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.

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.

Hypoxia-targeted radiotherapy dose painting for head and neck cancer using (18)F-FMISO PET: a biological modeling study.

BACKGROUND: This study investigates the use of (18)F-fluoromisonidazole (FMISO) PET-guided radiotherapy dose painting for potentially overcoming the radioresistant effects of hypoxia in head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: The study cohort consisted of eight patients with HNSCC who were planned for definitive radiotherapy. Hypoxic subvolumes were automatically generated on pre-radiotherapy FMISO PET scans. Three radiotherapy plans were generated for each patient: a standard (STD) radiotherapy plan to a dose of 70 Gy, a uniform dose escalation (UDE) plan to the standard target volumes to a dose of 84 Gy, and a hypoxia dose-painted (HDP) plan with dose escalation only to the hypoxic subvolume to 84 Gy. Plans were compared based on tumor control probability (TCP), normal tissue complication probability (NTCP), and uncomplicated tumor control probability (UTCP). RESULTS: The mean TCP increased from 73% with STD plans to 95% with the use of UDE plans (p < 0.001) and to 93% with HDP plans (p < 0.001). The mean parotid NTCP increased from 26% to 44% with the use of UDE plans (p = 0.003), and the mean mandible NTCP increased from 2% to 27% with the use of UDE plans (p = 0.001). There were no statistically significant differences between any of the NTCPs between the STD plans and HDP plans. The mean UTCP increased from 48% with STD plans to 66% with HDP plans (p = 0.016) and dropped to 37% with UDE plans (p = 0.138). CONCLUSION: Hypoxia-targeted radiotherapy dose painting for head and neck cancer using FMISO PET is technically feasible, increases the TCP without increasing the NTCP, and increases the UTCP. This approach is superior to uniform dose escalation.

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.

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.

White matter injury in the premature infant: a comparison between serial cranial sonographic and MR findings at term.

BACKGROUND AND PURPOSE: The accuracy of cranial sonography (US) in characterizing white matter (WM) injury in the premature infant is unclear. This study was aimed to assess the sensitivity and specificity of serial cranial US during the first 6 weeks of life in comparison to MR imaging at term (week of expected delivery) in characterizing the presence of WM injury in a cohort of 96 very low birth weight (VLBW) infants. METHOD: A blinded investigator reviewed serial cranial sonograms for the presence of WM echolucency and echodensity, including its duration and extent. These abnormalities were compared with a second independent investigator's evaluation to determine the sensitivity and specificity of cranial WM abnormalities at US. RESULTS: The presence of prolonged echodensity (>7 days) in the WM on neonatal cranial sonograms demonstrated low sensitivity (26%) and a low positive predictive value (36%) for the presence of noncystic WM injury, as detected on MR images at term. Extensive cystic lesions detected on MR images were all identified during earlier cranial US. CONCLUSION: Neonatal cranial US of the VLBW infant demonstrates high reliability in the detection of cystic WM injury but has significant limitations in the demonstration of noncystic WM injury. This deficiency of neonatal cranial US is important, because noncystic WM injury is considerably more common than cystic WM injury.

Intensity modulated radiation therapy dose painting for localized prostate cancer using ¹¹C-choline positron emission tomography scans.

PURPOSE: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using (11)C-choline positron emission tomography PET scans in patients with localized prostate cancer. METHODS AND MATERIALS: This was an RT planning study of 8 patients with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)). Three IMRT plans were generated for each patient: PLAN(78), which consisted of whole-prostate radiation therapy to 78 Gy; PLAN(78-90), which consisted of whole-prostate RT to 78 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy; and PLAN(72-90), which consisted of whole-prostate RT to 72 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP(PET)) and on prostatectomy-defined volumes (TCP(path)), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. RESULTS: All plans for all patients reached prescription doses while adhering to dose constraints. TCP(PET) values for PLAN(78), PLAN(78-90), and PLAN(72-90) were 65%, 97%, and 96%, respectively. TCP(path) values were 71%, 97%, and 89%, respectively. Both PLAN(78-90) and PLAN(72-90) had significantly higher TCP(PET) (P=.002 and .001) and TCP(path) (P<.001 and .014) values than PLAN(78). PLAN(78-90) and PLAN(72-90) were not significantly different in terms of TCP(PET) or TCP(path). There were no significant differences in rectal NTCPs between the 3 plans. CONCLUSIONS: IMRT dose painting for localized prostate cancer using (11)C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.