Cytokine profiling, pretreatment with anakinra, and tolerance development in platinum-induced mixed hypersensitivity reactions.

BACKGROUND: Cytokine-release reactions (CRR) induced by platinum-based chemotherapy, manifesting with fever, chills, and rigors, are poorly understood and not easily prevented by usual premedication or desensitization. OBJECTIVE: To gain a better understanding of platinum-induced CRR and to explore the use of anakinra as a tool to prevent its clinical manifestations. METHODS: A cytokine and chemokine panel was obtained before and after platinum infusion in 3 cases with a mixed (immunoglobulin E-mediated and CRR) platinum-induced hypersensitivity reaction and in 5 controls either tolerant or with an immunoglobulin E-mediated platinum-induced hypersensitivity reaction. Anakinra was given as premedication in the 3 CRR cases. RESULTS: Cytokine-release reaction was associated with a marked release of interleukin (IL)-2, IL-5, IL-6, IL-10, and tumor necrosis factor-ɑ in all cases whereas only IL-2 and IL-10 increased in some controls after platinum infusion, and to a lesser extent than in cases. Anakinra seemed to block CRR symptoms in 2 cases. In the third case, who initially had CRR symptoms despite anakinra, tolerance to oxaliplatin appeared to develop after repeated re-exposures, as suggested by the decreasing levels of cytokines after oxaliplatin, except IL-10, and the capacity to progressively shorten the desensitization protocol and taper the premedication, in addition to the negativization of the oxaliplatin skin test result. CONCLUSION: In patients with platinum-induced CRR, anakinra could be a useful premedication to block its clinical manifestations, and monitoring of IL-2, IL-5, IL-6, IL-10, and tumor necrosis factor-ɑ could help predict tolerance development, thereby allowing safe adjustments to the desensitization protocol and premedication.

Severe Paraneoplastic Dermatomyositis in a Patient With High-Grade Serous Ovarian Cancer.

BACKGROUND: Paraneoplastic dermatomyositis following a diagnosis of ovarian cancer is rare. There are very few cases reported on the management of severe forms. CASE: We report the case of a 50-year-old woman diagnosed with stage IIIC high-grade serous ovarian cancer and a severe form of paraneoplastic dermatomyositis requiring mechanical ventilation. She had significant comorbidities further adding to the complexity of the chemotherapy regimen. Intravenous immunoglobulin and corticosteroids were also administered. The dermatomyositis remained poorly controlled, and the patient was ultimately referred to palliative care. CONCLUSION: The necessity to treat the underlying neoplasia creates a fine balance between the aggressive treatments required and the clinical state of the patient. Multidisciplinary collaboration is warranted to offer best management.

Carboplatin Hyperthermic Intraperitoneal Chemotherapy in the Management of Primary Stage IVB Endometrial Cancer.

BACKGROUND: Endometrial cancer presenting with peritoneal metastases carries a poor prognosis. The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to the surgical management of these patients has been studied in recent years, but only with cisplatin. CASES: This is a series of 3 patients presenting with endometrial cancer and synchronous peritoneal metastases who underwent cytoreductive surgery and carboplatin HIPEC as primary treatment. Complete cytoreductive surgery was achieved for each patient. No grade 3-5 complications were observed. Two patients died at 12 and 18 months, respectively, and 1 patient was alive with disease at 29 months. CONCLUSION: This case series suggests that the addition of carboplatin HIPEC to the surgical management of peritoneal metastases from endometrial cancer is safe as primary treatment. However, long-term survival remains poor.

Esophagitis as a complication of the combination of lenvatinib and pembrolizumab for advanced endometrial cancer: A case report.

Background: Pembrolizumab is a monoclonal antibody targeting the programmed cell death protein 1 (PD-1). It is used in the management and treatment of various oncologic conditions. To name a few: refractory and advanced melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), renal cell carcinoma and gastric cancer. It is also approved for metastatic mismatch repair deficient (dMMR) endometrial carcinoma after failure of front-line chemotherapy. Lenvatinib is an oral multikinase inhibitor that targets vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor-a, RET, and KIT. The combination of lenvatinib and pembrolizumab has proven to be more effective together than as monotherapy. Here, we present the case of a patient who probably developed lenvatinib-related esophagitis, a complication not previously described in the literature to our knowledge.Case presentation.We describe a 65 years old female with metastatic endometrial cancer who presented dysphagia after a few months of lenvatinib plus pembrolizumab treatment. Upper endoscopy results revealed a very fragile upper esophageal mucosa with mucosal lacerations, consistent with grade 2 esophagitis. The biopsy showed esophagitis with mixed lymphocytic and eosinophilic inflammation and apoptotic component. Pembrolizumab was then stopped pending the results of the biopsy, following the recommendations of the gastroenterologist. Dysphagia, however, remained unchanged. In the meantime, the lenvatinib had to be stopped due to a dental procedure, and the patient noted a marked improvement in her symptoms. After discussion with the gastroenterologist, pembrolizumab was resumed and lenvatinib was suspended. The patient was also started on a PPI twice daily since the first digestive exploration. 1 month later, upper endoscopy showed complete recovery, the patient's symptoms improved, and lenvatinib was resumed. However, symptoms of dysphagia resumed a few days later. Lenvatinib was finally resumed at a reduced dose without reappearance in her symptoms. Conclusions: We present a case of oesophagitis as a likely complication of lenvatinib for advanced endometrial cancer. The initiation of PPI and dose reduction of the lenvatinib allowed the patient to successfully go back on treatment.

Combined Interval Cytoreductive Surgery and Carboplatin-Based Hyperthermic Intraperitoneal Chemotherapy in Advanced Primary High-Grade Serous Ovarian Cancer.

Combining interval cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in advanced epithelial ovarian carcinoma (EOC). Although limited, growing evidence regarding carboplatin-based HIPEC highlights its potential. This retrospective study included all patients with advanced primary high-grade serous ovarian cancer who underwent interval CRS combined with carboplatin-based HIPEC at our Canadian tertiary care center between 2014 and 2020. We identified 40 patients with a median age of 61 years. The median peritoneal cancer index was 13 and complete cytoreduction was achieved in 38 patients (95%). Median hospital stay was 13 days and there were four admissions to the intensive care unit (10%) and six readmissions (15%). Severe adverse events occurred in eight patients (20%) and there was no perioperative death. Recurrence was seen in 33 patients (82%) with a median DFS of 18.0 months and a median overall survival of 36.4 months. Multivariate analyses showed that age, peritoneal cancer index, completeness of cytoreduction, occurrence of severe complications, and bowel resection did not significantly impact DFS or OS in our cohort. Interval CRS combined with carboplatin-based HIPEC for advanced primary EOC is associated with acceptable morbidity and oncological outcomes. Larger studies are required to determine the long-term outcomes.

The Impact of Computed Tomography Measurements of Sarcopenia on Postoperative and Oncologic Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal metastases (PM) but is associated with significant postoperative morbidity. The aim of this study was to determine the prognostic value of computed tomographic (CT)-measured sarcopenia on postoperative outcomes and survival in patients undergoing CRS-HIPEC for PM from various origins. A retrospective cohort study was conducted between 2012 and 2020. Three-hundred and twelve patients (mean age 57.6 ± 10.3, 34.3% male) were included, of which 88 (28.2%) were sarcopenic. PM from a colorectal origin was the most common in both groups. The proportion of major postoperative complications (Clavien-Dindo ≥ III) was not higher in the sarcopenic group (15.9% in sarcopenic patients vs. 23.2% in nonsarcopenic patients, p = 0.17). The mean Comprehensive Complication Index scores, HIPEC-related toxicities, length of hospital stay, and duration of parenteral nutrition were comparable regardless of sarcopenia status. In the multivariate logistic regression analysis of severe complications, only peritoneal carcinomatosis index reached statistical significance (OR, 1.05; 95% CI, 1.01 to 1.08, p = 0.007). Sarcopenia did not impact origin-specific overall survival on Cox regression analysis. Sarcopenia was not associated with worse rates of postoperative severe complications or worse survival rates. Future prospective studies are required before considering sarcopenia as part of preoperative risk assessment.

Rectal anastomosis and hyperthermic intraperitoneal chemotherapy: Should we avoid diverting loop ileostomy?

INTRODUCTION: Literature on rectal anastomosis and diverting ileostomy in patients treated with hyperthermic intraperitoneal chemotherapy (HIPEC) is limited. This study assesses the safety of rectal anastomoses during cytoreductive surgery (CRS) and HIPEC, with and without fecal diversion, and its morbidity when performed. MATERIALS AND METHODS: From January 2012 to January 2020, patients with peritoneal metastases who underwent CRS and HIPEC that required a rectal anastomosis were included in this single-hospital retrospective chart review. RESULTS: 84 patients were included, of which 29 had a diverting loop ileostomy. The rectal anastomotic leak (AL) rate for the series was 8.3%. Factors associated with AL were male gender (p = 0.031) and increased BMI (p < 0.0005). Diverting loop ileostomy was associated with a significant decrease of clinically significant rectal AL (0% vs 12.7%, p = 0.045). However, the 90-day readmission rate was higher in this group (37.9% vs 10.9%, p = 0.003). Stoma reversal surgery was performed for all patients, but 3 patients experienced AL (10.7%). CONCLUSIONS: This study suggests that creation of a diverting loop ileostomy may be an effective strategy to prevent symptomatic rectal AL following CRS with HIPEC. However, it is also associated with an increased readmission rate and increased risk of AL following reversal surgery.

Hyperthermic intraoperative thoracoabdominal chemotherapy for stage IVB epithelial ovarian carcinoma.

•Full-thickness diaphragmatic infiltration with pleural effusion in advanced epithelial ovarian cancer is challenging.•Short-term control of malignant pleural effusion with HITAC for advanced epithelial ovarian cancer seems feasible.•Carboplatin is safe when used as HIPEC or HITAC agent for advanced epithelial ovarian cancer.

Recurrent High-grade Ovarian Immature Teratoma with Peritoneal Dissemination.

BACKGROUND: Peritoneal dissemination of ovarian immature teratoma in children is a rare entity and is associated with a poor prognosis. There are no guidelines on the optimal management of these patients with regard to surgery and systemic treatments. CASE: This is the case of a 16-year-old patient who experienced an early recurrence of immature teratoma with peritoneal dissemination after surgery and systemic chemotherapy failure, and was treated with an aggressive salvage cytoreductive surgery. She was still disease-free 6 months after her second surgery. SUMMARY AND CONCLUSION: Upfront aggressive surgical management with complete cytoreductive surgery is recommended when patients present with disease recurrence and peritoneal dissemination of ovarian immature teratoma. Such cases should be managed in centers with local expertise in the treatment of peritoneal surface malignancies.