Dataset Information

Outcomes of Patients With Single-Node Metastasis of Human Papillomavirus-Related Oropharyngeal Cancer Treated With Transoral Surgery.

ABSTRACT:

Importance

Regional lymph node metastasis remains an important prognostic factor in patients with oropharyngeal squamous cell carcinoma (OPSCC). Although survival among patients with regional metastasis in human papillomavirus (HPV)-related OPSCC is more favorable compared with patients who are HPV negative, prognostic variables associated with failure in patients with single-node metastasis are not known.

Objective

To evaluate recurrence and survival in patients with HPV-related OPSCC with single-lymph node metastasis treated with transoral surgery.

Design, setting, and participants

A retrospective cohort study was conducted of 207 adults with newly diagnosed p16-positive OPSCC and pathology-confirmed single-node disease who underwent surgical resection with or without adjuvant therapy at 2 tertiary academic medical centers from January 1, 2007, to December 31, 2016. Statistical analysis was performed from September 1, 2018, to September 1, 2020.

Interventions

Surgery alone (n = 59), surgery with adjuvant radiation (n = 75), or surgery with adjuvant chemoradiation (n = 73).

Main outcomes and measures

The primary outcome was regional recurrence. Secondary outcomes included overall survival, any recurrence, and identification of factors associated with regional recurrence and overall survival.

Results

Among 207 patients, 178 (86%) were men, with a median age of 57 years (range, 35-82 years) at the time of surgery. Median follow-up was 36.2 months (range, 7-127 months). Regional recurrence occurred in 11 patients (5%). Of these, 1 patient (9%) was lost to follow-up after diagnosis, 1 (9%) was treated with palliative chemotherapy, and 9 (82%) were treated with curative intent. Ultimately, 7 patients received successful salvage treatment, and 3 died with disease. Overall, there were 21 patients (10%) with any recurrence, with 4 patients (19%) experiencing local recurrence, 11 (52%) experiencing regional recurrence, and 6 (29%) experiencing distant metastasis. The 5-year overall survival was 95% (95% CI, 89%-98%) for all patients. Older age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), advanced T stage (OR, 3.5; 95% CI, 0.9-14.0), and positive margins (OR, 10.9; 95% CI, 1.8-67.5) were associated with increased regional recurrence. Extranodal extension (OR, 0.2; 95% CI, 0.04-0.8), lymph node size greater than 3 cm (OR, 0.2; 95% CI, 0.1-0.7), and adjuvant therapy (OR, 0.08; 95% CI, 0.02-0.4) were associated with decreased regional recurrence. Advanced comorbidities (hazard ratio, 6.20; 95% CI, 1.4-27.7), lymphovascular invasion (hazard ratio, 4.7; 95% CI, 1.0-21.2), and regional recurrence (hazard ratio, 16.0; 95% CI, 3.1-82.0) were associated with worse overall survival.

Conclusions and relevance

The findings of this cohort study suggest that patients with HPV-related OPSCC and single-node disease undergoing surgical resection with or without adjuvant treatment have excellent survival. Adjuvant therapy appears to improve regional control. Among patients with regional recurrence of OPSCC, there is a high rate of successful salvage treatment.

SUBMITTER: Chen SY

PROVIDER: S-EPMC7645757 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV+) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV+ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV-) OPC, certain HPV+ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV+ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV+ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1-T2 classification (89.3% vs. 72.0%; p = 1.1 × 10-2), stages I-II (92.1% vs. 82.2%; p = 4.6 × 10-2), and stages III-IV (82.8% vs. 62.2%; p = 5.7 × 10-2) and for HPV- patients (85.5% vs. 33.3%; p < 1.0 × 10-6). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV+ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC.

Project description:BackgroundTreatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized that upfront surgery and neck dissection followed by reduced-dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression-free survival (PFS) and overall survival while reducing toxicity.MethodsThis study was a nonrandomized phase II trial for early-stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced-dose radiotherapy. Patients with previously untreated p16-positive HPVOPC and <20 pack years' smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors [perineural invasion, lymphovascular invasion]; 50-Gy radiotherapy), or group 3 (poor prognostic pathologic factors [extranodal extension [ENE], more than three positive lymph nodes and positive margin]; concurrent 56-Gy chemoradiotherapy with weekly cisplatin).ResultsFifty-four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow-up was 43.9 months (9.6-75.8). Disease-specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan-Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6-59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0-42.7 months); one subject remains alive with disease.ConclusionThe results indicate that upfront surgery with neck dissection with reduced-dose radiation for T1-2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de-escalation strategy in HPVOPC.Implications for practiceTransoral robotic surgery can provide a safe platform for de-escalation in carefully selected patients with early-stage human papillomavirus-related oropharyngeal cancer. In this clinical trial, disease-specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.

Project description:IMPORTANCE:Treatment of oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and can be associated with significant morbidity. Transoral robotic surgery (TORS) has emerged as a treatment modality for OPSCC, but data comparing outcomes between patients treated with TORS-based therapy and nonsurgical therapy are limited. OBJECTIVE:To compare survival and gastrostomy prevalence between patients with OPSCC treated with TORS-based therapy and those treated with nonsurgical therapy. DESIGN, SETTING, AND PARTICIPANTS:This retrospective matched-cohort study identified patients with OPSCC treated at the University of Washington and University of Minnesota tertiary care medical centers from January 1, 2005, to December 31, 2013. Each patient treated with TORS-based therapy was matched by stage with as many as 3 patients treated with nonsurgical therapy. Final follow-up was completed on April 1, 2015. MAIN OUTCOMES AND MEASURES:Disease-free survival, overall survival, and gastrostomy tube prevalence. RESULTS:One hundred twenty-seven patients met the study criteria (113 men [89.0%]; 14 women [11.0%]; median [interquartile range] age, 57 [52-63] years); 39 patients who underwent TORS were matched to 88 patients who underwent nonsurgical therapy. Compared with the nonsurgical group, more patients had p16-positive tumors in the TORS group (30 of 31 [96.8%] vs 30 of 37 [81.1%] among patients with known p16 status). No statistically significant difference in survival between treatment groups was found in multivariable analysis (disease-free survival hazard ratio, 0.22; 95% CI, 0.04-1.36; P?=?.10). Patients who received TORS-based therapy had lower gastrostomy tube prevalence after treatment (13 of 39 [33.3%] vs 74 of 88 [84.1%]) for a univariable relative risk of 0.43 (95% CI, 0.27-0.67; P?<?.001) and a multivariable relative risk of 0.43 (95% CI, 0.27-0.68; P?<?.001). Gastrostomy prevalence decreased by time after treatment for both groups (TORS group: 3 of 34 [9%] at 3 months to 1 of 33 [3%] at 12 months; nonsurgical group: 37 of 82 [45%] at 3 months to 7 of 66 [11%] at 12 months). CONCLUSIONS AND RELEVANCE:Patients undergoing TORS for OPSCC have statistically indistinguishable survival but lower gastrostomy prevalence compared with patients undergoing nonsurgical therapy for stage-matched OPSCC. TORS offers promise for improved swallowing function in patients with OPSCC.

Project description:ImportanceThe treatment of oropharyngeal cancer has undergone a paradigm shift in the past 2 decades, with an increase in the use of nonoperative treatment owing to poor functional outcomes associated with traditional surgical approaches. Transoral robotic surgery (TORS) allows surgical resection of oropharyngeal cancer (OPC) with less morbidity through a minimally invasive approach.ObjectiveTo investigate the relationship among TORS and short- and long-term outcomes and costs in surgically treated patients with OPC.Design, setting, and participantsRetrospective cross-sectional analysis of 3573 patients who underwent an ablative procedure for OPC in 2010 to 2012 using the MarketScan Commercial Claim and Encounters database.Main outcomes and measuresThe association between TORS and short- and long-term outcomes, length of hospitalization, and treatment-related costs was analyzed using descriptive statistics and multivariate regression modeling.ResultsTransoral robotic surgery was performed in 304 surgical cases (8.5%); 94.7% of patients were 40 to 64 years old, and 70.7% were male. The use of TORS increased from 4.1% of surgical cases in 2010 to 13.2% of surgical cases in 2012. Patients who underwent TORS had a lower rate of tracheotomy during treatment (3.9% vs 11.4%), and posttreatment gastrostomy tube use (21.9% vs 34.2%), compared with patients undergoing non-TORS procedures. On multivariate analysis, TORS was not associated with significant differences in postoperative complications or length of hospitalization. There was no significant difference in the odds of receiving postoperative radiation therapy between patients who underwent TORS and those who did not; however, among patients receiving radiation therapy, chemoradiation was significantly less likely following TORS (odds ratio [OR], 0.52; 95% CI, 0.29-0.90). TORS was associated with significantly decreased odds of posttreatment gastrostomy (OR, 0.54; 95% CI. 0.30-0.95) and tracheostomy during treatment (OR, 0.17; 95% CI, 0.06-0.55) at 1 year, and was associated with significantly decreased overall treatment-related costs of care (mean incremental cost, -$22 724).Conclusions and relevanceThe use of TORS for surgical resection of OPC is increasing in the United States and is associated with significantly lower use of adjuvant chemoradiation, late gastrostomy and tracheostomy dependence, and lower overall treatment-related costs of care. These data have implications for discussions of value in OPC care at a time of health care reform.

Project description:ImportanceIn recent years, transoral robotic surgery (TORS) has emerged as a useful treatment for oropharyngeal squamous cell carcinoma (OPSCC). In appropriately selected patients, the use of TORS may allow avoidance of adjuvant chemotherapy and/or radiotherapy, thereby avoiding the long-term adverse effects of these therapies.ObjectiveTo compare functional speech, swallowing, and quality-of-life outcomes longitudinally between those undergoing TORS only and those undergoing TORS and adjuvant radiotherapy (TORS+RT) or TORS and chemoradiotherapy (TORS+CRT).Design, setting, and participantsThis prospective, longitudinal cohort study performed from June 1, 2013, through November 31, 2015, included 74 patients undergoing TORS for initial treatment of OPSCC at a single tertiary academic hospital.Main outcomes and measuresData were collected at baseline, postoperatively (7-21 days), at short-term follow-up (6-12 months), and at long-term follow-up (>12 months). The quality-of-life metrics included the 10-item Eating Assessment Tool and the University of Michigan Head and Neck Quality of Life instrument. Data were also collected on tumor staging, surgical and adjuvant therapy details, patient comorbidities, tracheostomy and feeding tube use, and functional speech and swallowing status using the Performance Status Scale for Head and Neck Cancer Patients.ResultsSeventy-four patients were enrolled in the study (mean [SD] age, 61.39 [7.99] years; 68 [92%] male). Median long-term follow-up was 21 months (range, 12-36 months). The response rates were 86% (n = 64) postoperatively, 88% (n = 65) at short-term follow-up, and 86% (n = 64) at long-term follow-up. In all 3 groups, there was a significant worsening in pain and all swallowing-related measures postoperatively. There was subsequent improvement over time, with different trajectories observed across the 3 intervention groups. Postoperative dysphagia improved significantly more quickly in the TORS-only group. At long-term follow-up, weight loss differed between the TORS-only and TORS+RT groups (mean difference, -16.1; 97.5% CI, -29.8 to -2.4) and the TORS-only and TORS+CRT groups (mean difference, -14.6; 97.5% CI, -29.2 to 0) in a clinically meaningful way. In addition, the TORS-only group had significantly better scores than the TORS+CRT group on the Performance Status Scale-Eating in Public scale (mean difference, 21.8; 97.5% CI, 4.3-39.2) and Head and Neck Quality of Life-Eating scale (mean difference, 21.2; 97.5% CI, 4.0-38.3).Conclusions and relevancePatients who underwent TORS+CRT demonstrated poorer long-term outcomes, with continued dysphagia more than 1 year after surgery. These findings support the investigation of adjuvant de-escalation therapies to reduce the long-term adverse effects of treatment.