Primary Tumor Site In Patients Research Articles

Diagnostic accuracy of f18-fluorodeoxyglucose positron emission tomography-computed tomography in the evaluation of carcinoma of unknown primary: A single-center study

Background: The term carcinoma of unknown primary (CUP) is not a single disease entity that it can be explicated as the recognition of metastasized tumor, in which the primary origin of the malignancy from an organ or site remains occult. The term refers to a clinical disorder that revolves around and represents a diversified metastatic tumor group, for whom the diagnostic investigations are unable to pinpoint the primary site of the tumor, comprising extensive radiological techniques, invasive endoscopic procedures, and histopathology, many which fail to diagnose the primary site. Aims and Objectives: The study was conducted to ascertain the diagnostic accuracy of fluorine-18 labeled fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) in the evaluation of CUP. The secondary objective of the study was to identify rate of the primary malignancies localized on 18F-FDG PET-CT that presents as CUP in local settings. Materials and Methods: The prospective and cross-sectional study included patients with CUP who underwent 18F-FDG PET-CT scans between October 2021 and February 2022. The primary site localized on 18F-FDG PET-CT was confirmed through biopsy and histology. False-negative and false-positive patients were ascertained through biopsy and/or follow-up of 6 months. Results: Of a total of 63 patients, 57.1% were male, while 42.9% were female with a mean age of 56.27 years. The overall detection rate of primary tumor (PT) site on 18F-FDG PET-CT was 88.8%. Abnormal sites and indicative of primary malignant tumor were correctly detected in 79.36% that were truly positive proven on biopsy. False-negative rate of scan was 4.76%, though malignancy was proven through other investigations or follow-up, while 6.36% had true negative and 9.52% showed false-positive results on the scan. In this study, the calculated diagnostic accuracy of 18F-FDG PET-CT identified as 85.7%, sensitivity 94%, specificity 40%, positive predictive value 89.2%, and negative predictive value 57.1%. Conclusion: 18F-FDG PET-CT demonstrated high sensitivity and diagnostic accuracy ascertaining the PT site in patients with CUP in our study population.

Sensitivity of [18F]FDG PET/CT and classification of the primary tumor site in patients with carcinoma of unknown primary.

The aim of this study is to find the sensitivity of the [18F]FDG PET/CT and the classification of the primary sites of carcinoma of unknown primary (CUP) as a single-center experience. Sixty-eight patients with a mean age of 62.43 ± 12.78 years were included in this study retrospectively. Sixty-five patients had biopsy or surgery after PET/CT, which revealed pathological diagnoses of malign primary tumors, while primary tumor site could not be detected in three patients with histopathological examination. We evaluated the primary site of CUP with [18F]FDG PET/CT. Primary sites of three patients were not determined by histopathological examination. Malign lesions indicating the primary site of tumor were identified in 52 of 68 patients with PET/CT correctly. The primary tumor was lung cancer in 14 patients, cholangiocellular cancer in 9 patients, lymphoma in 9 patients, pancreas cancer in 6 patients, gastric cancer in 4 patients, ovary cancer in 4 patients, colon cancer in 4 patients, breast cancer in 3 patients, hepatocellular cancer in 2 patients, rectal cancer in 2 patients, sarcoma in 2 patients, esophagus, renal cell cancer, squamous cell cancer, endometrium cancer, malign melanoma, and multiple myeloma in 1 patient with histopathological examination. PET/CT was false positive in one patient. There were 13 patients in whom primary tumor could not be localized by PET/CT, but was diagnosed by histopathological evaluation. PET/CT should be the first-line diagnostic tool for CUP, other diagnostic imaging tools should be applied after a negative whole-body PET/CT.

Mucoepidermoid carcinoma: Evaluating the prognostic impact of primary tumor site

Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland malignancies. Our aim was to evaluate the prognostic impact of primary tumor site in patients with MEC. Material and MethodsThis cohort identified 308 patients with MEC who underwent primary surgery between 1985 and 2015. Survival outcomes were determined using the Kaplan–Meier method. Hazard ratios for primary site were determined using the Cox proportional-hazards model. ResultsOne hundred eighty (58%) patients were diagnosed with minor and 128 (42%) with major salivary gland cancer. Primary site in the minor salivary gland group included 137 (44%) oral cavity, 38 (12%) pharynx, 3 (0.9%) nasal cavity, and 2 (0.6%) trachea and larynx. The major salivary gland group included 118 (38%) parotid, 8 (3%) submandibular, and 2 (0.6%) sublingual. With a median follow-up of 73 months, 5-year overall survival and disease-specific survival were 84% and 91%, respectively. Patients with tumors located in the hard palate and retromolar trigone had the best survival, while patients with tumors located in the paranasal sinuses and submandibular gland had the poorest survival. After controlling for tumor grade and stage, MEC primary site was not predictive of survival or recurrence. On multivariate analysis, worse DSS was associated with stage III–IV tumors (HR: 7,11; 95% CI: 1.19–26.43; p = 0.0034) and high-grade tumors (HR: 19.12; 95% CI: 2.26–162.77; p = 0.0068). ConclusionsWhile high grade and advanced overall stage were found to be independent predictors of worse survival, primary tumor site was not predictive of poor outcome.

Role of FDG PET/CT for detection of primary tumor in patients with extracervical metastases from carcinoma of unknown primary

AimTo explore the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP). We evaluated patient outcomes as overall survival (OS). Materials and methodsIn a single-center, retrospective study (2005–2019), patients with extracervical metastases from CUP underwent FDG PET/CT to detect primary tumor sites. The final diagnosis was based on histopathology/or clinical follow-up of at least 12 months. ResultsA total of 83 patients [Male 41 (49%), mean age 59 ± 14 years, range: 32–83 years] fulfilled the inclusion/exclusion criteria and were enrolled for analysis. The primary tumor was detected in 36 out of 83 (43%) patients based on histopathology/or clinical follow-up. PET/CT suggested the primary tumor site in 39 (47%) patients with diagnostic accuracy of 87%, sensitivity 89%, specificity 85%, PPV 82%, NPV 91% and detection rate 39%. Patients with oligometastases (<3) (2.16 years, 1.04–2.54) and primary unidentified (1 year, 0.34–2.14) had longer median survival time compared to the patients with multiple metastases (0.67 years, 0.17–1.58, p = 0.009) and primary identified (0.67 years,0.16–1.33, p = 0.002). The SUVmax of the primary or metastatic lesions with maximum uptake was not significantly related to survival. ConclusionsPET/CT could reveal the primary tumor site in 39% of the patients. It demonstrated the metastatic disease burden and distribution in patients with ‘primary obscured’, which directs management. Patients with multiple metastases and primary identified had a poorer prognosis. In patients with primary unidentified after PET/CT, a further search was futile.

Pivotal role of PET/CT in characterization of occult metastasis with undetermined origin

BackgroundThe purpose of this multicenter diagnostic accuracy test study was conducted to assess the role of positron emission tomography/computed tomography in the detection of primary tumor in cases of metastasis of undetermined primary site, to estimate its capability in detecting additional lesions as well as evaluating disease burden and staging. This multicentric diagnostic accuracy test study included 175 patients with pathologically proven, radiologically, and/or clinically suspected metastatic lesions of undetermined primary site. Clinical, surgical, and histopathologic findings and correlative imaging modalities were used to assess the results of PET/CT; the accuracy of PET/CT was expressed in terms of sensitivity and specificity, positive and negative predictive values.ResultsThe study included 175 patients; PET-CT-positive lesions suggestive of primary malignant tumors were detected in 105 out of 175 patients. These lesions were pathologically proven to be malignant (true positive) in 100/175 patients (57.1%). Five out of 175 patients (2.9%) proved to be falsely positive after pathologic assessment; 70 out of 175 patients (40%) were negative for detection of primary malignancy all over the body by PET/CT (true negative) with no false negative results. PET/CT achieved a sensitivity of 100%, and specificity of 93.3% in detection of unknown primary tumor location.ConclusionPET/CT is an effective modality for early detection of the primary tumor site in patients with cancer of undetermined primary (CUP) which facilitates early selection of appropriate treatment protocols that will improve patients’ prognosis.

DS-Screen: Prospective analysis of the expression status of FGFR2 and HER2 in colorectal and gastric cancer population.

431 Background: FGFR2 and HER2 proteins are well-known molecular targets for cancer therapy, and there are emerging attractive protein-targeted agents such as second generation antibody-drug conjugates. However, there are still limited information about the expression status of FGFR2 and HER2 in gastrointestinal cancer and their relationship to patient background with cancer. In this study, expression status of FGFR2 and HER2 in advanced/metastatic gastric cancer (GC) and colorectal cancer (CRC) were prospectively analyzed in clinical setting. Moreover, eligible patients for the clinical trials of DS-1123 or DS-8201, which are FGFR2- or HER2-targeting anti-cancer agent respectively, were screened. Methods: Patients with advanced/metastatic GC, gastroesophageal junctional cancer (GEJ), and CRC were enrolled. Expression status of FGFR2 and HER2 were prospectively analyzed by IHC and/or FISH. Results: A total of 565 patients (GC; 160, GEJ; 16, CRC; 389) have been enrolled in this study from November 2016 to June 2018. FGFR2 expression (IHC 1+~3+) was observed in 24%, 44%, and 3% of GC, GEJ, and CRC respectively. HER2 expression (IHC 2+, 3+) was observed in 24%, 44%, and 17% of GC, GEJ, and CRC respectively. Expression levels of FGFR2 and HER2 seemed to be not correlated with each other in all 3 types of cancer. Distributions of expression level of FGFR2 or HER2 were slightly different among the histological types in GC. In CRC, distribution of HER2 expression level was also slightly different among the histological types and HER2 expression level was higher in KRAS/NRAS wild type compared to KRAS/NRAS mutant. There was no association between HER2 expression level and primary tumor sites in patients with CRC. Slight concordance of HER2 expression was observed between IHC and FISH in CRC. A total of 7 patients have been enrolled in clinical trials of DS-1123 or DS-8201 through this study based on the analysis findings. Conclusions: This study showed insights into the expression status of FGFR2 and HER2 in GC and CRC as a large-scale prospective analysis. Seven patients who had no standard therapy could access exploratory new drug based on targetable agents through this study. Clinical trial information: 163380.

The impact of primary tumor site on outcomes of treatment with etoposide and cisplatin in grade 3 gastroenteropancreatic neuroendocrine carcinoma.

213 Background: Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a heterogeneous disease in terms of embryonic origin, aggressiveness, prognosis, and genomic profiling. Data regarding the efficacy of etoposide and cisplatin (EP) as a standard treatment of the primary tumor site in GEP-NEC are limited. Methods: We analyzed 64 patients with histopathologically confirmed metastatic GEP-NEC who received EP at Samsung Medical Center, Seoul, Korea, between January 2010 and January 2018. Based on primary tumor site, outcome of treatment with EP was evaluated. Results: Primary sites included 22 foregut-derived GEP-NECs (stomach, n = 6; duodenum, n = 4; pancreas, n = 12), 4 midgut-derived GEP-NECs, 5 hindgut-derived GEP-NECs of the rectum, 25 GEP-NECs originating from the hepatobiliary (HB) tract, and 12 GEP-NECs involving only intra-abdominal lymph nodes. No patient had a complete response (CR) and 17 had a partial response (PR), resulting in a 27.9% response rate (RR). When evaluating the efficacy of EP based on primary tumor site, the RR was most favorable in GEP-NECs involving only intra-abdominal lymph nodes, followed by GEP-NECs originating from foregut, midgut, HB, and hindgut. However, no statistically significant difference was observed for RR based on primary tumor site (p = 0.821). Similarly, no significant differences were found for progression-free survival (PFS) among patients with GEP-NECs arising from various primary tumor sites. Conclusions: Results from this study showed thatRR and PFS associated with EP treatment were not different based on the primary tumor site in patients with advanced or metastatic GEP-NEC.

Bone metastasis pattern of cancer patients with bone metastasis but no visceral metastasis

BackgroundBone metastasis of cancer can be a result from systemic blood spreading or vertebral venous plexus spreading. Systemic blood pathway induced bone metastasis can happen in any bone in the body since the spreading is considered to be random. However, it remains unknown whether there is any pattern of vertebral venous plexus related bone metastasis. In this study, we explored bone metastasis patterns in patients whose primary tumors had been well identified. MethodsWe included 290 consecutive cancer patients with bone metastases but no visceral metastases, out of 2559 patients whose bone metastases were diagnosed by positron emission tomography/computed tomography, between Jan 2015 and Oct 2017 at the Fudan University Shanghai Cancer Center. We excluded those with visceral metastasis to ensure that our study focused on metastasis through the vertebral venous plexus. And we analyzed the distribution and pattern of skeletal metastases. ResultsOf the 290 patients, 28 had head and neck tumors, 178 had thorax tumors, 49 had abdominal tumors and 35 had pelvic tumors; 102 (35%) had only one bone containing a metastasis and 188 (65%) had multiple bones containing metastases. Overall, metastases to the thoracic skeleton were more common in patients with thorax tumors than in other patients (81% vs. 67%, P = 0.007); metastases to the cervical spine or thoracic bones were more common in patients with primary tumors above the diaphragm than those below the diaphragm (82% vs. 66%, P = 0.002). Among those with only one bone containing a metastasis (n = 102), patients with head and neck tumors had a higher incidence of cervical spine metastasis than other patients (25% vs. 2%, P = 0.03), those with thorax tumors had a higher incidence of thoracic bone metastasis than other patients (56% vs. 35%, P = 0.035), and those with pelvic tumors had a higher incidence of pelvis bone metastasis than other patients (78% vs. 27%, P = 0.000054). ConclusionsIn patients with only one bone containing a metastasis but no visceral metastasis, bones near the primary were more likely to be first metastasized. This may be a valuable clue to primary tumor sites in patients with cancers of unknown primaries.

The impact of primary tumor site on outcomes of treatment with etoposide and cisplatin in grade 3 gastroenteropancreatic neuroendocrine carcinoma.

Background: Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a heterogeneous disease in terms of embryonic origin, aggressiveness, prognosis, and genomic profiling. Data regarding the efficacy of etoposide and cisplatin (EP) as a standard treatment of the primary tumor site in GEP-NEC are limited.Materials and Methods: We analyzed 64 patients with histopathologically confirmed metastatic GEP-NEC who received EP at Samsung Medical Center, Seoul, Korea, between January 2010 and January 2018. Based on primary tumor site, outcome of treatment with EP was evaluated.Results: Primary sites included 22 foregut-derived GEP-NECs (stomach, n = 6; duodenum, n = 4; pancreas, n = 12), 4 midgut-derived GEP-NECs, 5 hindgut-derived GEP-NECs of the rectum, 25 GEP-NECs originating from the hepatobiliary (HB) tract, and 12 GEP-NECs involving only intra-abdominal lymph nodes. No patient had a complete response (CR) and 17 had a partial response (PR), resulting in a 27.9% response rate (RR). When evaluating the efficacy of EP based on primary tumor site, the RR was most favorable in GEP-NECs involving only intra-abdominal lymph nodes, followed by GEP-NECs originating from foregut, midgut, HB, and hindgut. However, no statistically significant difference was observed for RR based on primary tumor site (P = 0.821). Similarly, no significant differences were found for progression-free survival (PFS) among patients with GEP-NECs arising from various primary tumor sites.Conclusion: Results from this study showed that RR and PFS associated with EP treatment were not different based on the primary tumor site in patients with advanced or metastatic GEP-NEC.

Recurrence and Survival in Patients With Merkel Cell Carcinoma Undergoing Surgery Without Adjuvant Radiation Therapy to the Primary Site.

The use of adjuvant radiation therapy (RT) to the primary site in Merkel cell carcinoma (MCC) is not uncommon. However, the need for adjuvant RT to the primary site in patients at low risk for local recurrence is questionable. To examine the occurrence of true local, satellite, in-transit, regional, and distant recurrences in patients undergoing surgery alone without adjuvant RT to the primary site. To establish overall survival (OS), MCC-specific survival (MCCSS), and disease-free survival (DFS) relationships in a cohort of patients with MCC. Our University of Michigan Multidisciplinary MCC Program database was used to obtain characteristics and outcome measures for 104 patients (105 primary MCCs) with tumors less than 2 cm in diameter. The majority of patients were treated between July 2006 and November 2012. Outcome measures included the occurrence of true local, satellite, in-transit, regional, and distant recurrences. End points included OS, MCCSS, and DFS. Overall, information for 55 men and 49 women with 105 primary MCCs was obtained; 19 patients developed recurrent disease, and the mean time to first recurrence was 10.7 months. True local recurrence occurred in 1 patient with concurrent in-transit recurrence. Satellite recurrence occurred in 1 patient with concurrent regional recurrence. Four additional patients developed in-transit metastases. Thirteen patients had a regional recurrence component, 4 patients had distant metastases, and 6 patients developed subsequent regional and/or distant recurrences. Stratified by initial pathologic stage, the OS and MCCSS at 48 months were estimated to be 85.0% (95% CI, 71.8%-92.3%) and 94.4% (95% CI, 83.4%-98.2%) for patients with stage 1A/B disease and 63.2% (95% CI, 36.6%-81.1%) and 78.1% (95% CI, 50.0%-91.5%) for patients with stage 3A disease. The OS and MCCSS at 24 months for patients with stage 3B disease were both 50.0% (95% CI, 5.8%-84.5%). In selected MCC patients with primary tumors less than 2 cm in diameter treated with surgery alone without adjuvant RT to the primary site, we found a low occurrence of true local recurrences and satellite recurrences. This relatively low rate of local recurrence questions the need for adjuvant RT to the primary tumor site in patients with small low-risk lesions.

Initial Surgery and Survival in Stage IV Breast Cancer in the United States, 1988-2011.

Management of the primary tumor site in patients with metastatic breast cancer remains controversial. To evaluate the patterns of receipt of initial breast surgery for female patients with stage IV breast cancer in the United States, with particular attention to women who survived at least 10 years. A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) program. Female patients diagnosed as having stage IV breast cancer between 1988 and 2011 and who did not receive radiation therapy as part of the first course of treatment were included (N = 21 372). Kaplan-Meier estimates of median survival and descriptive statistics were used to compare patient and tumor characteristics by receipt of breast surgery at diagnosis. A Royston-Parmar survival model and logistic regression analysis assessed demographic and clinical factors associated with survival and prolonged survival (of at least 10 years). Differences in survival, particularly survival of at least 10 years, by receipt of initial surgery to the primary tumor. Among the 21 372 patients, the median survival increased from 20 months (1988-1991) to 26 months (2007-2011). During this time, the rate of surgery declined (odds ratio [OR], 0.16; 95% CI, 0.12-0.21). Even so, receipt of surgery was associated with improved survival in multivariate analysis, which controlled for patient and clinical characteristics, along with time period (hazard ratio, 0.60; 95% CI, 0.57-0.63). For women diagnosed as having cancer before 2002 (n = 7504), survival of at least 10 years was seen in 9.6% (n = 353) and 2.9% (n = 107) of those who did and did not receive surgery, respectively (OR, 3.61; 95% CI, 2.89-4.50). In multivariate analysis, survival of at least 10 years was associated with receipt of surgery (odds ratio, 2.80; 95% CI, 2.08-3.77), hormone receptor-positive disease (OR, 1.76; 95% CI, 1.25-2.48), older age (OR, 0.41; 95% CI, 0.32-0.54), larger tumor size (OR, 0.37; 95% CI, 0.27-0.51), marital status of being separated at the time of diagnosis (OR, 0.67; 95% CI, 0.51-0.88), and more recent year of diagnosis (OR, 1.43; 95% CI, 1.02-1.99). Survival in stage IV breast cancer has improved and is increasingly of prolonged duration, particularly for some women undergoing initial breast surgery. As systemic therapy advances provide better control of distant disease in stage IV breast cancer, and as women present with lower distant disease burdens, these findings on initial surgery to the primary tumor may be of importance.

Diagnostic and prognostic values of (18)F-FDG PET/CT in cervical nodal metastatic carcinoma of unknown primary site

Objective To investigate the diagnostic and prognostic values of 18F-FDG PET/CT in patients with cervical nodal metastases from carcinoma of unknown primary site (CCUP). Methods A total of 137 consecutive patients(95 males, 42 females, age range 24-84 (55.77±11.71) years) with histological proven CCUP who underwent 18F-FDG PET/CT imaging to find primary tumors from March 2010 to June 2015 were retrospectively analyzed. The gold standard was the final pathological diagnosis or clinical long-term follow-up (≥6 months) results. The diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT imaging in detecting primary tumors were calculated. Kaplan-Meier analysis was conducted for survival analysis and to identify the presence of any prognostic factors, such as age, gender, presence or absence of distant metastasis, region of involved cervical lymph nodes, left (right)-side/both sides of lymph node involvement, histopathologic tumor type and primary site found or not by PET/CT imaging. Results Primary tumors were confirmed in 96 patients, of which 87 patients were diagnosed correctly by 18F-FDG PET/CT imaging. The diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 90.6% (87/96), 80.5% (33/41), 87.6% (120/137), 91.6% (87/95) and 78.6% (33/42) respectively. Primary tumors were found most commonly in the head, neck and lung. However, the false positive and negative lesions were also mainly seen in those sites. Distant metastasis and the inferior region of cervical lymph node metastasis were associated with the worst survival (χ2=20.990 and 12.277, both P 6.5 were of higher mortality risk than those with SUVmax≤6.5 (χ2=7.120, P<0.01). Conclusions Whole-body 18F-FDG PET/CT scan is a significant and valuable tool in the identification of the primary tumor site in patients with CCUP. Furthermore, according to the distant metastasis and region of cervical lymph nodes metastasis, 18F-FDG PET/CT scans are of value in prognostic evaluation even if without the need to identify the primary tumors. Key words: Neoplasm metastasis; Lymph nodes; Neck; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose

Cutaneous anaplastic large-cell lymphoma (ALCL): A comparative clinical feature and survival outcome analysis of 52 cases according to primary tumor site

Cutaneous anaplastic large-cell lymphoma (ALCL) is primary extranodal or secondary to nodal disease. We sought to analyze clinical features and survival outcomes by primary tumor site in patients with cutaneous ALCL. Clinical features, survival outcomes, and prognostic factors of 52 patients with primary or secondary cutaneous ALCL to primary nodal disease were retrospectively evaluated using medical records. Although skin lesion characteristics did not significantly differ between groups, the head and neck location was more common in primary cutaneous ALCL, whereas cutaneous lesion extent was greater in secondary cutaneous ALCL. Skin lesion extent in primary cutaneous ALCL was indicative of extracutaneous dissemination development and skin lesion relapse. Neither anaplastic lymphoma kinase expression nor clinical stage affected skin lesion characteristics in secondary cutaneous ALCL. Patients with primary rather than secondary cutaneous ALCL demonstrated better survival outcomes. The skin lesion extent and location on the leg were associated with the tendency toward a poorer prognosis in primary cutaneous ALCL. The secondary cutaneous ALCL prognosis was not influenced by skin lesion characteristics. This was a retrospective study in a single institution. Survival outcomes and prognostic factors in cutaneous ALCL differed by primary tumor site.

Diagnostic Accuracy of 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in the Evaluation of Carcinoma of Unknown Primary

Objective:Detection of primary tumor site in patients with carcinoma of unknown primary (CUP) syndrome has always been a diagnostic dilemma, necessitating extensive workup. Early detection of primary tumor site coupled with specific therapy improves prognosis. The low detection rate of the primary tumor site can be attributed to the biological behavior or the small size of the primary tumor to be detected by conventional imaging. The objective of this study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) in detecting CUP.Methods:A retrospective, cross-sectional analysis of 100 PET-CT scans of patients with CUP syndrome between November 2009 and December 2013 was performed. Eighteen patients whose final histopathology results could not be obtained for correlation were excluded from analysis. The hypermetabolic sites were assessed in correlation with histopathology. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive values were assessed for PET-CT.Results:Out of the 82 patients, primary tumor was correctly identified in 57.3% patients by 18F-FDG PET-CT (true positive). The PET-CT scan results were negative for primary site localization in 15% of patients (false negative). While 21% had true negative results, 7.3% displayed false positive results. PET-CT scan upstaged the disease in 27% cases. Overall, the diagnostic accuracy was found to be 78%, sensitivity 80%, specificity 74%, positive predictive value 88.7% and negative predictive value 59%.Conclusion:Our data supports the utility of 18F-FDG PET-CT scan in the localization and staging of CUP syndrome.

The role of 18F-FDG PET-CT in the detection of unknown primary malignancy: a retrospective study.

This study aimed to retrospectively evaluate the role of 18F-FDG PET/CT imaging in the detection of unknown primary tumor sites in patients with a suspicious malignancy. We retrospectively examined the 18F-FDG PET/CT images of 50 unknown primary malignancy patients. The malignancy of the lesions with increased 18F-FDG uptake on PET images was defined by interpreting the nondiagnostic CT images that were obtained with the PET study. The primary tumor site was decided according to the combined PET/CT findings, and the results were subsequently confirmed with a histopathological examination. Fifty patients (29 M; 21 F) aged 18-85 years were included in the study. The sample included 32 malignant and 18 benign lesions according to the histopathological evaluation. 18F-FDG PET/CT study accurately identified malignant lesions in 28 (average SUVmax ± SD: 8.27 ± 7.22) and benign lesions in 12 (average SUVmax ± SD: 3.63 ± 3.07) patients; these findings were histopathologically confirmed. PET/CT correctly detected the primary tumor site in 16 (50%) of 32 patients. 18F-FDG-PET/CT identified the primary tumor site well in 50% of our cases. We propose that 18F-FDG PET/CT imaging may help to accurately detect malignant lesions in patients with unknown primary tumors.

Development and validation of a microRNA based diagnostic assay for primary tumor site classification of liver core biopsies

Identification of the primary tumor site in patients with metastatic cancer is clinically important, but remains a challenge. Hence, efforts have been made towards establishing new diagnostic tools. Molecular profiling is a promising diagnostic approach, but tissue heterogeneity and inadequacy may negatively affect the accuracy and usability of molecular classifiers. We have developed and validated a microRNA-based classifier, which predicts the primary tumor site of liver biopsies, containing a limited number of tumor cells. Concurrently we explored the influence of surrounding normal tissue on classification. MicroRNA profiling was performed using quantitative Real-Time PCR on formalin-fixed paraffin-embedded samples. 278 primary tumors and liver metastases, representing nine primary tumor classes, as well as normal liver samples were used as a training set. A statistical model was applied to adjust for normal liver tissue contamination. Performance was estimated by cross-validation, followed by independent validation on 55 liver core biopsies with a tumor content as low as 10%. A microRNA classifier developed, using the statistical contamination model, showed an overall classification accuracy of 74.5% upon independent validation. Two-thirds of the samples were classified with high-confidence, with an accuracy of 92% on high-confidence predictions. A classifier trained without adjusting for liver tissue contamination, showed a classification accuracy of 38.2%. Our results indicate that surrounding normal tissue from the biopsy site may critically influence molecular classification. A significant improvement in classification accuracy was obtained when the influence of normal tissue was limited by application of a statistical contamination model.

Outcome of patients with metastatic colorectal cancer depends on the primary tumor site (midgut vs. hindgut)

The aim of this study was to investigate the impact of midgut versus hindgut as the primary tumor site in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy with FuFIRI or mIROX. We analyzed 423 patients from a phase III trial that randomized patients in a 1 : 1 fashion to either FuFIRI or mIROX. The cohort was grouped into midgut (n=82) and hindgut (n=341) primary tumors. The primary tumor site (midgut vs. hindgut) was correlated with parameters of treatment efficacy and survival. Our cohort comprised 82 patients presenting with primary midgut tumors and 341 with primary hindgut tumors. Tumors of midgut origin compared with hindgut origin were associated with inferior outcome. Objective response rate was 37 versus 43% (P=0.34), median progression-free survival was 6.0 versus 8.2 months (P=0.024, hazard ratio: 0.75), and median overall survival was 13.6 versus 21.8 months (P=0.001, hazard ratio: 0.65). Patients with midgut mCRC showed a clear trend toward inferior outcome in both study arms. However, the effect appeared less pronounced in the mIROX arm. Further datasets from large trials with various regimens are required as confirmation.

New diagnostic agent approved for lymphatic mapping

FDA and Navidea Biopharmaceuticals Inc. on March 13 announced the approval of technetium Tc 99m tilmanocept injection, or Lymphoseek, as an aid in identifying the first lymph node that drains the primary tumor site in patients with breast cancer or melanoma. The radiopharmaceutical is the first new

Prevalence of Known and Unknown Primary Tumor Sites In Spinal Metastasis Patients

Study Design: A retrospective study.Objectives: Three objectives have been designated for this study: (1) to determine the prevalence of identifiable and non-identifiable primary tumor sites in patients with spinal metastasis, (2) to identify the most common site of the known primary tumor sites, and (3) to identify the factors associated with survival time.Summary of Background Data: The spine is the third most common metastatic site for several primary visceral carcinomas. The primary tumor site could not be identified in 15% to 20% of patients who had been diagnosed of with a skeletal metastasis. Most of the previous studies on skeletal metastasis have not been limited to spinal metastasis alone.Methods: Between January 2007 and July 2011 reviews were done for 82 patients with spinal metastasis who had not received a previous diagnosis of carcinoma. The assessment parameters included the following: general demographic data, Karnofsky score, Frankel score, number of spinal vertebra affected, region of the spine affected by metastasis, other skeletal metastasis site, visceral metastasis, known or unknown primary sites of metastasis, histological cell type of metastasis, and the survival period. The log-rank test and Cox proportional hazard model were used to study the survival analysis.Results: Of the 82 patients included in the study, 56 were male. The mean age was 57 years. 86.6% had a known primary carcinoma site while the remaining 13.4% had none. The two most common known carcinoma sites were the lung and biliary systems. Among the 11 unknown primary sites, the most common histological finding was adenocarcinoma. The mean survival period was 8.7 ± 11.7 months. The survival analysis revealed two statistically significant factors: the primary tumor site’s aggressiveness (P<0.005) and the presence of visceral metastasis (P<0.05).Conclusion: The prevalence of identifiable primary site was 86.6% and the most common site was the lungs followed by the biliary system. The primary carcinoma site’s aggressiveness and the presence of visceral metastasis were the factors associated with patient survival.

A Prospective Comparison of 18F-FDG PET/CT and CT as Diagnostic Tools to Identify the Primary Tumor Site in Patients with Extracervical Carcinoma of Unknown Primary Site

The aim of the present study was to evaluate prospectively the diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and conventional CT regarding the ability to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP) site. From January 2006 to December 2010, 136 newly diagnosed CUP patients with extracervical metastases underwent (18)F-FDG PET/CT. A standard of reference (SR) was established by a multidisciplinary team to ensure that the same set of criteria were used for classification of patients, that is, either as CUP patients or patients with a suggested primary tumor site. The independently obtained suggestions of primary tumor sites using PET/CT and CT were correlated with the SR to reach a consensus regarding true-positive (TP), true-negative, false-negative, and false-positive results. SR identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 TP primary tumor sites and CT identified 43 TP primary tumor sites. No statistically significant differences were observed between (18)F-FDG PET/CT and CT alone in regard to sensitivity, specificity, and accuracy. In the general CUP population with multiple extracervical metastases (18)F-FDG PET/CT does not represent a clear diagnostic advantage over CT alone regarding the ability to detect the primary tumor site.