Intravitreal chemotherapy in the management of retinoblastoma in a resource-limited setting

Intravitreal chemotherapy (IVitC) in the management of retinoblastoma has increased the rate of globe salvage, specifically in patients with recurrent disease and associated vitreous seeds. A significant number of children with retinoblastoma in developing countries present late, resulting in higher intraocular tumour-stage at presentation. Treatment requirements for such tumours usually include intravenous chemotherapy (IVC) and/or intra-arterial chemotherapy (IAC). While IVC has a long usage track record and a good efficacy, it has been reported to be associated with higher recurrence rates in a significant number of patients. Intra-arterial chemotherapy has the advantage of lower recurrence rates but requires personnel with advanced interventional radiology skills and has limited efficacy in treating intravitreal seeds. Intravitreal chemotherapy has gained popularity recently, largely because of its superior efficacy in the management of vitreous seeds, subretinal seeds and recurrent retinal tumour. An 8-month-old male infant initially presented with bilateral retinoblastoma, International Classification System for Intraocular Retinoblastoma (ICRB) Group E in the right eye and Group B on the left eye. The right eye was enucleated and currently has a prosthesis. The left eye had tumours that initially responded to brachytherapy and transpupillary thermotherapy (TTT). Approximately two years later his tumours recurred with vitreous seeds and were successfully managed with the use of cryotherapy and intravitreal chemotherapy. The simplicity of the technique of IVitC and its efficacy in controlling vitreous seeds and recurrent retinal tumours makes this route of regional chemotherapy a viable one in areas with limited expertise and resources such as South Africa.

Efficacy of Regional Chemotherapy Approach in Peritoneal Metastatic Gastric Cancer

Peritoneal spread is frequent in gastric cancer (GC) and a palliative condition. After failure to systemic chemotherapy (sCTx) remaining therapeutic options are very limited. We evaluated the feasibility and efficacy of locoregional chemotherapy (RegCTx) in peritoneal metastatic GC. In total, 38 (23 male and 15 female) patients with peritoneal metastatic GC after failure of previous sCTx and unresectable disease were enrolled in this study. Using the hypoxic abdominal stop-flow perfusion, upper abdominal perfusion and intraarterial infusion technique in total 114 cycles with Cisplatin, Adriamycin and Mitomycin C were applied. No significant procedure related toxicity was noticed- especially no Grade 3 or 4 toxicity occurred. With the RegCTx approach a median overall survival of 17.4 months was achieved. Patients who had undergone previously resection of the GC the median overall survival was even better with 23.5 months. RegCTx is a promising, safe and efficient approach in diffuse metastatic GC. The evaluation of RegCTx in the setting of multimodal treatment approach at less advanced stages is also warranted.

PEG-BCT-100 in Combination With Capecitabine and Oxaliplatin (PACOX) in Patients With Advanced Hepatocellular Carcinoma: A Phase I Study Results

Introduction: We investigated the safety and efficacy of PEG-BCT-100 in combination with oxaliplatin and capecitabine (PACOX) in advanced HCC patients.Methods: This was a single centre phase 1 trial to assess the safety and tolerability of PACOX. All the enrolled subjects received treatment in 3-weekly cycles: IV PEG-BCT-100 2.7 mg/kg on day 1, 8 and 15 of each cycle; oral capecitabine 1000 mg/m2 twice daily on day 1-14 of each cycle and IV oxaliplatin on day 1. Three dose levels of oxaliplatin (85 mg/m2, 100 mg/m2 or 130 mg/m2) were studied to define the maximum tolerated dose (MTD). Adverse events (AEs), efficacy by RECIST v1.1, time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were studied.Results: Seventeen patients were enrolled at 3 doses of oxaliplatin: 85 mg/m2 (8 patients), 100 mg/m2 (3 patients), and 130 mg/m2 (6 patients). The median age was 55 years; all had local-regional chemotherapy or target therapy such as sorafenib, but no systemic chemotherapy. Most common AEs were nausea (82%), injection site reaction (76%), palmar-plantar erythrodysesthesia (59%), oral mucositis (53%) and vomiting (53%). There was no dose-limiting toxicity (DLT). Median duration on study was 8 weeks overall. In 14 evaluable cases, one achieved partial response (PR), 4 had stable disease (SD); disease control rate was 36% (5/14); most responses were observed in the 130 mg/m2 cohort with 1 PR and 2 SDs (3/6 or 50%). The median TTP, PFS were both 7.0 weeks. Overall median OS was 10.7 months; the median OS was not reached at 19.4 months of follow-up in the third cohort.Conclusion: The PACOX regimen demonstrated good anti-cancer activity and survival advantage in advanced pre-treated HCC with favourable safety profile. It warrants further phase II/III studies.

IMPROVING THE SELECTIVE TREATMENT OF THYMUS TUMORS USING INTRA-ARTERIAL CHEMOEMBOLIZATION

Epithelial tumors of the thymus occur in the thymus and include thymomas and carcinomas of the thymus. Thymomas are the most common primary tumor in the anterior mediastinum, but are generally rare (1.5 cases / 1,000,000). Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymic carcinomas often have metastases. The 5-year survival of patients with thymoma reaches 90%. At the same time, the 5-year survival rate for thymic carcinoma is approximately 55% (NCCN Guidelines. Version 1.2020).Surgical treatment as an independent method can be used only when there are thymus tumors in encapsulated and minimally invasive tumors in the first degree, rarely in the second degree. In all other cases, patients are subject to combined, complex or conservative treatment. In combined and complex treatment, preference should be given to neoadjuvant methods, which allows to achieve regression of the tumor, reduces its volume, limits the invasion of surrounding tissues, as well as to transform the inoperable process into operability.Endovascular technologies, namely regional chemotherapy, in the preoperative period, as a preparatory stage, will increase the level of ablastics and antiblastics in surgical treatment of thymus and reduce the percentage of cytostatics on the whole body, as in intravenous administration. At patients with a paraneoplastic syndrome it is necessary to increase term of regression of displays of these syndromes.Intra-arterial administration of chemotherapeutics has certain advantages:• cytostatics in the arteries that supply blood to the tumor are injected directly into the affected area, which allows you to significantly increase the concentration of the drug in the tumor itself;• reduces the toxic effects of chemotherapy on the whole body;• longer action of drugs allows long-term contact of the cytostatic with tumor cells at all stages of the cell cycle.Another main detail of treatment is that after the introduction of the cytostatic, it is necessary to introduce special emboli (microspheres) to block the removal of the chemotherapeutic agent.The analysis of treatment is taking into account the stage, anamnestic data, the development of clinical manifestations, the results of laboratory and instrumental methods of examination.According to our evidence, taking into account clinical and anamnestic (complaints), laboratory, instrumental (CT OGK with IV contrast), certain conclusions were made in the treatment of thymic tumors.According to our observations, a method of complex treatment of thymic tumors was developed. In this technique, we used regional chemotherapy (namely intra-arterial administration of chemotherapy-cytostatics) as the main method.Object of study. Epithelial tumors of the thymus gland. Subject of study. Indicators of survival and quality of life of patients with malignant thymoma without surgical treatment. The results of radical surgical treatment after regional chemotherapy. Indicators of ablastic and antiblastic. Indicators of results of patients with paraneoplastic syndrome.The aim of the study. Increase the effectiveness of treatment of patients with epithelial tumors of the thymus by using intra-arterial chemoembolization as a neoadjuvant therapy to create ischemia and high concentrations of cytostatics in tumors for a long period of time to achieve devitalization of tumor tissue and reduce overall toxicity of chemotherapy.Objectives of the study.1. To determine the causes of unsatisfactory results of treatment of patients with epithelial tumors of the thymus using standard methods2. Improve the technique of intra-arterial chemoembolization in epithelial tumors of the thymus gland (technology, choice of cytostatics)3. To study the dynamics of biochemical markers (AFP, HGT) and antibodies to acetylcholine in paraneoplastic syndrome using intra-arterial chemoembolization4. To study pathomorphological changes in tumor tissue using intra-arterial chemoembolization5. To compare the clinical efficacy (increased tumor operability) of intra-arterial chemoembolization in the complex therapy of patients with epithelial tumors of the thymus gland.

ATRT-06. RESULTS OF MULTICENTER TRIAL CONCERNING THE TREATMENT OF CHILDREN WITH ATYPICAL TERATOID RHABDOID TUMORS OF THE CENTRAL NERVOUS SYSTEM UNDER 3 YEARS OLD

Objective To evaluate the prognostic factors in children with AT/RT aged under 3 years. Patients and methods: The prognostic factors were analyzed in 106patients under 3 years who got treatment and follow-up from 2008 to 2020.There were 41children younger than 12 months and 65patients older than 12 months. The location of the tumor was infratentorial in 58 patients, supratentorial in 46, and spinal cord in 2. There were 54 boys and 52 girls. Among the patients,57 had stage M0,36 had stage М+ or a multifocal tumor, and 13 had stage Mx. All the patients had undergone surgical treatment: total tumor removal in 27, subtotal-33, partial-42, biopsy - 4;67patients had got chemoradiotherapy according to the ATRT-2006(IRS III) protocol; 15, MUV-ATRT protocol; 3, CWS protocol; 9, EU-RHAB protocol; 6, HIT-SKK protocol; and 6 according to individual treatment schemes.12 patients received HDC with AuHCR. Results 47 are alive,1 was lost to follow-up, and 58 died:52 of progressive disease,6 of chemotherapy complications. The five-year PFS was 0.27; the five-year OS was 0.40. The PFS was significantly better in patients older than 12months old compared to patients under 12months: 0.33 and 0.17, respectively; p=0.0047. The PFS after total resection was higher than after subtotal resection, partial resection, and tumor biopsy: 0.51, 0.29, 0.09, and 0%, respectively (p=0.025).The PFS after radiotherapy was markedly higher compared to patients without radiotherapy: 0.63 and 0.0, respectively (р<0.001). The tumor location, stage, and gender did not affect the PFS. The survival rate was statistically significantly higher among the patients who had got treatment according to the ATRT-2006 protocol compared to MUV-ATRT,EU-RHAB, individual therapeutic regimens, CWS, and HIT-SKK: 0.33, 0.26, 0.11, 0.30, and 0.0, respectively; p=0.0020. The PFS was higher among the patients who had got intraventricular/intrathecal chemotherapy; p=0.0002. HDC with AuHCR did not statistically affect the PFS; p=0.0546.In multivariate analysis, the PFS was influenced by the age, tumor location, extent of surgery, radiotherapy, regional chemotherapy, HDC with AuHCR. Conclusions The survival of patients with CNS AT/RT aged under 3years significantly depended on the patients’ age, extent of surgery, chemotherapy protocol, radiotherapy, and regional administration of chemotherapeutic drugs.

Comparative analysis of regional chemotherapy methods on an experimental rat model with peritoneal carcinomatosis

Peritoneal carcinomatosis is a variant of implantation metastasis of tumors sprouting the serous membrane of an organ. At the moment, the most effective treatment for this disease is regional chemotherapy. Systemic chemotherapy is not effective enough. The standard for the treatment of peritoneal carcinomatosis was cytoreductive interventions followed by open or closed hypertermic intraperitoneal chemoperfusion (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC). Purpose of the study: in an animal experiment to compare the efficacy and safety of regional chemotherapy methods HIPEC and PIPAC Materials and methods: the study was conducted on 44 rats of Wistar females. To simulate carcinomatosis, a strain of ascites ovarian tumor (OA) from the Russian Oncology Cancer Research Center N.N. Petrova. was used. The safety of the technique was evaluated clinically and based on laboratory blood tests. Efficiency - based on mass spectrometry, pathomorphological data and in assessing the life expectancy of animals. Results: the conducted methods HIPEC (open, closed) and PIPAC have shown their safety in experiments on laboratory animals. The closed HIPEC technique is most effective. The analysis of the incidence of postoperative complications demonstrated a greater aggressiveness of open and closed techniques compared to the more “sparing” PIPAC method. Conclusions: the experiment showed comparable safety of all animals tested. Due to the peculiarities of the technique, the PIPAC method can be used as an option for multi-stage treatment in cases where CPC and HIPEC are not possible due to a high index of peritoneal carcinomatosis, and as a neoadjuvant treatment to prevent peritoneal carcinomatosis. In any case, the prospects for using this method require further research.

Implementation of hepatic artery infusion (HAI) chemotherapy for unresectable colorectal liver metastases (CRLM): The University of Miami experience.

96 Background: In patients with unresectable liver-confined CRLM, regional chemotherapy via HAI in combination with modern systemic chemotherapy (CT) can achieve hepatic disease control and expand surgical resectability. We describe patient selection and early outcomes following implementation of a HAI program at our tertiary referral academic center. Methods: We analyzed demographics, previous systemic treatment, primary tumor location, molecular profiling, extent of hepatic/extrahepatic disease, perioperative HAI outcomes (toxicity, conversion to resection/ablation, radiographic response), and overall survival (OS) in CRLM patients selected for HAI treatment (01/2018—06/2020) after multidisciplinary review. Results: Of 35 patients with unresectable CRLM (primary: colon, n = 24; rectum, n = 11) selected for HAI, 57% were heavily pre-treated (with at least 2 lines of pre-HAI systemic chemotherapy), 71% had a Fong clinical risk score ≥3, 86% presented with synchronous disease, 80% had bilobar metastasis, and 86% had > 5 tumors. All tumors were microsatellite stable, with 20% harboring KRAS/NRAS mutations and none had class I/II BRAF mutations. HAI was initiated at a median 14 (IQR 3, 64) months after CRLM diagnosis, and administered for a median of 7 (range 2, 16) cycles; 91% of patients (31/34) received concurrent HAI and systemic chemotherapy. Although most (69%) patients experienced some degree of hepatic toxicity during HAI therapy resulting in FUDR dose reduction and steroid administration, biliary sclerosis requiring intervention was observed in only 3 (9%) of patients. The overall perioperative morbidity was 17%, and there were no surgical-related 90-day mortalities following HAI pump placement. Excluding patients who initiated HAI treatment within the last 3 months of the study period (n = 3), 13 of 32 patients (41%) were rendered disease-free in the liver following complete resection and/or ablation in combination with HAI/systemic chemotherapy; in the remaining 19 patients (59%), hepatic progression-free survival was 7.3 months (IQR 4, 12). At a median follow-up of 11.2 months, post-HAI median OS for the overall cohort was 12.3 (IQR 7, 20) months. Patients undergoing complete resection/ablation demonstrated improved survival compared with those with progressive disease (median 20 vs 12 months, respectively). Conclusions: Implementation of a HAI program for multimodality liver-directed management of unresectable CRLM is feasible and is associated with meaningful clinical outcomes unlikely to be achieved with systemic therapy alone in heavily pre-treated patients.