Background
To determine the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR antibody cetuximab conjugated with a ...light-activatable dye (IRDye
®
700DX), in Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
Methods
Patients received a single fixed dose (640 mg/m
2
) of RM-1929 and a fixed light treatment dose (50 J/cm
2
for superficial illumination; 100 J/cm fiber diffuser length for interstitial illumination). Safety, tumor response (modified RECIST v1.1 by central radiology review), pharmacokinetics, and immunogenicity were evaluated.
Results
Three Japanese patients were enrolled who had failed ≥ 3 prior lines of therapy including radiation, chemotherapy, cetuximab, and immunotherapy. Target lesions were: submental lesion; right superficial cervical node lesion and oropharynx lesion; and external auditory canal lesion. All patients experienced ≥ 1 treatment-emergent adverse event (TEAE), but none were considered dose-limiting. TEAEs were mild to moderate in severity except for one grade 3 application-site pain, which was transient, resolved without sequelae within 24 h, and did not affect study treatment administration. Thirteen of 17 TEAEs reported were possibly or probably related to study treatment. Three patient reports of application-site pain and localized edema were deemed probably related to study treatment. Objective response was observed in two patients (both partial responses). The third patient had disease progression. RM-1929 concentrations and pharmacokinetic parameters were similar in all patients. No patients tested positive for anti-drug antibodies.
Conclusions
RM-1929 photoimmunotherapy showed a manageable safety profile in rHNSCC. Tumor response in these heavily pre-treated patients was clinically meaningful and warrants further investigation.
Clinical trial registration
The trial was registered with the Japanese registry of clinical trials as jRCT2031200133.
Abstract
Objective
Concomitant chemoradiation therapy is a standard treatment for head and neck cancer. Thus, salvage surgery has become a necessary treatment. The aim of the study was to evaluate ...the results of salvage surgery by each site of the head and neck, especially the oropharynx, hypopharynx and larynx.
Methods
This was a retrospective, single-institute study. The primary endpoint was overall survival. Secondary endpoints were disease-free survival, the locoregional control rate after salvage surgery, the indication rate for salvage surgery, the reasons for contraindications to salvage surgery, the post-operative complication rate and the predictors of survival.
Results
Three-year overall survival after salvage surgery was 58.8% in the salvage surgery group and 8.59% in the other treatment group (P < 0.0001). Regarding overall survival and disease-free survival after salvage surgery, there was no difference among sites. Regarding locoregional control rate among sites, there was no significant difference. The oropharyngeal cancer group had the lowest rate of salvage primary resection. Surgical margin and local and regional recurrence or residual disease were predictors on univariate and multivariate analyses.
Conclusions
Salvage surgery is effective for recurrent or residual cases after concomitant chemoradiation therapy. For oropharyngeal cancer, local control is important, and for oropharyngeal cancer and hypopharyngeal cancer, distant metastasis is important.
Salvage surgery for head and neck cancer has become a necessary treatment. This article evaluates the results of salvage surgery by each site of the head and neck.
Abstract
Background
Second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma adversely affect patients’ outcomes and the quality of life; however, an ...adequate surveillance schedule remains unclear.
Methods
We analyzed 330 patients with early esophageal squamous cell carcinoma who underwent endoscopic resection and were registered in the multicenter cohort study to evaluate adequate surveillance for detection of second primary head and neck cancers. Gastrointestinal endoscopists examined the head and neck regions after 3–6 months of endoscopic resection for esophageal squamous cell carcinoma and subsequently every 6 months. An otolaryngologist also examined the head and neck regions at the time of endoscopic resection for esophageal squamous cell carcinoma and at 12 months intervals thereafter.
Results
During the median follow-up period of 49.4 months (1.3–81.2 months), 33 second primary head and neck cancers were newly detected in 20 patients (6%). The tumor site was as follows: 22 lesions in the hypopharynx, eight lesions in the oropharynx, two lesions in larynx and one lesion in the oral cavity. The 2-year cumulative incidence rate of second primary head and neck cancers was 3.7%. Among them, 17 patients with 29 lesions were treated by transoral surgery. One patient with two synchronous lesions was treated by radiotherapy. Two lesions in two patients were not detected after biopsy. All patients were cured with preserved laryngeal function.
Conclusions
Surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months could detect second primary head and neck cancers at an early stage, thereby facilitating minimally invasive treatment.
Abstract
Objectives
Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of ...this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers.
Methods
Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy.
Results
A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of <13 mm (odds ratio: 1.96, P=0.026), tumors located on the anterior surface of the epiglottis/valleculae (odds ratio: 2.98, P=0.045) and inside of the pyriform sinus (odds ratio: 2.28, P=0.046) were associated with missed cancers.
Conclusions
This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate.
Tumors located on the anterior surface of the epiglottis/valleculae and inside of the pyriform sinus were associated with missed cancers during endoscopy. High-quality upper gastrointestinal endoscopy and awareness are necessary.
Hypopharyngeal cancers frequently go undetected until advanced stages. However, recent advances in endoscopic technology have enabled earlier detection of hypopharyngeal cancer. We evaluated the ...effectiveness of larynx-preserving surgery for hypopharyngeal cancer.
We retrospectively analyzed 99 patients with hypopharyngeal squamous cell carcinoma who underwent partial hypopharyngectomy with larynx preservation between September 1992 and December 2009 at the National Cancer Center Hospital East. Of these, 91 patients underwent larynx-preserving surgery as initial treatment; eight patients underwent salvage surgery for recurrent disease after previous radiotherapy. Also, 9 of our patients had undergone previous radiotherapy in the head and neck for a different cancer. Before surgery, the TNM stage and tumor location was recorded. Free-flap reconstruction was performed in 60 patients, while the hypopharyngeal mucosa was closed without a free flap in 39 patients.
The 5-year overall survival rate in our cohort was 66.9%, and 59 patients are currently alive without recurrence. Thirty-three patients died due to primary recurrence (n = 5), regional recurrence (n = 10), distant metastasis (n = 9), postoperative death (n = 1), and unrelated disease (n = 8). Laryngeal function could not be preserved in 19 patients, 2 of whom had undergone previous radiotherapy, and 7 of whom had undergone both previous radiotherapy and other salvage surgeries.
Partial hypopharyngectomy can preserve laryngeal function in patients with pharyngeal cancer with careful patient selection.
Photoimmunotherapy is a novel cancer treatment that recently became covered by national health insurance in Japan, but treatment decision-making remains challenging for unresectable advanced or ...recurrent head and neck cancer. We aimed to clarify the characteristics of patients for whom photoimmunotherapy was indicated by a retrospective chart review. Patients aged ≥20 years diagnosed with advanced or recurrent head and neck cancer who started receiving systemic therapy at the National Cancer Center Hospital East from January 2016 through December 2020 were retrospectively analyzed. Before and after first-line systemic therapy, patients were classified into 3 groups according to eligibility for photoimmunotherapy: eligible, potentially eligible, and ineligible. In total, of 246 patients evaluated-194 after exclusions were analyzed-108 were deemed ineligible for treatment. Of the remaining 86 patients, 8 were considered potentially eligible and 9 eligible. Of the nine eligible patients, four became ineligible after receiving first-line systemic therapy due to disease progression. Our results suggest that the indication of photoimmunotherapy should be considered before, during, and after systemic therapy for unresectable locally advanced or recurrent head and neck cancer.
Photoimmunotherapy is a new treatment modality in which a tumor-targeting monoclonal antibody is combined with a photoactivated dye and a laser is applied to destroy tumor cells. In Japan, insurance ...reimbursement for this treatment started in January 2021 for unresectable locally advanced or locally recurrent head and neck cancer. We used photoimmunotherapy to treat two patients with recurrent nasopharyngeal squamous cell carcinoma (NPSCC). The first patient was diagnosed with NPSCC (T1N0M0) and treated with definitive radiotherapy, leading complete response. A local recurrence was observed and treated with photoimmunotherapy. Seven months have passed, complete response is archived. The second patient was diagnosed with NPSCC (cT2N1M1). Multimodal therapy led to a complete response for all lesions. A local recurrent lesion appeared, and photoimmunotherapy has been repeatedly performed. The lesion was controlled as a stable disease for about one year. Photoimmunotherapy could be an effective treatment for local recurrence of NPSCC after radiotherapy.
Objectives
This study aimed to evaluate the efficacy of chemoradiotherapy (CRT) for patients with advanced cancer of the external auditory canal (EAC) by analyzing the outcome of the patients.
...Methods
This is a multi‐institutional retrospective survey, and we reviewed the medical records of the subjects. A total of 181 patients with tumor (T)3 or T4 tumor in 17 institutions were enrolled. Further analysis was performed for 74 patients who underwent CRT under curative intent.
Results
Overall 5‐year survival rates of the patients who underwent CRT (n = 74) were 54.6%. Those of the patients who underwent CRT with modified TPF (docetaxel, cisplatin CDDP, and 5‐fluorouracil) regimen (n = 50) and CRT with CDDP regimens (n = 24) were 64.4% and 36.7%, respectively. Significant differences were observed between these two groups.
Conclusion
Given the tendency that head and neck surgeons prefer CRT for advanced larger cancer of the EAC, CRT for advanced EAC cancer using the modified TPF regimen showed good clinical outcomes.
Level of Evidence
4 Laryngoscope, 131:E870–E874, 2021
Background The significance of induction chemotherapy (IC) in the treatment of squamous cell carcinoma of the head and neck (SCCHN) with unresectable locoregional recurrence after curative surgery ...has not been clarified. The aim of this study was to evaluate the efficacy of IC followed by chemoradiotherapy (CRT) in these patients. Methods Among patients with unresectable locoregional recurrent SCCHN who had not undergone prior irradiation and were eligible for cisplatin, we conducted a retrospective analysis of patients who received CRT following IC with paclitaxel, carboplatin, or cetuximab (IC-PCE group) and those who received CRT without prior IC (CRT group) between June 2013 and August 2021. Result Forty-two patients were included. The CRT group and IC-PCE group consisted of 15 and 27 patients, respectively. Primary site was the oral cavity (n=25), oropharynx (n=3), hypopharynx (n=13) and larynx (n=1). Objective response rate (ORR) with IC-PCE was 55.6%; 24 patients (88.9%) subsequently received CRT. ORR after completion of CRT was significantly better in the IC-PCE group (95.8% in the IC-PCE group vs. 66.7% in the CRT group, p=0.024). Progression-free survival (PFS) of the total population on median follow-up of 2.4 years (range: 0.8-7.3) tended to be better in the IC-PCE group (2-year PFS: 55.6% in the IC-PCE group vs. 33.3% in the CRT group, log-rank p =0.176), especially in oral cancer (2-year PFS: 37.5% in the IC-PCE group vs. 0% in the CRT group, log-rank p =0.015). Conclusion Therapeutic strategies including IC-PCE in patients with unresectable locoregional recurrent SCCHN after curative surgery may contribute to improved prognosis, especially in oral cancer.
The occult neck metastasis rate of cT4aN0 glottic cancer was 33%. Ipsilateral levels IIA, III and VI should be dissected. Levels IIB and IV can be omitted to avoid complications.
Abstract
Objective
...The indication for elective neck dissection for patients with clinically T4aN0 (cT4aN0) glottic cancer is not established. The objective of this study was to evaluate the role of elective neck dissection for patients with cT4aN0 glottic cancer.
Methods
We assessed patients with cT4aN0 laryngeal squamous cell carcinoma who underwent total laryngectomy between 1998 and 2014 and conducted a retrospective analysis. We considered occult neck metastasis positive when confirmed by histological analysis. When patients with late neck metastases did not undergo therapeutic neck dissection, the presence of occult neck metastasis was judged on the basis of computed tomography. The validity of elective neck dissection for patients with cT4aN0 glottic cancer was assessed from comparisons the rates of occult neck metastases of supraglottic and subglottic cancers, which are generally recommended for elective neck dissection. The distribution of occult neck metastases in glottic cancer is described according to nodal levels.
Results
The rate of occult neck metastasis of cT4aN0 laryngeal cancer was 36% (14/39). There were no significant differences among the rates of glottic 7/21 (33%), supraglottic 3/8 (38%) and subglottic 4/10 (40%) cancers. Patients with glottic cancer did not have bilateral Level IIB and ipsilateral Level IV metastasis. One patient had contralateral Level IV metastasis. The metastases rates of ipsilateral Levels IIA, III, and VI were >10%.
Conclusions
We think that elective neck dissection is valid for cT4aN0 glottic cancer. Ipsilateral Levels IIA, III and VI should be dissected. The omission of neck dissection for bilateral Levels IIB and IV can be considered when there is a need to avoid complications.
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