Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis

Oral Oncol. 2018 Oct:85:60-67. doi: 10.1016/j.oraloncology.2018.08.014. Epub 2018 Aug 30.

Abstract

Objectives: Clinical perineural invasion (CPNI) of cutaneous head and neck cancer is associated with poor prognosis and presents a therapeutic dilemma. The purpose of this study was to determine the relationship between CPNI and nerve growth factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR on symptom control and disease-related outcomes.

Materials and methods: We retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who were treated with RT between 2010 and 2015 at our institution. Exact chi-square and Wilcoxon rank-sum tests compared patients with positive versus negative staining for TrkA and/or CD271. Gray's test determined differences in cumulative incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific mortality (CSM).

Results: Twenty-three patients had a median overall follow-up of 31.4 months from initial clinical symptoms and 19.7 months from pathological confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain (57%). Sixteen patients (70%) experienced symptom improvement or control, especially decreased pain (85%), within a median of 2.6 months from starting RT. The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall CSM were 11% and 25%, respectively. Patients who stained positively for TrkA and/or CD271 had significantly worse LRR compared to patients who stained negatively for both markers (p = 0.046).

Conclusion: Positive TrkA and/or CD271 staining predicts worse outcomes. Patients may benefit from aggressive RT for local control and symptom improvement. Future research is needed to identify the potential for anti-nerve growth factor therapies in CPNI.

Keywords: CD 271; Head and neck cancer; Imaging; Immunohistochemical staining; Nerve growth factor; Perineural invasion; Radiotherapy; Skin cancer; Symptom control; Trk A.

MeSH terms

  • Carcinoma, Basal Cell / chemistry
  • Carcinoma, Basal Cell / diagnostic imaging
  • Carcinoma, Basal Cell / pathology*
  • Carcinoma, Basal Cell / radiotherapy
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / radiotherapy
  • Chemoradiotherapy
  • Combined Modality Therapy
  • Cranial Nerves / diagnostic imaging
  • Cranial Nerves / pathology*
  • Follow-Up Studies
  • Head and Neck Neoplasms / chemistry
  • Head and Neck Neoplasms / diagnostic imaging
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Hypesthesia / etiology
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis
  • Nerve Tissue Proteins / analysis
  • Pain / etiology
  • Palliative Care
  • Peripheral Nerves / diagnostic imaging
  • Peripheral Nerves / pathology*
  • Prognosis
  • Radiosurgery
  • Receptor, trkA / analysis
  • Receptors, Nerve Growth Factor / analysis
  • Retrospective Studies
  • Single-Blind Method
  • Skin Neoplasms / chemistry
  • Skin Neoplasms / diagnostic imaging
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / radiotherapy
  • Tomography, X-Ray Computed

Substances

  • NGFR protein, human
  • NTRK1 protein, human
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor
  • Receptor, trkA