Adherence to Guideline-Concordant Care and Its Effect on Survival in Black Patients with Head and Neck Cancers: A SEER-Medicare Analysis.

BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), Black patients continue to have worse survival when compared with White patients. The cause of this disparity is multifaceted and cannot be explained by one etiology alone. To investigate this disparity, we used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine adherence to guideline-concordant care (GCC) as defined by the National Comprehensive Cancer Network. PATIENTS AND METHODS: In this retrospective study, Medicare beneficiaries diagnosed with nonmetastatic HNSCC as their first cancer between 1992 and 2011 and a random sample of Medicare controls matched to cases (2:1) diagnosed between 2004 and 2011 (n = 16,378), were included in this analysis. RESULTS: Black patients were less likely to receive GCC in advanced-stage oropharyngeal (66% vs. 74%; p = .007) and oral cavity (56% vs. 71%; p = .002) squamous cell carcinoma (SCC). On multivariate analysis, Black patients demonstrated an increased risk of death in advanced oropharyngeal (p < .001), oral cavity (p = .01), and hypopharyngeal (p = .01) SCC. CONCLUSION: Black patients did not consistently receive GCC across HNSCC subsites, contributing to the poorer outcomes seen when compared with White patients. Future research should focus on elucidating the mechanisms behind the non-GCC given to Black patients with HNSCC and other factors that may contribute to this disparity such as tumor biology. IMPLICATIONS FOR PRACTICE: Black patients with head and neck cancer (HNC) continue to have worse survival than White patients. This study examined if the racial disparity in survival from curable HNC is affected by adherence to guideline-concordant care (GCC). It was discovered that Black patients were less likely to receive appropriate treatment in certain HNCs. Although adherence to proper therapy was associated with improved survival in patients with HNC, the difference in survival, where Black patients had inferior outcomes, remained. This analysis uncovered a major contributor to the disparity seen in patients with HNC. As such, cancer centers serving a predominantly Black population with HNC can design specific clinical interventions to ensure GCC for all patients, potentially improving outcomes for everyone.

Clinical outcomes of black vs. non-black patients with locally advanced non-small cell lung cancer.

OBJECTIVES: The black population remains underrepresented in clinical trials despite reports suggesting greater incidence and deaths from locally advanced non-small cell lung cancer (NSCLC). We determined outcomes for black and non-black patients in a well-annotated cohort treated with either definitive chemoradiation (CRT; bimodality) or CRT followed by surgery (trimodality therapy). MATERIALS AND METHODS: A retrospective analysis of 355 stage III NSCLC patients treated with curative intent at the University of Maryland, Medical Center, between January 2000-December 2013 was performed. The Kaplan-Meier approach and the Cox proportional hazards models were used to analyze overall survival (OS) and freedom-from-recurrence (FFR) in black and non-black patients. The chi-square test was used to compare categorical variables. RESULTS: Black patients comprised 42% of the cohort and were more likely to be younger (p<0.0001), male (p=0.030), single (p<0.0001), reside in lower household income zipcodes (p<0.0001), have an Eastern Cooperative Oncology Group (ECOG) performance status >0 (p<0.001), and less likely to undergo surgery (p<0.0001). With a median follow-up of 15 months for all patients and 89 months for surviving patients (range:1-186 months), median OS times for black and non-black patients were 22 and 24 months, respectively (p=0.698). FFR rates were also comparable between the two groups (p=0.468). Surgery improved OS in both cohorts. Race was not a significant predictor for OS or FFR even when adjusted for other factors. CONCLUSIONS: We found similar oncologic outcomes in black and non-black NSCLC patients when treated with curative intent in a comprehensive cancer center setting, despite epidemiologic differences in presentation and receipt of care. Future efforts to improve outcomes in black patients could focus on addressing modifiable social disparities.

Long-term results of a randomized trial in locally advanced rectal cancer: no benefit from adding a brachytherapy boost.

PURPOSE/OBJECTIVE(S): Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer. METHODS AND MATERIALS: Between March 2005 and November 2008, 248 patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions). The primary trial endpoint was pathologic complete response (pCR) at the time of surgery; secondary endpoints included overall survival (OS), progression-free survival (PFS), and freedom from locoregional failure. RESULTS: Results for the primary endpoint have previously been reported. This analysis presents survival data for the 224 patients in the Danish part of the trial. In all, 221 patients (111 control arm, 110 brachytherapy boost arm) had data available for analysis, with a median follow-up time of 5.4 years. Despite a significant increase in tumor response at the time of surgery, no differences in 5-year OS (70.6% vs 63.6%, hazard ratio [HR] = 1.24, P=.34) and PFS (63.9% vs 52.0%, HR=1.22, P=.32) were observed. Freedom from locoregional failure at 5 years were 93.9% and 85.7% (HR=2.60, P=.06) in the standard and in the brachytherapy arms, respectively. There was no difference in the prevalence of stoma. Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration. CONCLUSIONS: Despite increased pathologic tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery.

Phase I trial of pelvic nodal dose escalation with hypofractionated IMRT for high-risk prostate cancer.

PURPOSE: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5½ weeks. METHODS AND MATERIALS: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. RESULTS: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving ≥30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 ± 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. CONCLUSIONS: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose escalation may be an option in any future exploration of potential benefits of pelvic radiation therapy in high-risk prostate cancer patients.

Characterization of positron emission tomography hypoxia tracer uptake and tissue oxygenation via electrochemical modeling.

PURPOSE: Unique uptake and retention mechanisms of positron emission tomography (PET) hypoxia tracers make in vivo comparison between them challenging. Differences in imaged uptake of two common hypoxia radiotracers, [(61)Cu]Cu-ATSM and [(18)F]FMISO, were characterized via computational modeling to address these challenges. MATERIALS AND METHODS: An electrochemical formalism describing bioreductive retention mechanisms of these tracers under steady-state conditions was adopted to relate time-averaged activity concentration to tissue partial oxygen tension (PO(2)), a common metric of hypoxia. Chemical equilibrium constants of product concentration to reactant concentration ratios were determined from free energy changes and reduction potentials of pertinent reactions reported in the literature. Resulting transformation functions between tracer uptake and PO(2) were compared against measured values in preclinical models. Additionally, calculated PO(2) distributions from imaged Cu-ATSM tracer activity concentrations of 12 head and neck squamous cell carcinoma (HNSCC) patients were validated against microelectrode PO(2) measurements in 69 HNSCC patients. RESULTS: Both Cu-ASTM- and FMISO-modeled PO(2) transformation functions were in agreement with preclinical measured values within single-deviation confidence intervals. High correlation (r(2)=0.94, P<.05) was achieved between modeled PO(2) distributions and measured distributions in the patient populations. On average, microelectrode hypoxia thresholds (2.5 and 5.0 mmHg) corresponded to higher Cu-ATSM uptake [2.5 and 2.0 standardized uptake value (SUV)] and lower FMISO uptake (2.0 and 1.4 SUV). Uncertainties in the models were dominated by variations in the estimated specific activity and intracellular acidity. CONCLUSIONS: Results indicated that the high dynamic range of Cu-ATSM uptake was representative of a narrow range of low oxygen tension whose values were dependent on microenvironment acidity, while FMISO uptake was representative of a wide range of PO(2) values that were independent of acidity. The models shed light on possible causes of these discrepancies, particularly as it pertains to image contrast, and may prove to be a useful methodology in quantifying relationships between other hypoxia tracers. Comprehensive and robust assessment of tumor hypoxia prior to as well as in response to therapy may be best provided by imaging of multiple hypoxia markers that provide complementary rather than interchangeable information.

Major late toxicities after conformal radiotherapy for nasopharyngeal carcinoma-patient- and treatment-related risk factors.

PURPOSE: To retrospectively analyze the factors affecting late toxicity for nasopharyngeal carcinoma. METHODS AND MATERIALS: Between 1998 and 2003, 422 patients were treated with a conformal technique with 2-Gy daily fractions to a total dose of 70 Gy. Conventional fractionation (5 fractions weekly) was used in 232 patients and accelerated fractionation (6 fractions weekly) in 190 patients. One hundred seventy-one patients were treated with the basic radiotherapy course alone (Group 1), 55 patients had an additional boost of 5 Gy in 2 fractions (Group 2), and 196 patients underwent concurrent cisplatin-based chemotherapy (Group 3). RESULTS: The 5-year overall toxicity rate was significantly greater in Group 3 than in Group 1 (37% vs. 27%, p = 0.009). Although the overall rate in Group 2 was not elevated (28% vs. 27%, p = 0.697), a significant increase in temporal lobe necrosis was observed (4.8% vs. 0%, p = 0.015). Multivariate analyses showed that age and concurrent chemotherapy were significant factors. The hazard ratio of overall toxicity attributed to chemotherapy was 1.99 (95% confidence interval, 1.32-2.99, p = 0.001). The mean radiation dose to the cochlea was another significant factor affecting deafness, with a hazard ratio of 1.03 (95% confidence interval, 1.01-1.05, p = 0.005) per 1-Gy increase. The cochlea that received >50 Gy had a significantly greater deaf rate (Group 1, 18% vs. 7%; and Group 3, 22% vs. 14%). CONCLUSION: The therapeutic margin for nasopharyngeal carcinoma is extremely narrow, and a significant increase in brain necrosis could result from dose escalation. The significant factors affecting the risk of deafness included age, concurrent chemoradiotherapy, and greater radiation dose to the cochlea.

Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group.

Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.