Avaliação do tratamento quimioterápico paliativo com o esquema LDE- paclitaxel em pacientes portadores de metástases ósseas por neoplasia maligna / Evaluation of palliative chemotherapy treatment with the LDEpaclitaxel regimen in patients with bone metastases from malignant neoplas

Introdução: Pacientes com câncer em estádios avançados e metástases ósseas frequentemente não apresentam condições clínicas para a realização de esquemas quimioterápicos convencionais subsequentes, restringindo as opções de tratamento. Anteriormente, demonstramos que nanopartículas artificiais lipídicas (LDE), semelhantes à lipoproteína de baixa densidade (LDL) rica em colesterol, são captadas por tecidos malignos, e quando associadas aos quimioterápicos, após injeção pela via endovenosa, reduz drasticamente a toxicidade do tratamento. Os objetivos deste presente estudo foram avaliar a resposta clínica ao tratamento quimioterápico com paclitaxel (PTX) associado à LDE; avaliar as toxicidades clínicas e laboratorial, e a capacidade da associação LDE-PTX em reduzir a dor oncológica relacionada às metástases ósseas em pacientes com carcinoma de mama, próstata e pulmão, previamente tratados e não elegíveis para tratamento quimioterápico convencional subsequente. Métodos: Dezoito pacientes (8 com câncer de mama, 5 de próstata e 5 de pulmão) com metástases ósseas foram incluídos. O tratamento consistiu no esquema LDE-PTX na dose convencional do PTX (175 mg/m2 de superfície corpórea de 3/3 semanas) e os pacientes foram avaliados por resposta clínica, redução da dor óssea, uso de medicamentos opióides, e ocorrência de fraturas ósseas patológicas. Resultados: No total, 104 ciclos de quimioterapia foram realizados, e nenhum paciente apresentou toxicidade clínica, laboratorial, assim como não houve fraturas patológicas. Dos 18 pacientes incluídos, 9 tiveram sobrevida livre de progressão de doença 6 meses. Houve em todos os pacientes redução da dor óssea, permitindo substituição da medicação opióide por analgésico não opióide. Conclusão: A melhora significativa na dor óssea sem que tenha ocorrido toxicidade do tratamento, e o tempo de não progressão de doença 6 meses na metade dos pacientes sugere que esses pacientes tenham se beneficiado consistentemente do tratamento com a LDE-PTX. Portanto, a LDE-PTX pode tornar- se uma opção terapêutica interessante em pacientes com carcinomas de próstata, mama ou pulmão em estágios avançados e sem condições clínicas de se submeterem a outros esquemas quimioterápicos convencionais

Introduction: Patients with advanced cancer and bone metastases usually do not have clinical conditions to perform additional conventional chemotherapy regimens, restricting treatment options. Previously, we showed that lipid core nanoparticles (LDE), similar to cholesterol-rich low-density lipoprotein (LDL), are taken up by malignant tissues, and when associated to chemotherapy, after endovenous injection, it drastically decreases the toxicity of the treatment. The objectives of this study were to evaluate the clinical response to chemotherapy treatment with paclitaxel (PTX) associated with LDE; to evaluate the clinical and laboratorial toxicities, and the ability of the LDE-PTX to reduce cancer pain related to bone metastases in patients with breast, prostate or lung carcinoma, previously treated and not eligible for subsequent conventional chemotherapy treatment. Methods: Eighteen patients (8 with breast cancer, 5 with prostate and 5 with lung) with bone metastases were included. Treatment consisted of the LDE-PTX regimen at a conventional dose of PTX (175 mg/m2 body surface area, 3/3 weeks) and patients were evaluated for clinical response, reduction in bone pain, use of opioid medications, and the occurrence of pathological bone fractures. Results: In total, 104 chemotherapy cycles were performed, and none of the patients showed clinical or laboratorial toxicities, as well as there were no pathological fractures. Of the 18 patients evaluated, 9 had progression-fee survival 6 months. Patients had decrease in bone pain allowing replacement of opioid medication by another non-opioid analgesic. Conclusion: Significant improvement in bone pain without treatment toxicity, and time to disease progression of 6 months in half of the patients suggest that these patients have consistently benefited with LDE-PTX treatment. Therefore, LDE-PTX may become an interesting therapeutic option in patients with advanced stage of prostate, breast or lung carcinomas and without clinical conditions to undergo other conventional chemotherapy regimens

Distant metastasis of salivary gland cancer: Incidence, management, and outcomes.

BACKGROUND: Distant metastases (DMs) are the primary cause of treatment failure in patients with salivary gland carcinoma. There is no consensus on the standard treatment. METHODS: Patients with DMs were identified from an institutional database of 884 patients with salivary gland cancer who underwent resection of the primary tumor between 1985 and 2015. Survival outcomes for patients with DMs were determined with the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with DM. RESULTS: Of the 884 patients identified, 137 (15%) developed DMs during follow-up. Most of the primary tumors (n = 77 [56%]) were located in a major salivary gland. At clinical presentation, 53% of the tumors were classified as T3 or T4, and 32% had clinical node metastases. The median time to DM was 20.3 months. The factors associated with shorter distant recurrence-free survival were male sex, high-risk tumor histology, and advanced pathological T and N classifications. Patients with bone metastases had a lower survival rate than patients with lung metastases. The total number of DMs in a patient was inversely associated with survival. Patients who underwent surgical resection of DMs had a significantly higher 5-year rate of metastatic disease-specific survival than patients who underwent observation or nonsurgical treatment (44%, 29%, and 19%, respectively; P = .003). CONCLUSIONS: In patients with DMs of salivary gland carcinoma, survival is negatively associated with high-grade histology, bone DMs, and the total number of DMs. Metastasectomy can help to lengthen disease-free survival.

Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment.

Blood-borne metastasis accounts for most cancer-related deaths and involves circulating tumor cells (CTCs) that are successful in establishing new tumors at distant sites. CTCs are found in the bloodstream of patients as single cells (single CTCs) or as multicellular aggregates (CTC clusters and CTC-white blood cell clusters), with the latter displaying a higher metastatic ability. Beyond enumeration, phenotypic and molecular analysis is extraordinarily important to dissect CTC biology and to identify actionable vulnerabilities. Here, we provide a detailed description of a workflow that includes CTC immunostaining and micromanipulation, ex vivo culture to assess proliferative and survival capabilities of individual cells, and in vivo metastasis-formation assays. Additionally, we provide a protocol to achieve the dissociation of CTC clusters into individual cells and the investigation of intra-cluster heterogeneity. With these approaches, for instance, we precisely quantify survival and proliferative potential of single CTCs and individual cells within CTC clusters, leading us to the observation that cells within clusters display better survival and proliferation in ex vivo cultures compared to single CTCs. Overall, our workflow offers a platform to dissect the characteristics of CTCs at the single cell level, aiming towards the identification of metastasis-relevant pathways and a better understanding of CTC biology.

The ongoing French metastatic breast cancer (MBC) cohort: the example-based methodology of the Epidemiological Strategy and Medical Economics (ESME).

PURPOSE: The currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme. PARTICIPANTS: All consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually. FINDING TO DATE: With a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort. FUTURE PLANS: These real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings. TRIAL REGISTRATION NUMBER: NCT03275311; Pre-results.

Impact and cost of preoperative computed tomography imaging on the management of patients diagnosed with high-grade endometrial cancer.

OBJECTIVE: To investigate the cost and impact of routine preoperative computed tomography (CT) in patients with high-grade endometrial cancer, and its role in identifying extrauterine disease. METHODS: We retrospectively identified patients with high-grade endometrial cancer who underwent routine CT scan prior to surgical procedure between September 1, 2005, and January 31, 2015. Cases in which CT findings led to alterations in the treatment plan were documented. Incidental findings unrelated to endometrial cancer diagnosis were captured. Cost of imaging and diagnostic procedures was based on Ontario's Physician Services-Schedule of Benefits. RESULTS: Of 179 patients included, 57 (31.9%) were diagnosed with stage 3-4 disease. CT showed evidence of metastatic disease in 30 (16.8%) patients; however, planned surgical procedure was altered in only nine (5.0%) cases. CT results showed incidental findings requiring follow-up in 78 (43.6%) cases, three of which were second malignancies. We estimate an expenditure of CAD$14 185.85 on routine imaging for every case in which surgical management was changed. CONCLUSIONS: Preoperative CT imaging is efficacious in identifying extrauterine disease in patients with high-grade endometrial cancer, although it seldom alters surgical management. Many of these CT scans will identify incidental findings requiring further interventions, resulting in substantial costs.

Past, Current, and Future Incidence Rates and Burden of Metastatic Prostate Cancer in the United States.

BACKGROUND: Metastatic prostate cancer (PCA) remains a highly lethal malignancy in the USA. As prostate-specific antigen testing declines nationally, detailed assessment of current age- and race-specific incidence trends and quantitative forecasts are needed. OBJECTIVE: To evaluate the current trends of metastatic PCA by age and race, and forecast the number of new cases (annual burden) and future trends. DESIGN, SETTING, AND PARTICIPANTS: We derived incidence data for men aged ≥45 yr who were diagnosed with metastatic PCA from the population-based Surveillance, Epidemiology, and End Results registries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined the current trends of metastatic PCA from 2004 to 2014, and forecast the annual burden and incidence rates by age and race for 2015-2025, using age-period-cohort models and population projections. We also examined alternative forecasts (2012-2025) using trends prior to the revised screening guidelines issued in 2012. RESULTS AND LIMITATIONS: Metastatic PCA, steadily declining from 2004 to 2007 by 1.45%/yr, began to increase by 0.58%/yr after 2008, which accelerated to 2.74%/yr following the 2012 United States Preventive Services Task Force recommendations-a pattern that was magnified among men aged ≤69 yr and white men. Forecasts project the incidence to increase by 1.03%/yr through 2025, with men aged 45-54 yr (2.29%/yr) and 55-69 yr (1.53%/yr) increasing more rapidly. Meanwhile, the annual burden is expected to increase 42% by 2025. Our forecasts estimated an additional 15 891 metastatic cases from 2015 to 2025 compared with alternative forecasts using trends prior to 2012. CONCLUSIONS: The recent uptick in metastatic PCA rates has resulted in forecasts that project increasing rates through 2025, particularly among men aged ≤69 yr. Moreover, racial disparities are expected to persist and the annual burden will increase considerably. The impact of the prior and current PCA screening recommendations on metastatic PCA rates requires continued examination. PATIENT SUMMARY: In this report, we assessed how the incidence of metastatic prostate cancer has changed over recent years, and forecast future incidence trends and the number of new cases expected each year. We found that the incidence of metastatic prostate cancer has been increasing more rapidly since 2012, resulting in a rise in both future incidence and the number of new cases by 2025. Future incidence rates and the number of new cases were reduced in alternative forecasts using data prior to the 2012 United States Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA) testing for prostate cancer. There is a need for additional research that examines whether national declines in PSA testing contributed to increases in rates of metastatic disease. The incidence of metastatic disease in black men is still expected to occur at considerably higher rates compared with that in white men.

Point of care assessment of melanoma tumor signaling and metastatic burden from µNMR analysis of tumor fine needle aspirates and peripheral blood.

This study evaluates µNMR technology for molecular profiling of tumor fine needle aspirates and peripheral blood of melanoma patients. In vitro assessment of melanocyte (MART-1, HMB45) and MAP kinase signaling (pERK, pS6K) molecule expression was performed in human cell lines, while clinical validation was performed in an IRB-approved study of melanoma patients undergoing biopsy and blood sampling. Tumor FNA and blood specimens were compared with BRAF genetic analysis and cross-sectional imaging. µNMR in vitro analysis showed increased expression of melanocyte markers in melanoma cells as well as increased expression of phosphorylated MAP kinase targets in BRAF-mutant melanoma cells. Melanoma patient FNA samples showed increased pERK and pS6K levels in BRAF mutant compared with BRAF WT melanomas, with µNMR blood circulating tumor cell level increased with higher metastatic burden visible on imaging. These results indicate that µNMR technology provides minimally invasive point-of-care evaluation of tumor signaling and metastatic burden in melanoma patients.

Biopsy Procedures and Molecular Testing Utilization and Related Costs in Patients with Metastatic Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements are key therapeutic targets for biomarker-driven treatment with an EGFR or ALK tyrosine kinase inhibitor (TKI) in patients with metastatic non-small cell lung cancer (NSCLC). To appropriately guide treatment decisions, since 2011, the National Comprehensive Cancer Network and the American Society of Clinical Oncology therefore recommend EGFR and ALK analysis in tumor samples obtained at the time of diagnosis in patients with non-squamous NSCLC. Currently, there are limited data on utilization patterns and cost of biopsy procedures and biomarker tests in patients with metastatic NSCLC who receive an EGFR or ALK TKI. OBJECTIVES: To (a) describe utilization patterns and costs associated with biopsy procedures and biomarker testing in patients with NSCLC who received erlotinib or crizotinib between 2009 and 2012 and (b) investigate the timing of these procedures relative to the erlotinib or crizotinib index date. METHODS: Adult patients with metastatic lung cancer were identified by ICD-9-CM diagnostic codes within the Truven Health Analytic MarketScan database. Patients were included in the analysis if they had an index erlotinib or crizotinib claim between January 1, 2009, and September 30, 2012 (index period) and were continuously enrolled for ≥ 12 months before the index claim. Because there is no specific ICD-9-CM diagnostic code for NSCLC, patients with metastatic lung cancer who received erlotinib or crizotinib were considered to have metastatic NSCLC. Using CPT and ICD-9-CM codes, lung biopsy procedures performed during the 24 months before or 12 months after the index claim date were identified. For every patient, biomarker testing claims for EGFR and ALK were identified using the molecular pathology stacked CPT code during the 2 months before or 1 month after the index date. The frequency of claims for biopsy procedures and biomarker testing was analyzed descriptively. The overall summary measures for biomarker testing, especially frequency of EGFR testing in patients receiving erlotinib, was also described as before and after 2011, the year when biomarker testing became part of the guidelines. Per patient and overall costs for biopsy procedures and biomarker testing were calculated from payer and patient perspectives. RESULTS: Of the 4,926 identified patients, 4,801 (97.5%) received erlotinib, and 125 (2.5%) received crizotinib. Biopsy procedure claims were identified for 3,579 (72.7%) patients, including 3,503 (73.0%) erlotinib recipients and 76 (60.8%) crizotinib recipients. Biomarker testing claims were identified for 675 (13.7%) patients, including 634 (13.2%) erlotinib recipients and 41 (32.8%) crizotinib recipients. Overall, most biomarker testing procedures (476 of 741) were identified in 435 (of 675) patients after year 2011. Also, among erlotinib recipients, percentage of patients receiving EGFR testing was increased over the index period. Per patient mean (SD) numbers of biopsy procedures and biomarker tests were 1.2 (1.1) and 0.2 (0.4), respectively. In the outpatient setting, per patient mean (SD) cost per biopsy procedure was $1,223 ($1,899) from the payer perspective and $60 ($147) from the patient perspective, whereas in the inpatient setting, it was $8,163 ($18,712) and $180 ($691), respectively. Among patients receiving at least 1 biomarker test, the per patient mean (SD) cost for the overall population was $891 ($1,062) and $43 ($229); for erlotinib recipients, it was $906 ($1,084) and $42 ($228); and for crizotinib recipients, it was $664 ($576) and $55 ($243) in payer and patient perspectives, respectively. CONCLUSIONS: This study provides insight into the use and cost of biopsy and biomarker testing procedures in patients with metastatic NSCLC. The low frequency of biomarker testing highlights the need for more awareness of testing to guide treatment decisions in these patients. Costs associated with biopsy procedures and biomarker testing provide insight into the economic impact on metastatic NSCLC patients treated with targeted therapy. DISCLOSURES: This study was sponsored by Merck & Co. Shinde is a study manager working for Merck under contract with AllSourcePPS, an Agile 1 company in Huntington Beach, California. Cao and Kothari are employees of Merck & Co., Kenilworth, New Jersey. Study concept and design were contributed primarily by Shinde and Kothari. Data analysis was performed by Cao. Data interpretation was performed by Shinde, Cao, and Kothari. Shinde wrote the manuscript with assistance from Cao and Kothari. The revision was completed primarily by Shinde and Kothari.

Guidelines of the French Society of Otorhinolaryngology (SFORL), short version. Extension assessment and principles of resection in cutaneous head and neck tumors.

Cutaneous head and neck tumors mainly comprise malignant melanoma, squamous cell carcinoma, trichoblastic carcinoma, Merkel cell carcinoma, adnexal carcinoma, dermatofibrosarcoma protuberans, sclerodermiform basalioma and angiosarcoma. Adapted management requires an experienced team with good knowledge of the various parameters relating to health status, histology, location and extension: risk factors for aggression, extension assessment, resection margin requirements, indications for specific procedures, such as lateral temporal bone resection, orbital exenteration, resection of the calvarium and meningeal envelopes, neck dissection and muscle resection.

Efectividad y seguridad de everolimus en terapia combinada con análogos de la somatostatina en pacientes con tumores metastásicos bien diferenciados de bajo grado o grado intermedio de origen neuroendocrino / Effectiveness and safety of everolimus in combination therapy with somatostatin analogs in patients with well differentiated low grade or intermediate degree metastatic tumors of neuroendocrine origin

Objetivo: examinar los beneficios y riesgos del uso de everolimus para el tratamiento de pacientes con tumor de origen neuroendocrino metastásico bien diferenciado de grado bajo o grado intermedio (gastrointestinal, pulmonar, pancreático), como uno de los criterios para informar la toma de decisiones relacionada con la posible inclusión de tecnologías en el Plan Obligatorio de Salud, en el marco de su actualización ordinaria para el año 2015. Metodología: se realizó una búsqueda de evidencia publicada en los últimos 5 años en las bases de datos: MEDLINE, EMBASE, la Librería Cochrane y LILACS, así como consulta a expertos temáticos, productores y comercializadores de la tecnología de interés para la evaluación. Dos evaluadores de manera independiente, tamizaron las referencias obtenidas, resolviendo las discrepancias por consenso.\r\nResultados: se identificaron 89 publicaciones en las bases de datos consultadas, Fueron incluidas 3 publicaciones: un ensayo una revisión sistemática de la literatura (RSL), un estudio de comparación indirecta ajustada y pareada y un ensayo clínico aleatorizado (ECA). Hasta el momento de la elaboración de este informe, con las estrategias diseñadas para la búsqueda de evidencia, hay un ECA fase 3 que evalúa la intervención de interés para esta evaluación. Conclusiones: Los nuevos agentes de terapia dirigida se han desarrollado e investigado en estudios recientes, pero la mayoría de estos, en estudios no aleatorizados. De acuerdo con los dos ECA identificados por la RSL incluida en este informe, las tecnologías de interés para esta evaluación son opciones válidas y aplicables en la práctica diaria para pacientes con tumores neuroendocrinos pancreáticos avanzados. Sin embargo, hay todavía varios aspectos no explorados tales como el posicionamiento óptimo de estas drogas entre sí y con respecto a la quimioterapia, a los radiofármacos o análogos de la somatostatina. Con los hallazgos aquí presentados no es posible obtener conclusiones sobre la eficacia comparativa para el tratamiento de pacientes con tumores metastásicos bien diferenciados de bajo grado o grado intermedio de origen neuroendocrino. Los resultados de seguridad muestran que los eventos adversos serios son más frecuentes en el grupo asignado a everolimus más octreotide APR que en el grupo asignado a placebo más octreotide APR. Los eventos adversos más frecuentes y conducentes al abandono del tratamiento con everolimus más octerotide APR son: fatiga, diarrea, deterioro general del estado físico, enfermedad pulmonar intersticial. Los eventos adversos grado 3 a 4 fue similar para las diferentes clases de agentes. Los agentes de quimioterapia tienen altos niveles de mielosupresión reversible, emesis (especialmente antes del uso de los antieméticos modernos) y toxicidad agente específica. Las terapias dirigidas (sunitib y everolimus tuvieron menos toxicidad grado 3 a 4 comparados con los agentes quimioterapéuticos.(AU)

Economic evaluation of diagnostic localization following biochemical prostate cancer recurrence.

OBJECTIVES: The aim of this study was to assess potential cost-effectiveness of using a prostate cancer specific functional imaging technology capable of identifying residual localized disease versus small volume metastatic disease for asymptomatic men with low but detectable prostate specific antigen (PSA) elevation following radical prostatectomy. METHODS: Markov modeling was used to estimate the incremental impact on healthcare system costs (2012 USD) and quality-adjusted life-years (QALYs) of two alternative strategies: (i) using the new diagnostic to guide therapy versus (ii) current usual care-using a combination of computed tomography, magnetic resonance imaging, and bone scan to guide therapy. Costs were based on estimates from literature and Medicare reimbursement. Prostate cancer progression, survival, utilities, and background risk of all-cause mortality were obtained from literature. Base-case diagnostic sensitivity (75 percent), specificity (90 percent), and cost (USD 2,500) were provided by our industry partner GE Healthcare. RESULTS: The new diagnostic strategy provided an average gain of 1.83 (95 percent uncertainty interval [UI]: 1.24-2.64) QALYs with added costs of USD 15,595 (95 percent UI: USD -6,330-44,402) over 35 years. The resulting incremental cost-effectiveness ratio was USD 8,516/QALY (95 percent UI: USD -2,947-22,372). RESULTS were most influenced by the utility discounting rate and test performance characteristics; however, the new diagnostic provided clinical benefits over a wide range of sensitivity and specificity. CONCLUSION: This analysis suggests a diagnostic technology capable of identifying whether men with biochemical recurrence after radical prostatectomy have localized versus metastatic disease would be a cost-effective alternative to current standard work-up. The results support additional investment in development and validation of such a diagnostic.

Cost effectiveness of a 92-gene assay for the diagnosis of metastatic cancer.

OBJECTIVES: To estimate the clinical and economic trade-offs involved in using a molecular assay (92-gene assay, CancerTYPE ID) to aid in identifying the primary site of difficult-to-diagnose metastatic cancers and to explore whether the 92-gene assay can be used to standardize the diagnostic process and costs for clinicians, patients, and payers. METHODS: Four decision-analytic models were developed to project the lifetime clinical and economic impact of incorporating the 92-gene assay compared with standard care alone. For each model, total and incremental costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and the proportion of patients treated correctly versus incorrectly were projected from the payer perspective. Model inputs were based on published literature, analyses of SEER (Surveillance Epidemiology and End RESULTS) data, publicly available data, and interviews with clinical experts. RESULTS: In all four models, the 92-gene assay increased the proportion of patients treated correctly, decreased the proportion of patients treated with empiric therapy, and increased quality-adjusted survival. In the primary model, the ICER was $50,273/QALY; thus, the 92-gene assay is therefore cost effective when considering a societal willingness-to-pay threshold of $100,000/QALY. These findings were robust across sensitivity analyses. CONCLUSIONS: Use of the 92-gene assay for diagnosing metastatic tumors of uncertain origin is associated with reduced misdiagnoses, increased survival, and improved quality of life. Incorporating the assay into current practice is a cost-effective approach to standardizing diagnostic methods while improving patient care. Limitations of this analysis are the lack of data availability and resulting modeling simplifications, although sensitivity analyses showed these to not be key drivers of results.

Retrospective evaluation of elastic stain in the assessment of serosal invasion of pT3N0 colorectal cancers.

Peritoneal involvement is an important adverse prognostic factor in colorectal cancer (CRC) and determines a shift in the pathologic tumor node metastasis stage. Because peritoneal involvement is difficult to identify, use of special stains highlighting the peritoneal elastic lamina and mesothelial surface has been proposed. This study aims to determine whether use of elastic stain or CK7 immunohistochemistry on a single tissue section can refine the level of tumor invasion and determine whether restaging based on this assessment has prognostic significance in pT3N0 CRCs. Elastic stains were applied to 1 block per case from 244 consecutively resected pT3N0M0 CRCs. CK7 was evaluated in a 169-case subset. The elastic lamina was identified in only 101 cases (41%). Of those, 60 cases (24.6%) displayed elastic lamina invasion (ELI). This finding was associated with significantly worse (P<0.001) disease-free survival (DFS) (5-y DFS=60%) and significantly worse (P=0.01) overall survival (OS) (5-y OS=66.7%) compared with patients with no ELI (5-y DFS=87.8%, OS=92.7%) and those for whom no elastic lamina was identified (5-y DFS=82.5%, OS=86.0%). CK7 staining highlighted mesothelial cells in only 27 of 169 cases tested and helped demonstrate serosal invasion in only 5 cases (3%). In summary, the use of a single elastic stain is a useful and inexpensive method to demonstrate peritoneal involvement by tumor and should be considered for routine use in all pT3N0 CRCs. As tumors with ELI have an adverse prognosis, we propose that they should be upstaged compared with pT3N0 tumors without ELI.

Biopsy-site changes in lung adenocarcinoma with prior core needle biopsy: a potential pitfall in the assessment of stromal invasion.

Although biopsy-site changes are known to cause diagnostic difficulties in thyroid and breast specimens, especially when assessing invasion, such changes have not been described in the lung. Assessment of invasion is important in lung cancers to distinguish bronchioloalveolar carcinoma [adenocarcinoma in situ (AIS)] from invasive adenocarcinoma. The aim of this study was to determine whether biopsy-site changes occur in the lung and whether they may impact this differential diagnosis. Lobectomy specimens were examined from patients whose previous core needle biopsies showed well-differentiated adenocarcinoma with a lepidic pattern. There were 26 adenocarcinomas, including 14 minimally invasive adenocarcinomas, 2 invasive well-differentiated adenocarcinomas, and 10 AISs. Biopsy-site changes were identified in 9 of 26 (35%), including 4 minimally invasive adenocarcinomas, 3 AISs, and 2 well-differentiated adenocarcinomas. The interval between biopsy and resection ranged from 12 to 45 days (mean, 26.1 d). The biopsy sites consisted of a linear scar composed of collagen and plump fibroblasts, ranging from 2.0 to 13.1 mm in length and 0.5 to 1.6 mm in width. Scattered lymphocytes and plasma cells were present in 8 cases, pigment-laden macrophages in 4, and foreign body giant cells in 3. Benign entrapped lung epithelium was present within the scar in all 9 and entrapped malignant epithelium in 4. Biopsy-site changes can be identified in a significant proportion of lung tumors after core needle biopsy. They need to be distinguished from tumor-related stromal reactions that are considered an indication of invasion and are important in the differentiation of AIS and invasive adenocarcinoma.

Costs of different follow-up strategies in early breast cancer: a review of the literature.

We reviewed the literature between January 1985 and June 2011 on the costs of different follow-up strategies for patients treated for early breast cancer. A total of 186 abstracts were retrieved of which eleven publications were considered relevant; 6 randomised clinical trials, 4 retrospective cohort studies and 1 'minisymposium'. The follow-up strategies, outcome measures and methods of analysis used in these studies vary widely, so no general conclusions can be drawn. However, from the results we infer that patient-led follow-up by a nurse practitioner, follow-up by a general practitioner, or telephone follow-up is feasible and cost-effective, without routine additional tests, except annual mammograms. In this era of increasing health care costs, cost-effectiveness, evaluated in a standardised way, should be taken into account in future clinical trials.

Histopathological assessment of metastasis.

In spite of advances in the fields of immunohistochemistry and molecular biology, in clinical practice much of the assessment of metastases still relies on light microscopy using conventional histological stains. This is not so much a reflection of a reluctance by histopathologists to adopt new techniques, but more an indication that for most malignancies an enormous amount of useful prognostic data can be gained from relatively unsophisticated assessment of tissues, and that many of the strongest studies of prognostic factors in malignancy predate the era of molecular diagnostics. Although it is undoubtedly true that newer techniques have added prognostic information in the assessment of many tumors, and many, such as the measurement of estrogen receptor status in breast cancer, could be considered routine, a skilled assessment of the morphology of the tissues still provides the fundamental basis of assessing prognosis in the vast majority of cases.

Diffusion-weighted MR imaging before and after contrast enhancement with superparamagnetic iron oxide for assessment of hepatic metastasis.

PURPOSE: The purpose of our study was to validate diffusion-weighted MRI (DWI) before and after superparamagnetic iron oxide (SPIO) injection for assessment of hepatic metastases. MATERIALS AND METHODS: Eighty-six hepatic metastases (size range, 0.3-4.7 cm; mean, 1.5 cm) verified pathologically or by follow-up imaging studies in 22 consecutive patients (17 men and 5 women; 44-83 years; mean age, 60 years) during a 13-month period were enrolled. Hepatic MRI, including DWI (b-factors=50, 400, 800 s/mm²) with breath-holding technique of single-shot spin-echo echo-planar imaging (TR/TE=1000/69 ms, average=2) before and after SPIO administration, were retrospectively reviewed by two independent radiologists with a 5-point scale confidence score for each hepatic lesion on pre-contrast DWI (pre-DWI), SPIO-enhanced DWI (SPIO-DWI), and SPIO-enhanced T2*-weighted imaging (SPIO-T2*wI). RESULTS: For all lesions, SPIO-T2*wI showed significantly higher confidence score in the diagnosis of hepatic metastases than pre-contrast or SPIO-DWI regardless of the size of b-factors (p<0.05) with only one exception; using b-factor=50 s/mm², the score of SPIO-T2*wI was still higher than SPIO-DWI but there was no statistical significance given by observer 1 (p=0.730). For the subcentimeter lesions (n=37), SPIO-T2*wI showed the highest score, and using b-factor= 50 or 400 s/mm² SPIO-DWI showed similar confidence scores to SPIO-T2*wI by both observers (p>0.05). Pre-DWI using b-factor=50 sec/mm² was also comparable with SPIO-T2*wI by observer 1 (p=0.060). CONCLUSION: Pre-DWI has a limited value for the assessment of hepatic metastases, however, the repetition of DWI after SPIO injection using small b-factors could complement SPIO-T2*wI, especially for subcentimeter lesions.

Cost of illness in patients with metastatic colorectal cancer.

OBJECTIVES: To estimate total costs and metastatic colorectal cancer (mCRC)-related costs and assess primary cost drivers of treating newly diagnosed mCRC patients after the introduction of biologic therapies. METHODS: Using a large national claims database, costs of mCRC patients were estimated in 2004-2009 by examining (1) the cost difference between mCRC patient and their matched non-cancer cohorts, and (2) mCRC-related costs. Costs were further assessed by phase of disease (diagnostic, treatment, and death). The survival analysis technique was used to estimate cost of handling variable length of follow-up and data censoring. RESULTS: A total of 6,746 mCRC patients met all eligibility criteria, 6,675 of them were matched to patients without cancer. Among the three phases of disease, the treatment phase was the longest (16.4 months). Compared with matched patients with no cancer, total monthly costs were $14,585 higher for mCRC patients, which was driven by higher inpatient ($7,546) and outpatient ($6,749) care (p < 0.001 for all comparisons). During the study period, cost share of biologics increased from 4.8% among patients diagnosed in 2004 to 9.4% for those diagnosed in 2008. CONCLUSIONS: The costs associated with treating mCRC are substantial. Inpatient and outpatient care remain key cost drivers in the medical management of mCRC. Cost chare of biologics was low, but increased between 2004 and 2009. The study sample only included patients with commercial and Medicare supplemental insurance in the US thus may not be generalizable to patients with other insurance or in other countries. Indirect costs associated with mCRC were not examined.