Agreement for tumor grade of ovarian carcinoma: analysis of archival tissues from the surveillance, epidemiology, and end results residual tissue repository.

BACKGROUND: Emerging data suggest that ovarian cancers differ by tumor grade. However, the reliability of microscopic grade from paraffin tissue in the general medical community and as reflected in population-based cancer registries is unknown. METHODS: We examined grade agreement between two gynecologic pathologists and the Surveillance Epidemiology and End Results Residual Tissue Repository (SEER). Grade agreement was assessed with percent observer agreement and kappa coefficients for 664 invasive ovarian carcinomas, using previously defined three-tier and two-tier grading systems. A random subset of ovarian carcinomas was selected to compare intra- and inter-pathologist agreement. RESULTS: Five hundred and eighty-six of SEER's 664 tumors were confirmed invasive. Percent agreement was 49 % with fair kappa coefficient = 0.25 (95 % CI: 0.20-0.30) for the 664 tumors. Agreement improved slightly when restricted to the 586 confirmed invasive cancers; it was better for high grade than low grade tumors, for two-tier than three-tier grading systems, and within (66 %) than between study pathologists (43 %). Grade was not a robust independent predictor of ovarian cancer-specific survival. CONCLUSIONS: Grade agreement was fair between SEER and study pathologists irrespective of grading system. Recorded grade in SEER should be used with caution and is probably not a reliable metric for ovarian cancer epidemiology.

Rubin H. Flocks and colloidal gold treatments for prostate cancer.

In the early 1950s, Rubin H. Flocks of the University of Iowa began to treat prostate cancer patients with colloidal gold (Au(198)) therapy, evolving his technique over nearly 25 years in 1515 patients. We reviewed the long-term outcomes of Flocks' prostate cancer patients as compared to those patients treated by other methods at the University of Iowa before Flocks' chairmanship. We reviewed archived patient records, Flocks' published data, and long-term survival data from the Iowa Tumor Registry to determine short- and long-term outcomes of Flocks' work with colloidal gold. We also reviewed the literature of Flocks' time to compare his outcomes against those of his contemporaries. The use of colloidal gold, either as primary or adjunctive therapy, provided short- and long-term survival benefit for the majority of Flocks' patients as compared to historical treatment options (p < 0.001). Flocks' use of colloidal gold for the treatment of locally advanced prostate cancer offered short- and long-term survival benefits compared to other contemporary treatments.

The occurrence of rare cancers in U.S. adults, 1995-2004.

OBJECTIVE: Rare cancers have been traditionally understudied, reducing the progress of research and hindering decisions for patients, physicians, and policy makers. We evaluated the descriptive epidemiology of rare cancers using a large, representative, population-based dataset from cancer registries in the United States. METHODS: We analyzed more than 9 million adult cancers diagnosed from 1995 to 2004 in 39 states and two metropolitan areas using the Cancer in North America (CINA) dataset, which covers approximately 80% of the U.S. population. We applied an accepted cancer classification scheme and a published definition of rare (i.e., fewer than 15 cases per 100,000 per year). We calculated age-adjusted incidence rates and rare/non-rare incidence rate ratios using SEER*Stat software, with analyses stratified by gender, age, race/ethnicity, and histology. RESULTS: Sixty of 71 cancer types were rare, accounting for 25% of all adult tumors. Rare cancers occurred with greater relative frequency among those who were younger, nonwhite, and of Hispanic ethnicity than among their older, white, or non-Hispanic counterparts. CONCLUSIONS: Collectively, rare tumors account for a sizable portion of adult cancers, and disproportionately affect some demographic groups. Maturing population-based cancer surveillance data can be an important source for research on rare cancers, potentially leading to a greater understanding of these cancers and eventually to improved treatment, control, and prevention.

Accuracy of the HPV status site-specific factor 10 (SSF-10) variable for patients with oropharyngeal cancers in the Iowa Cancer Registry, 2010-2014.

BACKGROUND: Surveillance, Epidemiology, and End Results Cancer Registries (SEER) began collecting human papillomavirus (HPV) status for upper aerodigestive tract cancers in 2010. However, classification of p16-testing was not included in the Collaborative Stage coding guidelines, potentially leading to inconsistent coding. METHODS: The HPV values for Iowa patients with oropharyngeal cancers (n = 824) were recoded based on modified guidelines that included p16 test results, and compared with the original guidelines. RESULTS: Forty percent of patients were recoded to a different value, and the HPV testing rate increased from 45% to 55%; 56% received p16-testing only. Of those originally coded as HPV-type 16 (n = 187), 89% were recoded to HPV-not otherwise specified (NOS). When comparing high-level positive/negative/not done categories, original coding captured 81% of patients with HPV-positive cancers. CONCLUSION: p16 was the most common HPV test but was inconsistently coded as HPV-testing. p16-positivity was also erroneously equated with HPV-type 16. Adding a separate p16 variable would improve consistency and accuracy of HPV coding.

Probability-based differential normalized fluorescence bivariate analysis for the classification of tissue autofluorescence spectra.

Differential normalized fluorescence (DNF) is an efficient and effective method for the differentiation of normal and cancerous tissue fluorescence spectra. The diagnostic features are extracted from the difference between the averaged cancerous and averaged normal tissue spectra and used as indices in tissue classification. In this paper, a new method, probability-based DNF bivariate analysis, is introduced based on the univariate DNF method. Two differentiation features are used concurrently in the new method to achieve better classification accuracy. The probability of each sample belonging to a disease state is determined with Bayes decision theory. This probability approach classifies the tissue spectra according to disease states and provides uncertainty information on classification. With a data set of 57 colonic tissue sites, probability-based DNF bivariate analysis is demonstrated to improve the accuracy of cancer diagnosis. The bivariate DNF analysis only requires the collection of a few data points across the entire emission spectrum and has the potential of improving data acquisition speed in tissue imaging.

What increased registry outreach may mean for cutaneous melanoma surveillance: impact of changes in Iowa.

BACKGROUND: Cutaneous melanoma (CM) is underreported to cancer registries, in part due to insufficient reporting in the nonhospital setting. The objective of this study was to better understand the impact of dermatologist and private pathology laboratory reporting on CM rates. METHODS: We examined the impact of targeted casefinding in private pathology laboratories and dermatology offices by the State Health Registry of Iowa (SHRI) on CM incidence, as well as the characteristics of nonhospital reported cases. RESULTS: Over the 39-year period (1973-2011), 22,541 cases of CM were captured by the SHRI; 16,183 (72%) were invasive melanoma cases and 6,358 (28%) were in situ cases. The incidence of invasive melanoma increased 3.6 fold between the time periods of 1973-1975 and 2009-2011 (6.6 vs. 24 per 100,000 person-years, respectively). If case reporting from private pathology laboratories and dermatology offices was not conducted, the 2009-2011 invasive CM rate would have decreased to 19.1. The ratio of invasive to in situ cases declined from 8:1 from 1973-1987 to less 2:1 from 2007-2011. Age at diagnosis also significantly increased across time periods, while the proportion of females declined. From 2007-2011, the majority (55%) of nonhospital cases were in situ, and 90% of the invasive cases were localized. A higher percentage of urban residents were attributed to nonhospital-based reporting sources compared to hospital-based sources (57% vs 45%, P < .0001) CONCLUSIONS: Electronic health records and incentivized Meaningful Use for reporting may provide an efficient method for nonhospital based providers to easily and accurately report CM cases to registries.

Small intestinal cancer: a population-based study of incidence and survival patterns in the United States, 1992 to 2006.

BACKGROUND: The etiology of cancers of the small intestine is largely unknown. To gain insight into these rare malignancies, we evaluated contemporaneous incidence and survival patterns. METHODS: Using small intestine cancer data from 12 population-based registries of the Surveillance, Epidemiology and End Results Program, we calculated age-adjusted and age-specific incidence rates (IRs), IR ratios, and relative survival (RS) rates. RESULTS: In total, 10,945 small intestine cancers (IR = 2.10/100,000 person-years) were diagnosed during 1992 to 2006, including carcinomas (n = 3,412; IR = 0.66), neuroendocrine cancers (n = 4,315; IR = 0.83), sarcomas (n = 1,084; IR = 0.20), and lymphomas (n = 2,023, IR = 0.38). For all histologic groups, males had significantly higher IRs than females, and distinct age-specific gender patterns were limited to intermediate-/high-grade lymphomas. Neuroendocrine cancer rates varied significantly by race, with rates highest among blacks and lowest among Asians/Pacific Islanders. Carcinoma IRs were highest among blacks; sarcoma IRs were highest among Asians/Pacific Islanders; and lymphoma IRs were highest among whites. Age-specific IR patterns were similar across racial/ethnic groups. During 1992 to 2006, duodenal cancer IRs increased more markedly than those for other subsites. RS varied little by gender or race. Neuroendocrine cancers had the most favorable RS, and carcinomas had the least favorable. The greatest improvement in 5-year RS from 1992 to 1998 to 1999 to 2005 was observed for sarcomas and lymphomas. CONCLUSIONS: Distinct small intestine cancer IR patterns according to histologic subtype suggest different underlying etiologies and/or disease biology, with susceptibility varying by gender, racial/ethnic groups, and subsite. Temporal patterns support a possible role for diagnostic bias of duodenal cancers. IMPACT: Future epidemiologic studies of small intestine cancer should consider histologic subtype by gender, race/ethnicity, and subsite.

Correlation coefficient mapping in fluorescence spectroscopy: tissue classification for cancer detection.

Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer detection.

The frequency of ipsilateral second tumors after breast-conserving surgery for DCIS: a population based analysis.

BACKGROUND: The diagnosis of ductal carcinoma in situ (DCIS) is increasing, although to the authors' knowledge there is no consensus regarding optimal treatment. This analysis of women treated with breast-conserving surgery (BCS) evaluated the impact of radiation therapy (RT) in patient outcomes. METHODS: The current study included a population-based sample of 1103 women residing in selected Surveillance, Epidemiology, and End Results (SEER) registries who were diagnosed with DCIS between 1991-1992. Data were obtained from the registry, physician follow-up, and pathology reports. Physicians were contacted in 1999 to determine whether the patient had developed a second event in the ipsilateral breast. For second events, pathology reports were reviewed to determine the presence of in situ or invasive disease. Registry data through 2001 were used to assess death rates and cause of death. Cox proportional hazards and logistic regression models were used to evaluate the rates of second events and breast carcinoma deaths between women treated with and without RT. RESULTS: Over an average of 91 months, 13.2% of women developed a second event. Rates of second events were 11% for women treated with BCS and RT compared with 15% for women treated with BCS only (adjusted hazards ratio, 0.64; 95% confidence interval, 0.44-0.92). Women receiving RT were significantly less likely to develop invasive breast carcinoma in the ipsilateral breast (adjusted odds ratio, 0.40). By 2001, the rate of death from breast carcinoma was 2.7%; in the group of women treated with BCS only compared with 0.8% in the group of women treated with BCS with RT. CONCLUSIONS: Among a population-based cohort, RT was found to significantly reduce the risk of second events in the ipsilateral breast, particularly invasive tumors, although not to the extent reported in clinical trials.

Interstitial thermal therapy in patients with localized prostate cancer: histologic analysis.

OBJECTIVES: To examine, by way of histologic examination, the destruction of excised prostate glands treated with thermal ablation. Thermal ablation treatment with permanently implanted temperature self-regulating rods is being used in the treatment of localized prostate cancer. METHODS: Four patients with biopsy-proven prostate cancer, who had been scheduled for routine radical prostatectomy with a gland size of less than 70 g, Gleason sum of 7 or less, and prostate-specific antigen values less than 10.0 ng/mL, were implanted with 70 degrees C rods under ultrasound and fluoroscopic control. The patients were then given multiple thermal treatments. Glands were removed and histologically analyzed to access the thermal destruction. RESULTS: Histologic examination revealed confluent thermal destruction within the rod array when the rods were placed end-to-end and no farther than 1 cm apart. Little necrosis was seen outside the array. To ensure the necessary destruction, the rods must be placed at the capsule, including posteriorly near the rectum. The results indicated that energy levels greater than 40 W-min/g of tissue should be used. This can be achieved by implanting 1.5 rods/g of prostate and treating the patient for 60 minutes. In 3 of the 4 patients, no residual cancer was found in the gland after thermal treatment. CONCLUSIONS: Histologic examination has aided in determining the implant density and treatment time and, therefore, the necessary energy, for adequate necrosis. The technique demonstrates the ability to destroy the prostate adequately, including tissue at the capsule. This new procedure appears promising in the treatment of localized prostate cancer.