Era Of Targeted Therapy Research Articles

Tamoxifen use in recurrent ovarian cancer in a Chinese population: A 15 -year clinical experience in a tertiary referral center.

AimTo review the clinical use and the effectiveness of tamoxifen in patients with advanced or recurrent ovarian cancer.MethodsA retrospective review of clinical records was conducted in patients who received tamoxifen for the treatment of ovarian cancer between 2002 and 2016. We reviewed the clinical setting that it was given, duration of use, patients' tolerability, clinical benefit and progression‐free survival. We also attempted to identify predictive markers for response.ResultsA total of 92 patients received tamoxifen during this 15‐year period. The patients received a median of 2.5 lines of chemotherapy before switching to tamoxifen, and they remained on tamoxifen for a median of 5.6 months (range 0–85 months), with 24 patients receiving it for more than 12 months. Seventy‐six patients continued on tamoxifen for more than 2 months. In this group, 75 patients had an evaluable response, either by CA 125 or clinically and clinical benefit rate (defined as complete, partial response and static disease) was seen in 42 patients (56%), with majority of patients having static disease. The median progression‐free survival was 5.3 months (95% confidence interval, 2.6–8.1). Tamoxifen was well tolerated. Hormone receptor status was not demonstrated to predict response.ConclusionPatients with advanced ovarian cancer who have failed previous lines of chemotherapy may achieve static disease with tamoxifen with minimal side effects. Tamoxifen may still have a role in the era of molecular target therapy.

Trends of Metastasis-Directed Treatments in Patients with Renal Cell Carcinoma: A Total Population-Based Analysis in Germany in the Era of Targeted Therapies

Introduction: We characterize trends of metastasis-directed treatments in patients with metastatic renal cell carcinoma (mRCC) in Germany in the targeted therapy era. Methods: We identified all cases with a diagnosis of renal cell carcinoma (ICD-10: C.64) and site-specific codes for secondary malignant neoplasms (C79.x) in combination with procedural codes for resection and radiation from the Institute of Hospital Remuneration and the German Federal Statistical Office (Destatis) between 2006 and 2014. We assessed site-specific temporal trends using estimated annual percent change (EAPC) linear regression. Results: Overall, 15,742 resections and 21,224 radiation treatments were recorded. These targeted lung (44.1% resections; 22.0% radiations), lymph node (14.0% resections; 12% radiations), bone (21% resections; 38% radiations), liver (9% resections; 7% radiations), adrenal (11% resections; 3% radiations), and CNS metastases (2% resections; 19% radiations). There was a significantly increasing trend for resection of lung (EAPC +1.33, p = 0.011), bone (EAPC +2.48, p = 0.014), and adrenal (EAPC +3.4, p = 0.003) metastases, while trends for resection of CNS metastases significantly decreased (EAPC –7.93, p = 0.005). Between Western and Eastern Germany linear trends of resection (EAPC +2.75, p < 0.001; EAPC –0.44, p = 0.54) and radiation (EAPC +1.08, p = 0.15; –3.41, p = 0.03) differed significantly. Conclusion: We observed an increasing trend for metastasis-directed resections and slightly declining numbers for radiation therapy in Germany for mRCC in the targeted therapy era. Treatment differed by geography. These findings suggest more aggressive treatment algorithms following the availability of targeted therapies and a yet diverging treatment landscape needing further exploration.

Video-assisted thoracoscopy in the diagnosis and treatment of malignant pleural disease

: The malignant pleural effusion is a common clinical issue, connected with metastatic tumors or with primary tumor of the pleura. This narrative review focuses on the video-assisted thoracic surgery (VATS) diagnostic approach and treatment modalities for management of malignant pleural effusion. We conducted searches for clinical studies and guidelines through Medline, Embase and Cochrane Library. Limiting the search to the last decade, we selected 29 papers: 5 randomized controlled trials, 9 prospective cohort studies, 11 retrospective studies, 3 guidelines and 1 survey. Malignant pleural effusion frequently affects the clinical evolution of patients with metastatic cancer and proper diagnosis in low risk patients is mandatory in the era of target therapy. Pleural biopsy, performed through pleuroscopy or VATS remains the gold standard for the diagnosis of malignant pleural effusion. The non-intubated VATS is a good combination of surgical skills and anaesthesiological management that could avoid risks of general anesthesia. The type and number of surgical access seems have no relevant impact on the short-term outcome. The best treatment to prevent the accumulation of pleural fluid remains the talc poudrage, possibly followed by talc slurry in case of recurrence.

Abstract CT222: Colon cancer in elderly patients: Retrospective analysis of targeted therapy era

Abstract Purpose: This study was conducted in order to evaluate the response rate, progression free survival (PFS), safety and prognostic factors of targeted combination chemotherapy in colon cancer patients older than 65 years. Methods: This retrospective study included 69 elderly patients (≥ 65 years) with metastatic Colon cancer who have not received palliative chemotherapy before. All patients were histologically confirmed colon cancer at Keimyung university Dongsan medical center from Jan 2007 to July 2017. All recruited patients received either cetuximab or bevacizumab every 2 weeks. Results: The median age was 73.35 (65-87) and 33 were right side, 32 were left, 2 were transverse and rest of 2 patients were multiple primary sites. Bevecizumab was administerd to 42 patients (60.9%) and cetuximab was administered to 27 patients (39.1%). Complete response was 9 patients (13%), partial response was 23 (33.3%) and progression disease was 9 (13.0%). Overall response rate was 31 (46.4%) and disease control rate was 42 (62.3%). Progression free survival was 12.038 ±1.565 months (95% CI: 8.97~12.12). The most common hematologic side effects was anemia with grade 3/4 in 14 (20.3%). Systemic chemotherapy with targeted agents were moderately tolerated with grade 3/4 neutropenia 40 (57.9%). Conclusion: In elderly patients with colon cancer, clinical outcomes showed similar results compared with prior clinical trials. Preventing such complications may improve survival. Citation Format: JIN YOUNG KIM, Sojin Shin, Mi Hwa Heo, Kang Kook Lee. Colon cancer in elderly patients: Retrospective analysis of targeted therapy era [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT222.

The role of income disparities on survival in metastatic clear cell renal cell carcinoma in the targeted therapy era.

The influence of socioeconomic status on metastatic clear cell renal cell carcinoma (RCC) in the target therapy era is still unknown. This study aimed to assess the role of income disparities on prognosis of mRCC in the targeted therapy era. Data of patients with mRCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Median household income (MHI) was used to represent patients' socioeconomic status, and its role on overall survival (OS) and cancer-specific survival (CSS) was evaluated. A total of 3791 patients with clear cell mRCC diagnosed between 2010 and 2015 were enrolled in cohort one. There was an obvious imbalance of race and insurance status in patients with difference MHI. Compared with patients in the poorest quartile 1 (Q1), those in the wealthiest Q4 had a 4-month prolonged OS (P < 0.01) and a 5-month prolonged CSS (P < 0.01), and those in Q3 and Q4 had significantlylower death risk. High income decreased cumulative cancer-specific mortality rates, and potentially favored survival in most subgroups. 6619 patients diagnosed between 2004 and 2015 were included in cohort two. We found that only those with Q4 income achieved a prolonged survival with statistical significance by comparing between patients diagnosed in 2004-2009 and 2010-2015. In the targeted therapy era, there were survival gaps of mRCC between patients with low- and high-income. Measures should be taken to develop a comprehensive and financially sustainable plan of cancer treatment for greater equity.

836 - Performance of a new risk assessment tool for patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy in the targeted therapy era: REMARCC score

836 - Performance of a new risk assessment tool for patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy in the targeted therapy era: REMARCC score

844 - Predictive factors for recurrence after complete metastasectomy in patients with metastatic renal cell carcinoma in the targeted therapy era

844 - Predictive factors for recurrence after complete metastasectomy in patients with metastatic renal cell carcinoma in the targeted therapy era

Melanoma Brain Metastases in the Era of Target Therapies: An Overview.

Malignant melanoma is the third most common type of tumor that causes brain metastases. Patients with cerebral involvement have a dismal prognosis and their treatment is an unmet medical need. Brain involvement is a multistep process involving several signaling pathways such as Janus kinase/signal Transducer and Activator of Transcription (JAK/STAT), Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT), Vascular Endothelial Growth Factor and Phosphatase and Tensin Homolog (PTEN). Recently therapy that targets the MAPK signaling (BRAF/MEK inhibitors) and immunotherapy (anti-CTLA4 and anti-PD1 agents) have changed the therapeutic approaches to stage IV melanoma. In contrast, there are no solid data about patients with brain metastases, who are usually excluded from clinical trials. Retrospective data showed that BRAF-inhibitors, alone or in combination with MEK-inhibitors have interesting clinical activity in this setting. Prospective data about the combinations of BRAF/MEK inhibitors have been recently published, showing an improved overall response rate. Short intracranial disease control is still a challenge. Several attempts have been made in order to improve it with combinations between local and systemic therapies. Immunotherapy approaches seem to retain promising activity in the treatment of melanoma brain metastasis as showed by the results of clinical trials investigating the combination of anti-CTL4 (Ipilimumab) and anti-PD1(Nivolumab). Studies about the combination or the sequential approach of target therapy and immunotherapy are ongoing, with immature results. Several clinical trials are ongoing trying to explore new approaches in order to overcome tumor resistance. At this moment the correct therapeutic choices for melanoma with intracranial involvement is still a challenge and new strategies are needed.

Surgical-only treatment of pancreatic and extra-pancreatic metastases from renal cell carcinoma - quality of life and survival analysis

BackgroundTreatment of pancreatic metastases (PM) from renal cell carcinoma (RCC) is still an issue between surgeons and oncologists, in the era of target-therapy.MethodsData from 26 patients undergoing resection of PM and extra-PM from RCC, with R0 intention were retrospectively analysed. No one received adjuvant chemotherapy. Patients were divided into two groups; Group A comprehends 14 patients who developed synchronous (5) or methacronous (9) extra-PM. Group B comprehends 12 patients that developed PM only.ResultsNo intraoperative mortality was recorded. Complications occurred in 14 patients (53.8%), all but 2 (7.26%) were graded I and II according to Clavien-Dindo classification.Recurrences occurred in 8 patients (30.8%), of whom, 5 (62.5%) were submitted for further resections in other sites.Three-, five- and ten-year observed overall survival were respectively 88,5% [95%CI: 0,56 – 1,33], 76,9% [95%CI: 0,47 – 1,19] and 50% [95%CI: 0,20 – 1,03]. Disease-free survival was 65,4% [95%CI: 0,38 – 1,05], at 3 years, 57,7% [95%CI 0,323 – 0,952] at 5 years and 42,9% [95%CI 0,157 – 0,933], at 10 years. QoL analysis, through WHOQOL-BREF questionnaire, assessed at last available follow up revealed a mean score of 75,9 ± 11,6 on 100 points.ConclusionDespite no significant differences in survival between patients affected by Pancreatic or Extra-Pancreatic metastases, PM patients seems to show better outcome when managed surgically. mRCC patients, eligible for radical metastasectomy, tend to have long survival rates, reduced recurrence rates and good QoL.Study registrationThis paper was registered retrospectively in ClinicalTrials.gov with Identification number: NCT03670992.

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma

BackgroundCytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. ObjectiveWe aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. Design, setting, and participantsData from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). Outcome measurements and statistical analysisLogistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. Results and limitationsIntraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08–1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38–5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08–2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03–0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20–7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. ConclusionsMorbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. Patient summaryWe studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications.

MP14-07 PERFORMANCE OF A NEW RISK ASSESSMENT TOOL FOR PATIENTS WITH METASTATIC RENAL CELL CARCINOMA UNDERGOING CYTOREDUCTIVE NEPHRECTOMY IN THE TARGETED THERAPY ERA: REMARCC SCORE

MP14-07 PERFORMANCE OF A NEW RISK ASSESSMENT TOOL FOR PATIENTS WITH METASTATIC RENAL CELL CARCINOMA UNDERGOING CYTOREDUCTIVE NEPHRECTOMY IN THE TARGETED THERAPY ERA: REMARCC SCORE

MP14-14 PREDICTIVE FACTORS FOR RECURRENCE AFTER COMPLETE METASTASECTOMY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMAIN THE TARGETED THERAPY ERA

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Apr 2020MP14-14 PREDICTIVE FACTORS FOR RECURRENCE AFTER COMPLETE METASTASECTOMY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMAIN THE TARGETED THERAPY ERA Toshio Takagi*, Kazuhiko Yoshida, Tsunenori Kondo, Hironori Fukuda, Hiroki Ishihara, Hirohito Kobayashi, Junpei Iizuka, Masayoshi Okumi, Hideki Ishida, and Kazunari Tanabe Tokyo Toshio Takagi*Toshio Takagi* More articles by this author , Kazuhiko YoshidaKazuhiko Yoshida More articles by this author , Tsunenori KondoTsunenori Kondo More articles by this author , Hironori FukudaHironori Fukuda More articles by this author , Hiroki IshiharaHiroki Ishihara More articles by this author , Hirohito KobayashiHirohito Kobayashi More articles by this author , Junpei IizukaJunpei Iizuka More articles by this author , Masayoshi OkumiMasayoshi Okumi More articles by this author , Hideki IshidaHideki Ishida More articles by this author , and Kazunari Tanabe TokyoKazunari Tanabe Tokyo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000839.014AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Complete metastasectomy is expected to improve the survival of patients with metastatic renal cell carcinoma (mRCC). However, many patients develop re-recurrence, despite achieving complete remission with surgery.The aim of the present study was to investigate oncological outcomes such as recurrent free survival (RFS) after complete metastasectomy in patients with mRCC and analyze the predictive factors for recurrence after complete metastasectomy in the targeted therapy era. METHODS: This study included patients who underwent metastasectomy and achieved complete remission after surgery for mRCC between 2008 and 2018. All patients underwent nephrectomy or partial nephrectomy for primary lesion and were diagnosed as having RCC. Patients who received adjuvant systemic therapy after metastasectomy were excluded. Fifty-one patients were included in the final study population. RESULTS: The median age was 65 years. The distribution of MSKCC risk classification was favorable risk group in 22 (43%) patients, intermediate risk group in 27 (53%) patients, and poor risk group in 2 (4%) patients. Pathological subtype was clear cell RCC in 42 (82%) patients and papillary RCC in 8 (17%) patients. Tumor grades 1, 2 and 3 were observed in 5 (10%) patients, 33 (65%) patients, and 13 (25%) patients, respectively. One metastatic site was observed in 45 (88%) patients. Sarcomatoid features were found in 2 (4%) patients. The median duration from nephrectomy to metastasectomy was 32 months. The median follow-up duration was 49 months. During the study periods, 39 (74%) patients developed recurrence after complete metastasectomy, with median time from metastasectomy to tumor recurrence of 22 months. The 2- and 5-year RFS were 45% and 25%, respectively. Multivariate Cox regression revealed that ≥2 metastatic sites (vs. 1 site; HR=4.52; p=0.0171) and sarcomatoid features (HR=11.5; p=0.0171) were independent predictive factors for recurrence (table). CONCLUSIONS: The number of metastatic sites and sarcomatoid features were associated with recurrence after complete metastasectomy, which suggests that careful observation is required for such patients, even after achieving complete remission with metastasectomy. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e201-e201 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Toshio Takagi* More articles by this author Kazuhiko Yoshida More articles by this author Tsunenori Kondo More articles by this author Hironori Fukuda More articles by this author Hiroki Ishihara More articles by this author Hirohito Kobayashi More articles by this author Junpei Iizuka More articles by this author Masayoshi Okumi More articles by this author Hideki Ishida More articles by this author Kazunari Tanabe Tokyo More articles by this author Expand All Advertisement PDF downloadLoading ...

MP14-04 PREOPERATIVE TUMOR MEASUREMENTS ARE INDEPENDENTLY PREDICTIVE OF OVERALL SURVIVAL FOLLOWING CYTOREDUCTIVE NEPHRECTOMY

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Apr 2020MP14-04 PREOPERATIVE TUMOR MEASUREMENTS ARE INDEPENDENTLY PREDICTIVE OF OVERALL SURVIVAL FOLLOWING CYTOREDUCTIVE NEPHRECTOMY Daniel Shapiro*, Jose Karam, Philippe Spiess, Jay Raman, Mary Westerman, Wade Sexton, Logan Zemp, Alyssa Bilotta, Glenn Allen, Surena Matin, Christopher Wood, and E. Jason Abel Daniel Shapiro*Daniel Shapiro* More articles by this author , Jose KaramJose Karam More articles by this author , Philippe SpiessPhilippe Spiess More articles by this author , Jay RamanJay Raman More articles by this author , Mary WestermanMary Westerman More articles by this author , Wade SextonWade Sexton More articles by this author , Logan ZempLogan Zemp More articles by this author , Alyssa BilottaAlyssa Bilotta More articles by this author , Glenn AllenGlenn Allen More articles by this author , Surena MatinSurena Matin More articles by this author , Christopher WoodChristopher Wood More articles by this author , and E. Jason AbelE. Jason Abel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000839.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Studies suggest that overall survival (OS) following cytoreductive nephrectomy (CN) is associated with preoperative tumor measurements including primary tumor diameter, number of metastatic sites, sum of metastatic tumor diameters and primary tumor percent of overall burden. Current risk models, however, do not account for tumor burden. This study evaluated associations between OS and preoperative tumor measurements for patients treated with CN during the targeted therapy era. METHODS: Data for consecutive mRCC patients treated with CN at 4 institutions from 2006-2017 were analyzed after determining IMDC risk category, primary tumor (PT) diameter, number of metastatic sites, sum of metastatic tumor diameters and PT percentage of overall burden. All patients had either CT or MRI within 1 month of surgery which was used for tumor measurements. Univariate and multivariable (MV) Cox models evaluated tumor measurement and IMDC risk associations with OS. RESULTS: A total of 617 patients were available for analysis. Median follow-up of patients alive at last follow-up was 42 months (IQR 23-68). Median PT diameter was 10.0 cm (IQR 7-13cm), number of metastatic sites was 2 (IQR 1-2), sum of metastatic tumor diameters was 4.5 cm (IQR 2-10cm) and PT percent of overall burden was 73.7% (IQR 60-85%). After univariate analysis, all 4 tumor burden measures were associated with OS (p≤0.001 for all). MV models evaluating IMDC risk category with individual tumor burden measurements demonstrated that all measures were predictive as continuous variables: PT diameter (HR 1.03, 95% CI 1.01-1.06, p=0.007), sum of metastatic tumor diameters (HR 1.04, 95% CI 1.02-1.05, p<0.001), PT percent of overall burden (HR 0.43, 95% CI 0.27-0.68, p<0.001), and number of metastatic sites (HR 1.52, 95% CI 1.25-1.85, p<0.001). Additional MV models were created using clinically significant tumor measurement cutoffs and IMDC risk groups. OS was independently associated with IMDC intermediate (HR 3.17, 95% CI 1.84-5.44, p<0.001) and poor risk (HR 3.85, 95% CI 2.21-6.70, p<0.001), PT percentage of overall burden <90% (HR 1.41, 95% CI 1.05-1.89, p=0.021), and >2 metastatic sites (HR 1.60, 95% CI 1.29-2.00, p<0.001). CONCLUSIONS: Primary tumor and metastatic disease burden are independently associated with OS following CN. Future risk models should include tumor burden measurements. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e196-e196 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Shapiro* More articles by this author Jose Karam More articles by this author Philippe Spiess More articles by this author Jay Raman More articles by this author Mary Westerman More articles by this author Wade Sexton More articles by this author Logan Zemp More articles by this author Alyssa Bilotta More articles by this author Glenn Allen More articles by this author Surena Matin More articles by this author Christopher Wood More articles by this author E. Jason Abel More articles by this author Expand All Advertisement PDF downloadLoading ...

Redefining the Role of Surgical Management of Metastatic Renal Cell Carcinoma.

The treatment landscape for metastatic renal cell carcinoma (mRCC) continues to evolve with ongoing advancements in systemic therapy, raising further questions about the optimal role of surgery in the management of mRCC. Herein, we provide a context and review of the recent evidence concerning the role of surgical therapy for patients with mRCC including cytoreductive nephrectomy and distant metastatectomy. One randomized trial has been published in the targeted therapy era suggesting that initial systemic therapy is non-inferior to cytoreductive nephrectomy among patients with intermediate and poor-risk mRCC. Delaying cytoreductive nephrectomy until after systemic therapy may be a viable treatment approach, although a high level of evidence is lacking. Additional questions remain regarding the sequence of surgery with systemic therapy, utility of distant metastatectomy, as well as the application of these findings to the current generation of immunotherapy. Recent evidence challenges the need of upfront cytoreductive nephrectomy for unselected patients with mRCC. However, surgical therapy continues to play an important role in the management of the disease.

Predictive factors for recurrence after complete metastasectomy in patients with metastatic renal cell carcinoma in the targeted therapy era

ObjectivesComplete metastasectomy is expected to improve the survival of patients with metastatic renal cell carcinoma (mRCC). However, many patients develop re-recurrence, despite achieving complete remission with surgery. We examined recurrence-free survival (RFS) and analyzed predictive factors for recurrence after complete metastasectomy. MethodsFifty-one patients with mRCC who underwent complete metastasectomy between 2008 and 2018 were included in this study. Multivariate Cox regression analyses were performed to identify the prognostic factors for RFS. ResultsOf 51 patients, 6 (12%) had multiple metastatic sites and 45 (88%) had solitary metastasis. The pathological subtype was clear cell in 42 (82%), papillary in 8 (17%), and other subtype in 1 (2%) patient. Sarcomatoid features were found in 2 (4%) patients. The Memorial Sloan Kettering Cancer Center risk category was favorable in 43%, intermediate in 53%, and poor in 4% of patients. The median duration from nephrectomy to metastasectomy was 32 months. Of the total cohort, 39 patients (74%) developed recurrence after complete metastasectomy. The median RFS was 22 months, and the 2- and 5-year RFS rates were 45% and 25%, respectively. Multivariate Cox regression revealed that ≥2 metastatic sites (vs. 1 site; HR = 4.52; P = 0.024) and sarcomatoid features (HR = 11.5; P = 0.0171) were independent predictive factors for recurrence. The 2- and 5-year cancer-specific survival rates were 98% and 82%, respectively. ConclusionThe number of metastatic sites and sarcomatoid features were associated with recurrence after complete metastasectomy, which suggests that careful observation is required for such patients, even after achieving complete remission with metastasectomy.

From Traditional Histology to Next-Generation Pathology: A Review of The Workflow for the Characterisation and Molecular Profiling of Non-Small Cell Lung Cancer Samples

The clinical management of non-small cell lung cancer has shown unprecedented progress into the era of target therapies and immuno-oncology. Despite significant recent achievements in the treatment of these patients, identification of all the clinically actionable alterations required for patient management remains challenging, particularly when dealing with cytological or small bioptic samples. Many investigations have assessed the role of diagnostic tools currently available, including immunohistochemistry and sequencing assays. It is extremely important to be aware of the minimum adequacy criteria for pathology laboratories to ensure correct management of the biological samples in non-small cell lung cancer, including cytological, cell blocks, and histological specimens. In this review, the authors provide a comprehensive overview of the gold standard requirements, processing parameters, and turnaround time for the final integrated report, and additionally outline the values and limitations of the different bioptic strategies.

Expectations for overall survival in mRCC patients who were selected for upfront cytoreductive nephrectomy in the targeted therapy era.

646 Background: Surgical selection is critical to obtain the best outcomes for mRCC patients treated with cytoreductive nephrectomy (CN). Prior studies suggest that international metastatic disease consortium (IMDC) poor risk patients should not be considered for upfront CN because of expectation for short overall survival (OS). The purpose of this study is to evaluate OS among IMDC risk categories for patients treated with upfront cytoreductive nephrectomy during the targeted therapy era at five independent institutions. Methods: After IRB approval, data for consecutive mRCC patients treated with CN at 5 institutions from 2006-2017 was analyzed. Kaplan-Meier method was used to estimate survival from date of surgery and univariate/multivariable Cox models were used to evaluate associations with OS. Results: Of 1163 patients who were treated with CN at 5 institutions, 914 (79%) patients were treated without neoadjuvant systemic therapies. Preoperative IMDC risk category for upfront CN patients was favorable in 71 (8%), intermediate in 598 (65%), and poor in 245 (27%) patients. Median age was 61 (53-68) and median Charlson co-morbidity index was 1 (0-2). Median (IQR) patient follow-up for patients alive at last follow-up was 42.7 months (23, 69). The median OS (IQR) following upfront nephrectomy was 115.4 months (33,NR) for favorable risk patients, 28.6 months (9-65) for intermediate risk patients and 21.8 months (10-47) for poor risk patients. No differences were identified in OS among 5 different institutions (p=0.11) Of 245 poor risk patients, OS was not associated with co-morbidity status or age were not associated with OS (p=0.77, 0.92). Percentage survival at 1, 2, 3 and 5 years was 69%, 48%, 34%, and 20% in the poor risk cohort. Conclusions: Conclusions: After stratification by the IMDC model, observed survival following upfront cytoreductive nephrectomy in this multi-institutional cohort was longer than expected from prior studies, which may be partially attributed to surgical selection bias.

Preoperative metastatic disease burden to predict overall survival following cytoreductive nephrectomy independent of IMDC risk category.

652 Background: Studies suggest that overall survival (OS) following cytoreductive nephrectomy (CN) is associated with preoperative tumor measurements including primary tumor diameter, number of metastatic sites, sum of metastatic tumor diameters and primary tumor percent of overall burden. Current risk models, however, do not account for tumor burden. This study evaluated associations between OS and preoperative tumor measurements for patients treated with CN during the targeted therapy era. Methods: Data for consecutive mRCC patients treated with CN at 4 institutions from 2006-2017 were analyzed after determining IMDC risk category, primary tumor (PT) diameter, number of metastatic sites, sum of metastatic tumor diameters and PT percentage of overall burden. Univariate and multivariable (MV) Cox models evaluated tumor measurement and IMDC risk associations with OS. Results: A total of 617 patients were available for analysis. Median PT diameter was 10.0 cm (IQR 7-13cm), number of metastatic sites was 2 (IQR 1-2), sum of metastatic tumor diameters was 4.5 cm (IQR 2-10cm) and PT percent of overall burden was 73.7% (IQR 60-85%). After univariate analysis, all 4 tumor burden measures were associated with OS (p≤0.001 for all). MV models evaluating IMDC risk category with individual tumor burden measurements demonstrated that all measures were predictive as continuous variables: PT diameter (HR 1.03, 95% CI 1.01-1.06, p=0.007), sum of metastatic tumor diameters (HR 1.04, 95% CI 1.02-1.05, p&lt;0.001), PT percent of overall burden (HR 0.43, 95% CI 0.27-0.68, p&lt;0.001), and number of metastatic sites (HR 1.52, 95% CI 1.25-1.85, p&lt;0.001). Additional MV models were created using clinically significant tumor measurement cutoffs and IMDC risk groups. OS was independently associated with IMDC intermediate (HR 3.17, 95% CI 1.84-5.44, p&lt;0.001) and poor risk (HR 3.85, 95% CI 2.21-6.70, p&lt;0.001), PT percentage of overall burden &lt;90% (HR 1.41, 95% CI 1.05-1.89, p=0.021), and &gt;2 metastatic sites (HR 1.60, 95% CI 1.29-2.00, p&lt;0.001). Conclusions: PT and metastatic disease burden are independently associated with OS following CN. Future risk models should include tumor burden measurements.

A Survey on Classification Analysis for Cancer Genomics: Limitations and Novel Opportunity in the Era of Cancer Classification and Target Therapies

A Survey on Classification Analysis for Cancer Genomics: Limitations and Novel Opportunity in the Era of Cancer Classification and Target Therapies

Regulatory T Cells in Severe Persistent Asthma in the Era of Monoclonal Antibodies Target Therapies.

Asthma is an immunoinflammatory disease characterized by bronchial hyper-reactivity to different external stimuli. New monoclonal target treatments have been developed, but few studies have investigated the role of regulatory T cells in severe asthma and the modulatory effect of biological therapy on regulatory T cell functions. Their dysfunction may contribute to the development and exacerbation of asthma. Here we review the recent literature on the potential immunological role of regulatory T cells in the pathogenesis of severe asthma. The analysis of the role of regulatory T cells was performed in terms of functions and their possible interactions with mechanisms of action of the novel treatment for severe asthma. In an era of biological therapies for severe asthma, little data is available on the potential effects of what could be a new therapy: monoclonal antibody targeting of regulatory T cell numbers and functions.