Metabolic activity of breast cancer metastatic lesions on positron emission tomography/computed tomography: comparison with histological and biological characteristics of primary tumor
Dragana Šobić-ŠaranovićMilica StojiljkovićSnežana ŠušnjarStrahinja OdalovićVera ArtikoS. PavlovićIsidora Grozdic MilojevicVladimir Obradović
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Abstract:
Higher intensity of FDG uptake on PET/CT in primary tumor is seen in patients with IDC compared to ILC, also in high grade tumours, tumours with negative ER and higher Ki67 values, while data are inconsistent in case of relation between primary tumor's PgR and HER2 expression with its metabolic activity levels.On account of the lack of studies that include research of breast cancer metastatic lesion metabolism level and its relation to tumor histology and biology, our goal was to investigate the association of metastatic lesions' glucose metabolism level on PET/CT with different histological and biological characteristics of primary tumor.In a total number of N=100 patients, highest SUVmax values for each patient were used in testing difference between metastatic metabolic activity in patients with different tumor histology, grade, ER, PgR and HER2 status, subtype, as well in testing relation of Ki67 index to metastasis' metabolism level.In testing difference between histological types of breast cancer, SUVmax values were also compared separately for each specific anatomical site (regional and distant lymph nodes, bones and liver).No difference was found regarding metastatic SUVmax values in patients with primary IDC (n=55, median SUVmax 9.70) and ILC (n=34, median SUVmax 7.20) independently of anatomic site, and for each of analysed sites separately.No difference was found as well between SUVmax detected in metastasis in patients with different grade (grade II: n=58, median SUVmax 7.70; grade III: n=12, median SUVmax 10.20), ER (59 positive, median SUVmax 8.50; 22 negative, median SUVmax 8.05), PgR (55 positive, median SUVmax 8.50; 23 negative, median SUVmax 7.80), and HER2 (14 positive, median SUVmax 6.84; 51 negative, median SUVmax 8.63) expression in primary tumor, and between patients with different tumor subtype.Ki67 was also not associated with tumor metastatic SUVmax values (n=11, r s = -0.21,p=0.53).We conclude that there is no association of primary breast cancer histological type, grade, ER, PgR, HER2 and Ki67 expression with metabolic activity in metastasis detected on PET/CT.Keywords:
Standardized uptake value
Primary tumor
Histology
PET-CT
Objective To compare the prognostic values of metabolic parameters from pretreatment PET/CT between limited disease (LD) and extensive disease (ED) small cell lung cancer (SCLC) patients. Methods Data on 118 newly diagnosed SCLC patients (50 LD and 68 ED) who underwent pretreatment positron emission tomography–computed tomography (PET/CT) were reviewed. For PET, metabolic parameters were measured for: (1) primary tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis; and (2) all tumor lesions, SUVmax of the hottest tumor, whole body metabolic tumor volume (WBMTV), and whole body total lesion glycolysis (WBTLG). Prognostic values of metabolic parameters and other clinical variables were analyzed to predict overall survival (OS). Results In LD, SUVmax of the primary tumor was an independent prognostic factor for OS. Patients with high SUVmax showed significantly worse OS than those with low SUVmax. In ED, WBMTV and WBTLG were independent prognostic factors for OS. Patients with high WBMTV or WBTLG showed significantly worse OS than those with low WBMTV or WBTLG. Conclusions SUVmax of primary tumor was the only independent prognostic factor for OS in LD SCLC patients. WBMTV and WBTLG were independent prognostic factors in ED SCLC patients.
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655 Background: HER-2 overexpression, a predictive marker of tumor aggressiveness and responsiveness to therapy, occurs in 20–30% of breast cancer. Although breast cancer is a heterogeneous disease, HER-2 evaluation is done in primary tumor. HER-2 was measured in both primary and metastases to evaluate whether heterogeneity between primary breast cancer and metastatic sites exists in HER-2 overexpression and the effect of HER-2 on treatment decisions. Methods: Biopsies from primary breast cancer and corresponding metastases of 58 patients were studied. HER-2 overexpression was evaluated immunohistochemically (IHC) in all primary and metastatic sites using CB11 monoclonal antibody and DAKO Hercept-Test scoring. Positive results were confirmed by fluorescence in situ hybridization (FISH). Results: Median time from primary tumor to diagnosis of metastases was 4.5 years (range 1–12 years). Discordance in HER-2 overexpression between primary and metastatic sites was 14% (8 of 58 patients). In 1 patient (2%), HER-2 was negative in metastasis but positive in primary. In 7 (12%) patients HER-2 was positive in metastases and negative in primary. Concordance in HER-2 in primary and metastatic sites was found in 50 (86%) of patients (95% CI: 70.6–94.4). Three patients with HER-2 positive in metastatic sites and negative in primary responded to trastuzumab therapy. Conclusions: HER-2 is an important predictive biological marker for treatment of breast cancer. Possible discordance of HER-2 overexpression between primary and metastatic sites should be considered when making treatment decisions of metastatic sites. No significant financial relationships to disclose.
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Abstract Cancer therapy exerts a strong selection pressure that shapes tumor evolution. Recent studies have demonstrated high rates of concordance (greater than 80%) between primary tumor and recurrences. The main objective of our study was to demonstrate the molecular evolution of breast cancer using next-generation sequencing (NGS) at initial diagnosis and after metastatic progression beyond at least 1 line of treatment. Methods: We conducted a retrospective analysis of tumors in patients with metastatic breast cancer (MBC). Breast cancer specimens from metastatic sites following at least 1 line of treatment were obtained and analyzed using NGS from an existing prospective molecular profiling study (NCT02416518). Eligible participants from this study had their archival primary tumor specimens obtained and analyzing using the same NGS techniques. Samples were analyzed using Foundation One NGS, evaluating 343 genomic alterations. Concordance of genomic alterations from initial diagnosis to disease progression after metastatic recurrence was the primary endpoint. This study population was from an integrated, community-based healthcare system, serving rural populations primarily in the Dakotas and Minnesota. Results: A total of 10 patients had evaluable primary tumors and matched metastatic specimens. For the 20 tumors evaluable for matched analysis, we found 126 unique gene alterations from the 343 genes assayed, of which 31 (24.6%) were actionable (defined as alterations with established or investigational therapeutics based on literature review). Each tumor had an average of 30.4 alterations (range 15-43) and 7 actionable alterations, (range 0-12). There was only 1 patient that had no actionable alteration in the primary or metastatic tumor. Taking the 10 individual patients into consideration, we found a concordance rate of 64% for all gene alterations and a 61.2% concordance rate for the actionable gene alterations between the two time points. The most common actionable alteration was the activating PIK3CA gene alteration, which had 100% concordance in the 6 patients that had the alteration. The other key actionable alterations with 100% concordance involved the AR, BRCA2, CCND1, CDKN2B, ERBB2, PTEN, and ROS1. Conclusion: Contrasting with prior studies, in our small sample there was moderate concordance of gene alterations between primary and metastatic tumor samples. Despite this, high concordance of key actionable alterations (PIK3CA, PTEN, CCND1, ERBB2) was maintained throughout the disease course. This suggests therapeutic potential early on in the disease course, as key actionable driver mutations are present at diagnosis and persist beyond metastatic disease progression. Citation Format: Anu G. Gaba, Steven F. Powell, Paul A. Thompson, Megan L. Landsverk, Chun-Hung Chan, Jennifer L. Weiss, Lora J. Black, James M. Ford. Concordance of genomic alterations between primary and metastatic matched breast tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3601A.
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Purpose: We evaluated the use of metabolic parameters of F-18 fluorodeoxyglucose positron emission tomography (FDG PET) for the assessment of the primary tumor and nodal metastasis in predicting survival in nasopharyngeal carcinoma (NPC) patients. Materials and Methods: The F-18 FDG PET/CT (computed tomography) scans of 46 consecutive newly diagnosed NPC patients were retrospectively reviewed. Maximal standardized uptake value (SUVmax) corrected for lean body mass of primary tumor (pSUVmax) and highest SUVmax of cervical lymph nodes (nSUVmax) were recorded. The association of FDG uptake and 2-year disease-free survival (DFS) was examined. Results: Significantly better DFS was found in patients with pSUVmax <7.5 and nSUVmax <6.5 (P = 0.042 and P = 0.019, respectively). In multivariate analysis, both pSUVmax and nSUVmax were significant independent predictors of DFS. Conclusions: The SUVmax of the primary tumor and nodal metastasis are useful parameters for predicting DFS in NPC patients.
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The aim of this study was to investigate the predictability of occult lymph node metastasis using maximum standardized uptake value (SUVmax) in the primary tumor on pre-treatment 18-fluorodeoxyglucose positron emission tomography FDG-PET in oral squamous cell carcinoma (OSCC) patients who were clinically node negative (cN0) before surgery. A retrospective analysis of all patients treated at the University Hospital Zurich from 2007 to 2016 for OSCC with available pre-therapeutic FDG-PET was performed. We assessed the correlation of SUVmax of the primary tumors with the presence of occult nodal disease in the neck dissection specimen (pN+). The study included a total of 71 patients. In the nodal negative group (cN0/pN0), the median SUVmax of primary tumors was 9.0 (interquartile range (IQR) 7.4-13.9), while it was 11.4 (IQR 9.9-15.7) in the occult metastatic group (cN0/pN+). The difference was statistically significant (independent samples median test, P = 0.037). In a multivariable model, the only independent predictor of occult metastatic disease for cN0 patients was a SUVmax ≥ 9.5 (P = 0.028). Further, primary tumors with SUVmax ≥ 9.5 had a significantly higher risk of local recurrence (Log rank test, P = 0.020). In conclusion, we showed that higher SUVmax (≥9.5) of the primary tumor is associated with higher occurrence of occult metastatic nodal disease and worse local survival. High SUVmax of the primary tumor may encourage clinicians towards more aggressive treatment.
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We retrospectively evaluated the relationships between primary tumor F-fluorodeoxyglucose (FDG) uptake measured as the maximum standardized uptake value (SUV(max)) and local extension, and nodal or distant metastasis in patients with cervical cancer on pretreatment FDG positron emission tomography-computed tomography (PET-CT).Forty-three patients (mean age, 55.14 years; range, 34-90 years) with cervical cancer who underwent FDG PET-CT scans for staging before the initiation of treatment were included in the study. Primary tumor SUV(max) was calculated; clinical tumor stages, presence of local extension, sites of lymph node and distant organ metastases were recorded. The patients were divided into low and high SUV groups by using the median primary tumor SUV(max). The low SUV group consisted of 21 patients with SUV(max) less than 13.5, the high SUV group consisted of 22 patients with SUV(max) > or = 13.5. Their data were compared statistically.The average SUV(max) was 9.6+/-2.6 and 19.9+/-4.9 in the low and high SUV groups, respectively. In the low SUV group, six patients (29%) had a local extension, eight (38%) had pelvic and/or para-aortic lymph node metastasis, and one had distant organ metastasis (4.7%). In the high SUV group, 10 patients (45%) had a local extension, 16 (73%) had pelvic and/or para-aortic lymph node metastasis, and two (9%) had distant organ metastases. There was a significant difference in the lymph node metastasis rate between the two groups (P<0.05), but differences in local extension and distant organ metastasis were not statistically significant (P>0.05). In addition, there was a moderate correlation between SUV(max) and clinical tumor stages (r=0.40, P=0.0075).Higher primary tumor FDG uptake predicts higher nodal metastatic potential in cervical cancer patients. Patients with higher SUV(max) in cervical tumor may need a close follow-up because of their higher metastatic potential.
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Distant metastasis has become the predominant model of treatment failures in patients with locoregionally advanced nasopharyngeal carcinoma. Effort should therefore be made to stratify locoregionally advanced nasopharyngeal carcinoma patients into different groups based on the risk of metastasis to improve prognosis and tailor individualized treatments. This study aims to assess the value of primary gross tumor volume and the maximum standardized uptake value for predicting distant metastasis–free survival of patients with locoregionally advanced nasopharyngeal carcinoma. A total of 294 locoregionally advanced nasopharyngeal carcinoma patients who were identified from prospectively maintained database and underwent fluor-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging before treatment were included. The maximum standardized uptake value was recorded for the primary tumor (SUVmax-P) and neck lymph nodes (SUVmax-N). Computed tomography-derived primary gross tumor volume was measured using the summation-of-area technique. At 5 years, the distant metastasis–free survival rate was 83.7%. The cut-off of the SUVmax-P, SUVmax-N, and primary gross tumor volume for distant metastasis–free survival was 8.95, 5.75, and 31.3 mL, respectively, by receiver operating characteristic curve. In univariate analysis, only SUVmax-N (hazard ratio: 7.01; 95% confidence interval: 1.70–28.87; p < 0.01) and clinical stage (hazard ratio: 3.03; 95% confidence interval: 1.67–5.47; p = 0.007) were confirmed as independent predictors of distant metastasis–free survival. A prognostic model was derived by SUVmax-N and clinical stage: low risk (SUVmax-N < 5.75 regardless of clinical stage), medium risk (stage III and SUVmax-N ≥ 5.75), and high risk (stage IV and SUVmax-N ≥ 5.75). Multivariate analysis revealed that SUVmax-N and the prognostic model remained independent prognostic factors for distant metastasis–free survival (p = 0.023 and p < 0.001, respectively), but the clinical stage became insignificant (p = 0.133). Furthermore, the adjusted hazard ratios for the prognostic model were higher than SUVmax-N (hazard ratio = 6.27 vs 5.21, respectively). In summary, compared with SUVmax-P, SUVmax-N may be a better predictor of distant metastasis–free survival for patients with locoregionally advanced nasopharyngeal carcinoma. Combining SUVmax-N with clinical stage gives a more precise picture in predicting distant metastasis.
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Purpose: The aim of this study is to evaluate the predictive value of primary tumor characteristics, including F-18 fluorodeoxyglucose positron emission tomography (FDGPET) parameters of tumor maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for lymph node (LN) metastasis in patients with non-small cell lung cancer (NSCLC). Material and methods: One hundred and four patients with NSCLC who had undergone FDG-PET and sequential surgical treatment were enrolled into this retrospective study. The relationships between primary tumor characteristics and pathologic results of LN metastasis were examined. All of the measurements of LN SUVmax, primary tumor SUVmax, SUVmean, MTV, and TLG were performed using OsiriX. Results: Primary tumor characteristics of tumor size, grade, presence of microscopic lymphovascular invasion, tumor SUVmax, MTV, and TLG were significantly associated with LN metastasis. After adjustment with multivariate analysis, LN SUVmax and primary tumor TLG ≥ 35 were independent predictors for LN metastasis. Patients were stratified into low and high TLG groups. In the low TLG group, the negative predictive value (NPV) of conventional threshold of LN SUVmax ＜2.5 was excellent at 94.1%. By contrast, the positive predictive value (PPV) of LN SUVmax ≥2.5 was very low at 6.7%. In the high TLG group, the NPV was decreased to 73.3%. The PPV was much higher than that in the low TLG group at 42.9%. Conclusion: LN metastasis is associated with primary tumor characteristics. LN SUVmax and primary tumor TLG ≥35 are both independent predictors for LN metastasis. Primary tumor TLG can stratify the risk of LN metastasis and might improve LN staging in patients with NSCLC.
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