Purpose Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is treatment-responsive. Definitive chemoradiation results in high cure rates but causes long-term toxicity ...and may represent overtreatment of some patients. This phase II trial evaluated whether complete clinical response (cCR) to induction chemotherapy (IC) could select patients with HPV-associated OPSCC for reduced radiation dose as a means of sparing late sequelae. Methods Patients with HPV16 and/or p16-positive, stage III-IV OPSCC received three cycles of IC with cisplatin, paclitaxel, and cetuximab. Patients with primary-site cCR to IC received intensity-modulated radiation therapy (IMRT) 54 Gy with weekly cetuximab; those with less than cCR to IC at the primary site or nodes received 69.3 Gy and cetuximab to those regions. The primary end point was 2-year progression-free survival. Results Of the 90 patients enrolled, 80 were evaluable. Their median age was 57 years (range, 35 to 73 years), with the majority having stage T1-3N0-N2b OPSCC and a history of ≤ 10 pack-years of cigarette smoking. Three cycles of IC were delivered to 77 of the 80 patients. Fifty-six patients (70%) achieved a primary-site cCR to IC and 51 patients continued to cetuximab with IMRT 54 Gy. After median follow-up of 35.4 months, 2-year progression-free survival and overall survival rates were 80% and 94%, respectively, for patients with primary-site cCR treated with 54 Gy of radiation (n = 51); 96% and 96%, respectively, for patients with < T4, < N2c, and ≤ 10 pack-year smoking history who were treated with ≤ 54 Gy of radiation (n = 27). At 12 months, significantly fewer patients treated with a radiation dose ≤ 54 Gy had difficulty swallowing solids (40% v 89%; P = .011) or had impaired nutrition (10% v 44%; P = .025). Conclusion For IC responders, reduced-dose IMRT with concurrent cetuximab is worthy of further study in favorable-risk patients with HPV-associated OPSCC. Radiation dose reduction resulted in significantly improved swallowing and nutritional status.
•Despite improvement in recent years, adherence rates remain suboptimal, around 75%•Adherence to NCCN guidelines is associated with improved survival, regardless of treatment modality.•Different ...non-adherence causes result in reduced overall survival compared with adherent patients.
Understanding the prevalence of guideline non-adherence among patients with advanced head and neck cancer (HNC) and its impact on survival may facilitate increased adherence. Our objective was to perform a detailed analysis of overall National Comprehensive Care Network (NCCN) guideline adherence in a national cohort.
Using the National Cancer Database, we analyzed site-specific NCCN guideline adherence for treatment of 100,074 overall stage III and IVA HNC patients from 2004 to 2013. Main outcomes were guideline adherence rates and overall survival (OS). Adherence was categorized by treatment: surgery/ radiation. Reasons were categorized as: (1) high risk; (2) refusal; (3) not planned.
After exclusion, the care of 25,620 patients was defined as non-adherent (25.6%), yet adherence rates significantly improved across the study’s years. After multivariate analysis, non-adherence was associated with age ≥ 65, female gender, black race, comorbidity score ≥ 1, insurance status, clinical staging, primary site, and facility type. Patients not managed according to NCCN guidelines had a significantly reduced OS compared with patients treated on-guideline (hazard ratio (HR) = 1.51 (95 %CI 1.48–1.54), p < 0.001). ‘Not planned’ patients had reduced OS when compared to adherent patients (HR = 1.27 (95 %CI 1.23–1.30), p < 0.001). Off-guideline treated patients due to ‘risk factors’ had a decrease in overall survival (OS) compared with other reasons (p < 0.001 for all).
Despite improvement over time, non-adherence to NCCN guidelines for advanced stage HNC remains high. Non-adherence is associated with decreased OS, regardless of the reason. Despite concerns from both patient and physician, efforts should be made to increase guideline awareness and adherence.
Background
The eighth edition of the AJCC Cancer Staging Manual (AJCC 8) incorporates depth of invasion (DOI) into the pathologic tumor (pT) classification and pathologic extranodal extension (pENE) ...into the pathologic nodal (pN) classification for oral cavity squamous cell carcinoma (OCSCC). This study evaluated the incidence and prognostic importance of stage migration as a result of these changes in the AJCC 8 staging system.
Methods
From the National Cancer Database, cohorts were identified from patients with OCSCC undergoing definitive surgery between 2004 and 2013 for pT (n = 7184), pN (n = 13,627), and pathologic stage (pStage) analysis (n = 5580).
Results
DOI and pENE were prognostic in all groups except for pN3 according to the seventh edition of the AJCC Cancer Staging Manual (AJCC 7). Upstaging was seen in 12.4% of patients for the pT classification, in 13.3% for the pN classification, and in 24.8% for the overall pStage grouping. Notably, upstaging led to similar or improved 5‐year overall survival (OS) for every AJCC 8 pT/N classification except pStage IVB. Patients with AJCC 7 pT1 tumors that were upstaged to AJCC 8 pT3 tumors had improved OS in comparison with the remainder of the pT3 group (71.7% vs 43.7%; P < .0001). A multivariable analysis of upstaged pT3N0 patients demonstrated a reduced risk of death with the receipt of postoperative radiotherapy (PORT; hazard ratio, 0.56; 95% confidence interval, 0.33‐0.95; P = .03).
Conclusions
Upstaging is common in AJCC 8, and patients with upstaged tumors demonstrate improved survival; these factors should be kept in mind when one is interpreting data with the new staging system. PORT may reduce deaths among newly upstaged pT3N0 patients, and further study is needed in this area.
Upstaging is common in the eighth edition of the AJCC Cancer Staging Manual, and patients with upstaged tumors demonstrate improved survival; these factors should be kept in mind when one is interpreting data with the new staging system. Postoperative radiotherapy may reduce deaths among newly upstaged pT3N0 patients, and further study is needed in this area.
Background
The authors measured epigenetic age acceleration (EAA) during and after cancer treatment and its association with inflammation and fatigue, which is a debilitating symptom in patients with ...cancer.
Methods
Patients who had head and neck cancer without distant metastases were assessed before, immediately after, and at 6 months and 12 months postradiotherapy. Blood DNA methylation was assessed using a proprietary bead chip (the Illumina MethylationEPIC BeadChip). EAA was calculated using the Levine epigenetic clock (DNAmPhenoAge), adjusted for chronological age. Fatigue was assessed using the Multidimensional Fatigue Inventory‐20. Inflammatory markers were measured using standard techniques.
Results
Most patients (N = 133) were men, White, had advanced disease, and received concurrent chemoradiation. EAA changes over time were significant, with the largest increase (4.9 years) observed immediately after radiotherapy (P < .001). Increased EAA was associated with elevated fatigue (P = .003) over time, and patients who had severe fatigue experienced 3.1 years higher EAA than those who had low fatigue (P < .001), which was more prominent (5.6 years; P = .018) for patients who had human papillomavirus‐unrelated disease at 12 months posttreatment. EAA was also positively associated with inflammatory markers, including C‐reactive protein (CRP) and interleukin‐6 (IL‐6), over time (P < .001), and patients who had high CRP and IL‐6 levels exhibited increases of 4.6 and 5.9 years, respectively, in EAA compared with those who had low CRP and IL‐6 levels (P < .001). CRP and IL‐6 mediated the association between EAA and fatigue (CRP: 95% CI, 0.060‐0.279; IL‐6: 95% CI, 0.024‐0.220).
Conclusions
Patients with head and neck cancer experienced increased EAA, especially immediately after treatment completion. EAA was associated with greater fatigue and inflammation, including 1 year after treatment. Inflammation may be a target to reduce the impact of age acceleration on poor functional outcomes.
Patients with head and neck cancer experience increased epigenetic age acceleration, especially immediately after treatment completion. Epigenetic age acceleration is associated with greater fatigue and inflammation, including 1 year posttreatment.
The interval between neoadjuvant chemoradiation treatment and surgery has been described as an important predictor of pathologic response to therapy in nonesophageal cancer sites. We retrospectively ...reviewed our experience with patients who underwent neoadjuvant chemoradiation and esophagectomy to better understand the impact of the timing of surgery on pathologic complete response rates in esophageal cancer.
Two hundred thirty-one sequentially treated patients from 2000 to 2011 were identified for this study; 88 of these patients completed neoadjuvant chemoradiation followed by esophagectomy at our institution. The interval between completion of chemoradiation and surgery was calculated for each patient. The patients were categorized into quartiles and also into 3-week interval groups. Treatment factors and surgical morbidity data, including the estimated blood loss and length of operative stay, were also assessed.
Quartiles for the neoadjuvant chemoradiation to surgery interval were less than 45 days, 46 to 50 days, 51 to 63 days, and 64+ days. Corresponding pathologic complete response rates were 12.5%, 20.0%, 22.7%, and 40.9% (p = 0.03). Results for 3-week intervals were similar (p = 0.02). There was no association between increasing time interval between the ending of neoadjuvant chemoradiation to surgery and length of stay longer than 2 weeks.
A longer interval between completion of neoadjuvant chemoradiation and surgery was associated with higher pathologic complete response rates without an impact on surgical morbidity.
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