Immunotherapy before head and neck cancer surgery does not increase complications

April 27, 2022

3 min read



Philips R, et al. Abstract AHNS09. Presented at: American Head & Neck Society Annual Meeting at COSM 2022; April 27-28, 2022; Dallas.

Disclosures: Philips reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.

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DALLAS — Neoadjuvant immunotherapy did not increase risk for complications among patients who underwent surgery for head and neck cancers, according to study results presented at American Head & Neck Society Annual Meeting.

“Neoadjuvant immunotherapy is safe with the idea that definitive surgery will be performed within 4 to 8 weeks,” researcher Ramez Philips, MD, a fourth-year resident in the department of otolaryngology — head and neck surgery at Thomas Jefferson University Hospitals, told Healio. “Chemotherapy in addition to immunotherapy preoperatively might lead to risk for worse surgical outcomes.”

Background and methods

Immunotherapy has led to major improvements in treatment of metastatic head and neck cancer, and it is being used more commonly in the neoadjuvant setting.

Advantages include an abundance of neoantigens in unresected tumors and systemic elimination of occult metastases, with theoretical advantages of pathologic response and pathologic downstaging, Philips said.

However, immune-related adverse events can lead to persistent morbidity and treatment delays. Prior reports suggest approximately 15% of patients experience such events, Philips said.

“Adverse events are well-studied. The question really is, what is the effect of immunotherapy on complications [after definitive surgery],” Philips said.

Philips and colleagues conducted a retrospective study to compare surgical, medical and overall complications among patients with head and neck cancers who underwent major head and neck surgery with or without neoadjuvant immunotherapy.

Researchers also sought to identify factors that predicted increased complications.

The analysis included 463 patients who underwent ablation and free flap reconstruction (29%) or transoral robotic surgery (71%) for primary head and neck squamous cell carcinoma at a tertiary institution between 2017 and 2021.

All patients who received neoadjuvant immunotherapy had done so as part of clinical trials.

Eighty-three patients (17.9%) received neoadjuvant immunotherapy.

Twenty-one patients received the PD-L1 inhibitor durvalumab (Imfinzi, AstraZeneca); of these, five received durvalumab alone and 16 also received metformin.

Sixty-two patients received the PD-1 inhibitor nivolumab (Opdivo, Bristol Myers Squibb); of these, 14 also received an IDO1 inhibitor, 13 received tadalafil, 21 received chemotherapy with paclitaxel and carboplatin, and 14 received nivolumab alone.

Demographics appeared similar between patients who received neoadjuvant immunotherapy and those who did not.

However, patients who received surgery without neoadjuvant immunotherapy had significantly higher rates of advanced T stage (T3/T4 (25.3% vs. 22.9%; P = .003), nodal disease (77.7% vs. 67.5%; P = .0497), lymphovascular invasion (33.2% vs. 16.9%; P = .0003) and perineural invasion (29.2% vs. 18.1%; P = .039).

“This could be for one of two reasons,” Philips said. “It’s either selection bias that favors clinical trials or pathologic response leading to downstaging. We’re still trying to investigate which one of those it is.”

Thirty-day postoperative overall complication rate served as the primary outcome. Secondary outcomes included delays or cancellation of definitive surgery.

Key findings

Researchers reported an 18% complication rate among patients who underwent upfront surgery and a 15% complication rate among those who received neoadjuvant immunotherapy.

Results showed no statistically significant differences in overall, medical or surgical complications between treatment groups.

Further analysis of patients who received neoadjuvant immunotherapy showed 6% experienced grade 3/grade 4 immune-related adverse events and 4.8% required surgical delay. Four patients required surgery cancellation — one due to grade 3/grade 4 adverse events, one due to refusal , and two due to progressive disease.

Univariable analysis identified several factors associated with risk for overall complications among patients who received neoadjuvant immunotherapy. These included age, non-white race, higher Charlson Comorbidity Index, free flap vs. transoral robotic surgery, advanced T stage, nodal disease and concurrent chemotherapy.

Multivariable analysis only identified concurrent carboplatin/paclitaxel (OR = 5.5; 95% CI, 1.5-20.3) in neoadjuvant setting to be predictive of increased risk for complications.

An analysis that compared patients who underwent free flap reconstruction vs. transoral robotic surgery showed significantly higher rates of complications in the free flap group; however, receipt of neoadjuvant immunotherapy did not significantly impact complication rates.


“Outcomes after surgery are important for patients’ quality of life and satisfaction, as well as surgical outcomes,” Philips told Healio. “Neoadjuvant immunotherapy is a relatively new thing so it is very important that we explore how it may affect surgery. The findings were in line with what we anticipated.”

Philips emphasized that two patients with primary HNSCC did not undergo definitive surgery related to disease progression after neoadjuvant immunotherapy.

“This is an underreported factor in immunotherapy and requires meticulous counseling and can have enormous oncological implications,” he said.

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