IMPORTANCE Large patient cohorts are necessary to validate the efficacy of transoral robotic surgery (TORS) in the management of head and neck cancer. OBJECTIVES To review oncologic outcomes of TORS from a large multi-institutional collaboration and to identify predictors of disease recurrence and disease-specific mortality. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of records from 410 patients undergoing TORS for laryngeal and pharyngeal cancers from January 1, 2007, through December 31, 2012, was performed. Pertinent data were obtained from 11 participating medical institutions. INTERVENTIONS Select patients received radiation therapy and/or chemotherapy before or after TORS. MAIN OUTCOMES AND MEASURES Locoregional control, disease-specific survival, and overall survival were calculated. We used Kaplan-Meier survival analysis with log-rank testing to evaluate individual variable association with these outcomes, followed by multivariate analysis with Cox proportional hazards regression modeling to identify independent predictors. RESULTS Of the 410 patients treated with TORS in this study, 364 (88.8%) had oropharyngeal cancer. Of these 364 patients, information about post-operative adjuvant therapy was known about 338: 106 (31.3) received radiation therapy alone, and 72 (21.3%) received radiation therapy with concurrent chemotherapy. Neck dissection was performed in 323 patients (78.8%). Mean follow-up time was 20 months. Local, regional, and distant recurrence occurred in 18 (4.4%), 15 (3.7%), and 10 (2.4%) of 410 patients, respectively. Seventeen (4.1%) died of disease, and 13 (3.2%) died of other causes. The 2-year locoregional control rate was 91.8% (95% CI, 87.6%-94.7%), disease-specific survival 94.5% (95% CI, 90.6%-96.8%), and overall survival 91% (95% CI, 86.5%-94.0%). Multivariate analysis identified improved survival among women (P = .05) and for patients with tumors arising in tonsil (P = .01). Smoking was associated with worse overall all-cause mortality (P = .01). Although advanced age and tobacco use were associated with locoregional recurrence and disease-specific survival, they, as well as tumor stage and other adverse histopathologic features, did not remain significant on multivariate analysis. CONCLUSIONS AND RELEVANCE This large, multi-institutional study supports the role of TORS within the multidisciplinary treatment paradigm for the treatment of head and neck cancer, especially for patients with oropharyngeal cancer. Favorable oncologic outcomes have been found across institutions. Ongoing comparative clinical trials funded by the National Cancer Institute will further evaluate the role of robotic surgery for patients with head and neck cancers.
To investigate the expression of programmed death-ligand 1 (PD-L1) and immune checkpoints and their prognostic value for resected head and neck squamous cell cancer (HNSCC). PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC), abundance of tumor-infiltrating lymphocytes (TILs), and expression of the immune checkpoints were investigated in 402 HNSCC patients. PD-L1 expression on TC and IC was categorized into four groups according to the percentage of PD-L1-positive cells. PD-L1 positivity was defined as ≥5% of cells based on immunohistochemistry. High PD-L1 expression on IC, but not TC, was an independent favorable prognostic factor for RFS and OS adjusted for age, gender, smoking, stage, and HPV. High frequencies of CD3+ or CD8+ TILs, Foxp3+ Tregs, and PD-1+ TILs were strongly associated with favorable prognosis. PD-L1 was exclusively expressed on either TC or IC. Transcriptome analysis demonstrated that IC3 expressed higher levels of the effector T cell markers than TC3, suggesting that PD-L1 expression is regulated via an adaptive IFNγ-mediated mechanism. High PD-L1 expression on IC, but not TC, and high abundance of PD-1+ T cells and Foxp3+ Tregs are favorable prognostic factors for resected HNSCC. This study highlights the importance of comprehensive assessment of both TC and IC.
The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.
Robot-assisted SOND via a modified face-lift or retroauricular approach in cN0 oral cavity SCC was feasible compared to conventional technique and showed a clear cosmetic benefit. Longer operation time remains the drawback of this procedure. However, it could be considered for patients who require SOND and prefer to avoid external neck scar.
Although the aspect of invasiveness could be improved, endoscopic hemithyroidectomy via a unilateral axillo-breast approach without gas insufflation is safe and effective and appears to provide better cosmetic results and a shorter operation time than other endoscopic methods for managing selective unilateral benign thyroid lesions.
Background: T cells exhibit heterogeneous functional states in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) can reinvigorate only the stem cell-like progenitor exhausted T cells, which suggests that inhibiting the exhaustion progress will improve the efficacy of immunotherapy. Thus, regulatory factors promoting T cell exhaustion could serve as potential targets for delaying the process and improving ICI efficacy. Methods: We analyzed the single-cell transcriptome data derived from human melanoma and non-small cell lung cancer (NSCLC) samples and classified the tumor-infiltrating (TI) CD8 + T cell population based on PDCD1 (PD-1) levels, i.e., PDCD1-high and PDCD1-low cells. Additionally, we identified differentially expressed genes as candidate factors regulating intra-tumoral T cell exhaustion. The co-expression of candidate genes with immune checkpoint (IC) molecules in the TI CD8 + T cells was confirmed by single-cell trajectory and flow cytometry analyses. The lossof-function effect of the candidate regulator was examined by a cell-based knockdown assay. The clinical effect of the candidate regulator was evaluated based on the overall survival and anti-PD-1 responses. Results:We retrieved many known factors for regulating T cell exhaustion among the differentially expressed genes between PDCD1-high and PDCD1-low subsets of the TI CD8 + T cells in human melanoma and NSCLC. TOX was the only transcription factor (TF) predicted in both tumor types. TOX levels tend to increase as CD8 + T cells become more exhausted. Flow cytometry analysis revealed a correlation between TOX expression and severity of intra-tumoral T cell exhaustion. TOX knockdown in the human TI CD8 + T cells resulted in downregulation of PD-1, TIM-3, TIGIT, and CTLA-4, which suggests that TOX promotes intra-tumoral T cell exhaustion by upregulating IC proteins in cancer. Finally, the TOX level in the TI T cells was found to be highly predictive of overall survival and anti-PD-1 efficacy in melanoma and NSCLC.
The possibility of postsurgical hypothyroidism after hemithyroidectomy is no longer a new subject. Although many previous studies have mentioned posthemithyroidectomy hypothyroidism, the incidence and contributing factors for hypothyroidism remain uncertain. We intended to evaluate the incidence and the time of development of hypothyroidism after hemithyroidectomy and to analyze the relationship of posthemithyroidectomy hypothyroidism with preoperative biochemical parameters and postoperative histopathological findings. From February 2001 through December 2004, 287 consecutive cases of hemithyroidectomized patients were retrospectively analyzed; 136 of these patients were included in this study after the exclusion criteria were applied. The relationship between posthemithyroidectomy hypothyroidism and several parameters such as sex, age, preoperative free T4, TSH, microsomal antibody (Ab), thyroglobulin antibody (Ab) levels and lymphocytic infiltration of the resected gland was statistically analyzed. Postoperative hypothyroidism developed in 58 patients (42.6%). In hypothyroid group, 11 patients (19%) showed overt hypothyroidism and 47 patients (81%) showed subclinical hypothyroidism. Preoperative TSH value was significantly higher in the hypothyroid group (2.15+/-1.30 microU/ml) compared to the euthyroid group (1.29+/-0.9 microU/ml). Positive ratio of preoperative microsomal Ab and thyroglobulin Ab were significantly higher in hypothyroid group (38.9 and 41.9%) compared to euthyroid group (3.6 and 19.3%) (P <0.05). In addition, patients with a higher grade of lymphocytic infiltration were found to have a higher probability of developing hypothyroidism. About 85% of postoperative hypothyroidism was detected between 1 and 6 months postoperatively. We might predict the possibility of developing the posthemithyroidectomy hypothyroidism especially in case of preoperatively positive microsomal antibody, thyroglobulin antibody and high-grade lymphocytic infiltration of the resected gland. In addition, our findings support the recommendation for regular serum TSH follow-up at least for 12 months after hemithyroidectomy.
For all of the patients, robotic total thyroidectomy with MRND (levels II, III, IV, V) via unilateral RA approach was successfully completed without any significant intraoperative complications or conversion to open or other approach methods. The total operation time was defined as the time from initial skin incision to removal of the final specimen, which was an average 306.1 ± 11.1 min (Table 2). This included the time for skin flap elevation and neck dissection under gross vision (87 ± 2.8 min), setting up the robotic system for RAND (6.8 ± 2.4 min), console time using the robotic system for RAND (59.3 ± 2.2 min), flap elevation for thyroidectomy (11.3 ± 2.5 min), robotic arms docking for ipsilateral thyroidectomy (6.3 ± 2.5 min), console time for ipsilateral thyroidectomy (61.3 ± 2.1 min), robotic arms docking for contralateral thyroidectomy (6.3 ± 2.5 min), and console time for contralateral thyroidectomy (61.8 ± 2.1 min). The working space created from RA incision was sufficient, and manipulations of the robotic instruments through this approach were technically feasible and safe without any mutual collisions throughout the entire operation. It also allowed for an excellent magnified surgical view enabling visualization of important local anatomical structures. There was no postoperative vocal cord palsy due to recurrent laryngeal nerve injury. However, two patients developed transient hypoparathyroidism, which resolved in the end without the need for calcium or vitamin D supplementation after certain period of medical management (Table 3). Also, there was no incidence of postoperative hemorrhage or hematoma formation, although a single patient developed a postoperative seroma on postoperative day 9, which was managed conservatively without the need for further surgical intervention. On average, the wound catheter was removed 6.8 ± 1 days after surgery and the patient was discharged from the hospital at an average 11 ± 2.8 days from admission (Table 1). Final surgical pathology confirmed the diagnosis of papillary carcinoma for every patient. The total number of cervical nodes retrieved from CCND and MRND was 9.8 ± 4 and 33.1 ± 11 respectively, and the number of positive metastatic nodes was 3 ± 1.4 and 7.3 ± 1.7 respectively (Table 1). In three patients (patients 2, 3, and 4), the presence of one parathyroid gland was each verified in the pathology specimen. All four patients have received high-dose (150 mCi) radioiodine ablation (RAI) therapy after the operation and are being followed up (average 11.3 months, range 9-13 months) on a regular basis with no evidence of recurrence (post-RAI, most recent, nonsuppressed thyroglobulin range 0.1-0.4 ng/ml, antithyroglobulin antibody range 13.7-147.5 IU/ml). (ABSTRACT TRUNCATED)
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