurer J, Palma DA. Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial. BMC Cancer. 2020 Feb 14;20(1):125. doi: 10.1186/s12885-020-6607-z.

  PMID: 32059705 BACKGROUND

• Nichols AC, Yoo J, Hammond JA, Fung K, Winquist E, Read N, Venkatesan V, MacNeil SD, Ernst DS, Kuruvilla S, Chen J, Corsten M, Odell M, Eapen L, Theurer J, Doyle PC, Wehrli B, Kwan K, Palma DA. Early-stage squamous cell carcinoma of the oropharynx: radiotherapy vs. trans-oral robotic surgery (ORATOR)--study protocol for a randomized phase II trial. BMC Cancer. 2013 Mar 20;13:133. doi: 10.1186/1471-2407-13-133.

  PMID: 23514246 BACKGROUND

• Siu LL, Waldron JN, Chen BE, Winquist E, Wright JR, Nabid A, Hay JH, Ringash J, Liu G, Johnson A, Shenouda G, Chasen M, Pearce A, Butler JB, Breen S, Chen EX, FitzGerald TJ, Childs TJ, Montenegro A, O'Sullivan B, Parulekar WR. Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma: A Randomized Clinical Trial. JAMA Oncol. 2017 Feb 1;3(2):220-226. doi: 10.1001/jamaoncol.2016.4510.

  PMID: 27930762 BACKGROUND

• A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer. Published online August 8, 2009. Accessed August 15, 2024. https://clinicaltrials.gov/study/NCT00956007

  BACKGROUND

• Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, Jones CU, Dunlap NE, Seaward SA, Spencer S, Galloway TJ, Phan J, Dignam JJ, Le QT. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019 Jan 5;393(10166):40-50. doi: 10.1016/S0140-6736(18)32779-X. Epub 2018 Nov 15.

  PMID: 30449625 BACKGROUND

• Hu M, Kim ANH, Emeto TI, Collins M, Chopping A, Lin C. Metastatic cutaneous squamous cell carcinoma to the parotid: Adjuvant radiotherapy and treatment outcomes. J Med Radiat Sci. 2023 Jun;70(2):161-170. doi: 10.1002/jmrs.650. Epub 2023 Feb 15.

  PMID: 36790039 BACKGROUND

• Hong TS, Kriesel KJ, Hartig GK, Harari PM. Parotid area lymph node metastases from cutaneous squamous cell carcinoma: implications for diagnosis, treatment, and prognosis. Head Neck. 2005 Oct;27(10):851-6. doi: 10.1002/hed.20256.

  PMID: 16114004 BACKGROUND

• Coombs AC, Butler A, Allison R. Metastatic cutaneous squamous cell carcinoma of the parotid gland: prognostic factors. J Laryngol Otol. 2018 Mar;132(3):264-269. doi: 10.1017/S0022215117001323. Epub 2017 Jul 5.

  PMID: 28677515 BACKGROUND

• Chen AM, Grekin RC, Garcia J, Bucci MK, Margolis LW. Radiation therapy for cutaneous squamous cell carcinoma involving the parotid area lymph nodes: dose and volume considerations. Int J Radiat Oncol Biol Phys. 2007 Dec 1;69(5):1377-80. doi: 10.1016/j.ijrobp.2007.05.005. Epub 2007 Aug 8.

  PMID: 17689882 BACKGROUND

• Voruganti IS, Poon I, Husain ZA, Bayley A, Barnes EA, Zhang L, Chin L, Erler D, Higgins K, Enepekides D, Eskander A, Karam I. Stereotactic body radiotherapy for head and neck skin cancer. Radiother Oncol. 2021 Dec;165:1-7. doi: 10.1016/j.radonc.2021.10.004. Epub 2021 Oct 11.

  PMID: 34648871 BACKGROUND

• Biau J, Thivat E, Millardet C, Saroul N, Pham-Dang N, Molnar I, Pereira B, Durando X, Bourhis J, Lapeyre M. A multicenter prospective phase II study of postoperative hypofractionated stereotactic body radiotherapy (SBRT) in the treatment of early-stage oropharyngeal and oral cavity cancers with high risk margins: the STEREO POSTOP GORTEC 2017-03 trial. BMC Cancer. 2020 Aug 5;20(1):730. doi: 10.1186/s12885-020-07231-3.

  PMID: 32758188 BACKGROUND

• Mohamad I, Karam I, El-Sehemy A, Abu-Gheida I, Al-Ibraheem A, Al-Assaf H, Aldehaim M, Alghamdi M, Alotain I, Ashour M, Bushehri A, ElHaddad M, Hosni A. The Evolving Role of Stereotactic Body Radiation Therapy for Head and Neck Cancer: Where Do We Stand? Cancers (Basel). 2023 Oct 16;15(20):5010. doi: 10.3390/cancers15205010.

  PMID: 37894377 BACKGROUND

• Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, Chan C, Churn M, Cleator S, Coles CE, Goodman A, Harnett A, Hopwood P, Kirby AM, Kirwan CC, Morris C, Nabi Z, Sawyer E, Somaiah N, Stones L, Syndikus I, Bliss JM, Yarnold JR; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020 May 23;395(10237):1613-1626. doi: 10.1016/S0140-6736(20)30932-6. Epub 2020 Apr 28.

  PMID: 32580883 BACKGROUND

• Raldow AC, Chen AB, Russell M, Lee PP, Hong TS, Ryan DP, Cusack JC, Wo JY. Cost-effectiveness of Short-Course Radiation Therapy vs Long-Course Chemoradiation for Locally Advanced Rectal Cancer. JAMA Netw Open. 2019 Apr 5;2(4):e192249. doi: 10.1001/jamanetworkopen.2019.2249.

  PMID: 30977859 BACKGROUND

• Newman JG, Hall MA, Kurley SJ, Cook RW, Farberg AS, Geiger JL, Koyfman SA. Adjuvant therapy for high-risk cutaneous squamous cell carcinoma: 10-year review. Head Neck. 2021 Sep;43(9):2822-2843. doi: 10.1002/hed.26767. Epub 2021 Jun 7.

  PMID: 34096664 BACKGROUND

• Melo GM, Guilherme LH, Palumbo MDN, Rosano M, Neves MCD, Callegari FM, Abrahao M, Cervantes O. Parotidectomy and neck dissection in locally advanced and relapsed cutaneous squamous cell carcinoma of the head and neck region. Braz J Otorhinolaryngol. 2022 Nov-Dec;88 Suppl 4(Suppl 4):S152-S162. doi: 10.1016/j.bjorl.2021.11.007. Epub 2021 Dec 10.

  PMID: 35042657 BACKGROUND

• Veness MJ, Palme CE, Smith M, Cakir B, Morgan GJ, Kalnins I. Cutaneous head and neck squamous cell carcinoma metastatic to cervical lymph nodes (nonparotid): a better outcome with surgery and adjuvant radiotherapy. Laryngoscope. 2003 Oct;113(10):1827-33. doi: 10.1097/00005537-200310000-00031.

  PMID: 14520114 BACKGROUND

• O'Brien CJ, McNeil EB, McMahon JD, Pathak I, Lauer CS, Jackson MA. Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland. Head Neck. 2002 May;24(5):417-22. doi: 10.1002/hed.10063.

  PMID: 12001070 BACKGROUND

• O'Brien CJ, McNeil EB, McMahon JD, Pathak I, Lauer CS. Incidence of cervical node involvement in metastatic cutaneous malignancy involving the parotid gland. Head Neck. 2001 Sep;23(9):744-8. doi: 10.1002/hed.1106.

  PMID: 11505484 BACKGROUND

• Hinerman RW, Indelicato DJ, Amdur RJ, Morris CG, Werning JW, Vaysberg M, Kirwan J, Mendenhall WM. Cutaneous squamous cell carcinoma metastatic to parotid-area lymph nodes. Laryngoscope. 2008 Nov;118(11):1989-96. doi: 10.1097/MLG.0b013e318180642b.

  PMID: 18849863 BACKGROUND

• Thom JJ, Moore EJ, Price DL, Kasperbauer JL, Starkman SJ, Olsen KD. The Role of Total Parotidectomy for Metastatic Cutaneous Squamous Cell Carcinoma and Malignant Melanoma. JAMA Otolaryngol Head Neck Surg. 2014 Jun;140(6):548-54. doi: 10.1001/jamaoto.2014.352.

  PMID: 24722863 BACKGROUND

• Gregoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA, Lee A, Le QT, Maingon P, Nutting C, O'Sullivan B, Porceddu SV, Lengele B. Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiother Oncol. 2014 Jan;110(1):172-81. doi: 10.1016/j.radonc.2013.10.010. Epub 2013 Oct 31.

  PMID: 24183870 BACKGROUND

• Bradley PJ. Parotid lymph nodes in primary malignant salivary neoplasms. Curr Opin Otolaryngol Head Neck Surg. 2022 Apr 1;30(2):99-106. doi: 10.1097/MOO.0000000000000772.

  PMID: 35255046 BACKGROUND

• Likhacheva A, Awan M, Barker CA, Bhatnagar A, Bradfield L, Brady MS, Buzurovic I, Geiger JL, Parvathaneni U, Zaky S, Devlin PM. Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin: Executive Summary of an American Society for Radiation Oncology Clinical Practice Guideline. Pract Radiat Oncol. 2020 Jan-Feb;10(1):8-20. doi: 10.1016/j.prro.2019.10.014. Epub 2019 Dec 9.

  PMID: 31831330 BACKGROUND

• Eggermont CJ, Eggermont AMM. Shifting landscape in skin cancer incidence: the rising tide of cutaneous squamous cell carcinoma and potential implications for prevention. Br J Dermatol. 2024 Mar 15;190(4):460-461. doi: 10.1093/bjd/ljad480. No abstract available.

  PMID: 38099564 BACKGROUND

Central Study Contacts

Palma

CONTACT

519-685-8500; david.palma@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Schulich School of Medicine & Dentistry, University of Western Ontario

Study Record Dates

• First Submitted: August 28, 2025
• First Posted: January 13, 2026
• Study Start: October 21, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2035
• Last Updated: January 13, 2026

Record last verified: 2026-01

Locations

CA (1)