Jonn Wu

Treatment planning constraints to avoid xerostomia in head-and-neck radiotherapy: an independent test of QUANTEC criteria using a prospectively collected dataset.

PURPOSE The severe reduction of salivary function (xerostomia) is a common complication after radiation therapy for head-and-neck cancer. Consequently, guidelines to ensure adequate function based on parotid gland tolerance dose-volume parameters have been suggested by the QUANTEC group and by Ortholan et al. We perform a validation test of these guidelines against a prospectively collected dataset and compared with a previously published dataset. METHODS AND MATERIALS Whole-mouth stimulated salivary flow data from 66 head-and-neck cancer patients treated with radiotherapy at the British Columbia Cancer Agency (BCCA) were measured, and treatment planning data were abstracted. Flow measurements were collected from 50 patients at 3 months, and 60 patients at 12-month follow-up. Previously published data from a second institution, Washington University in St. Louis (WUSTL), were used for comparison. A logistic model was used to describe the incidence of Grade 4 xerostomia as a function of the mean dose of the spared parotid gland. The rate of correctly predicting the lack of xerostomia (negative predictive value [NPV]) was computed for both the QUANTEC constraints and Ortholan et al. recommendation to constrain the total volume of both glands receiving more than 40 Gy to less than 33%. RESULTS Both datasets showed a rate of xerostomia of less than 20% when the mean dose to the least-irradiated parotid gland is kept to less than 20 Gy. Logistic model parameters for the incidence of xerostomia at 12 months after therapy, based on the least-irradiated gland, were D(50) = 32.4 Gy and and γ = 0.97. NPVs for QUANTEC guideline were 94% (BCCA data), and 90% (WUSTL data). For Ortholan et al. guideline NPVs were 85% (BCCA) and 86% (WUSTL). CONCLUSION These data confirm that the QUANTEC guideline effectively avoids xerostomia, and this is somewhat more effective than constraints on the volume receiving more than 40 Gy.

Toxicity and outcomes in combined modality treatment of head and neck squamous cell carcinoma: cisplatin versus cetuximab.

AIMS The standard of care for locally advanced head and neck squamous cell carcinoma (HNSCC) is radiation therapy (RT) with concurrent cisplatin (CIS). Patients with renal or cardiac dysfunction, hearing loss or poor performance status (PS) may receive RT and cetuximab (CET) at our institution. This study compares treatment toxicities and outcomes. METHODS AND MATERIALS All patients treated with curative intent RT and concurrent CIS (100 mg/m 2 Day 1, 22, 43) or CET (400 mg/m 2 Day -7, 250 mg/m 2 weekly during RT) between August 2007 and July 2010 were reviewed and toxicity and outcomes analyzed. RESULTS Among 349 subjects (262 RT-CIS, 87 RT-CET) characteristics were similar except in age, head and neck subsite and RT fractionation. RT-CIS required more dose reductions, delays, and unplanned admissions and received less intended systemic therapy (ST). Weight loss and gastrostomy-tube use were similar. RT-CIS caused more nausea/vomiting, while RT-CET was associated with more dermatitis and acneiform rash. With mean follow-up of 20 months and 16 months, RT-CIS subjects experienced improved 1-year locoregional control (LRC) (90% vs. 72%, P < 0.01), disease-free survival (DFS) (83% vs. 67%, P < 0.01) and overall survival (OS) (90% vs. 80%, P = 0.04). On multivariate analysis type of ST was associated with LRC and DFS, but not OS. CONCLUSIONS In patients with locally advanced HNSCC, CIS and CET were associated with different toxicity profiles. RT-CIS was associated with improved LRC and DFS, but similar OS compared to RT-CET.

25 Year survival outcomes for squamous cell carcinomas of the head and neck: Population-based outcomes from a Canadian province

OBJECTIVES Long term outcomes of patients with head and neck cancer (HNC) are rarely reported, but of potential benefit to clinicians and researchers. Squamous cell carcinomas (SCC) of the head and neck represent a heterogeneous group of cancers. The purpose of this population based study is to describe primary site specific, long term outcomes of HNC. METHODS All patients from a Canadian province diagnosed between 1986 and 1990 with SCC of the oral cavity, pharynx, and larynx were identified. Chart review and patient data were abstracted through the provincial cancer registry database. Survival analysis was performed with Kaplan Meier methods, while differences in survival between groups were assessed with log-rank tests. Multivariable analysis was performed using Cox-regression. RESULTS 1657 patients were analyzed during the study period. Almost half (50.9%) of the cases were advanced stage (stage III IV) at presentation. Two, 5, 15 & 25year overall survival (OS) and HNC specific survival for all the patients were 64%, 46%, 21%, 11% and 74%, 63%, 53% & 49%, respectively. OS and HNC-specific mortality were statistically inferior among men, older age at diagnosis, advanced stages of disease, and was primary cancer site specific, with worse survival in oropharyngeal & hypopharyngeal sites, p<0.001. CONCLUSIONS Survival rates vary by primary HNC site, and the overall survival & HNC specific survival differ over this long follow up assessment. Head and neck cancer specific death is most common in the first five years, and is subsequently dominated by competing causes of mortality. These results are useful as a reference tool for clinicians, researchers, and trainees.

The Impact of Peer Review of Volume Delineation in Stereotactic Body Radiation Therapy Planning for Primary Lung Cancer: A Multicenter Quality Assurance Study

Introduction: Although the value of peer review is increasingly recognized, there is little research documenting its impact in the setting of stereotactic body radiation therapy (SBRT) for lung cancer. This study determines the dosimetric effect of peer review of tumor and normal tissue contouring in lung SBRT planning. Methods: Forty anonymized lung SBRT plans were retrospectively evaluated post treatment. Each plan was independently reviewed by two to three radiation oncologists using established institutional guidelines. For each structure, reviewers recorded recommendations for “no change,” “minor change,” “major change,” or “missing contour” and provided a modified or new contour as needed. Dose–volume histograms were analyzed for dosimetric violations. Results: Among 472 contoured structures evaluated, recommendations from peer review were 107 major change (23%), 176 minor change (37%), 157 no change (33%), and 32 missing (7%). Common major changes involved the skin (n = 20), heart (n = 18), and proximal bronchial tree (n = 15). Dose constraints were not achieved for 25 new or recontoured structures (5%), of which 17 involved the planning target volume (PTV). Among cases with PTV violations, the mean prescription dose coverage to the modified PTVs was 90%, compared with the protocol standard of greater than or equal to 95% coverage. The remaining violations involved the ribs (n = 5), spinal canal (n = 2), and heart (n = 1). Conclusions: Peer review of structure contouring resulted in significant changes in lung SBRT plans. Recontouring of several plans revealed violations of dose limits, most often involving inadequate PTV coverage. Peer review, especially of target volume delineation, is warranted to improve consistency and quality in lung SBRT planning.

Incidence of second metachronous head and neck cancers: Population‐based outcomes over 25 years

The primary objective was to determine the incidence of second metachronous head and neck cancers (HNC) following an index HNC and estimate their overall survival.

Dose delivery analysis of weekly versus 3-weekly cisplatin concurrent with radiation therapy for locally advanced nasopharyngeal carcinoma (NPC).

Objective:The purpose of this study was to analyze the dose delivery and toxicity of weekly cisplatin versus high-dose cisplatin given every 3 weeks in a tertiary oncology clinic. Methods:From January 2000 to July 2009, patients with biopsy-proven nasopharyngeal carcinoma receiving concurrent cisplatin with curative-intent radiation therapy (RT) were included. Before 2005, most patients received cisplatin (Q3) (100 mg/m2 intravenously days 1, 22, and 43 of RT) and 3-dimensional conformal RT (66 Gy, 33 fractions). After 2005, most patients received weekly cisplatin (Q1) (40 mg/m2 intravenously weekly for 7 wk of RT) and intensity-modulated radiotherapy (70 Gy, 35 fractions). Results:Seventy-three patients were analyzed: 45 for Q1 and 28 for Q3. Cumulative doses ≥200 mg/m2 were achieved in 80% of Q1 and 86% of Q3 patients, respectively. Dose reduction due to toxicity was required in 2/45 (4%) of Q1 patients compared with 11/28 (39%) of Q3 patients (P=0.0003). Toxicities in Q1 and Q3 patients included: hospitalization for acute toxicity in 20% and 35.7%; mean weight loss 10.85% and 8.75%; percutaneous endoscopic gastrostomy tube placement in 25.6% and 29.6%; and grade 3 dehydration in 11.1% and 17.9%, respectively. Median follow-up time was 3 years for Q1 and 6 years for Q3 patients. Median disease-free survival was 46 months for the Q1 group and 53 months for the Q3 group (P=0.667). There was no difference in overall survival between Q1 and Q3. Conclusions:In this series, weekly 40 mg/m2 cisplatin and 3-weekly 100 mg/m2 cisplatin showed similar deliverability, toxicity profiles, and outcomes. At our center, weekly cisplatin is standard of care for patients with locally advanced nasopharyngeal carcinoma undergoing chemoradiotherapy.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

Objectives:The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Methods:Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Results:Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. Conclusions:In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

Treatment Outcomes of Locally Advanced Oropharyngeal Cancer: A Comparison Between Combined Modality Radio-Chemotherapy and Two Variants of Single Modality Altered Fractionation Radiotherapy

PURPOSE To compare outcomes in patients with locally advanced oropharyngeal cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT). METHODS AND MATERIALS Subjects were 321 consecutive patients with newly diagnosed oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and December 2005 at the BC Cancer Agency with RT-CT (n = 157), AccRT (n = 57), or HypoRT (n = 107). Outcomes examined were disease-specific survival (DSS), locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate of hospitalization for acute complications. RESULTS Median follow-up was 3.4 years. Three-year Kaplan-Meier DSS with RT-CT, AccRT, and HypoRT were 80%, 81%, and 74%, respectively (p = 0.219). Cox regression analysis identified treatment modality as a significant factor affecting DSS (p = 0.038). Compared with RT-CT, the hazard ratio (HR) for DSS was 1.0 with AccRT and 2.0 with HypoRT (p = 0.021). Kaplan-Meier pairwise comparisons found no significant difference in LRC and OS between RT-CT and AccRT. HypoRT was associated with significantly lower LRC (p = 0.005) and OS (p = 0.008) compared with RT-CT. There were significant differences in the rates of G-tube use (p < 0.001) and of hospitalization (p = 0.036) among the three treatment groups, with the most frequent rates observed in the RT-CT group. CONCLUSIONS In patients with locally advanced oropharyngeal cancer, AccRT conferred DSS, LRC, and OS comparable to that of RT-CT. Patients treated with RT-CT experienced higher rates of treatment-related acute toxicities. HypoRT was associated with the least favorable outcomes.

Regional radiation dose susceptibility within the parotid gland: effects on salivary loss and recovery.

PURPOSE Xerostomia is one of the most likely late toxic effects of radiotherapy treatment in patients with head-and-neck cancers. Modern treatment techniques can incorporate knowledge of complication risk into treatment plans. To this end, the authors attempt to quantify the regional radiotherapy dose-dependence of salivary output loss and recovery in a prospective study. METHODS Salivary output was collected from patients undergoing radiotherapy treatment for head-and-neck cancers at the BC Cancer Agency between February 2008 and May 2013. Regional dose-dependence (i.e., dose susceptibility) of loss and recovery is quantified using nonparametric (Spearmans rank correlation coefficients, local linear regression) and parametric (least-sum of squares, least-median of squares) techniques. RESULTS Salivary flow recovery was seen in 79 of 102 patients considered (p < 0.0001, Wilcoxon sign rank test). Output loss was strongly correlated with left- and right parotid combined dose φ = min (DL,  45 Gy) + min (DR,  45 Gy), and can be accurately predicted. Median early loss (three months) was 72% of baseline, while median overall loss (1 yr) was 56% of baseline. Fitting an exponential model to whole parotid yields dose sensitivities A3m = 0.0604 Gy(-1) and A1y = 0.0379 Gy(-1). Recovery was not significantly associated with dose. Hints of lateral organ sub-segment dose-response dimorphism were observed. CONCLUSIONS Sub-segmentation appears to predict neither loss nor recovery with any greater precision than whole parotid mean dose, though it is not any worse. Sparing the parotid to a combined dose φ of <50 Gy is recommended for a patient to keep ≈40% of baseline function and thus avoid severe xerostomia at 12 months post-treatment. It seems unlikely that a populations mean recovery will exceed 20%-30% of baseline output at 1 yr after radiotherapy treatment using current (whole-organ based) clinical guidelines.

Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation

1Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada, 2Department of Medical Physics, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, 3Department of Medicine and Applied Sciences, University of California, San Diego, La Jolla, California, USA and 4Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada