Discussion
nausea, hypopharyngeal carcinomas, malignancy, HNSCCs, oropharyngeal carcinomas, infection, tongue-base carcinomas, tumour, peripheral atypical hyperplasia, multiple primary mucosal lesions, HNSCC, hypothyroidism, primary lesions, pharyngeal fistula, rashes
LYMPHATIC FISTULA, REGRESSION, RECURRENCE, METASTASIS, METASTATIC TUMOUR, ADVERSE EFFECTS, SURGICAL COMPLICATIONS, INFECTION, TUMOUR, BONE MARROW SUPPRESSION, CPS, HYPOTHYROIDISM, COMPLICATIONS, ATYPICAL HYPERPLASIA
The response rate to neoadjuvant therapy of the patients in our sample was high. The postoperative rate of pCR after surgical resection was 36.4% (8/22). Zinner et al. treated 26 patients with preoperative nivolumab combined with carboplatin and paclitaxel as neoadjuvant therapy and reported a pCR rate of 42% (After classification and analysis of the postoperative pathological examinations of the primary lesions and cervical lymph node lesions, we found that, of the 13 patients with postoperative residual lesions, only 1 had only residual lymph node tumour tissue with no residual primary lesion; 7 patients had residual primary lesions, but lymph nodes that were pathologically negative for metastatic tumour tissue and 5 patients had residual malignancy in both the primary lesion and cervical lymph nodes. The responses of the primary lesions and cervical lymph nodes to pembrolizumab combined with neoadjuvant chemotherapy were not synchronous, with lymph nodes showing a higher response rate than primary lesions. The CIAO study also reported a better response to immune checkpoint inhibitors in metastatic lymph nodes than primary lesions (CPS is the most widely used marker of the effects of anti-PD-1 drug therapy (Pembrolizumab combined with neoadjuvant chemotherapy provides favourable conditions for functional preservation during surgery. Many of the patients in this study had hypopharyngeal carcinomas and tongue-base carcinomas adjacent to the larynx. However, the overall rate of laryngeal function preservation was 90.9% (20/22). In the past, patients with hypopharyngeal carcinomas at T3 and above accompanied by unilateral vocal cord fixation were usually treated with total laryngectomy (In terms of surgical safety, no complications that affected surgery resulted from the neoadjuvant therapy. Nevertheless, immunotherapy is not without adverse effects, which include bone marrow suppression, nausea, rashes and hypothyroidism (Despite its advantages, pembrolizumab combined with neoadjuvant chemotherapy also presents challenges in surgical treatment. The most common postoperative surgical complications of the patients treated with neoadjuvant therapy were poor wound healing, infection around the tracheal stoma, pharyngeal fistula and lymphatic fistula. Most recovered from these complications with conservative treatment, but postoperative radiotherapy was delayed in several patients because of complications. In addition, it was found during surgery that 3 of the 22 patients had residuals at the first intraoperative incisal margin. Most of the 12 patients with residual lesions also had scattered lesions with shallow DOI (depth of invasion) accompanied by severe peripheral atypical hyperplasia. This suggests that, despite observable lesion regression after neoadjuvant therapy, residual microscopic lesions and atypical hyperplasia in the area of the primary lesion often remain. Therefore, in patients with apparent lesion regression, narrowing of the surgical scope is inadvisable. It is also necessary to standardise the safety boundary reservation and the submission of intraoperative incisal margins to prevent residuals. The problems with incisal margins have received little attention in previous studies on neoadjuvant therapy. This is largely because most previous research has used patients with oral and oropharyngeal carcinomas. In our study, hypopharyngeal carcinomas accounted for the vast majority of the patients, so safety-boundary-related problems were prominent.At follow-up, all 22 patients were in stable condition. The longest follow-up time was 19 months. One patient suffered local-regional lymph node recurrence. Long-term outcomes will become apparent with further postoperative follow-up. At present, the 3-year recurrence rate of patients with advanced HNSCCs is >50% (Analysis of the reasons for previous treatment failures in HNSCCs, represented by hypopharyngeal carcinomas, showed that multiple primary mucosal lesions due to physicochemical factors, submucosal invasion and high and occult metastasis of cervical lymph nodes were the main causes of local failure and early and rapid distant metastasis significantly affects long-term survival after surgery. Neoadjuvant therapy has the potential to improve long-term tumour immunity through immune memory. In addition, the response rate to preoperative neoadjuvant therapy was higher than that from anti-recurrence/metastasis treatment. This is likely because of the lower tumour heterogeneity, fewer drug-resistant clones and better immune status of the patients. It is conceivable that neoadjuvant therapy might be more effective to overcome the aforementioned adverse factors in HNSCC treatment and provide long-term tumour control and longer survival.