Management of Post-Operative Intermediate Risk Pathology in Head and Neck Sqaumous Cell Carcinoma (HNSCC)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Post-op intermediate-risk pathology:
    • Perineural Invasion (PNI)
    • Lymphovascular Invasion (LVI)
    • pT3
    • ENE-negative
    • Negative margins
  • Standard adjuvant plan: 
    • Postoperative radiation therapy (RT) alone (no concurrent cisplatin)
  • Why?:
    • Two landmark randomized trials established who benefits from adding cisplatin to adjuvant RT:
      • EORTC 22931 (Bernier, NEJM 2004):
      • RTOG 9501 (Cooper, NEJM 2004; 10-yr update 2012):
        • In the entire randomized population:
          • CRT did not significantly improve OS / DFS vs RT alone:
            • The KM benefit emerges only in the pre-specified subgroup with:
              • Positive margins and / or extranodal extension (ENE+):
                • Better LRC and DFS; OS trend
            • Outside that subgroup:
      • Comparative analysis of EORTC 22931 and RTOG 9501 (Bernier et al., Head & Neck 2005):
        • Concluded the most consistent benefit from adjuvant CRT is confined to:
          • ENE+ and / or positive margins
        • Features such as pT3, PNI, LVI, or multiple nodes without ENE:
          • Did not reproducibly show survival benefit from adding cisplatin PubMed+1
  • Guideline take-home:
    • Contemporary guidelines reflect these data:
      • For intermediate-risk pathology (PNI / LVI, pT3, multiple nodes without ENE, clear margins):
        • RT alone is recommended:;
          • Concurrent cisplatin is reserved for ENE+ and / or positive (or non-re-resectable “close”) margins JNCCN
    • Site-specific guidance (ASTRO 2024 HPV+ OPSCC):
      • Likewise recommends post-op RT alone for intermediate-risk categories:
  • Practical pearls:
    • Don’t over-treat intermediate-risk patients with cisplatin unless risk escalators exist (e.g., ENE+, positive / non-re-resectable close margin):
      • This avoids unnecessary nephrotoxicity / ototoxicity / neurotoxicity without proven survival gain:
        • KM patterns from RTOG 9501:
          • Show separation only in ENE + / R + PubMed
    • RT planning: 
      • Typical adjuvant doses 60 to 66 Gy to the primary bed / high-risk nodal regions with elective coverage as indicated by subsite and pathologic mapping (per institutional / NCCN frameworks) JNCCN
    • Clinical trials:
      • If available, consider enrollment for intermediate-risk biology:
        • Biomarkers, de-intensification / intensification questions
        • Observational work underscores prognostic value of PNI / LVI but does not establish a chemotherapy benefit post-operatively PMC+1
  • Bottom line: 
    • For PNI / LVI / pT3 (ENE-negative, margins clear):
      • Post-operative RT alone is the guideline-concordant standard.
    • Reserve cisplatin-RT for:
      • ENE+ and / or positive / irremediably close margins:
        • Which is where randomized trials (and their Kaplan–Meier curves):
          • Show the benefit of adding chemotherapy
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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