LGG-17. CLINICAL OUTCOME OF PEDIATRIC LOW GRADE GLIOMA WITH POSITIVE BRAF-FUSION TREATED WITH MEK INHIBITOR

Background Low grade glioma (LGG) is the most common central nervous system (CNS) tumor in children. Some are treated with surgery alone, while chemotherapy is given for unresectable tumor with clinical symptoms or progression. Conventional chemotherapy is effective but 30–40% patients may have reactivation of disease requiring re-treatment throughout lifetime. MEK inhibitor for BRAF-fusion positive LGG is a new treatment option for refractory cases. Methods Retrospective search in territory-wide pediatric oncology registry for children diagnosed with LGG from 2010–2020 in Hong Kong. To identify patients with molecular confirmed BRAF-fusion positive LGG and any treatment with MEK inhibitor. Results Twelve patients (N=12) were identified with BRAF-fusion positive LGG, male:female was 1:2, age 0.3–15.1yr (median 5.0yr) at presentation. The median follow up duration was 1.8yr. Five patients (42%) had surgical resection only. Seven patients (58%) were given chemotherapy with Carboplatin / Vincristine. Five out of seven (n=7) treated patients (71%) have partial response at their initial treatment. Two patients (29%) had progressive disease during treatment and switched to second-line chemotherapy, vinblastine however without improvement. Three patients required re-treatment as disease reactivation. Total five patients had refractory diseases were treated with MEK inhibitor, Trametinib including one diagnosed NF-1. All of them have adverse skin reaction and raised transaminase with one required dose reduction. They have been taking the MEK inhibitor for 0.1–3.3 yr with sustainable partial response. Conclusion Pediatric LGG has overall favourable prognosis. Some of them treated with surgery alone while conventional chemotherapy could also achieve satisfactory disease control. For refractory disease with BRAF-fusion positive, MEK inhibitor is a well tolerated treatment option showing sustainable partial response. However, prolonged medication and disturbing skin reaction are still a major concern for this group of patients. On-going clinical trials to compare conventional chemotherapy versus MEK inhibitor could give us more insight about the clinical benefit, patient selection and treatment duration.

Phase II clinical study of concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with localized urothelial cancer of bladder: Results for primary analyses and survival. BTCRC-GU15-023.

398 Background: Bladder cancer (BC) patients (pts) who are cisplatin ineligible/unfit for surgery, or locally advanced and unresectable have limited treatment options. DUART investigates if the combination of radiation therapy (RT) and checkpoint inhibitor, durvalumab (durva) is safe and effective in these pts. We recently reported that the combination was safe, tolerable and disease control rate (DCR) was 92% post durvaRT. Here we present interim efficacy data of our phase II study. Methods: Pts with pure or mixed urothelial bladder cancer (T2-4 N0-2 M0) were enrolled if their tumor was unresectable (35%), were unfit for surgery (50%) and/or cisplatin ineligible (89%). Primary endpoints: a) PFS at 1-yr b) DCR post adjuvant durva; Secondary endpoints: a) CR post durvaRT b) median PFS c) median OS. Pts were treated with durva (1500mg) Q4 wks x2 doses along with definitive RT (64.8Gy, 36 fractions over 7 wks) to the bladder and involved nodes followed by adjuvant durva Q4 wks x 1 yr. Response was evaluated with CT scan and cystoscopy+biopsy. Sample size was based on assumption that this regimen would increase 1 yr PFS by 25% compared to RT alone (50% to 75%); we assumed DCR of 75%. A total of 26 pts were needed to reach a statistical power of at least 80% at one-sided alpha of 5% and to allow for 10% drop out rate. Results: Twenty-six pts (19 males, 7 females) were enrolled, median age 74 yr (51-94). Sixty two percent of pts had >T2 disease, 31% had positive lymph nodes; 62% with unresectable tumor or were unfit for surgery due to comorbidities. At data cut off (9/30/2020) 20/26 pts were evaluable for DCR post adjuvant durva (3 pts with CR post durvaRT, did not get adjuvant therapy; 1 pt withdrew after 3 cycles for adjuvant durva and was on f/u with unconfirmed CR; 2 pts are still on adjuvant durva) and 25/26 for PFS and all 26 pts for OS. Post completion of adjuvant durva, DCR was seen in 70 % (14/20 with 10 CR; 3 PR; 1 SD; 6 PD). One-year probability of PFS was 73% (95% CI 56.4%, 94.4%), median PFS was 18.5 months. One-year OS probability was 83.8% (95% CI 70.4%, 99.7%) with two-year OS probability of 76.8 (95% CI 60.2%, 98%). Median OS has not been reached. We did not observe any correlation between clinical outcome and baseline tumor PD-L1 expression. Conclusions: DurvaRT followed by adjuvant durva demonstrated promising efficacy with 1-year PFS probability of 73%, 1- year OS probability of 83.8% and DCR of 70% in MIBC and locally advanced BC pts with comorbidities. Results will be updated prior to the final presentation. Efficacy was also seen in node (+) pts which led to the design of prospective randomized NCTN study. Induction chemo followed by chemo+durvaRT+ adjuvant durva vs. chemoRT combination is being evaluated in the ongoing EA8185 clinical trial (ECOG-ACRIN/NRG study) for node (+) BC pts. Clinical trial information: NCT02891161.

Serum CA 19-9 of Pancreatic Solid Mass Patients in Dr. Cipto Mangunkusumo National Central General Hospital

Background: Pancreatic cancer is a lethal disease associated with poor prognosis. CA 19-9 is one of the elevated tumor markers in pancreatic cancer. However, data regarding CA 19-9 serum levels in pancreatic cancer in Indonesia is still scarce. This study aims to evaluate the clinical use of CA 19-9 in pancreatic cancer patients in Dr. Cipto Mangunkusumo National Central General Hospital.Method: This study is a cross-sectional study that served data of demographic information, CA 19-9 level, TNM stage, site, histopathology, and resectability of pancreatic cancer. This study included 77 subjects. The data were collected from electronic medical records and registered data of patients in the Gastrointestinal Endoscopy Center, Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta between 2014 to 2019. Sensitivity and specificity analysis of CA 19-9 were performed using the ROC curve.Results: We found 77 pancreatic cancer patients with a mean age of 54.2+10.4 years old. Most of them were males (59,7%), were found at stadium IV (41,6%) and unresectable tumor (68,8%). Non-adenocarcinoma which was mainly found in the head of the pancreas (76,6%) were confirmed in 67,5% of patients. The sensitivity and specificity of CA-19 9 to diagnose adenocarcinoma pancreas were 32% and 62% (p=0.939).Conclusion: CA 19-9 should be used in aiding diagnosis, in conjunction with other modalities, such as radiological procedures and histopathology results. Measuring serum CA19-9 level in the early diagnosis could guide clinicians in determining the treatment and prognosis of pancreatic cancer.

Primary Mediastinal Germ Cell Tumors—The University of Western Ontario Experience

Extragonadal germ cell tumors account for 2–5.7% of germ cell tumors (GCTs). Of these, primary mediastinal GCTs (PMGCTs) are responsible for 16–36% of cases. Given the rarity of these tumors, specific treatment strategies have not been well defined. We report our experience in treating these complex patients. In total, 318 men treated at our institution with chemotherapy for GCTs between 1980 and 2016 were reviewed. PMGCT was defined as clinically diagnosed mediastinal GCT with no evidence of testicular GCT (physical exam/ultrasound). We identified nine patients diagnosed with PMGCT. All patients presented with an anterior mediastinal mass and no gonadal lesion; four patients also had metastatic disease. Median age at diagnosis was 30 years (range, 14–56) and median mass size at diagnosis was 9 cm (range, 3.4–19). Eight patients had non-seminoma and one had pure seminoma. All patients received cisplatin-based chemotherapy initially. Surgical resection was performed in four patients; three patients had a complete resection and one patient was found to have an unresectable tumor. At a median follow-up of 2 years (range, 3 months–28 years) six patients had progressed. Progression-free survival was short with a median of 4.1 months from diagnosis (range 1.5–122.2 months). Five patients died at a median of 4.4 months from diagnosis. One and 5-year overall survivals were 50% and 38%, respectively. PMGCT are rare and aggressive. Our real-life Canadian experience is consistent with current literature suggesting that non-seminoma PMGCT has a poor prognosis despite prompt cisplatin-based chemotherapy followed by aggressive thoracic surgery.

Glioma-initiating cells at tumor edge gain signals from tumor core cells to promote their malignancy

Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM heterogeneity is largely limited to the surgically resectable tumor core lesion while the seeds for recurrence reside in the unresectable tumor edge. In this study, stratification of GBM to core and edge demonstrates clinically relevant surgical sequelae. We establish regionally derived models of GBM edge and core that retain their spatial identity in a cell autonomous manner. Upon xenotransplantation, edge-derived cells show a higher capacity for infiltrative growth, while core cells demonstrate core lesions with greater therapy resistance. Investigation of intercellular signaling between these two tumor populations uncovers the paracrine crosstalk from tumor core that promotes malignancy and therapy resistance of edge cells. These phenotypic alterations are initiated by HDAC1 in GBM core cells which subsequently affect edge cells by secreting the soluble form of CD109 protein. Our data reveal the role of intracellular communication between regionally different populations of GBM cells in tumor recurrence.

Fabrication of Biodegradable Poly(caprolactone) Spherical-Microcarriers for Arterial Embolization

This study aimed to develop emulsification assisted with ultrasonic atomization (EUA) to make embolic biodegradable poly(caprolactone) (PCL) spherical-microcarriers with uniform particle size for mass production which was used to cure hepatocellular carcinoma, because this kind of embolic drugs is expensive at the current market due to their complex manufacturing process. The embolic spherical-microcarriers with sustained-releasing therapeutic agents can shrink an unresectable tumor into a respectable size. Through high frequency vibrating surface on the ultrasonic atomizer nozzle, the thin liquid film for PCL oil-phase solution was broken into the uniform PCL microdroplets (particle sizes are from 20 to 55 μm) with less medicine loss. To determine the optimal parameters to make PCL microcarriers, the ultrasonic module parameters including the concentration of PCL solution, vibrating amplitude of atomizer, feeding rate of PCL oil-phase solution and collection distance on the particle size of microdroplets were analyzed. Besides, a vertical circulation flow field of aqueous-phase poly(vinyl alcohol) (PVA) solution was created to enhance the separation of the microdroplets and increase the production of the PCL microcarriers, and about 8~11 wt% of PVA solution with high stable dispersion property was used to effectively improve the yield rate of PCL spherical-microcarriers (89.8~98.2 wt%). The final particle size of PCL microcarriers was ca. 5–18 μm, indicating an about 25–50% volume shrinkage from microdroplets to solid spherical-microcarriers.

Preoperative neoadjuvant targeted therapy for inoperable differentiated thyroid cancer: a case report

Background: The majority of differentiated thyroid cancer (DTC) has good prognosis after a careful standardized therapy according to the current guidelines. However, approximately 13% to 15% of DTC shows surprisingly aggressive behavior and invades the surrounding structures, and then a few is very difficult to remove. In that specific context, preoperative neoadjuvant targeted therapy may improve the clinical stage and create an opportunity for operation.Case presentation: We reported a case of 64-year-old woman with locally advanced papillary thyroid cancer (PTC) who presented with dysphagia due to seemingly unresectable tumor, which severely invaded the left esophagus at the junction of neck and thorax, difficult to undergo a safe and complete removal. With an approvement of institution ethics committee, this patient was treated with neoadjuvant therapy (apatinib 500mg orally qd).Six weeks later, the tumor dramatically shrunk from 56*37mm to 29*26mm with well-controlled mild hypertension. After 10 days interval of apatinib withdrawal, complete tumor excision was accomplished without esophagus fistula. Postoperative inhibition and radioiodine 131I ablation were performed. At one-year follow-up evaluation, no tumor recurrence or metastasis was observed.Conclusion: Preoperative short-termed targeted treatment for locally advanced inoperable DTC may become a promising neoadjuvant therapy, which can reduce the tumor size and decrease stage, thus being convenient for complete and safe removal.

Pancreatoblastoma. Case report and review of literature

Although pancreatoblastoma (PB) is a rare tumor, it is the most common malignant pancreatic tumor in children. Clinic presentation is insidious, so early diagnostic suspicion allows timely therapy. We reported 3 cases of PB treated at our center. The first two cases achieved complete disease response after full tumor resection. The first one is in complete remission at 7 months after chemotherapy. The second patient is in second complete remission at 206 months after diagnosis and 128 months after metastatic relapse. The third case died from disease progression 61 months after the initial metastatic unresectable tumor. Histology, clinical features and treatment options are discussed along with presentation of the cases.

Modern principles of hepatocellular carcinoma treatment

Aim. To improve the treatment outcomes, quality and life expectancy, prognosis in patients with hepatocellular carcinoma based on an analysis of treatment outcomes.Materials and methods. The analysis of the long-term results of treatment of 114 patients with hepatocellular carcinoma for 2015–2020 was carried out. Two groups of patients were distinguished: 41 (35.9%) patients were included in group I (a potentially resectable tumor with R0 surgery), and 63 (55.2%) patients were included in group II (advanced tumor does not suggest R0 resection).Results. Actuarial survival for patients with R0 surgery (48) was: 1 year – 85%, 3 years – 65%, 5 years – 55%; in patients with unresectable tumor after transarterial chemoembolization: 1 year – 65%, 3 years – 29%, 5 years – 11%; after local destruction methods – 0.5 years – 75%, 1 year – 36%, 1.5 years – 22%.Conclusions. The results of treatment of patients with hepatocellular carcinoma confirm the feasibility and effectiveness of a rational multidisciplinary approach. It allows you to achieve satisfactory results in multidisciplinary hospitals. The results are consistent with the data of large surgical centers.