Clinical and dosimetric risk stratification for patients at high-risk of feeding tube use during definitive IMRT for head and neck cancer.

INTRODUCTION: To identify organs to which dose limitation using intensity modulated radiotherapy (IMRT) can potentially modify the incidence and duration of feeding tube use, during and immediately following therapy for head and neck cancer. MATERIALS AND METHODS: One hundred and fourteen patients treated with definitive IMRT (± concurrent chemotherapy) head and neck mucosal cancers were included. Patients received a prophylactic feeding tube and followed up by a dietician for at least eight weeks post-radiotherapy. Salivary and swallowing organs were delineated for each patient. Tumour and dosimetric variables were recorded for all patients and analysed for incidence and duration of feeding tube use for at least 25% of dietary requirements. RESULTS: Multivariate analysis showed T-classification ≥3 and level II lymphadenopathy as independent significant predictors of incidence and duration of feeding tube use in oral cavity, pharyngeal and supraglottic primaries. Mean dose deposited in the cervical oesophagus over 36Gy further increased the incidence and duration of feeding tube use. Mean dose deposited in the base of tongue and superior pharyngeal constrictor muscles affected incidence and duration of feeding tube use, respectively. DISCUSSION: In patients treated with definitive IMRT, T-classification and Level II lymphadenopathy, combined with a mean cervical oesophagus dose over 36Gy can a stratify patients into eight distinct risk groups for using feeding tubes for at least 25% of their dietary requirements.

The changing landscape of head and neck cancer radiotherapy patients: is high-risk, prolonged feeding tube use indicative of on-treatment weight loss?

INTRODUCTION: Precision radiotherapy relies heavily on optimal weight management. Our group previously developed a risk stratification model for patients at risk of prolonged feeding tube (FT) intervention. The study objective was to assess on-treatment weight loss according to stratified risk of prolonged FT use. METHODS: One hundred and one (n = 101) definitive head and neck radiotherapy patients were included in this study. Patients were stratified into high risk (HRi: T-classification ≥ 3 with level 2 Nodal disease), high-intermediate risk (HIRi: T-classification ≥ 3 without level 2 Nodes) and low-intermediate risk (LIRi: T-classification < 3 with level 2 Nodes) of prolonged FT use. Demographic variables and on-treatment weight loss were evaluated according to risk status. RESULTS: Oropharyngeal carcinoma (OPC) was present in a larger proportion in the LIRi cohort (HRi: 71%, HIRi: 52%, LIRi: 81%, P = 0.008). LIRi patients were more likely to have human papilloma virus (HPV)-associated disease (88%, P = 0.001). Never/minimal smoking (P = 0.003), good performance status (P < 0.001), healthy BMI (P = 0.050) and no pre-existing dysphagia (P < 0.001) were predominant within the LIRi prognostic group. LIRi patients lost significantly more weight in total (HRi = 4.8% vs. LIRi = 8.2%, P = 0.002; HIRi = 5.2% vs. LIRi = 8.2%, P = 0.006) and when using a FT (HRi = 4.6% vs. LIRi = 8.8%, P < 0.001; HIRi = 5.3% vs. LIRi = 8.8%, P = 0.002). CONCLUSIONS: Patients identified as low-intermediate risk of prolonged, ≥25% FT use report significantly increased weight loss compared with patients at higher risk of FT use. This cohort is typical of the increasing number of patients presenting with HPV-associated OPC. Results of this study suggest we should closely observe such patients throughout treatment, to ensure optimal weight maintenance, facilitating precision radiotherapy.

18F-FDG Metabolic Tumor Volume: Association with Short- and Long-Term Feeding Tube Use in Head and Neck IMRT.

The purpose of this study was to investigate whether the metabolic tumor volume (MTV) of head and neck primary tumors may be a significant prognostic factor for feeding tube (FT) use and FT dependence. Seventy-nine patients with evaluable primary tumors, pre-therapy FDG-PET scans, treated with definitive intensity-modulated radiotherapy (IMRT) (± concurrent chemotherapy) for head and neck mucosal cancers were included. MTV was quantified and recorded for the primary lesion using a minimum standardized uptake value (SUV) threshold of 2.0. Patients were recommended prophylactic FT and followed up by a dietician for at least eight weeks of post-radiotherapy. Associations between MTV, dose to swallowing organs at risk, FT use, and FT dependence were analyzed. MTV was positively correlated with gross tumor volume (GTV) (r = 0.7357; p < 0.0001). MTVs larger than 17 cc were associated with higher rates of FT use (87.8% vs. 69.5%, p = 0.0067) and FT dependence at six weeks (76.7% vs. 41.7%, p = 0.0024) and six months (25.0% vs. 8.7%, p = 0.0088). Increasing MTV was associated with increasing mean dose to the oral cavity (p = < 0.0001), tongue base (p = 0.0009), and superior (SPCM) (p = 0.0001) and middle pharyngeal constrictor muscles (MPCM) (p = 0.0005). Increasing MTV was associated with increasing maximum dose to oral cavity (p = 0.0028), tongue base (p = 0.0056), SPCM (p = 0.0037), and MPCM (p = 0.0085). Pre-treatment MTV is a reproducible parameter that can be generated at or prior to a pre-treatment Multidisciplinary Tumor Board and may expedite decisions regarding placement of prophylactic FTs. Prospective evaluation in larger series is required to determine whether MTV is a more useful prognostic variable for FT use than clinical T-classification.

Pretreatment risk stratification of feeding tube use in patients treated with intensity-modulated radiotherapy for head and neck cancer.

BACKGROUND: The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers. METHODS: One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements. RESULTS: Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries. CONCLUSION: In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use.

Dose-volume response in acute dysphagia toxicity: Validating QUANTEC recommendations into clinical practice for head and neck radiotherapy.

PURPOSE: To determine the validity of QUANTEC recommendations in predicting acute dysphagia using intensity-modulated head and neck radiotherapy. MATERIAL AND METHODS: Seventy-six consecutive patients with locally advanced squamous cell carcinoma (SCC) of the head and neck +/- systemic therapy were analyzed. Multiple dose parameters for the larynx (V50Gy, Dmean and Dmax) were recorded. Acute dysphagia toxicity was prospectively scored in all treatment weeks (week 1-6 or 1-7) using CTCAEv3 by three blinded investigators. QUANTEC larynx recommendations (V50Gy < 27%, Dmean < 44 Gy, Dmean < 40 Gy, Dmax < 66 Gy) were used to group the cohort (i.e. V50Gy < 27% vs. V50Gy > 27%). The proportion of patients with Grade 3 dysphagia was compared within each group. RESULTS: There was a significant reduction in the incidence of grade 3 toxicity in the V50Gy < or > 27% group at week 5 (14.3% vs. 45.2%, p = 0.01) and 6 (25.9% vs. 65.9%, p < 0.01). A significant reduction at week 5 (14.7% vs. 50.0, p = 0.02) and 6 (32.4% vs. 67.6%, p = 0.01) was seen in Dmean < 44 Gy when compared to Dmean > 44 Gy. Dmean < 40 Gy also delivered a significant reduction at week 5 (5.6% vs. 42.3%, p < 0.01) and week 6 (23.5% vs. 59.3%, p = 0.01). A significant toxicity reduction at treatment week 6 (28.0% vs. 63.0%, p = 0 < 01) was seen from Dmax < 66 Gy to Dmax > 66 Gy. V50Gy > 27% (p < 0.01), Dmean > 40 Gy (p = 0.01) and Dmax > 66 Gy (p < 0.01) were also predictors of Grade 3 dysphagia when analyzed with multiple clinical risk factors. CONCLUSIONS: QUANTEC late toxicity recommendations for dose to larynx during IMRT are a useful predictor for acute dysphagia toxicity in this patient cohort. Furthermore, this included chemoradiotherapy regimes and post-operative radiotherapy patients, allowing for prophylactic implementation of supportive care measures.

Toxicity and Long-Term Outcomes of Dose-Escalated Intensity Modulated Radiation Therapy to 74Gy for Localised Prostate Cancer in a Single Australian Centre.

PURPOSE: To report the toxicity and long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) for patients with localised prostate cancer. METHODS AND MATERIALS: From 2001 to 2005, a total of 125 patients with histologically confirmed T1-3N0M0 prostate cancer were treated with IMRT to 74Gy at the Austin Health Radiation Oncology Centre. The median follow-up was 5.5 years (range 0.5-8.9 years). Biochemical prostate specific antigen (bPSA) failure was defined according to the Phoenix consensus definition (absolute nadir + 2ng/mL). Toxicity was scored according to the RTOG/EORTC criteria. Kaplan-Meier analysis was used to calculate toxicity rates, as well as the risks of bPSA failure, distant metastases, disease-specific and overall survival, at 5 and 8-years post treatment. RESULTS: All patients completed radiotherapy without any treatment breaks. The 8-year risks of ≥ Grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 6.4% and 5.8% respectively, and the 8-year risks of ≥ Grade 3 GU and GI toxicity were both < 0.05%. The 5 and 8-year freedom from bPSA failure were 76% and 58% respectively. Disease-specific survival at 5 and 8 years were 95% and 91%, respectively, and overall survival at 5 and 8 years were 90% and 71%, respectively. CONCLUSIONS: These results confirm existing international data regarding the safety and efficacy of dose-escalated intensity-modulated radiation therapy for localised prostate cancer within an Australian setting.