Multiagent Systemic Chemotherapy Research Articles

ASO Visual Abstract:Outcomesof HepaticArtery-BasedTherapiesand Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

ASO Visual Abstract:Outcomesof HepaticArtery-BasedTherapiesand Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

Outcomes of Hepatic Artery-Based Therapies and Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis

BackgroundTreatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed.ObjectiveA systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI).MethodsOutcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR).ResultsA total of 32, 7, 9, and 14 publications were included in the HAI-S, TACE-S, and TARE-S chemotherapy arms. The 6/12/24/36-month OS estimates for HAI-S, TACE-S, TARE-S, FOLFOX, FOLFIRI, and FOLFOXIRI were 97%/80%/54%/35%, 100%/83%/40%/14%, 82%/61%/34%/21%, 96%/83%/53%/36%, and 96%/93%/72%/55%. Similarly, the 6/12/24/36-month PFS estimates were 74%/44%/19%/14%, 66%/20%/9%/3%, 57%/23%/10%/3%, 69%/30%/12%/7%, and 88%/55%/18%/11%. The corresponding CTR and RR rates were 31, 20%, unmeasurable (TARE-S), 35, 53; and 49, 45, 45, 50, 80%, respectively. The majority of chemotherapy studies included first-line therapy and liver-only metastases, whereas most HAI-S studies were pretreated. On subgroup analysis in first-line setting with liver-only metastases, the HAI-S arm had comparable outcomes to FOLFOXIRI and outperformed doublet chemotherapy regimens. Although triplet chemotherapy appeared to outperform other arms, high toxicity and inclusion of potentially resectable patients must be considered while interpreting results.ConclusionsHAI-S and multiagent chemotherapy are effective therapies for UCRLM. To make definitive conclusions, a randomized trial with comparable patient characteristics and line of therapy will be required. The upcoming EA2222 PUMP trial may help to address this question.

Paclitaxel protein bound (A) plus gemcitabine (G) plus cisplatin (C) and hydroxychloroquine (HCQ) neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC).

667 Background: Neoadjuvant therapy has become the consensus treatment for individuals with locally advanced (LA) and borderline resectable (BR) PDAC. Neoadjuvant therapy for resectable (R) PDAC has been in greater use due to concerns over micro metastases at diagnosis. Typical therapies involve the use of multiagent systemic chemotherapy with or without radiation therapy. In retrospective studies, Cancer Antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A), has shown promising clinical data in a previously reported study in advanced PDAC [JAMA Oncol. 2020;6(1):125-132]. HCQ has been shown to target autophagy in PDAC and has demonstrated higher response in combination with GA. We conducted a prospective, phase 2 clinical trial of patients with R, BR, and LA PDAC utilizing a regimen combining A + G + C + HCQ with the primary endpoint of CA 19-9 normalization (NCT04669197). Methods: Eligibility criteria include patients with histologically confirmed R, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2 on days 1, 8 of a 21-day cycle (IV) along with HCQ 600 mg po bid. Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate (by RECIST 1.1), and 2 year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date all planned 12 patients have been enrolled, 11 evaluable. 8 male, 4 female; age range 50 to 76 yo. Patient classifications is 3 R; 4 BR; 5 LAPC. Most common drug related grade (gr) 3-4 adverse events (AEs) are: thrombocytopenia gr 3 27%, gr 4 27%, anemia gr 3 36%, and neuropath gr 3 36%. CA 19-9 normalization occurred in 36% (4/11) who have completed at least 1 cycle of treatment. To date, 3 individuals went to surgery, with 3 achieving R0. Overall response rate in measurable patients is 45% (1CR, 4 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with non-metastatic PDAC, the use of A+G+C+HCQ resulted in a CA 19-9 normalization rate in 36% of individuals. Most patients did not go to surgery. The OS data is maturing. Supported by grants from the HonorHealth Foundation and Marley Foundation. Clinical trial information: NCT04669197 .

Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model.

Surgery, multiagent systemic chemotherapy, and radiation are used for patients with orbital retinoblastoma but are associated with unacceptable short- and long-term toxicity (including death). We studied orbital and systemic exposure of topotecan in the swine model after ophthalmic artery chemosurgery (OAC) and intravenous (IV) delivery. Landrace pigs (n = 3) underwent 30-minute OAC of topotecan (4 mg), and samples were serially obtained from the femoral artery and from a microdialysis probe inserted into the lateral rectus muscle sheath of the infused eye as a surrogate of the orbital irrigation. Animals were recovered, and, after a wash-out period, plasma and microdialysate samples from the contralateral eye were collected after a 30-minute IV infusion of topotecan (4 mg). Samples were quantified by high-performance liquid chromatography, and population pharmacokinetic analysis was conducted using MonolixSuite. After OAC, median topotecan exposure in the orbit was 5624 ng × h/mL (range 3922-12531) compared to 23 ng × h/mL (range 18-75) after IV infusion. Thus, topotecan exposure in the orbit was 218-fold (range 75-540) higher after OAC than after IV infusion despite comparable systemic exposure (AUCpl) between routes (AUCpl, OAC: 141 ng × h/mL [127-191] versus AUCpl, IV: 139 ng × h/mL [126-186]). OAC was more selective to target the orbit because the median (range) orbital-to-plasma exposure ratio was 44 (28-65) after OAC compared to 0.18 (0.13-0.40) after IV infusion. OAC of topotecan resulted in higher orbital exposure than after IV infusion and was a more selective route for local drug delivery. Patients with orbital retinoblastoma may benefit from a multimodal treatment strategy including OAC therapy.

Combined multiagent chemotherapy and radiotherapy is associated with prolonged overall survival in patients with non-operatively managed stage II-III pancreatic adenocarcinoma.

Most patients with pancreatic adenocarcinoma (PDAC) do not undergo surgical resection. The role of radiotherapy (RT) in non-operatively managed localized pancreatic adenocarcinoma is unclear. The National Cancer Database (2010-2016) was queried for patients with clinical stage II-III PDAC treated with multiagent systemic chemotherapy (CT)+/- RT but not surgery. Factors associated with the receipt of RT and overall survival were compared after adjusting for patient demographics and clinical characteristics. A total of 14,921 patients were included, of whom 9279 received CT and 5382 received CT+RT. Patients treated with CT+RT were more likely to be younger (65vs66yrs), treated at non-academic facilities (48.8%vs46.7%), have private insurance (40.3%vs36.5%), and have clinical T4 tumors (53.6%vs48.7%). Most patients who were treated with RT received external beam radiotherapy (89.3%), and the median dose was 5,000cGy. Median time to start of RT was 129 days. CT+RT was associated with longer overall survival (15.9vs11.8mos,p<0.001), and remained associated with survival on multivariable analysis (HR 0.74, 95%CI 0.70-0.78). On a 4-month conditional survival analysis, combined CT+RT remained associated with improved survival compared to CT alone (16.0vs13.1mos,p<0.001). In patients with non-operatively managed localized pancreatic adenocarcinoma, combined radiotherapy and multiagent systemic chemotherapy is associated with improved overall survival compared to chemotherapy alone.

High-intensity local treatment of clinical node-positive urothelial carcinoma of the bladder alongside systemic chemotherapy improves overall survival.

Clinical node-positive urothelial carcinoma of the bladder (cN+UCaB) is a rapidly fatal disease with limited information on comparative-effectiveness of available treatment options. We sought to examine the impact of high-intensity vs. conservative local treatment (LT) regimens in management of these patients alongside systemic chemotherapy. We identified 3,227 patients within the National Cancer Data Base who underwent multiagent systemic chemotherapy along with either high-intensity or conservative LT for primary cN+UCaB between 2004-2016. Patients who received no LT, TURBT alone, or <50 Gy radiation therapy to the bladder were included in the conservative group, while patients that received radical cystectomy with pelvic lymphadenectomy or ≥50 Gy radiation therapy with TURBT were included in the high-intensity group. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS). Additionally, to assess whether the benefit of high-intensity LT differs by baseline mortality risk, we tested an interaction between 5-year predicted life-expectancy and the LT type. Overall, 784 (24.3%) and 2,443 (75.7%) cN+UCaB patients underwent high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier analysis demonstrated OS to be significantly higher in the high-intensity group compared to the conservative group: 5-year OS 28.4% vs. 18.3%, respectively (Log-rank P<0.001). IPTW-adjusted multivariable Cox regression analysis confirmed the benefit of high-intensity LT in prolonging OS (HR 0.63, P<0.001). Interaction analysis showed that high-intensity LT approach was associated with longer OS in all patients regardless of their baseline 5-year life-expectancy (Pinteraction=0.79). Eligible patients with cN+UCaB should be considered for aggressive local treatment alongside multiagent systemic chemotherapy. Prospective trials are needed to validate these preliminary findings.

Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer: A Comparison of Short- and Long-term Oncologic Outcomes.

To evaluate the impact of neoadjuvant multi-agent systemic chemotherapy and radiation (TNT) vs neoadjuvant single-agent chemoradiation (nCRT) and multi-agent adjuvant chemotherapy on overall survival (OS), tumor downstaging, and circumferential resection margin (CRM) status in patients with locally advanced rectal cancer. Outside of clinical trials and small institutional reports, there is a paucity of data regarding the short and long-term oncologic impact of TNT as compared to nCRT. Adult patients with stage II-III rectal adenocarcinoma were identified in the National Cancer Database [2006-2015]. Out of 8,548 patients, 36% received TNT and 64% nCRT. In the cohort, 13% had a pCR and 20% a neoadjuvant rectal (NAR) score <8. In multivariable analysis, as compared to nCRT, TNT demonstrated numerically higher pCR rates ( P = 0.05) but had similar incidence of positive CRM ( P = 0.11). Similar results were observed with NAR scores <8 as the primary endpoint. After adjusting for confounders, OS was comparable between the 2 groups. Additional factors independently associated with lower OS included male gender, uninsured status, low income status, high comorbidity score, poorly differentiated tumors, abdominoperineal resection, and positive surgical margins (all P <0.01). In separate models, both pCR and a NAR score <8 were associated with improved OS. In this national cohort, TNT was not associated with better survival and/or CRM negative status in comparison with nCRT, despite numerically higher downstaging rates. Further refinement of patient selection and treatment regimens are needed to establish effective neoadjuvant platforms to improve outcomes of patients with rectal cancer.

Meta-Analysis of Survival and Development of a Prognostic Nomogram for Malignant Pleural Mesothelioma Treated with Systemic Chemotherapy.

Simple SummaryMalignant pleural mesothelioma (MPM) is a rare cancer with an aggressive disease course. For patients who are medically inoperable or surgically unresectable, multi-agent systemic therapy remains an accepted standard-of-care around the world. Given the rare incidence of MPM and the disease’s aggressive nature, novel clinical trial designs are required. The purpose of this meta-analysis is to provide baseline summative survival estimates as well as evaluate the influence of prognostic variables to provide comparative estimates for future trial designs. In this study, a nomogram model was created to estimate survival with treatment with platinum-pemetrexed using covariates known to be associated with survival, including median age, gender, ECOG performance status, tumor stage, and tumor pathology subtype. Collaborative efforts can drive the change in the right direction, and appreciable progress has to be facilitated and newer trial designs may need to pave the way for future innovations in this rare disease.(1) Purpose: Malignant pleural mesothelioma (MPM) is a rare cancer with an aggressive course. For patients who are medically inoperable or surgically unresectable, multi-agent systemic chemotherapy remains an accepted standard-of-care. The purpose of this meta-analysis is to provide baseline summative survival estimates as well as evaluate the influence of prognostic variables to provide comparative estimates for future trial designs. (2) Methods: Using PRISMA guidelines, a systematic review and meta-analysis was performed of MPM studies published from 2002–2019 obtained from the Medline database evaluating systemic therapy combinations for locally advanced or metastatic disease. Weighted random effects models were used to calculate survival estimates. The influence of proportions of known prognostic factors on overall survival (OS) were evaluated in the creation of a prognostic nomogram to estimate survival. The performance of this model was evaluated against data generated from one positive phase II study and two positive randomized trials. (3) Results: Twenty-four phase II studies and five phase III trials met the eligibility criteria; 2534 patients were treated on the included clinical studies. Ten trials included a platinum-pemetrexed-based treatment regimen, resulting in a pooled estimate of progression-free survival (PFS) of 6.7 months (95% CI: 6.2–7.2 months) and OS of 14.2 months (95% CI: 12.7–15.9 months). Fifteen experimental chemotherapy regimens have been tested in phase II or III studies, with a pooled median survival estimate of 13.5 months (95% CI: 12.6–14.6 months). Meta-regression analysis was used to estimate OS with platinum-pemetrexed using a variety of features, such as pathology (biphasic vs. epithelioid), disease extent (locally advanced vs. metastatic), ECOG performance status, age, and gender. The nomogram-predicted estimates and corresponding 95% CIs performed well when applied to recent randomized studies. (4) Conclusions: Given the rarity of MPM and the aggressive nature of the disease, innovative clinical trial designs with significantly greater randomization to experimental regimens can be performed using robust survival estimates from prior studies. This study provides baseline comparative values and also allows for accounting for differing proportions of known prognostic variables.

Combined multiagent chemotherapy and radiotherapy is associated with improved survival compared to chemotherapy alone in patients with non-operatively managed stage II-III pancreatic adenocarcinoma

Presenter: Kavin Sugumar MD | Case Western Reserve University School of Medicine Background: The majority of patients diagnosed with pancreatic adenocarcinoma (PDAC) do not undergo surgical resection. The role of systemic chemotherapy (CT) is well defined, but the role of radiotherapy (RT) in non-operatively managed localized pancreatic adenocarcinoma is unclear. We used a large administrative database to compare survival between patients treated with CT and those treated with CT+RT. Methods: The National Cancer Database (2010-2016) was queried for patients with clinical stage II-III PDAC who were managed non-operatively and treated with multiagent systemic CT +/- RT. We analyzed for demographic and clinical variables associated with the receipt of RT by multivariable logistic regression analysis. Overall survival was compared, adjusting for demographic and clinical variables by Cox proportional hazards regression analysis. Results: A total of 14,921 patients were included, of whom 9,279 received CT and 5,382 received CT+RT. Patients treated with CT+RT were younger (65 vs 66 years), more often treated at non-academic facilities (48.8% vs 46.7%) and more often had private insurance (40.3% vs 36.5%). Additionally, patients who received CT+RT had a higher proportion of clinical T4 tumors (53.6% vs 48.7%). Median time from diagnosis to start of multiagent CT was similar between patients treated with CT compared to those treated with CT+RT (29 vs 28 days). For patients treated with CT+RT, most patients received external beam radiotherapy (89.3%), median time to start of RT was 129 days, and the median dose was 5000 cGy. On multivariable analysis, factors associated with receipt of RT included age (OR 0.99, 95% CI 0.98-0.99), Medicaid (OR 0.72, 95% CI 0.58-0.88), clinical T4 tumors (OR 1.28, 95% CI 1.04-1.57), clinical N1 disease (OR 0.89, 95% CI 0.80-0.98), and CA19-9 >37 U/ml (OR 0.85, 95% CI 0.77-0.95). CT+RT was associated with longer overall survival (15.9 vs 11.8 months, p<0.001, Figure A), and remained independently associated with survival on multivariable Cox proportional hazards analysis (HR 0.74, 95%CI 0.70-0.78) compared to CT alone. On a 4-month conditional survival analysis, combined CT+RT remained associated with improved overall survival compared to CT alone (16.0 vs 13.1 months, p<0.001, Figure B). Conclusion: In patients with localized pancreatic adenocarcinoma that do not undergo surgical resection, combined radiotherapy and multiagent systemic chemotherapy is associated with improved overall survival compared to chemotherapy alone.

Femur Diafizinde Ewing Sarkom ve Literatür İncelemesi

Ewing sarcoma is one of the most common malignant tumors in the first two decades after osteosarcoma. With the recent systemic multiagent chemotherapy agents, there has been a significant decrease in mortality and recurrence rates. Ewing sarcoma usually involves the diaphyseal region of long bones. Many methods have been described in the literature regarding the treatment of bone defects after bone resections in this region. The young age of the patients revealed that the biological treatment option should be at the forefront. In this case, we reconstructed the bone defect in the femur with a non-vascularized fibular graft. Keywords: Ewing sarcoma, malignant bone tumour, bone defect

Radiation-Based Approaches As an Alternative to Stem Cell Transplant for Relapsed/Refractory Classical Hodgkin Lymphoma: A Multicenter Retrospective Analysis

Radiation-Based Approaches As an Alternative to Stem Cell Transplant for Relapsed/Refractory Classical Hodgkin Lymphoma: A Multicenter Retrospective Analysis

Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016.

When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC. Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression. Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P<0.0001; absolute percentage: 62.3% to 43.8%). Similar trends by year for PTR were observed among each of the subgroups, although patients with colon primary, young adults (age younger than 50 y), and patients also undergoing metastasectomy were more likely to undergo PTR (P<0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with a later year of diagnosis (adjusted odds ratio=2.21, 95% confidence interval: 2.04-2.40, P<0.0001). From 2000 to 2016, there was a sharp decline in the rate of PTR for patients with metastatic CRC, while the use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC.

Abstract B05: Paclitaxel protein bound plus gemcitabine plus cisplatin and paricalcitol neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC)

Abstract Background: Localized PDAC management has recently evolved. Due to concerns over micrometastases at diagnosis, the use of neoadjuvant chemotherapy for PDAC has become more common. Typical therapies involve the use of multiagent systemic chemotherapy with or without radiation therapy. Cancer antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A) has shown promising clinical data in a previously reported study in advanced PDAC (J Clin Oncol 2017;35:suppl 4S; abstract 341). We conducted a prospective, phase 2 clinical trial of patients with resectable, BR, and LA PDAC utilizing a regimen combining A + G + C + paricalcitol (P) with the primary endpoint of CA 19-9 normalization (NCT03138720). Methods: Eligibility criteria include patients with histologically confirmed resectable, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2, P at a fixed dose of 25 μg on days 1, 8 of a 21-day cycle (all treatment IV). Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate, and 2-year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date, 21 of the planned 24 patients have been enrolled: 11 male, 10 female; age range 49 to 85 yo. Patient classifications are 7 R; 7 BR; 7 LAPC. Most common drug-related grade (gr) 3-4 adverse events (AEs) are thrombocytopenia gr 3 40%, gr 4 33%, anemia gr 3 60%, and hypophosphatemia 13%. Of the 21, 16 are evaluable for maximum percent decrease in CA 19-9. CA 19-9 normalization occurred in 44% (7/16) who have completed at least 1 cycle of treatment. To date, 9 individuals went to surgery, with 8/9 achieving R0 (no pCR). Overall response rate in measurable patients is 26% (4/15 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with nonmetastatic PDAC, the use of A+G+C+P resulted in a CA 19-9 normalization rate in 44% of individuals. The study is ongoing and OS data are maturing. (Supported by grants from the HonorHealth Foundation and Marley Foundation.) Citation Format: Erkut Borazanci, Gayle Jameson, Courtney Snyder, Frank Tsai, Michael Gordon, Sunil Sharma, Carol Guarnieri, Amar Thosani, Syed Rahmanuddin, Ronald Korn, Steven Sckolnik, Paula Sedivy, Susan Haag, Kevin Gosselin, Daniel Von Hoff, Albert Amini. Paclitaxel protein bound plus gemcitabine plus cisplatin and paricalcitol neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B05.

Primary mediastinal large B-cell lymphoma with extensive cardiac involvement

Data regarding the optimal therapeutic approach of patients with primary mediastinal B-cell lymphoma and cardia c involvement are limited. Reports suggest that multi-agent systemic chemotherapy, along with radiation therapy, may be effective in the treatment of these patients.

Isolated Central Nervous System Chloroma as a Presenting Sign of Relapsed Pediatric Acute Lymphoblastic Leukemia.

Central nervous system (CNS) chloromas are an exceedingly rare presentation of CNS relapse in acute lymphoblastic leukemia (ALL). We report a relapsed ALL patient who presented with 2 separate chloromas and cerebrospinal fluid lymphoblastocytosis, and outline a treatment plan of systemic chemotherapy and CNS-directed radiation therapy. A review of the literature indicates that multiagent chemotherapy combined with CNS radiotherapy is effective, with hematopoietic stem cell transplantation used in half of reported cases. We conclude that intensive systemic multiagent chemotherapy with CNS-directed radiation therapy can be successfully used to treat relapsed pediatric ALL with CNS lymphoblastic chloroma.

Effectiveness of transurethral resection (TUR) plus systemic chemotherapy as definitive treatment for muscle-invasive bladder cancer (MIBC).

481 Background: TUR + neoadjuvant cisplatin-based chemotherapy achieves a pathologic complete response in 30-40% of patients with MIBC. Prior studies have demonstrated that long-term survival is possible for a subset of patients with MIBC treated with TUR plus chemotherapy alone, but such analyses have been limited by small sample sizes and poor generalizability. The objective of our study was to describe the characteristics and outcomes of patients managed with this approach using a large national registry. Methods: Within the National Cancer Database (2004-2012), we identified 1,003 patients who were treated with TUR + multi-agent systemic chemotherapy, without radiation, as definitive treatment for cT2-T4aN0M0 urothelial carcinoma of the bladder. Baseline characteristics were compared relative to those of 12,138 patients treated during the same period of time with radical cystectomy ± perioperative chemotherapy. Treatment outcomes were assessed using Kaplan-Meier analysis. Results: Compared to patients who were treated with cystectomy ± perioperative chemotherapy, patients treated with TUR + chemotherapy alone were significantly older (≥75 years old 37% vs. 30%; p &lt; 0.0001), had a higher clinical T stage (cT3: 14% vs. 12%; cT4: 12% vs 7%; p &lt; 0.0001) and were more frequently treated in non-academic facilities (66% vs. 49%; p &lt; 0.0001). There were no significant differences between groups regarding gender, Charlson comorbidity index, insurance type or income/education level. The 30-day and 90-day mortality with TUR + chemotherapy was 0.2% and 4%, respectively. The 5-year survival rate for all patients treated with TUR + chemotherapy was 30.5% (95% CI 26.8, 34.2), and limited to patients with cT2 disease was 33.1% (95% CI 28.7, 37.5). Conclusions: This large real-world cohort representing the continuum of practice settings in the United States confirms that long-term survival is achievable in a subset of patients treated with TUR + chemotherapy alone for MIBC. Refinement of this bladder-sparing approach integrating putative predictive biomarkers of pathologic complete response is now the focus of recently initiated prospective clinical trials.

Cold Atmospheric Plasma in the Treatment of Osteosarcoma.

Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.” The current article summarizes the potential of CAP in the treatment of human OS and reviews the underlying molecular mode of action.

MP78-08 IMPROVED SURVIVAL OF CYTOREDUCTIVE SURGERY IN ADDITION TO CHEMOTHERAPY FOR METASTATIC UPPER TRACT UROTHELIAL CARCINOMA: RESULTS FROM THE NATIONAL CANCER DATA BASE

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II1 Apr 2017MP78-08 IMPROVED SURVIVAL OF CYTOREDUCTIVE SURGERY IN ADDITION TO CHEMOTHERAPY FOR METASTATIC UPPER TRACT UROTHELIAL CARCINOMA: RESULTS FROM THE NATIONAL CANCER DATA BASE Leilei Xia, Benjamin Taylor, Jose Pulido, Jeremy Bonzo, and Thomas Guzzo Leilei XiaLeilei Xia More articles by this author , Benjamin TaylorBenjamin Taylor More articles by this author , Jose PulidoJose Pulido More articles by this author , Jeremy BonzoJeremy Bonzo More articles by this author , and Thomas GuzzoThomas Guzzo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2096AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prior studies have shown a possible survival benefit of cytoreductive surgery (CS) in addition to the standard of care for the treatment of major metastatic urologic cancers, including renal cell carcinoma, prostate cancer, and bladder cancer. The objective of our study was to compare the survival outcomes of chemotherapy combined with CS (nephroureterectomy, nephrectomy, and/or ureterectomy) versus chemotherapy alone for the treatment of metastatic upper tract urothelial carcinoma (mUTUC). METHODS We identified patients who presented with mUTUC at diagnosis in the National Cancer Data Base (NCDB) from 2004 to 2014. Only patients who had multi-agent systemic chemotherapy with or without CS were included. Multivariable logistic regression was performed to identify the predictors of receiving CS. Kaplan-Meier survival, log-rank test, and multivariable Cox regression controlled for demographics, socioeconomic factors, and tumor characteristics were used to compare the overall survival (OS) between CS and no CS groups. RESULTS We included 657 patients in our study of which 202 (30.75%) underwent CS. Logistic regression showed that patients who were older (OR = 0.98, 95% CI = 0.96-1.00, P =0.038), diagnosed with ureteral cancer (OR = 0.42, 95% CI = 0.27-0.66, P < 0.001), and had cN+ disease (OR = 0.33, 95% CI = 0.21-0.54, P < 0.001) were less likely to receive CS. Patients who were treated at a community hospital (OR = 1.96, 95% CI = 1.35-2.86, P < 0.001) were more likely to receive CS. No difference was found in Charlson comorbidity index between the CS and no CS groups (P = 0.434). CS group had significantly higher median OS than no CS group (13.4 vs. 10.3 months, log-rank test P < 0.001, Figure 1). Cox regression showed that compared with chemotherapy alone, chemotherapy combined with CS was significantly associated with improved OS (HR = 0.57, 95%CI = 0.44-0.74, P < 0.001). CONCLUSIONS Consistent with various other malignancies, CS appears to provide a survival benefit for mUTUC. However, our study is limited by the observational study design. Studies with higher level of evidence, especially randomized controlled trials are needed to validate the findings and to better identify the patients who are most likely to benefit from CS. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1033-e1034 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Leilei Xia More articles by this author Benjamin Taylor More articles by this author Jose Pulido More articles by this author Jeremy Bonzo More articles by this author Thomas Guzzo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Efficacy of High-Intensity Local Treatment for Metastatic Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Analysis From the National Cancer Data Base.

Purpose Evidence from studies of other malignancies has indicated that aggressive local treatment (LT), even in the presence of metastatic disease, is beneficial. Against a backdrop of stagnant mortality rates for metastatic urothelial carcinoma of the bladder (mUCB) at presentation, we hypothesized that high-intensity LT of primary tumor burden, defined as the receipt of radical cystectomy or ≥ 50 Gy of radiation therapy delivered to the bladder, affects overall survival (OS). Patients and Methods We identified 3,753 patients within the National Cancer Data Base who received multiagent systemic chemotherapy combined with high-intensity versus conservative LT for primary mUCB. Patients who received no LT, transurethral resection of the bladder tumor alone, or < 50 Gy of radiation therapy delivered to the bladder were included in the conservative LT group. Inverse probability of treatment weighting (IPTW) -adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients who received high-intensity versus conservative LT. Results Overall, 297 (7.91%) and 3,456 (92.09%) patients with mUCB received high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer in the high-intensity LT group than in the conservative LT group (14.92 [interquartile range, 9.82 to 30.72] v 9.95 [interquartile range, 5.29 to 17.08] months, respectively; P < .001). Furthermore, in IPTW-adjusted Cox regression analysis, high-intensity LT was associated with a significant OS benefit (hazard ratio, 0.56; 95% CI, 0.48 to 0.65; P < .001). Conclusion We report an OS benefit for individuals with mUCB treated with high-intensity versus conservative LT. Although the findings are subject to the usual biases related to the observational study design, these preliminary data warrant further consideration in randomized controlled trials, particularly given the poor prognosis associated with mUCB.

Puerperal Choriocarcinoma After Normal Term Pregnancy: Surgery Role in Selected Cases

Choriocarcinoma is a malignant neoplasm that classically displays biphasic morphology (syncytiotrophoblasts, cytotrophoblasts and trophoblastic cells). The incidence after term pregnancy is unusual, being diagnosed in most of them because of symptoms due to metastases. We report a case of puerperal choriocarcinoma after a normal uncomplicated pregnancy. After the diagnosis, it was classified as FIGO Stage III malignant gestational trophoblastic neoplasia and high-risk choriocarcinoma. The patient began multiagent systemic chemotherapy biweekly (EMA-CO). Although her tumor marker was normalized after the 3rd cycle, the full-body scan showed a diminishing of the uterine mass but persistent lung metastases. The patient underwent an uncomplicated laparotomy hysterectomy and bilateral salpingectomy procedure. She completed 6 cycles of EMA-CO in total, after which lung lesions disappeared. She remains disease-free 12 months after diagnosis.