Incidence Of Metastases In Patients Research Articles

Association of multiparametric magnetic resonance imaging findings with oncologic outcomes in non-palpable localized prostate cancer.

281 Background: Multiparametric magnetic resonance imaging (mpMRI) is becoming increasingly integrated into the evaluation and medical decision making for localized prostate cancer. However, mpMRI findings have not been correlated with prostate cancer outcomes and therefore are not currently included in staging. The purpose of this study was to test the association between mpMRI detected extraprostatic extension with oncologic outcomes in patients with non-palpable prostate cancer. Methods: We used the Veterans Affairs Prostate Data Core to identify patients diagnosed with cT1N0M0 prostate cancer between 2000-2021 with an mpMRI prior to definitive treatment. We reviewed MRI reports to identify presence of extracapsular extension (MRI-T3a), seminal vesicle invasion (MRI-T3b), and adjacent organ invasion (MRI-T4). We assessed the impact of mpMRI findings on metastasis free survival with multivariable Fine-Gray competing-risks regression. Results: Overall, 3,142 veterans with cT1N0M0 prostate cancer were included. There were 1,411 (45%) Black patients. By clinical staging, 904 (29%) had low risk, 1,626 (52%) had intermediate risk, and 612 (19%) had high risk disease. The majority of patients were treated with radiation (N=2,267; 72%). There were 217 (7%) patients with MRI-T3a disease, 87 (3%) patients with MRI-T3b disease, and 26 (1%) patients with MRI-T4 disease. The median follow-up time was 5.4 years (90% CI, 1-13 years). The 5-year cumulative incidence of metastases for patients with low, intermediate, and high risk prostate cancer were 3% (95% CI, 2-4%), 7% (95% CI, 6-8%), and 15% (95% CI, 12-18%). The 5-year cumulative incidence of metastases for patients with MRI-T3a, MRI-T3b, and MRI-T4 disease were 15% (95% CI, 10-20%), 29% (95% CI, 29-39%), and 40% (95% CI, 13-66%). After controlling for age, race, risk stratification (which includes prostate specific antigen (PSA) and grade group), local therapy, and co-morbidities, the presence of MRI-T3a (HR 1.58, 95% CI 1.09-2.29, p=0.02), MRI-T3b (HR 3.38, 95% CI 2.31-4.95, p<0.0001), and MRI-T4 disease (HR 4.47, 95% CI 2.32-8.62, p<0.0001) were independently associated with worse metastasis free survival. Similar results were obtained with PSA and grade group as individual variables. Conclusions: Extraprostatic extension observed on mpMRI is independently prognostic of metastasis free survival in patients with non-palpable prostate cancer. mpMRI is a critical imaging modality that should be widely available for patients with prostate cancer, and studies are ongoing to define its role as a standard staging modality.

TYPE 2 DIABETES MELLITUS, ANEMIA, AND HYPERTENSION AS THE RISK FACTORS THAT AFFECT THE INCIDENCE OF METASTATIC BREAST CANCER

Background: Breast cancer is one of the most common gynecologic malignancies in women and the main cause of death in 25% of all cases. The main cause of death from breast cancer is metastases, it is estimated that 5-10% of breast cancers have metastasized at the time of early diagnosis with an advanced stage. Purpose: To analyze the risk factors that influence the incidence of metastases in patients with advanced breast cancer. Methods: This study is an analytic observational study with a cross-sectional design, the number of samples in the study was 120 patients. The inclusion criteria of the study sample were breast cancer patients with advanced stages III and IV in the last five years. Exclusion criteria were incomplete patient medical records. The sampling technique in this study was consecutive sampling. This research was conducted at Ibnu Sina Hospital, Makassar City. The variables analyzed in this study were type 2 diabetes mellitus, anemia, and hypertension which were tested with the chi-square test. Results: The results of this study showed that diabetes mellitus type 2 (p=0.00; Prevalence Rate [PR]=1.79; 95% CI=1.32-2.42) and anemia (p=0.03; Prevalence Rate [PR] = 1.82; 95% CI = 1.61-2.86) is a risk factor that affects the incidence of metastases in patients with advanced breast cancer. While the risk factor that has no effect is hypertension. Conclusion: Type 2 diabetes mellitus and anemia are risk factors that influence the incidence of metastases in breast cancer patients.

Role of Pre-Operative Brain Imaging in Patients with NSCLC Stage I: A Retrospective, Multicenter Analysis.

Simple SummaryLung cancer is the worldwide leading cause of cancer-related death among both genders, with about 230,000 patients/year being diagnosed in the US alone. It accounts for about 40% of all brain metastases, which already occur in around 3% of early-stage patients. Nonetheless, current international guidelines do not unanimously recommend brain imaging for use in the early stages of cancer. Some studies have suggested that surgical or radiosurgical treatment of brain metastases may provide better survival, especially in asymptomatic patients. Additionally, advances in genome analysis have identified molecular targets for pharmaceutical agents. These recent advancements in treatment stress the importance of studying incidence as well as patient and tumor characteristics in order to potentially adapt future guidelines and provide the best possible treatment for early-stage lung cancer. This multicentric study analyzed the data of 577 patients diagnosed with early-stage lung cancer who had been submitted for brain imaging at initial tumor staging.Background: Lung cancer is the worldwide leading oncological cause of death in both genders combined and accounts for around 40–50% of brain metastases in general. In early-stage lung cancer, the incidence of brain metastases is around 3%. Since the early detection of asymptomatic cerebral metastases is of prognostic value, the aim of this study was to analyze the incidence of brain metastases in early-stage lung cancer and identify possible risk factors. Methods: We conducted a retrospective multicentric analysis of patients with Stage I (based on T and N stage only) Non-Small Cell Lung Cancer (NSCLC) who had received preoperative cerebral imaging in the form of contrast-enhanced CT or MRI. Patients with a history of NSCLC, synchronous malignancy, or neurological symptoms were excluded from the study. Analyzed variables were gender, age, tumor histology, cerebral imaging findings, smoking history, and tumor size. Results were expressed as mean with standard deviation or median with range. Results: In total, 577 patients were included in our study. Eight (1.4%) patients were found to have brain metastases in preoperative brain imaging. Tumor histology was adenocarcinoma in all eight cases. Patients were treated with radiotherapy (five), surgical resection (two), or both (one) prior to thoracic surgical treatment. Other than tumor histology, no statistically significant characteristics were found to be predictive of brain metastases. Conclusion: Given the low incidence of brain metastases in patients with clinical Stage I NSCLC, brain imaging in this cohort could be avoided.

PD59-01 BAP1 LOSS IS ASSOCIATED WITH METASTASIS IN ADVANCED CLEAR CELL RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 May 2022PD59-01 BAP1 LOSS IS ASSOCIATED WITH METASTASIS IN ADVANCED CLEAR CELL RENAL CELL CARCINOMA Sari Khaleel, Anne Reiner, Cameron Brennan, Ibrahim Hussain, Samuel Berman, Ari Hakimi, and Nelson Moss Sari KhaleelSari Khaleel More articles by this author , Anne ReinerAnne Reiner More articles by this author , Cameron BrennanCameron Brennan More articles by this author , Ibrahim HussainIbrahim Hussain More articles by this author , Samuel BermanSamuel Berman More articles by this author , Ari HakimiAri Hakimi More articles by this author , and Nelson MossNelson Moss More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002644.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Mutations of the BAP1 tumor suppressor gene are found in 10-15% of clear cell renal cell carcinoma (ccRCC), portending a poor prognosis relative to BAP1-wildtype (BAP1-WT) tumors. However, it remains unclear if BAP1 loss predicts metastatic phenotype in ccRCC. We sought to assess the cumulative incidence of metastases in patients with BAP1-mutant (BAP1-MT) vs BAP1-WT ccRCC tumors. METHODS: We performed a retrospective review of 96 patients diagnosed with ccRCC with known BAP1 mutation status, managed at a tertiary care cancer center between 10/2001-9/2016, comparing patients with BAP1-MT (47 patients) to BAP1-WT (49 patients) tumors. For each patient, we retrieved clinical features and all metastatic events (MEs), accounting for the organ compartment and date of each individual ME noted on imaging and/or pathology reports. We hypothesized that BAP1-MT was associated with a higher likelihood of cumulative MEs overall, as well as a specific metastatic phenotype, defined as a predilection for cumulative MEs in one of two major compartments – bone or soft tissue (all non-bony compartments). Categorical and continuous outcomes were compared by BAP1 mutational status using Fisher’s exact test and Welch T-test, respectively, while cumulative incidence of MEs was compared between BAP1-MT and BAP1-WT using subdistribution hazard ratio (SD-HR) analysis. Analyses were performed using R package (R Foundation, v4.1). RESULTS: Median patient age at diagnosis was 58 years, with 20 (20.8%) patients presenting with metastatic disease at the time of diagnosis. Most patients were males (62, 64.6%), and underwent nephrectomy (84, 87.5%). Median follow-up was 52 months [IQR 22.25 – 78.25 months]. BAP1-MT and BAP1-WT did not differ significantly by age or BMI (p > 0.05). BAP1-MT patients had a higher AJCC stage on nephrectomy (p < 0.0001), with higher overall cumulative MEs (SD-HR 2.1, 95% CI 1.0-4.5, p = 0.05). Specifically, we noted a high incidence of MEs in bone (SD-HR 5.5, p = 0.02, 95% CI 1.3-23.5) followed by soft tissue (SD-HR 2.7, p = 0.001, 95% CI 1.5 – 5.0) (Figure 1). CONCLUSIONS: Mutations of the BAP1 gene were associated with higher stage disease and incidence of metastases overall, with a higher cumulative incidence of metastases in bone compared to soft tissue compartments, suggesting a potential metastatic phenotype for this mutation. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1018 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sari Khaleel More articles by this author Anne Reiner More articles by this author Cameron Brennan More articles by this author Ibrahim Hussain More articles by this author Samuel Berman More articles by this author Ari Hakimi More articles by this author Nelson Moss More articles by this author Expand All Advertisement PDF DownloadLoading ...

Incidence of brain metastases in patients with early HER2-positive breast cancer receiving neoadjuvant chemotherapy with trastuzumab and pertuzumab

The addition of pertuzumab (P) to trastuzumab (H) and neoadjuvant chemotherapy (NAC) has decreased the risk of distant recurrence in early stage HER2-positive breast cancer. The incidence of brain metastases (BM) in patients who achieved pathological complete response (pCR) versus those who do not is unknown. In this study, we sought the incidence of BM in patients receiving HP-containing NAC as well as survival outcome. We reviewed the medical records of 526 early stage HER2-positive patients treated with an HP-based regimen at Memorial Sloan Kettering Cancer Center (MSKCC), between September 1, 2013 to November 1, 2019. The primary endpoint was to estimate the cumulative incidence of BM in pCR versus non-pCR patients; secondary endpoints included disease free-survival (DFS) and overall survival (OS). After a median follow-up of 3.2 years, 7 out of 286 patients with pCR had a BM while 5 out of 240 non-pCR patients had a BM. The 3-year DFS was significantly higher in the pCR group compared to non-pCR group (95% vs 91 %, p = 0.03) and the same trend was observed for overall survival. In our cohort, despite the better survival outcomes of patients who achieved pCR, we did not observe appreciable differences in the incidence of BM by pCR/non-pCR status. This finding suggests that the BM incidence could not be associated with pCR. Future trials with new small molecules able to cross the blood brain barrier should use more specific biomarkers rather than pCR for patients’ selection.

Predictive Indicators of Brain Metastasis-Free Survival in Patients With Lung Cancer at a Chinese Cancer Center.

IntroductionMetastasis tumors of the brain derive mostly from lung cancer, breast cancer, melanoma, and more commonly among lung cancer patients. Once brain metastasis is diagnosed, the prognosis of untreated patients is shown to be very poor. In this study, we describe the clinical and pathological features of patients with lung cancer at our institution from 2009 to 2021. We also examined factors like gender, type, size, and location of the primary tumor and leukoaraiosis level at the first visit are associated with patients’ brain metastasis-free survival (the time free of brain metastases since the first diagnosis of lung cancer).Materials and methodsWe retrospectively reviewed patients with a final histologic diagnosis of lung cancer from September 2009 to January 2015. The evaluation included history, physical examination, and contrast-enhanced computerized tomography of the chest. Contrast-enhanced magnetic resonance imaging of the head was performed at the first visit and following treatment. The patients’ age, gender, tumor size, histology type, location of the lung tumor, and leukoaraiosis level at the first visit were recorded and correlated to the patients’ brain-metastasis-free survival time.ResultsThe study included 68 patients - 39 males and 29 females -with a mean age of 55.15 years (range 35-69 years). Adenocarcinoma was diagnosed in 47 patients (22 males and 25 females), Squamous carcinoma was diagnosed in 12 patients (9 males and 3 females), non-small cell lung carcinoma was diagnosed in 3 patients (2 males and one female), one male patient had the diagnosis of adenosquamous tumor and 1 male patient had the diagnosis of neuroendocrine tumor. Tumor size was <3 cm in 19 patients, 3-5 cm in 29 patients, 5-10 cm in 17 patients, and three other patients’ size was hard to measure. Of the 68 patients, 10 patients were detected as brain metastasis by magnetic resonance imaging at first diagnosis, 22 patients were diagnosed as brain metastasis during the follow-up visits, 36 patients were not found as brain metastasis until the last visit. According to the Cox regression univariate analysis, two factors were correlated to shorter brain metastasis-free survival: Not-squamous lung carcinoma (SCC) and higher location of the tumor. The multivariate statistical analysis correlated two factors to shorter brain metastasis-free survival: non-SCC histology type and age≥62.ConclusionsIn conclusion, we found that SCC had a lower incidence of brain metastasis in patients than other lung cancer types. According to the Cox regression multivariate analysis, age <62 and SCC were two protective factors of brain metastasis. According to the Cox regression univariate and analysis. The lower location of the tumor was the protective factor of brain metastasis. According to the Cox regression univariate analysis, other parameters, such as gender or tumor size, did not have a role in brain metastasis-free survival in these patients.

Clinicopathological Features and Prognoses in Patients With Brain Metastases From Small-Cell Esophageal Carcinoma: A Retrospective Analysis of 18 Patients.

Objective: This study aims to examine the clinical characteristics of patients with brain metastases (BM) from small-cell esophageal carcinoma (SCEC) and to explore the association of the corresponding factors with overall survival (OS).Methods: The data of 18 patients with brain metastases from SCEC, diagnosed from January 1, 2006, to December 31, 2018, in the Fourth Hospital of Hebei Medical University were analyzed retrospectively.Results: The 18 patients who were included in this study accounted for 6.7% of the patients with SCEC diagnosed from 2006 to 2018. Of the 18 patients, 8 (44.4%) were females. For the entire cohort, the median OS was 7 months, the 1-year OS was 22.2%, and the 2-year OS was 0%. For patients who received whole-brain radiotherapy (WBRT) and for those who did not (13 vs. 5), the median OS was 11.9 and 3 months, respectively, and the 1-year OS was 30.8 and 0%, respectively. When comparing diagnosis-specific Graded Prognostic Assessment (DS-GPA) scores of patients with BM from SCEC ranging from 2.5 to 4 and from 0 to 2, the median OS was 13.1 and 4 months, respectively, and the 1-year OS was 57.1 and 0%, respectively. In the univariable regression, patients who received WBRT had improved OS compared to those who did not (HR = 0.249, p = 0.018), and patients with a DS-GPA score of 2.5–4 were associated with improved OS compared with patients with a DS-GPA score of 0–2 (HR = 0.050, p = 0.005).Conclusion: The incidence of brain metastases in patients with SCEC is low, but the prognosis in those patients is very poor. The DS-GPA score may be a prognostic factor of patients with BM from SCEC. Brain radiotherapy could improve the survival of these patients.

Topographic distribution of lymph node metastasis in patients with stage IB1 cervical cancer: an analysis of 8314 lymph nodes

BackgroundSystematic pelvic lymphadenectomy or whole pelvic irradiation is recommended for the patients with stage IB1 cervical cancer. However, the precise pattern of lymphatic tumor spread in cervical cancer is unknown. In the present study we evaluated the distribution of nodal metastases in stage IB1 cervical cancer to explore the possibilities for tailoring cancer treatment.MethodsA total of 289 patients with cervical cancer of stage IB1, according to FIGO 2009, were retrospectively analyzed. All patients underwent laparoscopic radical hysterectomy (Querleu and Morrow type C2) and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy (level 2 or level 3 according to Querleu and Morrow) from October 2014 to December 2017. Lymph nodes removed from 7 well-defined anatomical locations as well as other tissues were examined histopathologically, and typed, graded, and staged according to the WHO/IARC classification.ResultsTotally 8314 lymph nodes were analyzed with the average number of 31.88 ± 10.34 (Mean ± SD) lymph nodes per patient. Nodal metastases were present in 44 patients (15.22%). The incidence of lymphatic spread to different anatomic sites ranged from 0% (presacral) to 30.92% (obturator nodes). Tumor size above 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion were shown to be significantly correlated with the higher risk of lymphatic metastasis, while obesity (BMI ≥ 25) was independently negatively associated with lymphatic metastases.ConclusionsThe incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. Individual treatment could be considered for the selected low-risk patients who have smaller tumors and obesity and lack of the parametrial invasion or LVSI.

Advanced distal rectal cancer: possibilities of sphincter-sparing surgeries in combination with neoadjuvant therapy

Objective: to analyze the outcomes of sphincter-sparing surgeries in patients with advanced distal rectal cancer depending on the therapy they receive.Materials and methods. This study included 289 patients with advanced (stage T3N0–2M0) distal rectal cancer who have undergone sphincter-sparing surgeries. Patients were divided into three groups according to their treatment scheme. In group 1, we used combination treatment that included a short course of neoadjuvant radiotherapy supplemented by 3 multidirectional radiomodifiers (local microwave hyperthermia, rectal administration of a biopolymer composition containing metronidazole, and chemotherapy with capecitabine). Patients in group 2 received combination treatment that included neoadjuvant radiotherapy alone. Treatment outcomes in patients receiving combination therapy was compared to those of patients with similar characteristics and location of rectal tumors who have undergone surgery alone in N. N. Blokhin National Medical Research Center of Oncology (group 3).Results. We observed a significant decrease in the incidence of locoregional cancer metastasis in patients from group 1 compared to those from groups 2 and 3 (0.8 % vs 7.9 % and 18.2 % respectively). Moreover, patients in group 1 demonstrated better relapse-free survival than participants in groups 2 and 3 (79.6 % vs 52.6 % and 51 % respectively). The new scheme of combination therapy developed by our team (used in group 1) did not increase the incidence of postoperative complications. The best local disease control in group 1 was achieved in patients with middle rectal cancer who have undergone sphincter-sparing surgeries: none of 81 patients developed relapses, whereas the relapse-free survival rate reached 83 % compared to 56.9 % in group 1 and 41.7 % in group 3.Conclusions. The new treatment scheme that includes neoadjuvant radiotherapy supplemented by 3 multidirectional radiomodifiers can be used as one of the options increasing efficacy of radiotherapy and, therefore, efficacy of combination treatment in patients with advanced rectal cancer who undergo sphincter-sparing surgeries.

Incidence of brain metastases in patients receiving neoadjuvant chemotherapy (NAC) with trastuzumab and pertuzumab (HP) in HER2-positive early breast cancer (BC).

e12653 Background: The addition of pertuzumab in the neoadjuvant setting has become a standard of care in stage II-III HER2-positive BC. In the Katherine study the incidence of brain metastases (BM) at the follow-up of 3-years was 5.9 % in patients (pts) with residual disease who received TDM1. The aim of this study was to assess the incidence of BM in pts who received NAC with HP at a single center who were found to have pathological complete response (pCR) (ypT0/is ypN0) versus non-pCR at the time of surgery. Methods: Chart review on HER2-positive pts treated with NAC and HP between September 1, 2013 to May 1, 2018 was conducted. Only surgical specimens of pts whose pre-NAC specimens were internally reviewed for HER2 status by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were included in this analysis. Data on BM as component of distant recurrence along with invasive disease-free (IDFS) and overall survival (OS) were collected. Results: 540 pts were identified. Cases with no internally verified-HER2 status (387), equivocal status (10) and discordant internal assessment (13) were excluded. 130 pts with preoperative HER2 status confirmed by dedicated breast pathologists were included. Clinicopathological features are described in Table. pCR was achieved in 77/130 (60%) of cases, residual disease in 53/130 (40%). The median follow-up was 2.83 (0.35-5.3) years. The rate of BM as first presentation of distant disease was 3.8 % (3/77) and 3.7 % (2/53) in pts with pCR and non-pCR, respectively. Median time to development BM was 35 (13-58) months and 11.7 (9-14) months in the pCR group and non-pCR, respectively. Conclusions: In our cohort, the combination of HP was associated with a high pCR rate. At a median follow-up of 2.8 years, the incidence of BM appeared to be similar in pts who achieved pCR versus non-pCR. The data of IDFS and OS will be reported. Further data are needed to validate our findings before designing clinical trials to test prophylactic strategies to prevent BM. [Table: see text]

Rural patients are at risk for increased stage at presentation and diminished overall survival in osteosarcoma

BackgroundThere is an undefined relationship between access to regional referral centers and whether the eventual oncologic outcomes are influenced by distance, travel time, or residence in a rural community. MethodsWe used the Surveillance, Epidemiology and End Results (SEER) Program Database to capture all cases of high-grade osteosarcoma from 1990 to 2014 in Iowa, Utah, and New Mexico. Using univariate, Kaplan Meier survival analysis, and multivariate Cox proportional hazards modeling we analyzed patient and tumor characteristics. ResultsA total of 476 patients met the study criteria. There was an increased incidence of metastases for patients residing in a county with a greater than 2 -h drive to the nearest comprehensive cancer center (p = 0.021). Individuals residing in “rural” counties and “very rural” counties showed decreased 5-year survival (p = 0.007 and 0.003, respectively) when compared to those living in areas of higher population density. A multivariate regression analysis showed that the presence of metastasis (HR = 2.78 [95% CI: 1.88–4.10], p < 0.0001) and rural status (HR = 1.58 [95% CI: 1.03–2.43], p = 0.037) were risk factors for mortality when controlling for size of the tumor. ConclusionThe travel time to the nearest comprehensive center was associated with an increased incidence of metastasis on presentation in patients with osteosarcoma. Metastasis and rural status were independent risk factors for mortality. This investigation suggests that individuals living in rural counties may experience barriers to presentation, treatment, or surveillance that are not present in areas with a higher population density.

The impact of systemic treatment on brain metastasis in patients with non-small-cell lung cancer: A retrospective nationwide population-based cohort study.

e20572 Background: We performed a large-scale, retrospective, nationwide, cohort study of the incidence of brain metastasis in patients with advanced non-small-cell lung cancer (NSCLC) according to the systemic treatment administered. Methods: The data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2011 to November 30, 2016. Of the 29,224 patients newly diagnosed with stage IIIB or IV NSCLC who received first-line cytotoxic chemotherapy (CC group) or targeted therapy (TT group), 22,508 patients without brain metastasis were analyzed. Results: In total, 1,131 (5.0%) patients subsequently developed brain metastasis. The overall cumulative incidence of brain metastasis was significantly higher in the TT group than in the CC group (1-year cumulative incidence: 8.7 ± 0.6% vs. 3.8 ± 0.3%; 3-year: 17.2 ± 0.7% vs. 5.0 ± 0.3%, respectively; P &lt; 0.001), despite the higher rate of brain metastasis in the CC group at &lt; 3 years after diagnosis. Younger age, female sex, living in a rural area, anticoagulant use, and first-line TT (relative risk, 2.17 ± 0.03; 95% confidence interval, 1.92–2.50, P &lt; 0.0001) retained significant associations with subsequent brain metastasis after adjusting for all variables. Conclusions: In the Korean population, the overall cumulative incidence of brain metastasis was significantly higher in patients in the TT group than in those in the CC group; the former could be regarded as having mutations in the EGFR or ALK gene.

Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors—A Scandinavian Sarcoma Group study (SSG XX)

PurposeTo investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy. MethodsHigh-risk STS was defined as high-grade morphology (according to the Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II–III) and either vascular invasion or at least two of the following criteria: tumour size ≥8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4. ResultsFor the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2–8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1–78.4) with a local recurrence rate of 14.0% (95% CI: 7.8–20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2–8.7). The five-year OS was 76.1% (95% CI: 68.8–84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death. ConclusionsA benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.

Abstract P1-16-05: Incidence of skeletal-related events in patients suffering of bone metastsis from breast cancer treated with bisphosphonates or denosumab

Abstract Background Bone is a frequent site of metastases and typically indicates a short-term prognosis in breast cancer patients. Bone metastasis can rarely be cured, but often it can still be treated to slow down its growth and to improve quality of life. The relative incidence of bone metastases in patients with advanced metastatic breast cancer is 65-75%. Bisphosphonates and the human monoclonal RANKL-antibody Denosumab are the most common medical treatment of bone metastasis. Therefore we investigated their effect on skeletal-related events (SRE) in our patient collective. Materials and methods: A retrospective analysis of 143 patients with histologically proven breast cancer and bone metastasis at the department of Gynaecology and Obstetrics at the University of Saarland (Germany) between October 2009 and October 2013. SREs were defined as a pathological fracture, a bone surgery, a spinal cord compression and a radiation of bone metastasis. Patients were distributed into 5 different groups according to the treatment received. Group 1: bisphosphonate (n=63), Group 2: denosumab (n=55), Group 3: bisphosphonate switch to denosumab (n=16), Group 4: denosumab switch to bisphosphonate (n=4), Group 5: no anti-resorptive therapy (n=5). Progression of the bone metastasis without skeletal-related event (SRE) was defined as progressive disease. Results: At the time of diagnosis of the breast cancer the average age was of 55,2±13,1 years. At the time of data collection n=53 patients were alive, n= 83 had died during follow up, and n= 7 were lost-of follow up. The median follow up from the first diagnosis of the primary breast cancer and the end of data collection was of 88,6 ± 78,5 month. In 103 (72%) patients bone metastases were detected secondarily. 83 patients recieved an anti-resorptive therapy with bisphosphonates (q4w), 75 patients were treated with denosumab (q4w). In the overall collective, an SRE occured in 95 patients. 65.1% of Group 1(bisphosphonate) and 65.5% of Group 2 (densosumab) patients sufferd from an SRE. In the non-treatment Group 2, 5 patients were diagnosed with SRE. The Switch groups showed the most frequent SREs (Group 3: 81,3%), (Group 4: 75,0%) the median duration of treatment prior to the first SRE was 12,33 month in Group 1, 1,5 month in group 2, 38,2 month in Group 3 and 4 month in group 4. 63 of 95 patients received a treatment modification after the first SRE. The time period between the first and second SRE was 31,8 month in Group 1, 10,38 month in group 2, 38.71 month in group 3, 10 month in group 4 and 3 month in group 5. 3,5% of all patients in the overall collective were diagnosed with an osteonecrosis of the Jaw. Conclusion This data suggests that the anti-resorptive therapy with densoumab is equal to the bisphosphonate therapy to prevent the first skeletal-related event in patients with bone metastasis of breast cancer. After the first SRE patients benefit significantly of an anti-resorptive therapy compared to no treatment. In our population the prevention of a second SRE in group 3 (bisphosphonate switch to denosumab)showed the best results. Citation Format: von Heesen A, Nilges K, Radosa J, Gabriel L, Solomayer E-F, Juhasz-Böss I. Incidence of skeletal-related events in patients suffering of bone metastsis from breast cancer treated with bisphosphonates or denosumab [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-16-05.

Defining the role of lymphadenectomy for pancreatic neuroendocrine tumors: An eight institution study of 695 patients from the U.S. Neuroendocrine Tumor Study Group.

212 Background: Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined. Methods: Patients who underwent curative-intent resection of primary non-functional PanNETs at 8 institutions from 2000-2016 were analyzed. Tumors with poor differentiation and Ki-67 &gt; 20% were excluded. Preoperative factors associated with LN metastases were identified. A procedure specific target for LN retrieval to accurately stage patients was determined. Results: Of 2182 pts with GI NETs, 695 underwent resection of PanNETs. 33% of tumors were proximal (head/uncinate), and 67% were distal (neck/body/tail). 26% of pts (n = 158) had LN+ disease, which was associated with worse 5-yr recurrence-free survival (RFS) (60% vs 86%; p &lt; 0.001). Increasing number of +LNs was not associated with worse RFS. Preoperative factors associated with +LNs included tumor size ≥2 cm (OR 6.6; p &lt; 0.001), proximal location (OR 2.5; p &lt; 0.001), moderate vs well differentiation (OR 2.1; p = 0.006), and Ki-67≥3% (OR 3.1; p &lt; 0.001). LN metastases were also present in tumors without these risk factors: &lt; 2cm (9%), distal location (19%), well differentiated (23%), and Ki-67 &lt; 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage pts was not identified. For DP, however, removal of &lt; 7 LNs failed to discriminate 5-yr RFS between LN (+) and (-) pts ( &lt; 7 LNs: 72% vs 83%, p = 0.198; ≥7 LNs: 67% vs 86%, p = 0.002). Conclusions: Tumor size ≥2 cm, proximal location, moderate differentiation, and Ki-67≥3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. Pancreatoduodenectomy inherently includes sufficient LN retrieval, while distal pancreatectomy should aim to remove ≥7 LNs for accurate staging.

DYNAMICS OF BONE TRAP-5B LEVEL IN PATIENTS WITH BONE METASTASES OF RENAL CELL CANCER AT COMBINED TREATMENT

The objective of this study was to determine the sensitivity of tartrate-resistant acid phosphatase (Bone TRAP-5b) for early detection of bone metastases (BM) and to investigate the efficacy of bisphosphonates (BF) (zolendronic acid-ZA) in prevention of bone metastases in patients with Renal Cell Carcinoma (RCC). The 60 patients with RCC with proven BM were investigated to assess the sensitivity and specificity of Bone TRAP-5b. 95 patients with RCC with high level of tartrate-resistant acid phosphatase (Bone TRAP-5b) (8,5±0,2 IU/L) after radical surgical treatment were divided into two groups: 1-st group: (n=44) received zolendronic acid (ZA) (BF +), and 2-nd group (n=51) patients didn’t receive ZA (BF-). Patients of both subgroups were similar by age, sex, stage of disease. The levels of Bone TRAP-5b, Ca++, alkaline phosphatase, LDG were accessed every 3 months, and MRI imaging, bone scan with 99mTc every 6 month in both groups. We determined the high correlation between bone TRAP-5b and the presence of bone metastases (r=0,9; p &lt;0,05), but its level wasn’t dependent with the number of BM. The results showed the high sensitivity and specificity of Bone TRAP-5b at the critical value of 5.2 IU/L (98,3 % and 90,0 %), (χ2=64,6; p&lt;0.01). Using BF for the prevention of bone metastases in high risk group patients with RCC provides a significant difference in the incidence of bone metastases in patients.

Negative impact of leukoaraiosis on the incidence of brain metastases in patients with lung cancer

The embolization of cancer cells to cerebral vessels occurs early in the multi-step metastatic process. We aimed to determine whether the presence of leukoaraiosis (LA) before treatment would predict the development of brain metastases (BM) in patients with lung cancer. Between January 2014 and June 2015, 1007 patients underwent initial (i.e., prior to any chemotherapy) or routine magnetic resonance (MR) imaging of the brain and exhibited no evidence of BM. Of these, 189 underwent repeat MR imaging; 34 of 189 patients (18%) developed new BM, whereas 155 patients did not. LA was retrospectively evaluated according to Fazekas scale on the initial screening MR images of these 189 patients. The frequency of grade 0 periventricular hyperintensity (PVH) was greater among patients with BM, compared to those without BM (p = 0.001). In a multivariate analysis, patients with adenocarcinoma (95% confidence interval [CI] 1.8–171.8) and small cell carcinoma (95% CI 1.4–172.4) respectively developed BM at 9.3- and 8.8-fold higher rates than those with squamous cell carcinoma. Patients with grade 0 PVH developed BM at a rate 3.5-, 8.6-, and 3.6-fold higher rates than those with grade 1 (95% CI 1.4–9.0), 2 (95% CI 2.4–41.9), and 3 (95% CI 1.02–15.0), respectively. Lung cancer patients with grade 0 PVH on initial MR images have a high subsequent incidence of BM. PVH is a useful method for evaluating risk of BM.

Papillary Thyroid Carcinoma: Analysis of the Central Compartment's Lymph Nodes Metastases.

Papillary thyroid carcinoma is typical by regional lymph nodes metastases. Therefore we decided to analyse associated risk factors. In this retrospective study we focused on the incidence of metastatic involvement of the central compartment's lymph nodes correlated with age, size of the primary tumour, infiltration of thyroid gland capsule, positive lymphangioinvasion in order to assess risk factors. We analysed group of 156 patients with papillary carcinoma, who have undergone total thyroidectomy and bilateral elective central compartment neck dissection. We evaluated the occurrence of metastases, size, infiltration and lymphangioinvasion based on definitive histology of the whole group and separately for subgroups of patients under and over 45 years. We found metastatic involvement in 88 (56.4%) patients. When comparing the subgroups of patients under (73 patients) and over 45 years (83 patients), we found metastases in 56 vs. 32 (76.7% vs. 38.6%) patients. In the subgroup of younger patients we found significant higher incidence of metastases compared with the group of over 45 years, P < 0.001 (P = 0.000027). We found significant higher incidence of metastases in patients with positive capsule infiltration in the whole group, P < 0.001 (P = 0.00049); in the subgroup of under 45 years, P < 0.001 (P = 0.00091) and in patients with positive lymphangioinvasion in the whole group, P < 0.01 (P = 0.00177); in the subgroup of over 45 years, P < 0.001 (P = 0.0002). In patients with metastases we found tumour size ≥1cm more frequently in all groups. We recorded higher incidence of regional metastases in patients under 45 years, positive capsule infiltration, lymphangioinvasion. Age under 45 years itself does not correlate with less aggressive disease, to the contrary some of other analysed risk factors correlate with more aggressive disease.

699P - High incidence of metastases detected on 18F-FDG PET-CT in patients with gall bladder cancer incidentally discovered after laparoscopic cholecystectomy

Gall bladder cancer (GBC) is a relatively rare disease with clinical and imaging features similar to benign gall bladder diseases (BGBD) like gall stone disease or cholecystitis. A few of the BGBD patients who undergo laparoscopic cholecystectomy (LC) are later found to have GBC. In these patients, it is important to evaluate the extent of disease for further management. This study was conducted to evaluate the incidence of metastases in patients referred for 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) following incidental discovery of GBC after LC for BGBD. We retrospectively evaluated the data of patients referred to our department between January 2011 and December 2015 for FDG PET-CT with GBC diagnosed on histopathology (HP) after LC for BGBD. Abnormal FDG uptake on PET images corresponding to morphological abnormalities on contrast enhanced CT images was considered positive for disease. HP examination and clinical or imaging follow-up were used as the reference standard for confirmation of diagnosis. FDG PET-CT imaging was performed 1-8 (median 3.5) months after LC in 44 patients (8M, 36F) aged 30-75 (median 50.2) years. PET-CT was positive in 32/44 (72.7%) and negative in 12/44 patients (27.3%). Loco-regional disease was detected in 30/44 patients (68.2%) involving the gall bladder fossa, liver or regional lymph nodes. Metastatic seeding to the omentum, mesentery or laparoscopic port sites was found in 15 (34.1%) and distant metastasis in 5 patients (11.3%). Based on the reference standard, 28 patients had true positive scans. Findings in 4 scan-positive patients could not be confirmed; these were presumed false positive and remain on follow-up. All 12 scan-negative patients were true negative. PET-CT showed sensitivity, specificity, PPV, NPV and accuracy of 100%, 75.0%, 87.5%, 100%, and 90.9% respectively in detecting residual / recurrent disease. There is high propensity for seeding metastasis when GBC is discovered after LC for BGBD. FDG PET-CT has high diagnostic performance in detecting residual / recurrent disease as well as metastases in these patients.

Bevacizumab plus chemotherapy versus chemotherapy alone for preventing brain metastasis derived from advanced lung cancer

This retrospective analysis evaluated the mechanism of bevacizumab plus chemotherapy (BV+CT) for preventing brain metastasis derived from lung cancer. From the total of 159 patients with advanced non-small cell lung cancer (NSCLC), 110 received BV+CT and 49 received CT. After medication, both groups had 15 patients with brain metastases (14 vs 31%, P < 0.05). With BV+CT treatment, 40 patients (33.89%) survived, whereas only 11 patients (18.64%) survived with CT treatment. The outcome for the BV+CT group was significantly better than that for the CT group only for vascular endothelial growth factor (VEGF)-positive patients. A post-treatment with BV+CT was significantly reduced than with CT only for patients with high carbonic anhydrase-9 (CA9) expression. This retrospective analysis provides supportive evidence that BV+CT can significantly reduce the incidence of brain metastasis in patients with advanced NSCLC compared with CT alone. Vascular endothelial growth factor -positive patients may benefit more from BV treatment and the outcomes with BV may be related to CA9 expression.