Does the frequency of routine follow-up after curative treatment for head-and-neck cancer affect survival?

Background: Routine follow-up is a cornerstone of oncology practice, but evidence to support most aspects of follow-up is lacking. Our objective was to investigate the relationship between frequency of routine follow-up and survival. Methods: This population-based study used electronic health care data relating to 5310 patients from Ontario diagnosed with squamous-cell head-and-neck cancer during 2007-2012. Treatments included surgery (24.6%), radiotherapy with or without chemotherapy (52.4%), and combined surgery and radiotherapy (23%). We determined the oncologist who was following each patient after treatment; calculated the average follow-up visits to the oncologist during the subsequent 2.5 years for all patients who were doing well; and used Kaplan-Meier and multiple variable regression analysis to compare, by treatment, overall survival for patients in the high, typical, and low follow-up oncologist groups. Results: Many oncologists saw patients 40%-80% more often than other oncologists did. No relationship of appointment frequency with survival was observed for patients in any treatment group. Conclusions: The practice of routine follow-up varies and is costly both to a health care system and to patients. Without evidence about the effectiveness of current policies, further research is required to investigate new or optimal practices.

Variation in routine follow-up care after curative treatment for head-and-neck cancer: a population-based study in Ontario.

Background: The actual practices of routine follow-up after curative treatment for head-and-neck cancer are unknown, and existing guidelines are not evidence-based. Methods: This retrospective population-based study used administrative data to describe 5 years of routine follow-up care in 3975 head-and-neck cancer patients diagnosed between 2007 and 2012 in Ontario. Results: The mean number of visits per year declined during the follow-up period (from 7.8 to 1.9, p < 0.001). The proportion of patients receiving visits in concordance with guidelines ranged from 80% to 45% depending on the follow-up year. In at least 50% of patients, 1 head, neck, or chest imaging test was performed in the first follow-up year; that proportion subsequently declined (p < 0.001). Factors associated with follow-up practices included comorbidity, tumour site, treatment, geographic region, and physician specialty (p < 0.05). Conclusions: Given current practice variation and the absence of an evidence-based standard, the challenge in identifying a single optimal follow-up strategy might be better addressed with a harmonized approach to providing individualized follow-up care.

Symptom appraisal, help seeking, and lay consultancy for symptoms of head and neck cancer.

OBJECTIVE: Early diagnosis is important in head and neck cancer (HNC) patients to maximize the effectiveness of the treatments and minimize the debilitation associated with both the cancer and the invasive treatments of advanced disease. Many patients present with advanced disease, and there is little understanding as to why. This study investigated patients' symptom appraisal, help seeking, and lay consultancy up to the time they first went to see a health care professional (HCP). METHODS: We interviewed 83 patients diagnosed with HNC. The study design was cross sectional and consisted of structured telephone interviews and a medical chart review. We gathered information on the participant's personal reactions to their symptoms, characteristics of their social network, and the feedback they received. RESULTS: We found that 18% of the participants thought that their symptoms were urgent enough to warrant further investigation. Participants rarely (6%) attributed their symptoms to cancer. Eighty-nine percent reported that they were unaware of the early warning signs and symptoms of HNC. Fifty-seven percent of the participants disclosed their symptoms to at least one lay consultant before seeking help from an HCP. The lay consultants were usually their spouse (77%), and the most common advice they offered was to see a doctor (76%). Lastly, 81% of the participants report that their spouse influenced their decision to see an HCP. CONCLUSIONS: The results of this study suggest that patients frequently believe that their symptoms were nonurgent and that their lay consultants influence their decision to seek help from an HCP.

Surgery for diverticular disease results in a higher hernia rate compared to colorectal cancer: a population-based study from Ontario, Canada.

BACKGROUND: Incisional hernias are a well described complication of abdominal surgery. Previous studies identified malignancy and diverticular disease as risk factors. We compared incisional hernia rates between colon resection for colorectal cancer (CRC) and diverticular disease (DD). STUDY DESIGN: We performed a retrospective, population-based, matched cohort study. Provincial databases were linked through the Institute for Clinical Evaluative Sciences. These databases include all patients registered under the universal Ontario Health Insurance Plan. Patients aged 18-105 undergoing open colon resection, without ostomy formation between April 1, 2002 and March 31, 2009, were included. We excluded those with previous surgery, hernia, obstruction, and perforation. The primary outcomes were surgery for hernia repair, or diagnosis of hernia in clinic. RESULTS: We identified 4660 cases of DD. These were matched 2:1 by age and gender to 8933 patients with CRC for a total of 13,593. At 5 years, incisional hernias occurred in 8.3% of patients in the CRC cohort, versus 13.1% of those undergoing surgery for DD. After adjusting for important confounders (comorbidity score, wound infection, age, diabetes, prednisone and chemotherapy), hernias were still more likely in patients with DD [HR 1.58, 95% Confidence Interval (CI) 1.43-1.76, P < 0.001]. The only significant covariate was wound infection (HR 1.63, 95% CI 1.43-1.87, P < 0.001). CONCLUSION: Our study found that incisional hernias occur more commonly in patients with DD than CRC.

The cost of a patient activation intervention for achieving successful outcomes: results from the PAADRN randomized controlled trial.

In a large, pragmatic clinical trial, we calculated the costs of achieving four successful patient-centered outcomes using a tailored patient activation DXA result letter accompanied by a bone health brochure. The cost to achieve one successful outcome (e.g., a 0.5 standard deviation improvement in care satisfaction) ranged from $127.41 to $222.75. INTRODUCTION: Pragmatic randomized controlled trials (RCTs) should focus on patient-centered outcomes and report the costs for achieving those outcomes. We calculated per person incremental intervention costs, the number-needed-to-treat (NNT), and incremental per patient costs (cost per NNT) for four patient-centered outcomes in a direct-to-patient bone healthcare intervention. METHODS: The Patient Activation after DXA Result Notification (PAADRN) pragmatic RCT enrolled 7749 patients presenting for DXA at three health centers between February 2012 and August 2014. Interviews occurred at baseline and 52 weeks post-DXA. Intervention subjects received an individually tailored DXA result letter accompanied by an educational bone health brochure 4 weeks post-DXA, while the usual care subjects did not. Outcomes focused on patients (a) correctly identifying their results, (b) contacting their providers, (c) discussing their results with their providers, and (d) satisfaction with their bone healthcare. NNTs were determined using intention-to-treat linear probability models, per person incremental intervention costs were calculated, and costs per NNT were computed. RESULTS: Mean age was 66.6 years old, 83.8% were women, and 75.3% were non-Hispanic whites. The incremental per patient cost (costs per NNT) to increase the ability of a patient to (a) correctly identify their DXA result was $171.07; (b) contact their provider about their DXA result was $222.75; (c) discuss their DXA result with their provider was $193.55; and (d) achieve a 0.5 SD improvement in satisfaction with their bone healthcare was $127.41. CONCLUSION: An individually tailored DXA result letter accompanied by an educational brochure can improve four patient-centered outcomes at a modest cost. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01507662.

Corrigendum: Did the addition of concomitant chemotherapy to radiotherapy improve outcomes in hypopharyngeal cancer? A population-based study.

[This corrects the article on p. 266 in vol. 23, PMID: 27536177.].

Did the addition of concomitant chemotherapy to radiotherapy improve outcomes in hypopharyngeal cancer? A population-based study.

BACKGROUND: For oncologists and for patients, no site-specific clinical trial evidence has emerged for the use of concurrent chemotherapy with radiotherapy (ccrt) over radiotherapy (rt) alone for cancer of the hypopharynx (hpc) or for other human papilloma virus-negative head-and-neck cancers. METHODS: This retrospective population-based cohort study using administrative data compared treatments over time (1990-2000 vs. 2000-2010), treatment outcomes, and outcomes over time in 1333 cases of hpc diagnosed in Ontario between January 1990 and December 2010. RESULTS: The incidence of hpc is declining; the use of ccrt that began in 2001 is increasing; and the 3-year overall survival for all patients remains poor at 34.6%. No difference in overall survival was observed in a comparison of patients treated in the decade before ccrt and of patients treated in the decade during the uptake of ccrt. CONCLUSIONS: The addition of ccrt to the armamentarium of treatment options for oncologists treating head-and-neck patients did not improve outcomes for hpc at the population level.

Patient-activation and guideline-concordant pharmacological treatment after bone density testing: the PAADRN randomized controlled trial.

Patients often do not know or understand their bone density test results, and pharmacological treatment rates are low. In a clinical trial of 7749 patients, we used a tailored patient-activation result letter accompanied by a bone health brochure to improve appropriate pharmacological treatment. Treatment rates, however, did not improve. INTRODUCTION: Patients often do not know or understand their dual-energy x-ray absorptiometry (DXA) test results, which may lead to suboptimal care. We tested whether usual care augmented by a tailored patient-activation DXA result letter accompanied by an educational brochure would improve guideline-concordant pharmacological treatment compared to usual care only. METHODS: We conducted a randomized, controlled, double-blinded, pragmatic clinical trial at three health care centers in the USA. We randomized 7749 patients ≥50 years old and presenting for DXA between February 2012 and August 2014. The primary clinical endpoint at 12 and 52 weeks post-DXA was receiving guideline-concordant pharmacological treatment. We also examined four of the steps along the pathway from DXA testing to that clinical endpoint, including (1) receiving and (2) understanding their DXA results and (3) having subsequent contact with their provider and (4) discussing their results and options. RESULTS: Mean age was 66.6 years, 83.8 % were women, and 75.3 % were non-Hispanic whites. Intention-to-treat analyses revealed that guideline-concordant pharmacological treatment was not improved at either 12 weeks (65.1 vs. 64.3 %, p = 0.506) or 52 weeks (65.2 vs. 63.8 %, p = 0.250) post-DXA, even though patients in the intervention group were more likely (all p < 0.001) to recall receiving their DXA results letter at 12 weeks, correctly identify their results at 12 and 52 weeks, have contact with their provider at 52 weeks, and have discussed their results with their provider at 12 and 52 weeks. CONCLUSION: A tailored DXA result letter and educational brochure failed to improve guideline-concordant care in patients who received DXA.

Adherence to and uptake of clinical practice guidelines: lessons learned from a clinical practice guideline on chemotherapy concomitant with radiotherapy in head-and-neck cancer.

BACKGROUND: Clinical practice guidelines (cpgs) are systematically developed statements designed to assist practitioners and patients in making decisions about appropriate heath care interventions. Clinical practice guidelines are expensive and time-consuming to create. A cpg on concurrent chemotherapy with radiation therapy (ccrt) was developed in Ontario at a time when treatment approaches for head-and-neck cancer were changing significantly. METHODS: An assessment of treatments and outcomes based on electronic and chart data obtained from a population-based study of 571 patients with oropharynx cancer treated in Ontario (2003-2004) was combined with a review of relevant knowledge transfer (publications and presentations at major meetings) to understand variation in adherence to a cpg. RESULTS: In 9 Ontario cancer treatment centres, ccrt was used for 55% of all patients with oropharyngeal cancer; however, at the centres individually, that proportion ranged from 82% to 39%. Furthermore, there was no agreement on the chemotherapy regimen: 2-4 years later (a period during which newer regimens were emerging), only 4 of 9 centres were following the guideline for most patients. When outcomes of treated patients were compared for centres with "higher" and "lower" use of ccrt, no difference in survival was observed (p = 0.64). CONCLUSIONS: At a time of treatment evolution, the new guideline was controversial, and there are many reasons for the mixed adherence. An estimation of adherence should be included during both development and review of guidelines.

A comparison of published head and neck stage groupings in carcinomas of the tonsillar region.

BACKGROUND: The combination of T, N, and M classifications into stage groupings was designed to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. The authors tested the UICC/AJCC 5th edition stage grouping and seven other TNM-based groupings proposed for head and neck cancer to determine their ability to meet these expectations in a specific site: carcinoma of the tonsillar region. METHODS: The authors defined four criteria to assess each stage grouping scheme: 1) The subgroups defined by T and N comprising a given group within a grouping scheme have similar survival rates (hazard consistency); 2) The survival rates differ across the groups (hazard discrimination); 3) The prediction of cure is high (outcome prediction); and 4) The distribution of patients among the groups is balanced. The authors identified or derived a measure for each criterion and the findings were summarized using a scoring system. The range of scores was from 0 (best) to 7 (worst). Data were from a retrospective chart review on 642 cases of carcinoma of the tonsillar region treated with radiotherapy for cure at the Princess Margaret Hospital from 1970-1991. None of the patients had distant metastases. RESULTS: The scheme proposed by Synderman and Wagner, which was published in Otolaryngology Head and Neck Surgery in 1995 (vol.112, pages 691-4), scored best at 1.2. The UICC/AJCC scheme scored worst at 6.1. The hazard consistency ranged from a 3.1% average survival difference to 6.7% across the 8 schemes. The hazard discrimination measure varied by 28% from the best to worst scheme. Prediction varied by up to almost twofold across the schemes assessed. The distribution of patients varied from expected by between 0.13% and 0.57%. CONCLUSION: UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform as well as any of seven empirically-derived schemes the authors evaluated. The results of the current study suggest that the usefulness of the TNM system can be enhanced by optimizing the design of stage groupings through empirical investigation.

Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release.

Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not.

A comparison of published head and neck stage groupings in carcinomas of the oral cavity.

BACKGROUND: The combination of T, N, and M classifications into stage groupings is meant to facilitate a number of activities, including the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. We tested the UICC/AJCC 5th edition stage grouping and seven other TNM-based groupings proposed for head and neck cancer for their ability to meet these expectations in a specific site: carcinomas of the oral cavity. METHODS: We defined four criteria to assess each grouping scheme: (1) the subgroups defined by T, N, and M that make up a given group within a grouping scheme have similar survival rates (hazard consistency); (2) the survival rates differ among the groups (hazard discrimination); (3) the prediction of cure is high (outcome prediction); and (4) the distribution of patients among the groups is balanced. We identified or derived a measure for each criterion, and the findings were summarized by use of a scoring system. The range of scores was from 0 (best) to 7 (worst). The data are population based from a prospectively gathered series in Southern Norway, with 556 patients diagnosed from 1983 through 1995. Clinical stage assignment was used, and the outcome of interest was cause-specific survival. RESULTS: Summary scores across the eight schemes ranged from 1.66 for TANIS-3 to 6.50 for UICC/AJCC-5. The TANIS-7 staging scheme performed best on the hazard consistency criterion. The Kiricuta scheme performed best on the hazard discrimination criterion. Synderman predicted outcome best overall and Berg produced the most balanced distribution of cases among its groups. CONCLUSIONS: UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform as well as any of seven empirically derived schemes we evaluated. Our results suggest that the usefulness of the TNM system could be enhanced by optimizing the design of stage groupings through empirical investigation.

Time to first relapse as an outcome and a predictor of survival in patients with squamous cell carcinoma of the head and neck.

OBJECTIVE: To identify patterns and predictors of relapse and to determine whether the time to relapse influences survival. STUDY DESIGN: Multivariate anal. ysis of prospective database. METHODS: We present findings in 446 consecutive prospective patients from a regional cancer center with invasive squamous cell carcinoma who were treated for cure and were declared disease free. Time to relapse, site of relapse, and survival are reported by stage and site using bivariate and multivariate analysis. RESULTS: Thirty-six percent of patients relapsed. The median time to relapse was 8.3 months, and 95% of relapses occurred within 3 years. T stage in the TNM staging system was associated with relapse, and N stage was not. In patients who relapsed before the median time to relapse, prognosis was worse than in those who relapsed after that time.

The impact of comorbidity on the survival of patients with squamous cell carcinoma of the head and neck.

BACKGROUND: In North America, cigarette smoking and/or alcohol consumption not only cause head and neck cancer, they also cause many of the other diseases, illnesses, and conditions, also known as comorbidities, frequently found in our patients. Comorbidities can influence treatment decision making and treatment outcome. The aim of this study is to quantify the increased risk of comorbidity in our patients. METHOD: The survival of 655 consecutive patients with squamous cell carcinoma from a regional cancer center is analyzed. We compare the survival curves for all-cause death, death from cancer, and death from noncancer causes to the expected survival of age/sex-matched populations of Ontario residents, Canadian smokers, and Canadian nonsmokers. RESULTS: Of those patients who had not survived 5 years, 59% died of their index tumor, 23% would have been expected to die if they did not have head and neck cancer, and 18% died of the increased comorbidity associated with being a patient with head and neck cancer. DISCUSSION: Comorbidity, and specifically the increased comorbidity found in patients with head and neck cancer, is an important factor in overall survival.

Management and outcome of glottic cancer: a population-based comparison between Ontario, Canada and the SEER areas of the United States. Surveillance, Epidemiology and End Results.

OBJECTIVE: We compared treatment practice and outcome in glottic cancer in Ontario, Canada to that in the Surveillance, Epidemiology and End Results (SEER) program areas in the United States to determine whether the Ontario emphasis on the use of delayed combined therapy was associated with similar survival and better laryngectomy-free survival than the U.S. approach, which emphasizes greater use of surgery. METHODS: Electronic, clinical, and hospital data were linked to cancer registry data. The study groups compared on survival comprised all patients diagnosed from 1982 to the end of 1991 in Ontario (2324 patients) and in the SEER areas (5715 patients). Comparisons on initial treatment, laryngectomy rates, and laryngectomy-free survival were limited to subsets of these study populations due to data availability. Initial treatment data were provided by the SEER registries in the U.S. and by the cancer clinic and hospitalization data in Ontario. Information about laryngectomies performed subsequent to initial treatment was available from Medicare hospitalization data in the U.S. and from Canadian Institute for Health Information hospitalization data in Ontario. RESULTS: Although radiotherapy was the most common initial treatment in both areas, it was used more often in Ontario (84.4% versus 63.2% in the U.S. [p < 0.001]). Relative survival was not statistically different with a relative risk comparing SEER to Ontario of 1.09, 95% confidence interval (CI) (0.93, 1.29). Laryngectomy rates were similar with a relative risk of 1.01, 95% CI (0.67, 1.52), and it follows from the survival and laryngectomy rate comparisons that the laryngectomy-free survival was not statistically different (p = .95). CONCLUSIONS: There are large differences in the management of glottic cancer between the U.S. and Ontario and no corresponding differences in survival or laryngectomy-free survival. This work highlights a need for more clinical investigation into the relative merits of differing management policies in glottic cancer.

Cancers of the upper aerodigestive tract in Ontario, Canada, and the United States.

BACKGROUND: Squamous cancers of the upper aerodigestive tract (UADT) are related to the use of tobacco and/or alcohol, and in North America they are more common among the poor. They are usually locoregionally confined at diagnosis, and local treatment with surgery and/or radiation therapy is often curative. This study compares the incidence and survival of this group of diseases in Canada and the U.S., two North American neighbors with many cultural similarities but significant differences in their health care and social programs. METHODS: To describe and compare the case mix, incidence, and outcome of squamous cancers of the UADT in Ontario, Canada, and the U.S., we used the Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology, and End Results (SEER) registries in the U.S. to identify all cases of cancer with International Classification of Disease (ICD) codes 141, 143-9, 160-1, and a subset of 140, which were diagnosed between 1982 and 1994. ICD-O histology codes were placed into clinically relevant groupings, and ICD-9 site codes were grouped into sites as defined by the International Union Against Cancer and the American Joint Committee on Cancer. Age-adjusted incidence rates were calculated for each site. For the SEER registry, race specific incidence rates were also calculated. Observed and expected survival were plotted by site and registry, and from these, relative survival was calculated. Survival was compared during the first 5 years after diagnosis and during the next 5 years among patients who had survived the first 5 years. RESULTS: Of the 16,577 and 42,990 cases identified in the OCR and SEER registries, respectively, squamous cancer was by far the most common histology (94.1% in OCR, 94.6% in SEER) and will form the main subject of this report. The distribution of squamous cancers by site, subsite, age, and gender were remarkably similar in the two populations. Overall, the incidence was about 17% higher in the U.S. than in Ontario, and this difference was seen for all sites except the nasopharynx, which was more common in Ontario. The higher incidence in the U.S. in part reflects the much higher rate for African Americans than for Americans of other ethnic backgrounds. During the first 5 years after diagnosis, when most deaths from UADT cancer occur, there was a significant relative survival difference in favor of the U.S. for cancer of the supraglottis, and in favor of Ontario for cancer of the oral cavity. There was a nonsignificant trend in favor of Ontario for cancer of the nasopharynx. Within the SEER population, for all sites except the nasopharynx, 5-year relative survival was considerably worse for African Americans than for Americans of other ethnic backgrounds. Examination of survival beyond 5 years after diagnosis for patients who had survived the first 5 years revealed that for all sites, the observed survival continued to diverge markedly from the expected survival. The excess mortality ranged from less than 20% for glottic and nasopharyngeal cancers to about 30-40% for oropharyngeal and supraglottic cancers. CONCLUSIONS: Despite remarkable similarities in case mix between the two countries, UADT cancers were more frequent in the SEER population of the U.S. than in Ontario, and this was partly attributable to the much higher incidence among African Americans. Significant differences between the registries in 5-year survival were seen for several sites. African Americans with UADT cancers had much worse prognoses than did Americans of other ethnic backgrounds. Patients who survive their UADT cancer remain at a higher-than-expected risk of death even after they have been cured.

Using TNM staging to predict survival in patients with squamous cell carcinoma of head & neck.

BACKGROUND: There is a need for a classification system for prognosis based on the TNM system for patients with squamous cell carcinoma of the head and neck such that patient groupings are homogeneous within and heterogeneous between. METHODS: Six hundred fifty-five consecutive patients with invasive squamous cell carcinoma of the head and neck followed prospectively are split into a training set and a test set. Using the training set, the Cox Proportional Hazards Model and the outcome of dead with disease, we created homogeneous prognostic levels (PLs) based on RR. Using the test set, we compare our model to others in the literature. RESULTS: Using the training set, we identified five PLs, and using the test set, we demonstrated that our model is superior to others for both within-group homogeneity and between-group heterogeneity. CONCLUSIONS: A simple classification system can be used to group patients for survival and is valid for future study in prognostication.

Using the TNM system to predict survival in squamous cell carcinoma of the head and neck.

PURPOSE: To create a classification system for prognosis based on the TNM system for patients with squamous cell carcinoma of the Head and Neck such that patient groupings are homogeneous within and heterogenous between. METHOD: 655 consecutive patients with invasive squamous cell carcinoma of the Head and Neck followed prospectively are split into a training set and a test set. Using the training set, the Cox Proportional Hazards Model and the outcome of dead with disease, we create homogenous prognostic levels based on relative risk. Using the test set, we compare our model to others in the literature. RESULTS: Using the training set we identify 5 prognostic levels and using the test set we demonstrate that our model is superior to others for both within group homogeneity and between group heterogeneity. CONCLUSIONS: A simple classification system can be used to group patients for survival and is valid for future study in prognostication.