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Both the American Joint Committee on Cancer (AJCC) and Musculoskeletal Tumor Society (MSTS) staging systems for skeletal sarcomas have major weaknesses. A revised staging system for osteosarcoma (the Vanderbilt system) was developed based on exploratory analyses of the relative prognostic impacts of histologic grade, tumor size, local tumor extension, and specific anatomic sites of metastasis using case records from the National Cancer Database (N = 4,285). AJCC, MSTS, and Vanderbilt staging schemes were then compared using a separate, population-based cancer registry (the Surveillance, Epidemiology, and End Results database; N = 2,246) as a validation dataset. Predictive accuracy for 5-year sarcoma-specific survival was evaluated by comparing areas under receiver-operating characteristic curves generated from logistic regression. Three different concordance indices and Bayesian information criteria were also calculated for model comparisons. The Vanderbilt staging system showed comparable predictive accuracy for 5-year disease-specific survival (65%) compared to the AJCC (67%) and MSTS (67%) staging systems. Most cross-comparisons of model concordance were not significantly different either. Bayesian information criterion was lowest for the MSTS staging system. Substaging osteosarcoma by current anatomical criteria is ineffectual. A simplified staging system based only on histologic grade and the presence of distant metastasis to any anatomic site performs similarly to the current AJCC and MSTS staging systems by multiple statistical criteria and is proposed for clinical and pathological staging of osteosarcomas of the non-pelvic appendicular and non-spinal axial skeleton. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2802-2808, 2018.
© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
The AJCC recently published the 8th edition of its cancer staging system. Significant changes were made to the staging algorithm for soft tissue sarcoma (STS) of the extremities or trunk, including the addition of 2 additional T (size) classifications in lieu of tumor depth and grouping lymph node metastasis (LNM) with distant metastasis as stage IV disease. Whether these changes improve staging system performance is questionable. This retrospective cohort analysis of 21,396 adult patients with STS of the extremity or trunk in the SEER database compares the AJCC 8th edition staging system with the 7th edition and a newly proposed staging algorithm using a variety of statistical techniques. The effect of tumor size on disease-specific survival was assessed by flexible, nonlinear Cox proportional hazard regression using restricted cubic splines and fractional polynomials. The slope of covariate-adjusted log hazards for sarcoma-specific survival decreases for tumors >8 cm in greatest dimension, limiting prognostic information contributed by the new T4 classification in the AJCC 8th edition. Anatomic depth independently provides significant prognostic information. LNM is not equivalent to distant, non-nodal metastasis. Based on these findings, an alternative staging system is proposed and demonstrated to outperform both AJCC staging schemes. The analyses presented also disclose no evidence of improved clinical performance of the 8th edition compared with the previous edition. The AJCC 8th edition staging system for STS is no better than the previous 7th edition. Instead, a proposed staging system based on histologic grade, tumor size, and anatomic depth shows significantly higher predictive accuracy, with higher model concordance than either AJCC staging system. Changes to existing staging systems should improve the performance of prognostic models. Until such improvements are documented, AJCC committees should refrain from modifying established staging schemes.
Copyright © 2018 by the National Comprehensive Cancer Network.
BACKGROUND - The American Joint Committee on Cancer (AJCC) recently published the 8th edition of the AJCC Cancer Staging Manual. Major changes were made to the staging algorithm for retroperitoneal sarcoma; however, whether these changes improve staging system performance is questionable.
METHODS - This retrospective cohort analysis of 3703 adult patients with retroperitoneal sarcoma in the Surveillance, Epidemiology, and End Results (SEER) database compares a novel staging system incorporating histologic subtype of sarcoma with current and prior AJCC soft tissue sarcoma staging systems using multiple statistical techniques. The effect of tumor size on sarcoma-specific survival was also assessed by flexible, non-linear Cox proportional hazard regression using restricted cubic splines and fractional polynomials.
RESULTS - The relationship between the covariate-adjusted log hazard for disease-specific survival and tumor size is non-linear. Although the new AJCC T classification approximates this hazard fairly well, the overall prognostic impact of tumor size is limited after accounting for other predictive factors. Predictive accuracy and concordance indices of the AJCC 8th edition staging system for retroperitoneal sarcoma are significantly lower than the prior 7th edition. A proposed staging system incorporating histologic grade, tumor size, and histologic subtype is superior to both the AJCC 7th and 8th editions in predicting sarcoma-specific survival.
CONCLUSION - AJCC committees should not revise tumor staging algorithms unless the changes actually improve the staging system. A proposed staging scheme incorporating data regarding histologic subtype of sarcoma performs significantly better than both the 7th and 8th AJCC staging systems.
BACKGROUND & AIMS - We evaluated differences in treatment of black vs white patients with colon cancer and assessed their effects on survival, based on cancer stage.
METHODS - We collected data from the Surveillance, Epidemiology, and End Results-Medicare database and identified 6190 black and 61,951 white patients with colon cancer diagnosed from 1998 through 2009 and followed up through 2011. Three sets of 6190 white patients were matched sequentially, using a minimum distance strategy, to the same set of 6190 black patients based on demographic (age; sex; diagnosis year; and Surveillance, Epidemiology, and End Results registry), tumor presentation (demographic plus comorbidities, tumor stage, grade, and size), and treatment (presentation plus therapies) variables. We conducted sensitivity analyses to explore the effects of socioeconomic status in a subcohort that included 2000 randomly selected black patients. Racial differences in treatment were assessed using a logistic regression model; their effects on racial survival disparity were evaluated using the Kaplan-Meier method and the Cox proportional hazards model.
RESULTS - After patients were matched for demographic variables, the absolute 5-year difference in survival between black and white patients was 8.3% (white, 59.2% 5-y survival; blacks, 50.9% 5-y survival) (P < .0001); this value decreased significantly, to 5.0% (P < .0001), after patients were matched for tumor presentation, and decreased to 4.9% (P < .0001) when patients were matched for treatment. Differences in treatment therefore accounted for 0.1% of the 8.3% difference in survival between black and white patients. After patients were matched for tumor presentation, racial disparities were observed in almost all types of treatment; the disparities were most prominent for patients with advanced-stage cancer (stages III or IV, up to an 11.1% difference) vs early stage cancer (stages I or II, up to a 4.3% difference). After patients were matched for treatment, there was a greater reduction in disparity for black vs white patients with advanced-stage compared with early-stage cancer. In sensitivity analyses, the 5-year racial survival disparity was 7.7% after demographic match, which was less than the 8.3% observed in the complete cohort. This reduction likely was owing to the differences between the subcohort and the complete cohort in those variables that were not included in the demographic match. This value was reduced to 6.5% (P = .0001) after socioeconomic status was included in the demographic match. The difference decreased significantly to 2.8% (P = .090) after tumor presentation match, but was not reduced further after treatment match.
CONCLUSIONS - We observed significant disparities in treatment and survival of black vs white patients with colon cancer. The disparity in survival appears to have been affected more strongly by tumor presentation at diagnosis than treatment. The effects of treatment differences on disparities in survival were greater for patients with advanced-stage vs early-stage cancer.
Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
BACKGROUND - The incidence of secondary malignancies is increased in patients with malignant and premalignant conditions. Although neuroendocrine tumors (NET) are uncommon, their incidence is increasing. We evaluated the rate of additional malignancies in patients with NET.
METHODS - Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified a cohort of patients with pancreatic NET (PNET) or gastrointestinal NET (GINET). We determined the incidence of additional cancers diagnosed either before or after the diagnosis of PNET or GINET, by comparing these rates with the general population. Using multivariable regression, we evaluated factors that increased the risk of an additional malignancy.
RESULTS - A cohort of 9,727 NET patients was identified. A total of 3,086 additional cancers occurred in 2,508 patients (25.8 %). The most common sites of additional malignancies included colorectal (21.1 %), prostate (14.5 %), breast (13.3 %), and lung (11.6 %). Among patients with PNET, the incidence of breast, lung, uterine, lymph, and pancreatic cancers was less than expected in the general population, whereas in patients with GINET, the observed incidence of nearly all malignancies exceeded that expected. Increasing age, marital status, and localized NET were associated with increased risk.
CONCLUSION - Our study shows that the incidence of additional malignancies in patients with PNET and GINET is 25.8 %. Patients with GINET are at increased risk of additional malignancies, whereas patients with PNET have a decreased risk compared with the general population. More vigilant surveillance for secondary malignancies should be performed in patients with GINET. Studies investigating potential etiologic oncogenic pathways are warranted.
OBJECTIVES - The population-level incidence of vocal fold paralysis after thyroidectomy for well-differentiated thyroid carcinoma (WDTC) is not known. This study aimed to measure longitudinal incidence of postoperative vocal fold paralyses and need for directed interventions in the Medicare population undergoing total thyroidectomy for WDTC.
STUDY DESIGN - Retrospective cohort study.
SETTING - US population.
SUBJECTS AND METHODS - Subjects were Medicare beneficiaries. SEER-Medicare data (1991-2009) were used to identify beneficiaries who underwent total thyroidectomy for WDTC. Incident vocal fold paralyses and directed interventions were identified. Multivariate analyses were used to determine factors associated with odds of developing these surgical complications.
RESULTS - Of 5670 total thyroidectomies for WDTC, 9.5% were complicated by vocal fold paralysis (8.2% unilateral vocal fold paralysis [UVFP]; 1.3% bilateral vocal fold paralysis [BVFP]). Rate of paralyses decreased 5% annually from 1991 to 2009 (odds ratio 0.95; 95% confidence interval, 0.93-0.97; P < .001). Overall, 22% of patients with vocal fold paralysis required surgical intervention (UVFP 21%, BVFP 28%). Multivariate logistic regression revealed that the odds of postthyroidectomy paralysis increased with each additional year of age, with non-Caucasian race, with particular histologic types, with advanced stage, and in particular registry regions.
CONCLUSION - Annual rates of postthyroidectomy vocal fold paralyses are decreasing among Medicare beneficiaries with WDTC. High incidence in this aged population is likely due to a preponderance of temporary paralyses, which is supported by the need for directed intervention in less than a quarter of affected patients. Further population-based studies are needed to refine the population incidence and risk factors for paralyses in the aging population.
In the United States, renal cell carcinoma (RCC) has rapidly increased in incidence for over two decades. The most common histologic subtypes of RCC, clear cell, papillary, and chromophobe have distinct genetic and clinical characteristics; however, epidemiologic features of these subtypes have not been well characterized, particularly regarding any associations between race, disease subtypes, and recent incidence trends. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we examined differences in the age-adjusted incidence rates and trends of RCC subtypes, including analysis focusing on racial differences. Incidence rates increased over time (2001-2009) for all three subtypes. However, the proportion of white cases with clear cell histology was higher than among blacks (50% vs. 31%, respectively), whereas black cases were more likely than white cases to have papillary RCC (23% vs. 9%, respectively). Moreover, papillary RCC incidence increased more rapidly for blacks than whites (P < 0.01) over this period. We also observed that increased incidence of papillary histology among blacks is not limited to the smallest size strata. We observed racial differences in proportionate incidence of RCC subtypes, which appear to be increasing over time; this novel finding motivates further etiologic, clinical, molecular, and genetic studies.
© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
BACKGROUND - Racial disparities in access and survival have been reported in a variety of cancers. These issues, however, have yet to be explored in detail in patients with soft-tissue sarcomas (STS). The purpose of this paper was to investigate the independent role of race with respect to survival outcomes in STS.
METHODS - A total of 7601 patients were evaluated in this study. A SEER registry query for patients over 20 years old with extremity STS diagnosed between 2004 and 2009 (n=7225) was performed. Survival outcomes were analyzed after patients were stratified by race. Multivariable survival models were used to identify independent predictors of sarcoma-specific death. The Wilcoxon rank-sum test was used to compare continuous variables. Statistical significance was maintained at P<0.05.
RESULTS - This study showed that African American patients were more likely to die of their STS. They were younger at presentation (P=0.001), had larger tumors (P<0.001), had less surgery (P=0.002), received radiotherapy less frequently (P=0.024), had higher family income (P<0.001), and were less likely to be married (P<0.001). African American race by itself was not an independent predictor of death.
CONCLUSIONS - African Americans encounter death due to STS at a much larger proportion and faster rate than their respective white counterparts. African Americans frequently present with a larger size tumor, do not undergo surgical resection, or receive radiation therapy as frequently as compared with their white peers. Barriers to timely and appropriate care should be further investigated in this group of at-risk patients.
OBJECTIVE - Advances in multimodality therapy have led to increased survival for patients with metastatic colorectal cancer, but the impact on patients undergoing resection for colorectal liver metastases is unclear. The purpose of this study was to evaluate patterns of treatment for resectable colorectal liver metastases in the USA over the last two decades.
METHODS - Using the Surveillance, Epidemiology, and End Results-Medicare database, 1,926 patients who underwent hepatic resection for colorectal liver metastasis between 1991 and 2007 were included and divided into two cohorts: period 1 (1991-2000) and period 2 (2001-2007). Demographic data, treatment patterns, and outcomes of the two periods were compared by univariate methods. Multivariable regression models were constructed to predict the use of perioperative chemotherapy, postoperative complications, and 90-day mortality following liver resection.
RESULTS - The overall use of perioperative chemotherapy was 33 % and did not differ between periods, but shifted from postoperative to preoperative over time. By multivariable analysis, older age, black race, stage III primary cancer, and metachronous disease were predictive of lesser likelihood of chemotherapy use. The use of preoperative chemotherapy was not associated with any increase in perioperative morbidity or mortality.
CONCLUSIONS - Despite increased survival and widespread recommendations for the use of multimodality therapy, the overall resection rate and use of perioperative chemotherapy for resectable colorectal liver metastases remain underutilized and have not increased over time. Efforts to investigate barriers to the widespread use of multimodality therapy for these patients are warranted.
OBJECTIVE - To describe the characteristics of primary vaginal melanoma patients in the Surveillance, Epidemiology, and End Result database and to determine the outcome from the treatment approaches.
MATERIALS/METHODS - From the Surveillance, Epidemiology, and End Result registry, 201 patients with vaginal melanoma were identified. Patients' characteristics and prognostic factors including age, race, extent of surgery, and use of radiation therapy were obtained.
RESULTS - The median age was 68 years (range, 28-100 years). The population was 73% white, 11% black, and 16% Asian/American Indian. International Federation of Gynecology and Obstetrics staging results were stage I (46%), stage II (18%), stage III (3%), stage IVA (3%), stage IVB (12%), and unknown (18%). Treatment approach included surgical resection of the primary site in 70%, whereas 35% of the patients underwent lymph node resection. Approximately 40% of the patients received radiotherapy, which was primarily used in the adjuvant setting. Overall survival at 2 and 5 years was 24% and 15%, respectively. Presence of lymph nodes at diagnosis was associated with worse overall survival (hazard ratio, 1.98; P = 0.02). Adjuvant radiation did not offer a statistically significant overall survival advantage compared to surgery alone.
CONCLUSIONS - Vaginal melanoma is a rare diagnosis primarily affecting the elderly. Overall survival is low even for patients presenting with disease limited to the vagina. Lymph node involvement at diagnosis is strongly predictive of worse overall survival. Most patients are treated with surgical resection with varying use of adjuvant radiotherapy. Further research is needed to identify the etiology and improve the outcome of this aggressive disease.