Site Of Metastatic Involvement Research Articles

Stenting as a bridge to surgery in obstructing colon cancer: Long-term recurrence pattern and competing risk of mortality.

Stenting as a bridge to curative surgery (SBTS) for obstructing colon cancer (OCC) has been associated with possibly worse oncological outcomes. To evaluate the recurrence patterns, survival outcomes, and colorectal cancer (CRC)-specific death in patients undergoing SBTS for OCC. Data from 62 patients undergoing SBTS at a single tertiary centre over ten years between 2007 and 2016 were retrospectively examined. Primary outcomes were recurrence patterns, overall survival (OS), cancer-specific survival (CSS), and CRC-specific death. OS and CSS were estimated using the Kaplan-Meier curves. Competing risk analysis with cumulative incidence function (CIF) was used to estimate CRC-specific mortality with other cause-specific death as a competing event. Fine-Gray regressions were performed to determine prognostic factors of CRC-specific death. Univariate and multivariate subdistribution hazard ratios and their corresponding Wald test P values were calculated. 28 patients (45.2%) developed metastases after a median period of 16 mo. Among the 18 patients with single-site metastases: Four had lung-only metastases (14.3%), four had liver-only metastases (14.3%), and 10 had peritoneum-only metastases (35.7%), while 10 patients had two or more sites of metastatic disease (35.7%). The peritoneum was the most prevalent (60.7%) site of metastatic involvement (17/28). The median follow-up duration was 46 mo. 26 (41.9%) of the 62 patients died, of which 16 (61.5%) were CRC-specific deaths and 10 (38.5%) were deaths owing to other causes. The 1-, 3-, and 5-year OS probabilities were 88%, 74%, and 59%; 1-, 3-, and 5-year CSS probabilities were 97%, 83%, and 67%. The highest CIF for CRC-specific death at 60 mo was liver-only recurrence (0.69). Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictive of CRC-specific death. The peritoneum was the most common metastatic site among patients undergoing SBTS. Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictors of CRC-specific death.

Clinical markers of successful liquid biopsy-based genomic profiling in veterans with prostate cancer.

e17031 Background: Liquid biopsy with plasma circulating tumor DNA (ctDNA) is a noninvasive alternative to tissue genomic profiling. The yield of ctDNA is largely dependent upon the total amount and proportion of ctDNA in the total circulating DNA pool. Factors that predict successful genomic profiling via liquid biopsy amongst Veterans with prostate cancer are unknown. Methods: 764 veterans with prostate cancer who received liquid biopsy testing between February 2019-2021 were selected from the VA National Precision Oncology Program (NPOP) database. Baseline patient variables including age at specimen collection date, race, PSA, PSA doubling time (PSADT), sites of metastatic involvement (i.e., bone, brain, liver, lung, and lymph nodes), number of metastatic sites, Gleason score, and Gleason grade group were extracted from the VA Corporate Data Warehouse (CDW). Two independent approaches were used to define a successful liquid biopsy: Approach 1: Liquid biopsies with an alteration detected in one or more prostate cancer related genes ( AR, CDK12, SPOP, MED12, CCND1, BRAF, AKT1, TMPRSS2) (n = 337); Approach 2: Liquid biopsies with alterations detected in any gene detected by the Foundation One Liquid CDx assay (n = 670). We performed univariate and multivariate logistic regression analysis for Odds Ratio (OR), 95% confidence interval (CI), and conducted statistical significance tests to investigate associations between clinical factors and liquid biopsy test outcome. P-value < 0.05 was considered significant. Results: In Approach 1, the OR by univariate analysis was 4.80 (P < 0.001; 95% CI [3.09, 7.47]) for 4th PSA quantile group versus 1st PSA quantile group. The OR was 3.61 (P < 0.001; 95% CI [2.0, 6.5]) for PSADT less than 3 months versus PSADT more than 60 months; brain metastasis had the highest OR value among metastatic sites of 2.47 (P = 0.008; 95% CI [1.27. 4.8]). In multivariate analysis, PSA, PSADT and sites of metastasis remained significant risk factors. Statistical significance tests indicated PSA, PSADT, and sites of metastasis were significantly different between the success and failure groups. In Approach 2, no statistically significant associations were observed between the studied variables and any outcome. Conclusions: Factors such as PSA, PSADT, and metastatic site were significantly associated with a successful liquid biopsy of detecting prostate cancer related gene mutations, while the outcome of detecting any gene mutations was not statistically significant associated with studied variables in this study population. Given the likelihood that a significant number of non-prostate cancer mutations are likely due to clonal hematopoiesis, this finding is expected. Our findings may facilitate clinical decisions around genomic profiling by liquid biopsies in the absence of tumor tissue, thereby increasing the success rate of sequencing efforts for treatment selection.

The Role of Hypofractionated Radiation Therapy in the Management of Unresectable Hepatocellular Carcinoma (HCC)

Management of HCC without surgical resection or transplantation is poorly defined with no standard. Stereotactic body radiation therapy (SBRT) or hypofractionated image-guided radiotherapy (HIGRT), is an evolving, non-invasive, therapeutic option for patients with HCC delivering ablative doses with modest toxicity.We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT who presented to our University and Veterans Affairs (VA) radiation oncology departments from 2013 to 2019. Primary study endpoints included freedom from local progression, progression free survival, overall survival, and treatment-related toxicity.149 patients were included in our analysis with median delivered radiation dose of 50 Gy in 5 fractions. This included a total of 172 treatment courses, as 21 patients received more than one course (19 patients received 2 courses; 2 patients received 3 courses). Twenty-two of the re-treatment courses were to previously unirradiated lesions, while one course was delivered to a previously treated lesion exhibiting local progression. Sixty-nine percent (69%) of patients were Child-Pugh A and 89% had a baseline ALBI grade of 1-2 prior to treatment. A majority of patients (59%) had a single lesion with a median size of 2.70 cm (Q1 2.00, Q3 3.95). Fifty-seven percent (57%) of patients received a biologically effective dose (BEDα/β = 10) of at least 75 Gy and 48% of patients had undergone prior liver-directed therapy. All patients completed their intended treatment course with 1 patient (0.7%) experiencing Grade 3+ acute and 4 patients (2.6%) experiencing Grade 3+ late toxicities. Fifteen treatment courses (8.7%) resulted in non-classical radiation-induced liver disease (RILD), defined as an increase of 2 or more points in Child-Pugh score following radiation. With median follow up of 40 months, median overall survival was 25 months (95% CI 18-30 months). The 2-year freedom from local progression was 75% (95% CI 65-83%) overall, 64% (95% CI 48-77%) among patients who received BED ≤75 Gy and 86% (95% CI 72-93%) among those who received BED > 75 Gy. Median progression free survival was not reached. During the study period, 8.1% of patients developed regional nodal progression and 18.8% developed distant metastatic disease (42.9% osseous, 50.0% lung, 46.4% soft tissue/peritoneal/other involvement; multiple patients with more than one site of metastatic involvement).SBRT/HIGRT results in high rates of local control with minimal treatment related toxicities. Randomized, prospective trials should seek to establish SBRT/HIGRT as a standard local therapeutic option for patients with unresectable, non-metastatic HCC.

Retrospective Comparative Analysis of KRAS G12C vs. Other KRAS Mutations in mCRC Patients Treated With First-Line Chemotherapy Doublet + Bevacizumab.

BackgroundKRAS mutations in metastatic colorectal cancer (mCRC) define a subset of tumors that have primary resistance to anti-EGFR-based therapy. Data concerning whether different KRAS mutations may also have a prognostic value are lacking. Furthermore, novel KRAS G12C inhibitors are currently in development. The aim of our analysis was to compare response rates in patients treated with first-line chemotherapy doublet + Bevacizumab among different KRAS variants. Secondary end-points were progression free survival (PFS) and overall survival (OS).MethodsPatients with KRAS mutated mCRC treated with either FOLFIRI/FOLFOX/XELOX + Bevacizumab were eligible for enrollment. Patients whose tumor harbored NRAS mutations or that coexpressed also BRAF mutations were excluded from this retrospective analysis. Patients’ individual data were collected from patients’ records. Propensity score matching (nearest method, 1:2 ratio) was used to define the two different groups of patients for comparison (KRAS G12C mutated vs other KRAS variants). Eastern Cooperative Oncology Group Performance Status (ECOG PS), sex, metastatic site of involvement, synchronous vs metachronous metastatic disease, tumor sidedness, mucinous histology, primary tumor surgery, more than two lines of treatment for metastatic disease, and radical surgery of metastases were used as matching factors. Response rate (RR) was calculated by RECIST 1.1 criteria. Both progression free-survival and overall survival were calculated by Kaplan–Meier method. Categorical variables were compared by Fisher exact test for binomial variables and by chi-square test for all other instances. The level of statistical significance p was set at 0.05 for all tests.ResultsA total of 120 patients were assessed in the final analysis. Out of the 120 patients, 15 (12%) were KRAS G12C mutated. In the whole cohort of patients, 59/120 (49%) had partial response (PR), 42/120 (35%) had stable disease (SD), and 19/120 (16%) had progressive disease (PD) as the best response. In KRAS G12C patients, 4/15 (27%) had PR, 6/15 (40%) had SD, and the remaining 5/15 (33%) had PD as the best response. In patients with other KRAS mutations, 55/105 (52%) had PR, 37/105 (35%) had SD, and the remaining 13/105 (12%) had PD as the best response. The difference in RR between the two groups of patients was statistically significant (p=0.017). On the other hand, no difference in PFS (p=0.76) and OS (p=0.56) was observed. After matching procedures, the difference in response rates between KRAS G12C mutated patients vs the matched cohort of patients with other KRAS mutations remained statistically significant (p=0.016). KRAS G12C mutations were not associated with differences in sites of metastatic involvement, sex, and ECOG PS. On the other hand, synchronous vs metachronous metastatic disease (p=0.039), age > 75 years (p=0.043), and mucinous histology (p=0.008) were more frequent in G12C mutated tumors.ConclusionsIn our cohort of patients, it was observed that KRAS G12C mutations are associated with worse response rates compared to other KRAS variants when treated with standard chemotherapy doublet + Bevacizumab. On the other hand, both PFS and OS were not significantly different. Based on these findings, we believe that new treatment options focused on KRAS G12C inhibition should be tested mainly in first-line setting and in addition to standard chemotherapy doublet + Bevacizumab for mCRC patients, as they might “fill the gap” in response rates that was seen in our study.

Correlation between different levels of HER2 expression in circulating tumor cells (cHER2 ratio) and metastatic behavior in stageIVaggressive breast cancer.

3036 Background: The presence of HER2 expressing (HER2+) circulating tumor cells (CTCs) occurs often in metastatic breast cancer (MBC) patients (pts). We have previously showed that the ratio among CTCs expressing high level of HER2 and the total number of HER2+ CTCs (circulating HER2 ratio, cHer2 ratio) has a prognostic role in MBC patients. Here we further investigate the role of the cHER2 ratio in the process of metastatic spread. Methods: Under IRB-approved study we prospectively analyzed blood samples of patients with MBC enrolled before starting a new line of therapy. Samples were collected from pts treated at Northwestern University (Chicago, IL) between 2016 and 2020. CTCs were enumerated through CellSearch (Menarini Silicon Biosystems, Bologna, Italy) and characterized for HER2 expression using the CellSearch CXC Kit. HER2+ CTCs were divided in 3 different categories (1+,2+,3+) leaning on fluorescence intensity. Pts with <5 CTCs (stage IV indolent) were excluded from the analysis. The cHER2 ratio, defined as the sum of 2+ CTCs and 3+ CTCs divided by the total number of HER2+ CTCs, was used to split the remaining pts in 2 different cohorts: cHER2 ratio high (> 0.75) (cHER2high) and cHER2 ratio low (≤0.75) (cHER2low). The frequency of each metastatic site (i.e. liver, lung, central nervous system, bone, lymph nodes, skin/soft tissue, serosa) and the total number of different sites involved (1-7, ≤2 and >2 sites) were compared among the two sub-populations and analyzed through Fisher exact test. Results: Out of 98 pts enrolled, 77 were classified as cHER2low and 21 as cHER2high. We observed a higher frequency of oligometastatic pts (≤2 sites involved) in the cHER2high cohort (16, 76%), compared to only 29 (37%) in the cHER2low (p<0.005). Moreover, the cHER2 ratio was associated with a tropism toward specific sites of disease spread with higher incidence of liver, lung and lymph nodes metastases in the cHER2low cohort (p<0.05). No other statistical associations were observed in respect of specific organ tropism. The frequency of involvement for each metastatic site among the two cohorts are reported in the table. Conclusions: Measuring CTCs enumeration and HER2 expression we identified two cohorts, cHER2high and cHER2low, associated with distinct patterns of metastatic spread. The cHER2low pts were correlated to multiple sites of metastatic involvement, with particular tropism toward liver, lung and lymph nodes. These results confirm the prognostic role of the cHER2 ratio, suggesting a peculiar biological meaning of the HER2+ 1+ CTCs.[Table: see text]

An observational retrospective analysis of the main metastatic site and corresponding locoregional treatment as a prognostic factor in metastatic gastric cancer.

Despite novel drugs, the prognosis for patients with metastatic gastric cancer remains poor. In rare instances, locoregional therapies are used in addition to standard chemotherapy in patients with oligometastatic involvement. This type of approach has not been supported by solid published evidence. The aim of the present retrospective study was to assess the prognostic impact of factors such as metastatic site, tumour histology and locoregional treatment in patients with metastatic gastric cancer. A total of 184 patients with metastatic gastric or gastroesophageal junction adenocarcinoma who received at least one line of palliative therapy with doublet or triplet chemotherapy were enrolled in the current analysis. Median overall survival (OS) was 8.32 months (95% CI, 7.02–9.41) and median progression-free survival (PFS) was 4.16 months (95% CI, 3.24–5.08). Lung metastases vs. other sites of metastatic involvement [hazard ratio (HR), 0.27; P=0.0133] and intestinal histology (HR, 0.48; P=0.08) were significantly associated with an improved OS. Improved PFS was also observed (HR, 0.49; P=0.10 and HR, 0.72; P=0.08 for lung metastases and intestinal histology, respectively). Second line chemotherapy and locoregional treatment of metastases (surgery or radiotherapy) were associated with improved OS (HR, 0.52; P<0.0001 and HR, 0.35; P<0.0001, respectively). Multivariate analysis confirmed an independent prognostic role for OS only for locoregional treatment, second line treatment and intestinal histology. The present results suggested that the presence of lung metastases alone was not a relevant prognostic factor and was influenced by the availability of further lines of treatment or by locoregional treatments. Locoregional treatments in patients with oligometastatic disease should be offered as they allow prolonged survival in patients with otherwise relatively short life expectancy.

Evaluation of Clear Cell, Papillary, and Chromophobe Renal Cell Carcinoma Metastasis Sites and Association With Survival

There exists considerable biological and clinical variability between histologic variants of metastatic renal cell carcinoma (mRCC). Data reporting on patterns of metastasis in histologic variants of mRCC are sparse. To characterize sites of metastasis and their association with survival across the 3 most common histologic variants of mRCC: clear cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). In this multicenter, international cohort study, the International mRCC Database Consortium (IMDC) database was used to identify consecutive patients starting systemic therapy for mRCC between 2002 and 2019. Patients with mixed histologic subtype were excluded. Statistical analysis was performed from February to June 2020. Data regarding histologic subtype and sites of metastatic involvement at the time of first systemic therapy initiation were collected. The primary outcomes were prevalence of metastatic site involvement and overall survival (OS) from time of systemic therapy initiation. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. A total of 10 105 patients were eligible for analysis. Median (interquartile range) age at diagnosis was 60 (53-67) years, 7310 (72.4%) were men and 8526 (84.5%) underwent nephrectomy. Of these, 9252 (92%) had ccRCC, 667 (7%) had pRCC, and 186 (2%) had chrRCC. The median number of sites of metastasis was 2 (range, 0-7). In ccRCC, the most common sites of metastasis were lung (70%; 6189 of 8804 patients [448 missing]), lymph nodes (45%; 3874 of 8655 patients [597 missing]), bone (32%; 2847 of 8817 patients [435 missing]), liver (18%; 1560 of 8804 [448 missing]), and adrenal gland (10%; 678 of 6673 patients [2579 missing]). Sites of metastasis varied between subtypes. Lung, adrenal, brain, and pancreatic metastases were more frequent in ccRCC, lymph node involvement was more common in pRCC, and liver metastases were more frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (95% CI, 13.7-18.8 months) for the pleura and 50 months (95% CI, 41.1-55.5 months) for the pancreas. Compared with ccRCC, patients with pRCC tended to have lower OS, regardless of metastatic site. Sites of metastatic involvement differ according to histologic subtype in mRCC and are associated with OS. These data highlight the clinical and biological variability between histologic subtypes of mRCC. Patterns of metastatic spread may reflect differences in underlying disease biology. Further work to investigate differences in immune, molecular, and genetic profiles between metastatic sites and histologic subtypes is encouraged.

Characterizing sites of metastatic involvement in metastatic clear-cell, papillary, and chromophobe renal cell carcinoma.

5071 Background: There exists considerable biological and clinical variability between histologic variants of metastatic renal-cell carcinoma (mRCC). Data reporting on sites of metastatic involvement in less common histologies of mRCC are sparse. We sought to characterize the frequency of metastatic site involvement across the three most common histologies of mRCC: clear-cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). Methods: Using the International mRCC Database Consortium (IMDC) database, patients with mRCC starting systemic therapy between 2002-2019 were identified and sites of metastases at the time of systemic therapy initiation were documented. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. The primary outcomes were prevalence of metastatic site involvement and overall survival (OS). Patients with mixed histology were excluded. Results: 10,105 patients were eligible for analysis. Median age at diagnosis was 60, 72% were male and 79% underwent nephrectomy. 92%, 7% and 2% of patients had ccRCC, pRCC, and chrRCC, respectively. Frequency of metastatic site involvement across the histologic subtypes is shown in Table. Lung, adrenal, brain and pancreatic metastases were more frequent in ccRCC, lymph node involvement was most frequent in pRCC, and liver metastases were most frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (brain/pleura) and 50 months (pancreas). OS by site of metastatic involvement was compared between histologies for the four most common sites of metastases (lung, lymph nodes, bone, liver). As compared to patients with ccRCC, patients with pRCC had lower OS regardless of site of metastasis (p &lt; 0.05). Power was limited and thus differences in OS between ccRCC and chrRCC were not detectable. Conclusions: Sites of metastatic involvement differ based on histology in mRCC. These data highlight the clinical and biologic variability between histologic subtypes of mRCC and constitute the largest cohorts of patients with metastatic pRCC and chrRCC to report on sites of metastases. Sites of Metastatic Involvement by Histology. [Table: see text]

SAT-178 Incidence, Patterns of Clinical Presentation, and Outcomes of Patients with Brain Metastasis Due to Adrenocortical Carcinoma

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy, with a heterogeneous but, frequently, dismal prognosis; patients with metastatic ACC have a five-year survival that ranges between 0 and 28%. Metastatic ACC may be present at diagnosis or during follow-up as disease recurrences. The most common sites of metastatic lesions include the liver, lungs, lymph nodes and bones. The brain has only rarely been reported as a site of metastasis in this neoplasia and, to the authors’ knowledge, little is known regarding the incidence, patterns of clinical presentation and disease progression, and outcomes. Objective: The aim of this report was to describe the clinical characteristics of adult patients with ACC who developed brain metastasis evaluated at a tertiary oncological center (ICESP) from Brazil. Methods: Retrospective analysis of medical records including evaluation of laboratory and imaging exams and pathologic data (in cases where surgical resection of the metastasis was performed). Results: In the last ten years (2009-2019), fifty-four patients have been treated for ACC at ICESP; all of them with advanced disease (locally advanced disease and metastatic disease). The median age at the time of diagnosis of ACC was 44 (range 24-61 yrs.). No patients presented metastasis at central nervous system (CNS) at the initial diagnosis; however, during follow-up, we identified brain metastasis in six patients (11.1%). The median time between ACC diagnosis and the detection of brain metastasis was 20.8 months (range 5-53 mo.). In all of these six cases, at least three other sites of metastatic involvement were already present when the brain involvement was diagnosed and, therefore, all of them had already been treated with mitotane in association with at least one line of cytotoxic chemotherapy. The number of brain metastasis in each of these six patients varied from one to eight and median size of lesion was 1.7 cm (range 0.5-4.0 cm). Secondary headache and seizure were the main symptoms of presentation and one or two of these symptoms occurred in all but in one patient, in which diagnosis was due to screening with brain MRI. In four patients with stable disease elsewhere, surgical resection of one or two brain metastases was performed. In these cases, SF1-positive immunohistochemistry confirmed the adrenocortical origin of the lesion. The median time between CNS metastasis detection and death was 3.8 months (range 0.4-59.6 mo.), and complications due to brain metastasis were the leading cause of death. Conclusions: In our institute, brain metastasis occurred in 11.1% of advanced ACC, a prevalence that is higher than previously reported in literature. Despite the relative small number of patients included in this study, we highlight the possibility of brain metastasis in patients with ACC, particularly in cases with a prolonged disease course and multiple systemic treatments.

Sites of metastasis and survival in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).

642 Background: Across a variety of malignancies, sites of metastatic involvement are known to be associated with differences in survival. We sought to characterize the frequency and survival of patients with different sites of metastases in mRCC. Methods: Patients with mRCC starting treatment between 2002-2019 were identified and sites of metastatic involvement at time of systemic therapy initiation were documented. The primary outcomes of interest were prevalence of metastatic site involvement and overall survival (OS). Multivariable Cox regression models were performed to adjust for imbalances in IMDC risk factors. Results: A total of 10,320 patients were included. Median age at diagnosis was 60, 73% were male, 87% had clear-cell histology and 80% underwent nephrectomy. The most common sites of metastases were: lung (71%), lymph nodes (49%), bone (36%), liver (21%), adrenal (9%), brain (9%), pancreas (5%), pleura (4%) and thyroid (0.6%). Survival by metastatic site and adjusted hazard ratios are presented in Table. Conclusions: Metastases to endocrine organs (pancreas, thyroid, adrenal) are infrequent but are associated with the longest median OS, whereas bone, liver, pleura and brain metastases are associated with median OS &lt; 18 months. These benchmark values are useful for patient counseling and study design. Sites of metastatic involvement may reflect differences in underlying disease biology, and further work to investigate differences in immune, molecular and genetic profiles between metastatic sites is encouraged.[Table: see text]

Solitary pancreatic metastasis from a primary breast carcinoma: A case report

Breast cancer is the most frequent cancer among women. Common sites of metastatic involvement of breast cancer, in order of frequency, are bone, lung, pleura, soft tissues, and liver. Isolated metastasis to the pancreas from a primary breast cancer is a rare occurrence. Presented herein is a case of a 55-year-old female patient postmastectomy for breast carcinoma who developed signs and symptoms of obstructive jaundice secondary to a pancreatic head mass. It was documented to be metastatic from the primary breast cancer and was managed surgically to relieve the biliary obstruction.

18F-Fluorocholine PET/MRI in Restaging of Prostatic Carcinoma in Relation to PSA Level and Detection of Active Disease.

To evaluate our own experience with 18F- fluoromethylcholine-(FCH)-positron-emission tomography combined with magnetic resonance imaging (PET/MRI) in restaging of patients with prostatic carcinoma and elevated serum prostate-specific antigen (PSA) level. The analysis was performed on a sample of 100 male patients who underwent 18F-FCH-PET/MRI, with a mean age of 63.2 years (range=47-78 years). The imaging was performed using an integrated PET/MRI hybrid system after intravenous application of 18F-FCH at a dose of 1.25 MBq/kg. The number and sites of pathological accumulation of FCH related to local recurrence, nodal spread and skeletal metastases were compared to corresponding MRI findings; furthermore, the relation of PSA level and presence of FCH accumulation in tumorous tissue was assessed; finally we correlated the findings of different sites of metastatic involvement. In patients with a PSA level up to 2 ng/ml, accumulation in tumorous tissue of local recurrence or metastases was found in 83.33% in cases of biochemical relapse, and in patients with PSA level above 5 ng/ml in 100% of cases. In general, we found any finding explained rise of PSA level in 94% of patients. 18F-FCH-PET/MRI using an integrated system with 1,25 MBq/kg dosing of FCH is a valuable tool in evaluation of restaging in patients with prostatic carcinoma, with high detection rate even in those with a low serum PSA level.

Locoregional treatments and sites of metastatic involvement in metastatic gastric cancer patients: do they influence survival?

Locoregional treatments and sites of metastatic involvement in metastatic gastric cancer patients: do they influence survival?

Low positive yield from routine inclusion of the brain in whole-body 18F-FDG PET/CT imaging for noncerebral malignancies

This retrospective study was conducted to assess the incremental value, if any, of including the brain in whole-body fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) studies in patients with extracalvarial primary malignancies. The scan data of 5110 F-FDG PET/CT studies conducted from March 2009 to December 2011 were reviewed. Abnormal brain lesions were detected in 76/5110 patients who had undergone F-FDG PET/CT studies. Among them, 16 patients had lesions with F-FDG uptake less than that of the surrounding background and 54 had lesions with increased F-FDG uptake. Six patients had neither increased nor decreased tracer uptake in their brain lesions (identified on the CT component of the study). In the first group of patients, infarct was seen in four patients, treated brain metastases were seen in eight (five surgical and three through external beam radiotherapy), and untreated metastases were seen in four patients. In the 54 patients with increased uptake, metastatic lesions were identified in 51 and central nervous system involvement by systemic lymphoma in three. The third group showed metastases in four patients and central nervous system involvement by systemic lymphoma in one; one patient was lost to follow-up without a final diagnosis. Out of 63 patients with untreated cerebral metastases detected on the F-FDG PET/CT study, cerebral metastases were unknown before F-FDG PET/CT in 40 patients. Of these 40 patients, the brain was the only site of metastatic involvement in eight patients. Inclusion of the brain routinely in whole-body F-FDG PET/CT studies detected previously unknown metastases in only 0.7% (40/5110) of studies, with negligible impact (0.15%) on staging.

Clinical colorectal cancer (CRC) subsets in advanced disease: Patterns of metastatic spread to predict survival.

e14703 Background: Advanced CRC is a heterogeneous disease. Some patients exhibit diffuse metastatic spread while others show selective organ involvement. We aimed to investigate the frequency and survival implications of initial pattern of metastatic spread in a Mexican cohort. Methods: We retrospectively reviewed charts and radiologic images of patients with advanced CRC at our institution from 2004 to 2011. The initial pattern of spread was recorded. Categories depending on the predominant site of involvement were: 1) Locally advanced, 2) Hepatic, 3) Pulmonary, 4) Peritoneal or 5) Diffuse. Survival was estimated by the Kaplan Meier method and Log rank test used to determine survival differences among categories. Results: 179 patients with advanced CRC were identified. Median age was 60yo, 56% were male. Primary tumor location was 50.3% colon, 27.9% rectum, 17.9% recto-sigmoid and 3.4% had synchronous disease. 66% of patients had advanced disease at diagnosis and 34% were recurrent cases. Metastasis at diagnosis involved the liver in 105 (58.7%), peritoneum in 49 (27.4%), lung in 56 (31.3%) and non regional lymph nodes in 36 (20.1%) patients. Notably, 101 (56%) patients had a predominant site of metastatic involvement: locally advanced in 3 (1.7%), hepatic in 51 (28.5%), peritoneal in 21 (11.7%), pulmonary 21 (11.7%) while 78 patients (44%) had disseminated disease. Median overall survival was 15 months (n= 179) and differed according to predefined CRC subsets: 9, 13, 22, 23, and 52 months for peritoneal, disseminated, hepatic, locally advanced and pulmonary spread respectively p=.018 (significant after multivariate analysis). Other factors associated with better survival were female gender p=.040, absence of morbidity from primary tumor p=.27, resection of primary tumor p=.004, recurrent presentation p=.039, and access to 1stline chemotherapy p=.00. Conclusions: Over 50% of patients exhibited selective metastatic spread. Clinically defined subsets correlate with better (pulmonary) or worse (peritoneal/disseminated) survival. This finding might have implications in patient selection for regional therapies and encourage research to find the molecular determinants of this biologic behavior.

Trends in use of intravenous bisphosphonates in patients with prostate cancer and newly diagnosed metastases to bone in two large U.S. integrated health systems.

192 Background: Bone is a common site of metastatic involvement in patients (pts) with prostate cancer (PC). Bony metastases (mets) are associated with skeletal complications, which can cause significant morbidity and mortality. Intravenous bisphosphonates (IV BPs) have been proven to reduce the incidence and onset of skeletal complications. Patterns of use of IV BPs in clinical practice in pts with bone mets due to PC are largely unknown. Methods: Using the tumor registries and electronic data stores at two large US integrated health systems that serve a total of approximately 1.3 million persons, we retrospectively identified all pts aged ≥18 yrs with primary PC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Information on all administrations of IV BPs between date of diagnosis of bone mets and death, loss to follow-up, or end of study was extracted from administrative data stores and electronic medical records, which also were reviewed by trained medical abstractors for evidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, surgery to bone, radiation to bone). Results: We identified a total of 461 pts with primary PC and newly diagnosed bone mets. Mean (SD) age was 72.8 yrs (10.7 yrs); 75% were Caucasian, and 21% were African-American. Median duration of follow-up after diagnosis of bone mets was 1.3 yrs. One-fifth (20.2%) of study subjects received IV BPs (92% zoledronic acid, 8% pamidronate) during follow-up--10.8% prior to, and 9.3% after, first on-study SRE. Median time from diagnosis of bone mets to first administration of IV BPs was 1.7 yrs, and the median number of administrations was 3. The percentage of study subjects receiving IV BPs increased steadily over the 15-yr study period--from 7.5% among those newly diagnosed with bone mets in 1995-1999, to 19.8% among those newly diagnosed with bone mets in 2000-2004, to 27.5% among those newly diagnosed with bone mets in 2005-2009. Conclusions: Despite a high risk of SREs in pts with PC and bone mets, most such pts still do not receive IV BPs.

Risk of skeletal-related events (SREs) in patients with breast cancer (BC) and newly diagnosed metastases to bone.

91 Background: Bone is a common site of metastatic involvement in patients (pts) with BC. Bony metastases (mets) are often associated with SREs (spinal cord compression [SCC], pathologic fracture [PF], surgery to bone [SB], radiotherapy to bone [RT]). Skeletal complications cause significant morbidity and mortality. Current estimates of SRE risk come principally from randomized clinical trials. Information from routine clinical practice is limited. Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 yrs with primary BC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Electronic medical records were reviewed by trained abstractors for evidence of SREs between date of bone mets diagnosis and death, loss to follow-up, or end of study. Cumulative incidence of SREs was estimated in the presence of competing risk of death. Results: We identified a total of 378 pts with primary BC and newly diagnosed bone mets; 87 pts had evidence of SREs at initial diagnosis of bone mets and were excluded from the analyses. Among the remaining 291 pts, mean (SD) age was 58.2 yrs (14.3 yrs), and 99% were women; 48% were African-American and 46% were Caucasian. Median duration of follow-up after diagnosis of bone mets was 16.1 months (mos). At 12 mos, cumulative incidence of SREs was 44.5% (SCC, 5.2%; PF, 21.0%; SCC and/or PF, 23.3%; SB, 7.6%; RT, 34.3%) (Table). Corresponding figures at 24 mos were 53.8% (SCC, 7.5%; PF, 29.3%; SCC and/or PF, 32.5%; SB, 9.4%; RT, 41.7%). Approximately one-half (45.0%) of study subjects received intravenous bisphosphonates prior to SRE. Conclusions: Pts with BC in routine clinical practice are at high risk of SREs following initial diagnosis of bone mets. [Table: see text]

Primary Tumor Thickness as a Prognostic Factor in Merkel Cell Carcinoma: The Next Big Thing?

Fifty years ago, there was a cutaneous malignancy that was rapidly increasing in incidence and beginning to receive serious scrutiny by surgical oncologists, dermatopathologists, and dermatologists. It nearly always presented at a locally advanced stage with an expectation of a poor outcome. Prognostic factors were poorly understood, so the occasional patient with advanced disease who defied expectations and survived long-term was a notable and mysterious case. Controversy surrounded the management of the regional lymph nodes, despite recognition that they were frequently the first (and sometimes the only) site of metastatic involvement—in part because of pessimism that distant dissemination of tumor had already occurred and hence treating the nodes was a futile effort. The name of this malignancy? Melanoma. So what changed over the past 5 decades? One of the most significant advances in understanding the prognosis of melanoma came in 1969, when Wallace Clark and colleagues called attention to the prognostic significance of the level of tumor invasion into the dermis. Soon thereafter, Alexander Breslow introduced the micrometer measurement of tumor thickness that now bears his name. Importantly, Breslow showed that tumor thickness was a better prognostic marker than Clark’s levels of invasion or measured tumor diameter, while noting that ‘‘in general all measurements of tumor size increased with the stage of invasion, but there was a great deal of overlap.’’ Unfortunately, in 1970, relatively few melanomas were diagnosed at the earliest stages of thickness and invasion that portended a favorable prognosis. A second transformational event was the introduction of easily understandable and applicable diagnostic criteria for identifying pigmented lesions suspicious for representing early melanoma (and hence requiring biopsy)—the ABCD criteria. Increasingly, melanomas were diagnosed at an early stage where the expectation was for an excellent outcome, and those few patients who developed distant disease were an exception to the norm. Indeed, outcomes quickly improved to the point that aggressive surgical management of the regional nodes became controversial because of the perception that most patients would not have evidence of metastasis and hence were being subjected to morbidity without prospect of benefit. Of course, this set the stage for the third revolutionary development—sentinel lymph node biopsy. At last, melanomas with early dissemination to the regional nodes could be reliably identified and treated, and the number of cases with truly unexpected outcomes dramatically decreased. Even with recognizing how far we have come in this disease, thick melanomas are still a major challenge, especially in elderly patients. Once a melanoma exceeds 4 mm in thickness, while ulceration and sentinel node status retain prognostic importance, our ability to predict which patients will do well or poorly is fairly limited. Nonetheless, the recognition of the clinical significance of that 4 mm thickness cutoff has unequivocally improved our understanding of the natural history of melanoma. Today, there is another cutaneous malignancy, Merkel cell carcinoma, that is rapidly increasing in incidence and beginning to receive serious scrutiny by surgical oncologists, dermatopathologists, and dermatologists. It nearly always presents at a locally advanced stage, usually in This is an Editorial commentary regarding the article by Lim et al. doi:10.1245/s10434-012-2509-x.

Risk of skeletal-related events (SREs) in patients with prostate cancer (PC) and newly diagnosed metastases to bone.

e15197 Background: Bone is a common site of metastatic involvement in patients (pts) with PC. Bony metastases (mets) are often associated with SREs (spinal cord compression [SCC], pathologic fracture [PF], surgery to bone [SB], radiotherapy to bone [RT]). Skeletal complications cause significant morbidity and mortality. Current estimates of SRE risk come principally from randomized clinical trials. Information from routine clinical practice is limited. Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 yrs with primary PC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Electronic medical records were reviewed by trained abstractors for evidence of SREs between date of bone mets diagnosis and death, loss to follow-up, or end of study for evidence of first SRE. Cumulative incidence of SREs was estimated in the presence of competing risk of death. Results: We identified a total of 420 men with primary PC and newly diagnosed bone mets; 42 pts had evidence of SREs at initial diagnosis of bone mets and were excluded from the analyses. Among the remaining 378 pts, mean (SD) age was 72.7 yrs (9.8 yrs); 38% were Caucasian and 58% were African-American. Median duration of follow-up after diagnosis of bone mets was 17.1 months (mos). At 12 mos, cumulative incidence of SREs was 31.6% (SCC, 6.1%; PF, 15.0%; SCC and/or PF, 19.1%; SB, 3.9%; RT, 24.4%) (Table). Corresponding figures at 24 mos were 45.3% (SCC, 12.5%; PF, 22.2%; SCC and/or PF, 30.2%; SB, 6.2%; RT, 34.9%). Relatively few pts (14.6%) received intravenous bisphosphonates prior to SRE. Conclusions: Pts with PC in routine clinical practice are at high risk of SREs following initial diagnosis of bone mets. [Table: see text]

Risk of skeletal-related events (SREs) in patients with breast cancer (BC) and newly diagnosed metastases to bone.

e12024 Background: Bone is a common site of metastatic involvement in patients (pts) with BC. Bony metastases (mets) are often associated with SREs (spinal cord compression [SCC], pathologic fracture [PF], surgery to bone [SB], radiotherapy to bone [RT]). Skeletal complications cause significant morbidity and mortality. Current estimates of SRE risk come principally from randomized clinical trials. Information from routine clinical practice is limited. Methods: Using the tumor registry and electronic data stores at a large US Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 yrs with primary BC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Electronic medical records were reviewed by trained abstractors for evidence of SREs between date of bone mets diagnosis and death, loss to follow-up, or end of study. Cumulative incidence of SREs was estimated in the presence of competing risk of death. Results: We identified a total of 378 pts with primary BC and newly diagnosed bone mets; 87 pts had evidence of SREs at initial diagnosis of bone mets and were excluded from the analyses. Among the remaining 291 pts, mean (SD) age was 58.2 yrs (14.3 yrs), and 99% were women; 46% were Caucasian and 48% were African-American. Median duration of follow-up after diagnosis of bone mets was 16.1 months (mos). At 12 mos, cumulative incidence of SREs was 44.5% (SCC, 5.2%; PF, 21.0%; SCC and/or PF, 23.3%; SB, 7.6%; RT, 34.3%) (Table). Corresponding figures at 24 mos were 53.8% (SCC, 7.5%; PF, 29.3%; SCC and/or PF, 32.5%; SB, 9.4%; RT, 41.7%). Approximately one-half (45.0%) of study subjects received intravenous bisphosphonates prior to SRE. Conclusions: Pts with BC in routine clinical practice are at high risk of SREs following initial diagnosis of bone mets. [Table: see text]