Real-World Multicenter Experience in Tumor Debulking Prior to Blinatumomab Administration in Adult Patients With Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

Blinatumomab is an immunotherapeutic agent with dual specificity for CD3 and CD19 that is approved for the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). A steroid based pre-treatment is recommended before administering blinatumomab to patients with a high tumor burden to minimize the risk of tumor lysis syndrome, but the optimal debulking regimen and whether it can improve responses remain unclear. The present study retrospectively evaluated real-world outcomes following tumor debulking and blinatumomab infusion in R/R B-ALL adult patients treated at 7 Italian centers. Data were collected from 34 patients. The choice of the cytoreductive therapy was made by the treating clinician on an individual patient basis; regimens included chemotherapy (n=23), steroids (n=7) and tyrosine kinase inhibitors alone or in combination (n=4). The rate of complete responses (CR) and complete minimal residual disease (MRD) responses in CR patients were 67.6% and 81% respectively, after 2 cycles of blinatumomab. Moreover, among patients with a high tumor burden 50% obtained a CR, with 89% of them also achieving a complete MRD response. Favorable responses were also obtained in patients over 50 years of age at treatment initiation. Overall, 7 of 23 patients in CR after blinatumomab underwent hematopoietic stem cell transplantation. The results of this retrospective study highlight the heterogeneity in the use of pre-blinatumomab tumor debulking in real-life clinical practice. Nonetheless, debulking pre-treatment enhanced responses to blinatumomab compared to historic studies, indicating that this strategy may help to improve outcomes for R/R B-ALL patients.

IMMU-27. LONG TERM STABILIZATION OF RECURRENT HIGH-GRADE GLIOMA WITH PD-1 INHIBITOR PEMBROLIZUMAB IN TWO CASES

INTRODUCTION Despite PD-1 inhibition having success in many cancers, it has uncertain effects in brain tumors. We report two cases of recurrent high-grade gliomas that have remained stable for over one year since starting pembrolizumab. CASE REPORTS Case 1: A 59-year-old male was diagnosed with glioblastoma (GBM) without MGMT methylation or IDH mutation in late 2018 after surgery. He received radiation and temozolomide (TMZ) followed by adjuvant TMZ before tumor progression. He underwent second tumor debulking with recurrent GBM on pathology with negative PD-L1 expression. He started carboplatin. Progression was noticed after 7 to 8 cycles. Pembrolizumab was added. Tumor was stabilized. Carboplatin was completed after total 12 cycles and the patient has continued single agent of pembrolizumab for more than one year with stable brain MRIs. The patient has survived for 24 months since recurrence and 30 months since diagnosis. Case 2: A 53-year-old male had a brain tumor discovered on MRI in 2012 and received no treatment until resection in 2014. In 2016, he underwent second tumor debulking and was diagnosed with anaplastic oligodendroglioma with negative PD-L1 expression. He received radiation followed by PCV regimen. 17 months since diagnosis, he had first tumor progression on PCV. TMZ was started. 22 months since diagnosis, bevacizumab was initiated due to further growth. 33 months since diagnosis, pembrolizumab was added due to new lesions after 12-months of bevacizumab therapy. His tumor was stabilized. Bevacizumab was eventually discontinued. He has continued single agent pembrolizumab for 6 months so far. His tumor has been stable for 22 months since starting pembrolizumab. Survival has been 38 months from first recurrence and 7 years since tissue diagnosis. DISCUSSION These cases demonstrate the potential effects of anti-PD-1 immunotherapy in stabilizing recurrent high-grade glioma with combination of other treatment agents followed by single agent as maintenance therapy.

Venovenous Extracorporeal Membrane Oxygenation to Facilitate Removal of Endobronchial Tumors

Short-term extracorporeal membrane oxygenation is a useful adjunct to thoracic procedures. We report the cases of 2 middle-aged men who were supported with venovenous extracorporeal membrane oxygenation to facilitate tumor debulking and recanalization of the carina and mainstem bronchi. Neither patient had major complications or adverse events. These cases suggest that short-term extracorporeal membrane oxygenation is safe in patients undergoing complex resection or debulking of endobronchial lesions.

High-flow nasal oxygen for laryngeal tumor debulking: case report and current challenges

<p class="abstract">High-flow nasal oxygen (HFNO) has brought new opportunities in shared airway surgery. Contemporary challenges with its use in severely obstructive conditions such as laryngeal tumors still need to be addressed as there is discrepancy in its use and access among centres. We reported a case in which the use of HFNO allowed laryngeal tumor debulking while avoiding tracheotomy in a stridulous patient. The patient described was a 70 year old patient with stridor at rest secondary to a laryngeal tumor diagnosed five days before surgery. Tumor debulking could be safely initiated under general anaesthesia, which would not have been possible without HFNO. This report served as an example of an alternative to awake tracheotomy in the management of severely obstructive laryngeal pathology We wish to discuss through this case management of severely obstructive laryngeal pathology in the era of HFNO, while encouraging discussion on its potential benefits and limits.</p>

HIPEC for Ovarian Cancer: A Controversial Discussion

Peritoneal carcinomatosis is a sign of advanced disease of ovarian cancer. The prognosis of ovarian cancer is significantly improved after cytoreductive surgery with complete tumor debulking followed by platin based chemotherapy. If cytoreductive surgery results in a tumor free situation with remaining tumor less than 0.25 cm, HIPEC may further improve prognosis. Materials and methods: The results of the Krefeld study are presented and the literature is reviewed according to overall survival and progression free survival with or without HIPEC. In the Krefeld study, patients with ovarian cancer and peritoneal carcinomatosis underwent cytoreductive surgery. In patients with optimal tumor debulking, HIPEC was performed. The peri- and postoperative course was observed. Adverse events were recorded after the Clavien-Dindo classification. Results: 43 patients were treated with cytoreductive surgery and HIPEC. In all patients an optimal cytoreductive situation with remaining tumor less than 0.25 cm was achieved. HIPEC was performed with a cisplatin solution (50 mg/m2) at 41°C. The median age of the patients was 56 years (range: 32–74 years), the median peritoneal cancer index (PCI) was 13 (range: 4–21), the median operation time was 356 minutes (range: 192–507 minutes). The median time to postoperative systemic treatment with chemotherapy was 29 days (range 21–70). There was no postoperative surgically associated death. No adverse events were recorded in 16 (37.2%) of 43 patients, no grade III or IV adverse events were reported for 33 (76.7%) patients, and no grade IV adverse events were reported for 41 (95.3%) patients. Grade III adverse events occured in 19 (44.2%) of the 43 patients; a total of 29 grade III adverse events were reported in these 19 patients. Grade IV adverse events occured in 3 (7.0%) of the 43 patients; a total of 3 grade IV adverse events were reported. Two of them resulted in return to the operating room. This was a fistula of the distal small bowel caused by drainage and a revision of wound infection. Conclusion: In ovarian cancer multiple surgical procedures may be necessary in order to have macroscopically eradicated tumor tissue. Combined with HIPEC, this seems to have positive effects on the survival of patients with peritoneal carcinomatosis. Since we have no marked additional adverse events caused by HIPEC in our case series, HIPEC seems to be an additional treatment option of peritoneal carcinomatosis in ovarian cancer. This statement is strengthened by the literature review in that metaanalysis show significant improved OAS and PFS.

Surgical Strategy Based on Radiological 3D Reconstruction in a Giant Metastatic Neuroendocrine Tumor of the Pancreas: A Case Report of an Interdisciplinary Approach

Background. Neuroendocrine tumors (NETs) are a rare entity and are most commonly found in the gastroenteropancreatic tract. The clinical outcome depends on the potential resectability, grade, and stage. Here, we report a case of a tumor debulking in a metastatic NET of the pancreas. A 25-year-old woman with stable metastatic NET of the pancreas G2 T4N1M1 (hepatic, extrahepatic) already underwent several therapies. Case Presentation. A 25-year-old woman with stable metastatic NET of the pancreas G2 T4N1M1 (hepatic, extrahepatic) already underwent several pharmaceutical therapies. Due to the young age, the G2 characteristic, and the stable liver disease, the decision for debulking was made. Based on a 3D CT scan, an embolization was successfully performed directly prior to a pylorus-preserving pancreatic head resection, advanced interaortocaval lymph node dissection, and an atypical liver resection within segment VI. Histological workup revealed a stage pT3, G2, pN1 (29/34), pM1c (hepatic and extrahepatic), L1, V0, Pn0 with complete surgical resection of the primary tumor (180 mm). The excision of the liver segment V showed a completely resected metastasis. Conclusions. In this patient, extensive surgery of a pancreatic NET with the aim of a prolonged progression-free survival was performed. Close cooperation between different disciplines is absolutely mandatory. Modern imaging allowed a precise therapy plan to be worked out.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin---801 Cases from a Single Institution in China

Aim: As more and more centers has published their treatment results of pseudomyxoma peritonei (PMP) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the data from China is missing. Myxoma Department of Aerospace Hospital is the biggest center treating PMP in China. The purpose of this study is to report the early and long-term outcomes for PMP from this single center.Methods: 801 appendix-derived PMP out of 1008 consecutive patients treated in Myxoma Department of Aerospace Hospital between 2008 and 2019 were retrospectively analyzed.Results: Complete cytoreductive surgery (CCRS) was achieved in 240 (30%) patients with median PCI of 14(1~39), and the rest had maximal tumor debulking (MTD), HIPEC was implemented in 96.3% of CCRS and 78.6% of MTD. The major morbidity (grade III/IV) was 11.4% and the 30-day operative mortality is 0.7%. The 5- and 10-year OS of CCRS was 76.9% and 64.1%, which is significantly higher than MTD (5-, 10-year OS as 36.1%, 27.1%; p<0.001). On the univariate analysis, all prognostic factors (gender, PSS, interval time, prior chemotherapy, prior HIPEC, Peritoneal Cancer Index (PCI), completeness of cytoreduction (CC), HIPEC, pathology, present of serous ascites) were found to be associated with overall survival except for age. On multivariate analysis, only PCI>20, MTD, high pathologic grade and without HIPEC were independent factors predicting poorer prognosis.Conclusions: CCRS +HIPEC can benefit PMP well with controllable risks. MTD+HIPEC may benefit PMP as well when CCRS cannot be achieved after fully asscessment by an experienced peritoneal maglignacy center, but the surgery should be performed as limited as possible.

822 Local radiotherapy synergizes with tumor-specific TCR redirected T cells in the rejection of prostate cancer

BackgroundAdoptive T cell therapy (ACT) has become a promising option for cancer patients. While tumor-infiltrating lymphocytes were initially exploited as a source of tumor reactive lymphocytes, T cells genetically redirected to the tumor by TCR/CAR gene transfer are now in clinical validation. In the case of solid tumors, unfavorable immunosuppressive microenvironments remain recognized barriers to therapeutic efficacy. We have recently reported that the therapeutic activity of ACT against poorly immunogenic and indolent prostate cancer is improved by the concurrent targeting of the tumor stroma by mean of T cells redirected to an ubiquitously expressed minor histocompatibility antigen or a tumor vessel targeted TNF derivative. We have now taken the concept further and hypothesized that local radiotherapy (RT), might also synergize with ACT by promoting lymphocyte endothelial transmigration and tumor recognition, and ultimately favor abscopal effects.MethodsWe investigated the combination of local RT and ACT in TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) mice and in mice bearing subcutaneous B16/B16-OVA (MO4) or TRAMP-C2/TRAMP-C2-OVA tumors. Local RT was delivered by X-RAD SmART (the Small Animal Radiation Therapy) microirradiator in single dose or hypo-fractioned regimens. ACT consisted of T cells engineered with tumor-specific TCRs. Immunogenic consequences were analyzed by Real-Time PCR, and flow cytometry (FACS) analyses. Prostate tumor debulking was evaluated by histological analyses.ResultsWe found that local hypofractionated RT and ACT, while individually inefficacious in controlling tumor growth, concurred to the debulking of advanced prostate adenocarcinoma when used in combination in treating TRAMP mice. Mechanistically, exposing isolated tumor cells, or the TRAMP mouse prostate to hypo-fractionated RT regimens induced stronger type-I interferon (IFN-I) responses, when compared to single high dose. Acutely, hypofractionated RT promoted better immune tumor infiltration, among which TCR redirected effector cells.ConclusionsData support feasibility and efficacy of combining hypo-fractionated local RT with ACT in the form of TCR engineered T cells to promote prostate cancer recognition and eradication. Tumor debulking was observed in the absence of treatment-related toxicity. Systemic recirculation of TCR redirected T cells was observed. We are now investigating therapeutic effects at distal (metastatic) sites.AcknowledgementsThe authors acknowledge the support of the Italian Association for Cancer Research (AIRC)Ethics ApprovalThe studies involving animals were approved by The Institutional Ethical Committee (IACUC#999).