AHNS Series: Do you know your guidelines? Principles of treatment for locally advanced or unresectable head and neck squamous cell carcinoma

Fulcher, Cory D.; Haigentz, Missak; Ow, Thomas J.

doi:10.1002/hed.25025

Cited by 20 publications

(16 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study revealed that HPV-positive HNSCC tissues were more sensitive to radiotherapy (19). In HPV-negative HNSCC tissues, there was increased M2 macrophage infiltration compared with HPV-positive HNSCC tissues, and these macrophages released HB-EGF to induce radiotherapy resistance.…”

Section: Discussionmentioning

confidence: 54%

M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF

Liu

et al. 2020

Oncol Rep

View full text Add to dashboard Cite

The aim of the present study was to examine the potential role of human heparin-binding epidermal growth factor (HB-EGF) secreted by M2 macrophages in the development of radioresistance in head and neck squamous cell carcinoma (HNSCC). Immunohistochemistry was used to detect radiosensitivity in human papilloma virus (HPV)-positive and HPV-negative HNSCC tissues and immunohistochemical staining with specific antibodies for macrophage surface markers was used to assess the infiltration of M1 and M2 macrophages in HPV-positive and-negative HNSCC tissues. The expression of HB-EGF in HPV-positive and-negative HNSCC tissues was determined by multi-cytokine detection in order to determine the relationship between HB-EGF and radiosensitivity. M1 and M2 macrophages were co-cultured with the HNSCC cell line CAL27 and treated with HB-EGF and its neutralizing antibodies to assess radiation sensitivity. Finally, the major DNA double-strand break repair pathways required for the activation of HB-EGF and promotion of epidermal growth factor receptor (EGFR) were identified. The results revealed that radiosensitivity was higher in HPV-positive HNSCC compared with HPV-negative. There was a higher infiltration of M2 macrophages in HPV-negative HNSCC, which were revealed as the main source of HB-EGF secretion. Furthermore, it was determined that overexpression of HB-EGF induced radioresistance in HPV-negative HNSCC. HB-EGF promoted the activation of the non-homologous end-joining pathway by activating EGFR. To the best of our knowledge, this is the first study to demonstrate the association between HB-EGF and radiosensitivity in HNSCC. These results indicated that the secretion of HB-EGF by M2 macrophages could induce radioresistance of HPV-negative HNSCC.

show abstract

Section: Discussionmentioning

confidence: 54%

M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF

Liu

et al. 2020

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…The exact place of TPF induction chemotherapy for LAHNSCC over standard concomitant radiochemotherapy [ 10 ] has been questioned by several studies [ 20 – 25 ]. The National Comprehensive Cancer Network (NCCN) guidelines include induction chemotherapy with TPF followed by RT alone or by radiochemotherapy [ 26 ] as a validated treatment option. Indeed, TPF induction chemotherapy continues to be used due to a high response rate and an unequalled rapidity of response, often allowing a rapid regression of severe symptomatology (dyspnea, dysphagia, pain…).…”

Section: Introductionmentioning

confidence: 99%

Predictive factors of toxicity of TPF induction chemotherapy for locally advanced head and neck cancers

et al. 2021

View full text Add to dashboard Cite

Background The rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC). Methods Between June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities. Results Eighty-nine patients (79%) were male; the median age was 58 years [32–71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03). Conclusions TPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

show abstract

“…Therefore, the applicability of the clinical trial results to patients with RMHNC who do not precisely fit the eligibility criteria of pivotal clinical trials is unclear because the strict eligibility criteria in Checkmate-141 prevented enrollment of a broad patient population, even though real-world clinical data for those subtypes have been reported [9,10]. Various treatment modalities are used in HNC, including surgery, chemotherapy, radiotherapy, molecularly-targeted therapy, and immunotherapy [4,5,6,7,8,11,12,13]; the sequence and combination of HNC treatments vary, and treatment policies differ greatly depending on the primary site [14,15,16,17,18,19,20]. It is difficult for the strict eligibility criteria of clinical trials to reflect the diversity of real-world treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Real-World Outcomes and Prognostic Factors in Patients Receiving Nivolumab Therapy for Recurrent or Metastatic Head and Neck Carcinoma

Hori

Shinohara

Kojima

et al. 2019

Cancers

View full text Add to dashboard Cite

Recently, a global phase III study demonstrated that nivolumab markedly improved patient outcomes in recurrent or metastatic head and neck carcinoma (RMHNC). However, the efficacy of nivolumab in patients who are ineligible for clinical trials is unknown. We investigated nivolumab efficacy in real-world patients and prognostic factors associated with the response to nivolumab. This study was conducted at 11 institutes associated with Kyoto University and its Affiliated Hospitals-Head and Neck Oncology Group. In total, 93 patients with RMHNC who received nivolumab between May 2017 and May 2018 were retrospectively reviewed. Objective response rate (ORR), overall survival, and progression-free survival (PFS) were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. The ORRs in patients with squamous cell carcinoma (SCC) and non-SCC were 21.8% and 0%, respectively. In patients with SCC and non-SCC, the 1-year PFS rates were 28.7% and 8.9%, respectively. The hazard ratio (HR) for risk of PFS events (SCC versus non-SCC) was 2.28 (95% confidence interval: 1.21–4.1; log-rank p = 0.007). Univariate and multivariate analyses revealed radiotherapy history, platinum-refractory carcinoma, and treatment-related adverse events (TRAEs) as important prognostic factors associated with PFS in patients with SCC. In a real-world setting, non-SCC and platinum-refractory carcinoma were associated with a poorer prognosis, and a history of radiotherapy to the primary tumor, and the occurrence of TRAEs were associated with a better prognosis. These findings could be useful for clinicians and patients when selecting a treatment strategy.

show abstract

AHNS Series: Do you know your guidelines? Principles of treatment for locally advanced or unresectable head and neck squamous cell carcinoma

Cited by 20 publications

References 111 publications

M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF

M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF

Predictive factors of toxicity of TPF induction chemotherapy for locally advanced head and neck cancers

Real-World Outcomes and Prognostic Factors in Patients Receiving Nivolumab Therapy for Recurrent or Metastatic Head and Neck Carcinoma

Contact Info

Product

Resources

About