Implication of dental insurance status on patterns of pre-radiation dental extraction and risk of osteoradionecrosis of the jaw in head-and-neck cancer patients.

Oral toxicities such as osteoradionecrosis can be minimized by dental screening and prophylactic dental care prior to head and neck (HN) radiation therapy (RT). However, limited information is available about how dental insurance interacts with prophylactic dental care and osteoradionecrosis. To address this gap in knowledge, we conducted a cohort study of 2743 consecutive adult patients treated with curative radiation for HN malignancy who underwent pre-radiation dental assessment and where required, prophylactic dental treatment. Charts were reviewed to determine patient demographics, dental findings, dental treatment and development of osteoradionecrosis following radiation. Three insurance cohorts were identified: private-insured (50.4 %), public-insured (7.3 %), being patients with coverage through government-funded disability and welfare programs, and self-pay (42.4 %). More than half the public-insured patients underwent prophylactic pre-radiation dental extractions, followed by self-pay patients (44 %) and private-insured patients (26.6 %). After a median follow-up time of 4.23 years, 6.5 % of patients developed osteoradionecrosis. The actuarial rate of osteoradionecrosis in the public-insured patients was 14.7 % at 5-years post-RT, compared to 7.5 % in private-insured patients and 6.7 % in self-pay patients. On multivariable analysis, dental insurance status, DMFS160, age at diagnosis, sex, tumor site, nodal involvement, years smoked and gross income were all significant risk factors for tooth removal prior to HN radiation. However, only public-insured status, tumor site and years smoked were significant risk factors for development of osteoradionecrosis. Our findings demonstrate that lack of comprehensive dental coverage (patients who self-pay or who have limited coverage under public-insured programs) associates strongly with having teeth removed prior to HN RT. Nearly 1 in 6 patients covered under public-insurance developed osteoradionecrosis within 5 years of completing their treatment. Well-funded dental insurance programs for HN cancer patients might reduce the number of pre-RT extractions performed in these patients, improving quality of life post-RT.

Individualized risk assessment of distant metastases in oral cavity carcinoma: a validated predictive-score model.

BACKGROUND: We aimed to develop and validate a risk-scoring system for distant metastases (DMs) in oral cavity carcinoma (OCC). METHODS: Patients with OCC who were treated at 4 tertiary cancer institutions with curative surgery with or without postoperative radiation/chemoradiation therapy were randomly assigned to discovery or validation cohorts (3:2 ratio). Cases were staged on the basis of tumor, node, and metastasis staging according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control guidelines. Predictors of DMs on multivariable analysis in the discovery cohort were used to develop a risk-score model and classify patients into risk groups. The utility of the risk classification was evaluated in the validation cohort. RESULTS: Overall, 2749 patients were analyzed. Predictors (risk score coefficient) of DMs in the discovery cohort were the following: pathological stage (p)T3-4 (0.4), pN+ (N1: 0.8; N2: 1.0; N3: 1.5), histologic grade (G) 3 (G3, 0.7), and lymphovascular invasion (0.4). The DM risk groups were defined by the sum of the following risk score coefficients: high (>1.7), intermediate (0.7-1.7), and standard risk (<0.7). The 5-year DM rates (high/intermediate/standard risk groups) were 30%/15%/4% in the discovery cohort (C-index = 0.79) and 35%/16%/5% in the validation cohort, respectively (C-index = 0.77; both P < .001). In the whole cohort, this predictive model showed excellent discriminative ability in predicting DMs without locoregional failure (29%/11%/1%), later (>2 year) DMs (11%/4%/2%), and DMs in patients treated with surgery (20%/12%/5%), postoperative radiation therapy (34%/17%/4%), and postoperative chemoradiation therapy (39%/18%/7%) (all P < .001). The 5-year overall survival rates in the overall cohort were 25%/51%/67% (P < .001). CONCLUSIONS: Patients at higher risk for DMs were identified by use of a predictive-score model for DMs that included pT3-4, pN1/2/3, G3, and lymphovascular invasion. Identified patients may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies.

Association of Household Income at Diagnosis With Financial Toxicity, Health Utility, and Survival in Patients With Head and Neck Cancer.

Importance: While several studies have documented a link between socioeconomic status and survival in head and neck cancer, nearly all have used ecologic, community-based measures. Studies using more granular patient-level data are lacking. Objective: To determine the association of baseline annual household income with financial toxicity, health utility, and survival. Design, Setting, and Participants: This was a prospective cohort of adult patients with head and neck cancer treated at a tertiary cancer center in Toronto, Ontario, between September 17, 2015, and December 19, 2019. Data analysis was performed from April to December 2021. Exposures: Annual household income at time of diagnosis. Main Outcome and Measures: The primary outcome of interest was disease-free survival. Secondary outcomes included subjective financial toxicity, measured using the Financial Index of Toxicity (FIT) tool, and health utility, measured using the Health Utilities Index Mark 3. Cox proportional hazards models were used to estimate the association between household income and survival. Income was regressed onto log-transformed FIT scores using linear models. The association between income and health utility was explored using generalized linear models. Generalized estimating equations were used to account for patient-level clustering. Results: There were 555 patients (mean [SD] age, 62.7 [10.7] years; 109 [20%] women and 446 [80%] men) included in this cohort. Two-year disease-free survival was worse for patients in the bottom income quartile (<$30 000: 67%; 95% CI, 58%-78%) compared with the top quartile (≥$90 000: 88%; 95% CI, 83%-93%). In risk-adjusted models, patients in the bottom income quartile had inferior disease-free survival (adjusted hazard ratio, 2.13; 95% CI, 1.22-3.71) and overall survival (adjusted hazard ratio, 2.01; 95% CI, 0.94-4.29), when compared with patients in the highest quartile. The average FIT score was 22.6 in the lowest income quartile vs 11.7 in the highest quartile. In adjusted analysis, low-income patients had 12-month FIT scores that were, on average, 134% higher (worse) (95% CI, 16%-253%) than high-income patients. Similarly, health utility scores were, on average, 0.104 points lower (95% CI, 0.026-0.182) for low-income patients in adjusted analysis. Conclusions and Relevance: In this cohort study, patients with head and neck cancer with a household income less than CAD$30 000 experienced worse financial toxicity, health status, and disease-free survival. Significant disparities exist for Ontario's patients with head and neck cancer.

Inter-rater concordance and operating definitions of radiologic nodal feature assessment in human papillomavirus-positive oropharyngeal carcinoma.

BACKGROUND AND PURPOSE: This study aims to evaluate the reliability of radiologic nodal feature assessment in clinical node-positive human papillomavirus-positive oropharyngeal carcinoma. MATERIALS AND METHODS: Baseline CTs or MRIs of clinical node-positive human papillomavirus-positive oropharyngeal carcinoma diagnosed between 2012 and 2015 were reviewed independently by two neuroradiologists for seven nodal features: radiologic nodal involvement, cystic change, presence of necrosis, clustering, conglomeration, coalescence, and extranodal extension. Consensus operating definitions were derived after discussion. The features were re-reviewed in a randomly selected cohort. Levels of certainty (probability of presence: <25%, ∼50%, ∼75%, and >90%) were recorded. Interrater concordance was calculated using Cohen's kappa coefficient. RESULTS: A total of 413 patients (826 necks) were eligible. At initial review, the inter-rater kappa values for: radiologic nodal involvement, cystic change, necrosis, clustering, conglomeration, coalescence, and extranodal extension were 0.92, 0.64, 0.48, 0.32, 0.32, 0.62, and 0.56, respectively. A re-review of 94 randomly selected cases (188 necks) after consolidation of operating definitions for nodal features showed that the inter-rater kappa values of these features were 0.83, 0.62, 0.58, 0.32, 0.18, 0.68, and 0.74 when considering ≥50% certainty as positive, and improved to 0.94, 0.66, 0.59, 0.33, 0.19, 0.76, and 0.86 when considering ≥75% certainty as positive. CONCLUSION: Clearly defined nomenclature results in improved interrater reliability when assessing radiologic nodal features, especially for coalescent adenopathy and extranodal extension. Higher levels of certainty are associated with higher inter-rater agreement. Radiology reporting should include clear definitions of clinically relevant nodal features as well as levels of certainty to serve various needs in clinical care and research.

A cost-utility analysis comparing CT surveillance, PET-CT surveillance, and planned postradiation neck dissection for advanced nodal HPV-positive oropharyngeal cancer.

BACKGROUND: The cost utility of image-guided surveillance using computed tomography (CT) and positron emission tomography (PET)-CT to planned postradiation neck dissection (PRND) was compared for the management of advanced nodal human papillomavirus-positive oropharyngeal cancer following chemoradiation. METHODS: A universal payer perspective was adopted. A Markov model was designed to simulate four treatment approaches with 3-month cycles over a lifetime horizon: 1) CT surveillance, 2) standard PET-CT surveillance, 3) a novel PET-CT approach with repeat PET at 6 months postchemoradiation for equivocal responders, and 4) PRND. Parameters including probabilities of CT nodal progression/resolution, PET avidity, recurrence, and survival were obtained from the literature. Costs were reported in 2019 Canadian dollars and utilities were expressed in quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. RESULTS: PET-CT surveillance dominated CT surveillance and PRND in the base case scenario, and the novel PET-CT approach was the most cost-effective strategy across a wide range of variables tested in one-way sensitivity analysis. On probabilistic sensitivity analysis, novel PET-CT surveillance was the most cost-effective strategy in 78.1% of model iterations at a willingness-to-pay of $50,000/QALYs. Novel PET-CT surveillance resulted in a 49% lower rate of neck dissection compared with traditional PET-CT, and yielded an incremental benefit of 0.14 QALYs with average cost savings of $1309. CONCLUSIONS: Image-guided surveillance including PET-CT and CT are more cost effective than PRND. The novel PET-CT approach with repeat PET for equivocal responders was the dominant strategy and yielded both higher benefit and lower costs compared with standard PET-CT surveillance.

Assessment Criteria and Clinical Implications of Extranodal Extension in Head and Neck Cancer.

Tumor breaching the capsule of a lymph node is termed extranodal extension (ENE). It reflects aggressiveness of a tumor, creates anatomic challenges for disease clearance, and increases the risk of distant metastasis. Extranodal extension can be assessed on a pathology specimen, by radiology studies, and by clinical examination. Presence of ENE in a pathology specimen has long been considered a high-risk feature of disease progression and would ordinarily benefit from the addition of chemotherapy to adjuvant radiotherapy. Although the eighth edition of the Union for International Cancer Control/American Joint Committee on Cancer stage classification dichotomizes pathologic ENE according to its presence or absence, emerging evidence suggests that the extent of a pathologic ENE may provide additional value for risk stratification to guide adjuvant therapy. Recent data suggest that the prognostic importance of pathologic ENE is also applicable for HPV-associated head and neck squamous cell carcinoma. In addition, compelling data demonstrate that indisputable radiologic ENE is a powerful risk stratification tool to identify patients at high risk for treatment failure, especially distant metastasis, applicable for both HPV-positive and HPV-negative head and neck squamous cell carcinoma. However, the definition and taxonomy of radiologic ENE requires standardization. The goal of this review is to clarify the contemporary understanding of the prognostic implications of ENE in head and neck squamous cell carcinoma, present the nuances of what is presently known and unknown, and elucidate how to classify ENE pathologically and radiologically with an understanding of the strengths and weaknesses of each approach. Finally, with the development of several risk stratification methods, the relative role of ENE and other prognostic schema will be explored.

Sexual satisfaction in nasopharyngeal carcinoma survivors: Rates and determinants.

OBJECTIVES: Sexual health problems have been identified as an unmet need in head and neck cancer (HNC) survivors. In particular, little is known about such outcomes in survivors of nasopharyngeal cancer (NPC). MATERIALS AND METHODS: A cross-sectional study of NPC survivors with ≥4y follow-up was undertaken. Sexual satisfaction was assessed using the optional "I am satisfied with my sex life" item of the FACT-H&N. Other patient-reported outcomes measures were also captured including fatigue (FACIT-F), HNC symptom burden (MDASI-HN), emotional distress (HADS) and frontal function (FrSBE). Univariate and multivariate analyses were performed to determine factors influencing sexual satisfaction. RESULTS: The sexual satisfaction item was answered by 85/103 (83%) enrollees. Female (p < 0.001) and non-partnered (p = 0.0045) patients were more likely to abstain from answering. The distribution of responses were: "very much" (26%), "quite a bit" (21%), "somewhat" (20%), "a little bit" (13%) and "not at all" (20%). Sexual satisfaction was associated with multiple patient-reported measures on univariate analysis, including quality of life, fatigue, a priori selected HNC symptoms (pain, taste), emotional distress, frontal lobe function, body image and relationship strength. On multivariate analysis, only relationship strength and emotional distress remained significant. Sociodemographic factors (age, sex, marital status) and other selected orofacial toxicities were not significant. CONCLUSIONS: Nearly half (47%) of our sample reported being in the higher satisfaction range. While reassuring in the context of comparative population level data, a number of factors including toxicity, psychological and social factors were associated with sexual satisfaction responses. Prospective evaluation of this unmet need is required.

Characteristics of Radiotherapy Trials Compared With Other Oncological Clinical Trials in the Past 10 Years.

Importance: Modern precision radiotherapy is an innovative and effective treatment of cancer, yet it is unclear how radiotherapy trials are affected by expanding targeted and immune therapies and declining National Institutes of Health funding. Objective: To analyze and compare the characteristics of radiotherapy trials with other oncological trials registered on ClinicalTrials.gov. Design, Setting, and Participants: This is a cross-sectional analysis of trials registered on ClinicalTrials.gov between June 1, 2007, and May 8, 2017. Records of all 243 758 clinical studies registered by May 8, 2017, were downloaded, but only 25 907 interventional oncological trials registered between June 1, 2007, and May 8, 2017, and whose primary purpose was "treatment" were included in the final analysis. Trials were categorized according to cancer type and other registration information. Main Outcomes and Measures: Characteristics of radiotherapy trials were compared with characteristics of other oncological trials. Chronological shifts in radiotherapy trials were also analyzed. Results: Of the 25 907 trials selected, 1378 (5.3%) were radiotherapy trials and 24 529 (94.7%) were other oncological studies. The number of radiotherapy trials increased gradually from 94 (June 1, 2007, through May 31, 2008) to 192 (June 1, 2015, through May 31, 2016). Radiotherapy trials were less likely than other oncological studies to be registered before participant enrollment (763 of 1370 [55.7%] vs 16 105 of 24 434 [65.9%]; P < .001), to be blinded (45 of 1378 [3.3%] vs 2784 of 24 529 [11.3%]; P < .001), or to involve multiple geographic regions (2.4% vs 9.5%; P < .001), but they were more likely to be phase 2 to 3 (773 of 1124 [68.8%] vs 12 910 of 22 300 [57.9%]; P < .001) and to have a data-monitoring committee (839 of 1264 [66.4%] vs 11 728 of 21 060 [55.7%]; P < .001). Only a minority of radiotherapy trials were industry sponsored, which was significantly lower than for other oncological trials (80 of 1378 [5.8%] vs 10 651 of 24 529 [43.4%]; P < .001; adjusted odds ratio, 0.08; 95% CI, 0.06-0.10). The number of National Institutes of Health-sponsored radiotherapy trials decreased from 80 of 544 trials (14.7%) from 2007 to 2012 to 72 of 834 trials (8.6%) from 2012 to 2017 (P < .001). Radiotherapy trials with a sample size of more than 100 patients decreased from 155 of 543 trials (28.5%) from 2007 to 2012 to 157 of 833 trials (18.8%) from 2012 to 2017 (P < .001). Conclusions and Relevance: The limited number of and the scarcity of funding for radiotherapy trials is concerning given the integral role of radiotherapy in the clinical management of patients with cancer worldwide. A multidisciplinary collaboration to promote and fund more radiotherapy research is warranted.

Cost-Effectiveness Analysis of Radiation Therapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: The objective of this study was to compare the cost-effectiveness of transoral robotic surgery (TORS) versus the standard treatment modality for oropharyngeal squamous cell carcinoma (OPSCC), radiation therapy (RT), in a subset of patients with early-stage OPSCC. METHODS AND MATERIALS: We developed a microsimulation state-transition model associated with RT and TORS for patients with clinically staged T1N0M0 to T2N1M0 OPSCC. Transition probabilities, utilities, and costs for each health state were estimated from recently published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs (in 2014 US dollars), health benefits (quality-adjusted life-years [QALYs]), and cost-effectiveness ratios from a societal perspective. RESULTS: Under base-case assumptions, TORS was associated with modest gains in QALYs. RT yielded 10.43 QALYs at a cost of $123,410 per patient, whereas TORS yielded 11.10 QALYs at a cost of $178,480. This resulted in an incremental cost-effectiveness ratio of $82,190/QALY gained. The incremental cost-effectiveness ratio was most sensitive to the need for adjuvant therapy, cost of late toxicity, age at diagnosis, disease state utilities, and discount rate. Accounting for joint parameter uncertainty, RT had a higher probability of demonstrating a cost-effective profile compared with TORS, at 54% compared with 46%. CONCLUSIONS: By use of standard benchmarks for cost-effectiveness in the United States, TORS may be a cost-effective alternative for the subset of patients with early-stage OPSCC but demonstrates considerable sensitivity to assumptions around quality of life.

Expanding global access to radiotherapy.

Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries-a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015-35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015-35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015-35 (-$14·9 billion in low-income countries; -$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (-$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.

Comparison of Health State Utility Measures in Patients With Head and Neck Cancer.

IMPORTANCE: Accurate measurement of health state utilities (HU) is the cornerstone for cost-utility analyses and the valuation of quality of life for given health states. Current indirect methods of HU derivation lack face validity for patients with head and neck cancer. The appropriateness of these measures compared with direct methods, such as the standard gamble (SG), time trade-off (TTO), and visual analog scale (VAS), have not been assessed in this patient population. OBJECTIVE: To assess the convergent and construct validities of 5 different HU derivation methods in patients with head and neck cancer. DESIGN, SETTING, AND PARTICIPANTS: In a cross-sectional study, we recruited 100 consecutive patients with squamous cell carcinoma of the upper aerodigestive tract treated in the outpatient surgical oncology clinics of the Princess Margaret Cancer Centre from August 1 through October 31, 2014. We enrolled patients with a minimum of 3 months of follow-up after completion of treatment and no evidence of recurrent or metastatic disease. Participants completed SG, TTO, and VAS exercises, the EuroQoL instrument (EQ-5D), and the Health Utilities Index Mark 3 (HUI3) questionnaire. Data analysis was performed November 1 through December 15, 2014. EXPOSURES: Head and neck cancer and HU measures. MAIN OUTCOMES AND MEASURES: We assessed convergent validity of the 5 HU instruments through Spearman rank order correlation assessment. We determined construct validity through a priori hypotheses relating HU scores with clinical indexes of disease severity. RESULTS: The SG and TTO measures generated higher mean (SD) utility scores (0.91 [0.17] and 0.94 [0.14], respectively) than the VAS, EQ-5D, and HUI3 (0.76 [0.19], 0.82 [0.18], and 0.75 [025], respectively) (P < .001). The maximum score of 1.0 was reported in 60 of 99 cases (61%) for the SG and 75 of 99 cases (76%) for the TTO (a significant ceiling effect), in contrast to 5 of 99 cases (5%) for the VAS, 29 of 99 cases (29%) for the EQ-5D, and 6 of 99 cases (6%) for the HUI3. The VAS showed strong correlations with the EQ-5D (ρ = 0.63 [P < .001]) and HUI3 (ρ = 0.50 [P < .001]), and the HUI3 strongly correlated with the EQ-5D (ρ = 0.67 [P < .001]), whereas the SG and TTO generally correlated poorly with other HU measures (ρ range, 0.19-0.29) and with one another (ρ = 0.21 [P < .001]). The VAS, EQ-5D, and HUI3 were able to discriminate between participants who underwent salvage surgery compared with those who underwent primary surgery (mean [SD] utility scores, 0.48 [0.13] vs 0.76 [0.20] [P = .006], 0.62 [0.17] vs 0.83 [0.19] [P = .004], and 0.37 [0.29] vs 0.78 [0.22] [P = .004], respectively). Mean EQ-5D utility scores monotonically increased over time since completion of treatment (0.26 [P = .01]). The HUI3 yielded lower utility values for participants with laryngeal cancer (mean [SD], 0.59 [0.29]). The SG and TTO measures frequently generated utility scores that contradicted our hypothesized expectations. CONCLUSIONS AND RELEVANCE: Indirect HU measures may be more reflective of the health status of patients with head and neck cancer than direct measures. Current instruments lack face validity for attributes germane to this population.

Assessment of repeatability of hyperpolarized gas MR ventilation functional imaging in cystic fibrosis.

RATIONALE AND OBJECTIVES: Hyperpolarized (HP) gas magnetic resonance imaging (MRI) is an advanced imaging technique that provides high-resolution regional information on lung function without using ionizing radiation. Before this modality can be considered for assessing clinical or investigational interventions, baseline repeatability needs to be established. We assessed repeatability of lung function measurement using HP helium-3 MRI (HP (3)He MRI) in a small cohort of patients with cystic fibrosis (CF). MATERIALS AND METHODS: We examined repeatability of HP (3)He MR images of five patients with CF in four scanning sessions over a 4-week period. We acquired images on a Philips 3.0 Tesla Achieva MRI scanner using a quadrature, flexible, wrap-around, (3)He radiofrequency coil with a fast gradient-echo pulse sequence. We determined ventilation volume and ventilation defect volume using an advanced semiautomatic segmentation algorithm and also quantified ventilation heterogeneity. RESULTS: There were no significant differences in total ventilation volume, ventilation defect volume, ventilation defect percentage, or mean ventilation heterogeneity (repeated-measures analysis of variance, P = .2116, P = .2825, P = .2871, and P = .7265, respectively) in the patients across the four scanning sessions. CONCLUSIONS: Our results indicate that total ventilation volume, ventilation defect volume, ventilation defect percentage, and mean ventilation heterogeneity as assessed by HP gas MRI in CF patients with stable health are reproducible over time. This repeatability and the technique's capability to provide noninvasive high-resolution data on regional lung function without ionizing radiation make (3)He MRI a potentially useful outcome measure for CF-related clinical trials.

Transoral resection of pharyngeal cancer: summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia.

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.

Point-of-care outcome assessment in the cancer clinic: audit of data quality.

BACKGROUND AND PURPOSE: To assess the completeness and accuracy of stage and outcome data in the Anthology of Outcomes (AOs), a prospective point-of-care physician-collected electronic data system for patients at the Princess Margaret Hospital. MATERIAL AND METHODS: A random sample of 10% of the AO cases registered between July 2003 and December 2005 was drawn. An audit was conducted of the AO data compared with chart review and cancer registry. RESULTS: The AO system was applied first to a head and neck (HN) cancer patient cohort. From 1152 HN cases, 120 were audited. TNM stage was recorded in all cases. Discrepancy was found between the AO and primary data sources in 3-13% of cases. Physician review showed a 3% error rate in overall stage recorded in the AO. Sixty-two outcomes in 43 patients were found on chart review. No outcomes were incorrectly recorded in the AO. Nineteen (31%) outcomes in 17 patients were missed in the AO. CONCLUSIONS: Our experience has demonstrated the feasibility of real-time outcome recording at point-of-care. New processes needed to improve the completeness of capture of patient outcomes in the AO have more recently been introduced. This successful system has been expanded to other disease sites.

Cone-beam CT assessment of interfraction and intrafraction setup error of two head-and-neck cancer thermoplastic masks.

PURPOSE: To prospectively compare setup error in standard thermoplastic masks and skin-sparing masks (SSMs) modified with low neck cutouts for head-and-neck intensity-modulated radiation therapy (IMRT) patients. METHODS AND MATERIALS: Twenty head-and-neck IMRT patients were randomized to be treated in a standard mask (SM) or SSM. Cone-beam computed tomography (CBCT) scans, acquired daily after both initial setup and any repositioning, were used for initial and residual interfraction evaluation, respectively. Weekly, post-IMRT CBCT scans were acquired for intrafraction setup evaluation. The population random (sigma) and systematic (Sigma) errors were compared for SMs and SSMs. Skin toxicity was recorded weekly by use of Radiation Therapy Oncology Group criteria. RESULTS: We evaluated 762 CBCT scans in 11 patients randomized to the SM and 9 to the SSM. Initial interfraction sigma was 1.6 mm or less or 1.1 degrees or less for SM and 2.0 mm or less and 0.8 degrees for SSM. Initial interfraction Sigma was 1.0 mm or less or 1.4 degrees or less for SM and 1.1 mm or less or 0.9 degrees or less for SSM. These errors were reduced before IMRT with CBCT image guidance with no significant differences in residual interfraction or intrafraction uncertainties between SMs and SSMs. Intrafraction sigma and Sigma were less than 1 mm and less than 1 degrees for both masks. Less severe skin reactions were observed in the cutout regions of the SSM compared with non-cutout regions. CONCLUSIONS: Interfraction and intrafraction setup error is not significantly different for SSMs and conventional masks in head-and-neck radiation therapy. Mask cutouts should be considered for these patients in an effort to reduce skin toxicity.

Histologic assessment of peritumoral edema in soft tissue sarcoma.

PURPOSE: To evaluate whether satellite tumor cells can be identified histologically in the tissues surrounding a soft tissue sarcoma and whether their presence correlates with increased T(2)-weighted signal intensity on MRI. METHODS AND MATERIALS: Fifteen patients with a high-grade extremity or truncal soft tissue sarcoma underwent preoperative MRI. The extent of high T(2)-weighted signal changes in the tissues surrounding tumor, thought to represent peritumoral edema/reactive changes, was determined. Twelve patients received i.v. gadolinium, and contrast enhancement was determined. All patients underwent surgical resection in the absence of preoperative chemotherapy or radiotherapy. The presence of tumor cells in the surrounding tissues was determined histologically in representative paraffin-embedded sections and correlated with the MRI findings. RESULTS: The extent of peritumoral T(2)-weighted MRI signal changes ranged from 0 to 7.1 cm (mean, 2.5 cm); contrast enhancement ranged from 0 to 5.3 cm (mean, 1.1 cm). Sarcoma cells were identified histologically in the tissues beyond the tumor in 10 of 15 cases. In 6 cases, tumor cells were located within 1 cm of the tumor margin, and in 4 cases, malignant cells were found at a distance >1 cm and up to a maximum of 4 cm. The location of tumor cells beyond the margin did not correlate with tumor size nor did it correlate with the location or extent of peritumoral changes. CONCLUSION: The ability to identify tumor cells beyond the margin of a soft tissue sarcoma has important implications in planning appropriate targets for treatment. This could influence the use of new radiotherapy technologies such as intensity-modulated radiotherapy that aim to minimize treatment volumes through conformal planning.

Preoperative radiotherapy for adult head and neck soft tissue sarcoma: assessment of wound complication rates and cancer outcome in a prospective series.

Combination surgery and radiotherapy (RT) is frequently used in soft tissue sarcoma (STS). Because lower doses and smaller irradiation volumes are possible in preoperative RT (pre-op RT), this approach can be especially valuable in anatomic settings where critical organs are in close proximity to the RT target area. A recent multicenter phase III trial (SR.2 trial of the National Cancer Institute of Canada Clinical Trials Group) comparing pre-op RT against post-op RT for extremity STS has shown significantly higher major wound complication rates (35%) with pre-op RT. We postulated that wound complication rates may be less frequent in the head and neck with better vascularity and wider use of secondary wound reconstruction. Using a prospective database, we identified 40 consecutive patients with head and neck STS treated with pre-op RT (50 Gy) and subsequent (4 to 6 weeks later) resection between 1/89 and 8/99 in a single institution setting. Major wound complications (MWC) were classified by the identical criteria used in the SR.2 trial. Intracranial extension was evident in 5 patients, whereas 50% of the patients had large tumors (> 5 cm). Deep tumor was present in 34 (85%), and 6 (15%) were superficial to fascia. In this series, 31 patients (77.5%) had secondary reconstruction of the acquired soft tissue deficit. The actuarial 2-year local relapse-free rate was 80%, and the metastatic relapse-free rate was 85%. Major wound complications occurred in 8 of 40 patients (20%) within 120 days of surgery according to the SR.2 criteria: secondary wound surgery (3), readmission or prolonged hospital admission for wound care (2), deep packing (0), prolonged dressing changes (2), and invasive procedure for wound care (1). The latter was a minor wound management problem (a single outpatient drainage of a seroma) for the combined rate of 8/20 or 20%. Our findings show that (1) pre-op RT in head and neck STS is associated with lower rates of major wound complications compared to extremity cases; (2) pre-op RT provides high rates of local control in an adverse group of cases of adult head and neck STS; (3) the choice of scheduling of RT should be based on anatomic issues with emphasis on the trade-offs between RT doses and volumes versus wound morbidity for individual patients. This is especially important when tumor may be adjacent to critical head and neck structures which may be protected from the high-dose RT area.

Management and outcome differences in supraglottic cancer between Ontario, Canada, and the Surveillance, Epidemiology, and End Results areas of the United States.

PURPOSE: We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States. METHODS: Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis. RESULTS: Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P =.01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P =.40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P =.28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P =.10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P =.01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10(-3)). In stage III disease, the rates were 30% and 54%, respectively (P =.03), and in stage IV disease they were 33% and 64% (P =.002). CONCLUSION: There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.