Cervical cancer patient reported gastrointestinal outcomes: intensity/volumetric modulated vs. 3D conformal radiation therapy.

OBJECTIVE: To evaluate gastrointestinal (GI) patient reported outcomes (PROs) in cervical cancer patients treated with definitive radiotherapy (RT), comparing 3D conformal RT (3DCRT) vs. intensity modulated/volumetric modulated arc therapy (IMRT/VMAT). METHODS: An analysis of patients treated with definitive RT between 2015-2018 was performed. GI PROs were prospectively collected at baseline, during RT (acute), ≤12 weeks after RT (subacute), and >12 weeks after RT (late). GI PROs evaluated three symptom domains: bowel problems (BPs), bowel bother (BB), and abdominal problems (APs). Multiple linear regression analysis was performed to investigate associations between mean changes of symptom scores with clinical and dosimetric variables. RESULTS: The cohort included 167 patients. A total of 100 (60%) patients were treated with IMRT/VMAT and 67 (40%) with 3DCRT. In the subacute phase, the mean change of symptom scores from baseline in 3DCRT vs. IMRT/VMAT were +0.9 vs. -1.15 (p=0.004) for BP, +2.18 vs. -0.10 (p=0.019) for BB, and +1.41 vs. -0.38 (p=0.021) for AP. Likewise, in the late phase, mean changes were +0.72 vs. -0.82 (p=0.014) for BP, +1.98 vs. -0.03 (p=0.008) for BB, and +1.29 vs. -0.31 (p<0.001) for AP. On multiple linear regression, use of 3DCRT vs. IMRT/VMAT was associated with greater mean changes in subacute BP (p=0.023) and late phase AP (p=0.019). A higher small bowel V50Gy was associated increased symptom scores in late AP (p=0.012). CONCLUSION: 3DCRT was associated with significantly greater worsening of GI PRO symptom scores in the subacute and late phase. These data support the ongoing use of IMRT/VMAT in routine practice.

The Prognostic Impact of Radiotherapy Delays in Oropharynx Carcinoma and the Role of p16 Status.

OBJECTIVE: A retrospective analysis was performed to evaluate the prognostic significance of treatment delays (TDs) for oropharynx carcinoma patients treated with definitive radiotherapy (RT), comparing p16+ versus p16- disease. MATERIALS AND METHODS: Patients treated between 2012 and 2016 were analyzed (n=763). TD was defined as the time from pathologic diagnosis to initiation of RT. TD thresholds of ≤60, 61 to 90, and >90 days were used to stratify outcomes. Time on treatment (TOT) delays were estimated based on the RT fractionation. TOT delay of 1 to 3 days was compared with >3 days. Predictors of cancer-specific survival (CSS) and locoregional recurrence (LRR) were evaluated on multivariable analysis. RESULTS: Six hundred fifty (85%) patients had p16+ disease. On multivariable analysis, TOT delay of 1 to 3 days versus <1 day was associated with inferior CSS (hazard ratio [HR]=1.81; 95% confidence interval [CI]: 1.02-3.22). TD >90 versus ≤60 days (HR=1.68; 95% CI: 0.98-3.04) and 61 to 90 versus ≤60 days (HR=0.94; 95% CI: 0.60-1.48) was not associated with CSS. TD >90 versus ≤60 days (HR=1.29; 95% CI: 0.66-2.52), TD 61 to 90 versus ≤60 days (HR=0.98; 95% CI: 0.64-1.52), TOT 1 to 3 versus <1 day (HR=0.91; 95% CI: 0.39-2.11), and TOT >3 versus <1 day (HR=1.79; 95% CI: 0.80-3.99) were not associated with LRR. There was no interaction between p16 status and TD in relation to LRR (P=0.27) or CSS (P=0.17). CONCLUSIONS: TDs were not significantly associated with CSS or LRR. TOT of 1 to 3 days was associated with inferior CSS. p16 status should not be a significant factor when triaging RT start dates.

Population-based outcomes by immunosuppressed status in patients undergoing radiotherapy for oropharyngeal cancer.

INTRODUCTION: The incidence of immunosuppression in patients with oropharynx head & neck squamous cell carcinoma (SCC) is not well studied. This study evaluates disease characteristics and treatment outcomes in oropharynx SCC in patients with and without immunosuppression. METHODS: A retrospective review of all patients treated with radiotherapy for oropharynx SCC at BC Cancer from 2011 to 2016 was performed. Survival outcomes were assessed using Kaplan-Meier methods and competing risk analysis. Multivariate analysis and propensity score matching were performed. RESULTS: There were 1077 patients, of which 5.8% (n = 62) had an immunosuppressive medical condition or were taking long-term immunosuppressive medication at diagnosis. Median follow-up was 3.3 years. Three year OS for patients without immunosuppression was 79.5% (95% Confidence Interval [CI] 76.8-82.0%) and for those with immunosuppression was 64.6% (95% CI 50.9-75.3%) (hazard ratio [HR] 1.78, 95% CI 1.18-2.68, p = 0.0062). The three year disease recurrence for patients without immunosuppression was 24.9% (95% CI 22.2-27.7%) and 44.4% (95% CI 31.5-56.6%) for those with immunosuppression (HR 2.12, 95% CI 1.45-3.11, p = 0.0001). Multivariate analysis of disease free survival (DFS) found that active smoking, advanced TNM stage, base of tongue subsite, p16 negative and unknown, no concurrent chemotherapy, higher Charlson Comorbidity Index, and lower radiation dose were also associated with worse DFS (all p < 0.05). Immunosuppressed patients had worse DFS relative to patients without immunosuppression, p < 0.001, HR 1.97 (95% CI 1.33-2.91). CONCLUSION: Immunosuppression was an independent predictor of worse DFS in this large cohort of patients with oropharynx SCC.

FDG-PET/CT scan assessment of response 12 weeks post radical radiotherapy in oropharynx head and neck cancer: The impact of p16 status.

PURPOSE: To evaluate the predictive value of FDG-PET/CT for detection of residual disease after radical radiotherapy for patients with squamous cell carcinoma (SCC) of the oropharynx, comparing p16 positive (+) versus p16 negative (-) disease. METHODS AND MATERIALS: A retrospective analysis of patients with SCC of the oropharynx at our institution treated with radical radiotherapy between 2012 and 2016 was performed. The primary and lymph node metabolic responses were evaluated independently on the post-treatment FDG-PET/CT. The reference standard was pathology when available, subsequent post-treatment FDG-PET/CT results or clinical follow-up. RESULTS: Median follow-up time was 32 (30-34) months. 556 patients had p16+ disease and 92 had p16- disease. The median time of post-treatment FDG-PET/CT was 96 (45-744) days after radiotherapy completion: 68% had complete metabolic response (CMR) defined as mild non-focal or no uptake, 10% residual primary disease, 11% residual regional lymph node disease, 5% residual primary and regional disease, and 6% distant metastatic disease. The local positive predictive value (PPV) was 26% for p16+ versus 54% for p16- (p = 0.01) and the regional PPV was 31% for p16+ versus 58% for p16- (p = 0.01). The local negative predictive value (NPV) was 100% regardless of p16 status and the regional NPV was 100% for p16+ versus 99% for p16- (p = 0.33). For p16+ cases, regional specificity was 76.2% versus 91.1% (p = 0.0003), local PPV was 0 versus 30% (p = 0.06) and the regional PPV was 12% versus 35% (p = 0.06) for FDG-PET/CT scans performed at ≤12 weeks versus >12 weeks. Five-year overall survival for those with CMR was 87% versus 51% without CMR (p ≤ 0.001). CONCLUSIONS: Metabolic response on post-treatment FDG-PET/CT has excellent NPV regardless of p16 status. The PPV is significantly lower in those with p16+ versus p16- disease, with a significantly reduced regional specificity and a trend towards inferior predictive value if performed ≤12 weeks. CMR predicts for a significantly improved overall survival.