Comparison of Nausea and Vomiting Associated With Amino Acid Formulations Coinfused With Peptide Receptor Radionuclide Therapy: Commercial Parenteral Nutrition Formulas Versus Compounded Arginine/Lysine.

OBJECTIVES: Positively charged amino acids (AA) such as arginine/lysine are coinfused with radiolabeled somatostatin analogs to reduce rates of nephrotoxicity. In the phase 3 NETTER-1 trial, commercial AA formulations were used in association with 177Lu-DOTA-0-Tyr3-Octreotate (DOTATATE). These formulations were also used in an early-access program (EAP) before regulatory approval of 177Lu-DOTATATE. Our program transitioned to compounded l-arginine 2.5%/l-lysine 2.5% in 0.9% NaCl after commercial approval of 177Lu-DOTATATE. We sought to compare rates of nausea/vomiting with arginine/lysine versus commercial parenteral AA formulations. METHODS: Rates of nausea/vomiting of all 20 EAP patients who received commercial AAs (15% Clinisol) were compared with the first 29 patients to receive 177Lu-DOTATATE after commercial approval and coinfused with arginine/lysine. Other parameters reviewed included infusion rates, need for PRN nausea medications, and other toxicities. RESULTS: Seventeen percent of patients who received compounded arginine/lysine experienced nausea, compared with 100% of patients in the EAP group (P < 0.0001). Infusion-related reactions occurred in 3% of the arginine/lysine cohort versus 35% in the EAP group. Infusion durations were substantially shorter in the arginine/lysine cohort (reduced by 61%). CONCLUSIONS: Coinfusions of arginine/lysine with radiolabeled somatostatin analogs result in substantially lower rates of nausea/vomiting compared with commercial AA formulations designed for parenteral nutrition.

Adrenal crisis and death following transarterial chemoembolization of sarcoma liver metastases.

Adrenal crisis is a life-threatening complication of adrenal insufficiency which is triggered by physiological stressors such as injury, infection or a surgical procedure when the plasma concentration of adrenal corticosteroids is insufficient for physiological requirements. It is associated with a high mortality rate unless early diagnosis and treatment is initiated. We report a case of a patient with metastatic sarcoma and adrenal insufficiency who underwent right hepatic artery chemoembolization to control his intrahepatic metastases. He did not receive stress dose glucocorticoid and his glucocorticoid supplement medication was accidentally discontinued after embolization. He died due to an unrecognized adrenal crisis 2 days after embolization. This case suggests that embolization should be recognized as a stressor to prompt the need to continue chronic replacement of corticosteroids and to consider supplemental stress-dose corticosteroids. There is a growing population of patients on chronic corticosteroids for various conditions who may require tumor embolization. Therefore, it is important to consider adrenal crisis in post-embolization settings since the symptoms are non-specific and mortality can be avoided only if the diagnosis of adrenal crisis is considered and parenteral glucocorticoids administered.

Risk of Bowel Obstruction in Patients with Mesenteric or Peritoneal Disease Receiving Peptide Receptor Radionuclide Therapy.

Although radiation-induced mesenteritis or peritonitis can potentially exacerbate the risk of bowel obstruction, there are no data in the literature on the incidence of intestinal obstruction related to peptide receptor radionuclide therapy. Methods: The records of all patients treated with 177Lu-DOTATATE at Moffitt Cancer Center between April 2018 and October 2019 were evaluated. The number of patients who developed bowel obstruction within 3 mo of a 177Lu-DOTATATE treatment was divided by the total number of patients with preexisting peritoneal or mesenteric disease. Management strategies and outcomes were evaluated. Results: Of a total of 159 patients treated, 81 had baseline mesenteric or peritoneal disease, among whom 5 (6%) experienced at least 1 episode of bowel obstruction within 3 mo of treatment. Two of the patients underwent surgical exploration during obstruction describing a "frozen abdomen." All 5 responded at least temporarily to high-dose corticosteroid treatment and regained bowel function, but 2 patients eventually succumbed to progressive peritoneal disease. Conclusion: Peptide receptor radionuclide therapy can lead to bowel obstruction in patients with mesenteric or peritoneal disease, likely by inducing inflammation. Corticosteroids can potentially play a role in treatment and prophylaxis.

Prostatic Artery Embolization Is Safe and Effective for Medically Recalcitrant Radiation-Induced Prostatitis.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents 90% of all chronic prostatitis cases and may occur after radiation therapy (RT) for localized prostate cancer. Medical therapy is effective in approximately 50% of cases, with no therapy demonstrating consistent efficacy in refractory cases. Prostatic artery embolization (PAE) is effective in men with lower urinary tract symptoms and benign prostatic hyperplasia. We report clinical improvement after PAE in a case series of men with CP/CPPS after RT. METHODS AND MATERIALS: Nine men (median age 72 years; range, 61-83 years) with CP/CPPS after RT for prostate cancer underwent PAE. Baseline International Prostate Symptom Score was recorded in 5 patients (median 23; range, 4-26), Chronic Prostatitis Symptom Index score in 6 patients (median 22.5; range, 6-34), and quality of life (QoL) score in 8 patients (median 5; range, 2-6). Median baseline prostate volume was 49 cm3 (range, 22-123 cm3). Patients were followed up at 6 and 12 weeks with QoL, International Prostate Symptom Score, and/or Chronic Prostatitis Symptom Index score and magnetic resonance imaging. RESULTS: Technical success (ie, bilateral embolization) was achieved in 78% (n = 7) of patients with the other 2 patients having undergone unilateral embolization with no major complications. Clinical success was seen in 89% (n = 8) of patients and QoL improved in 78% (n = 7) during the follow-up period. CONCLUSION: CP/CPPS after RT for localized prostate cancer is a highly morbid condition, with medical therapy successful in only 50% of cases. PAE may be a successful therapy for medically recalcitrant CP/CPPS, and further studies are necessary to understand the best patient selection and scenario for PAE in the setting of CP/CPPS.

Liver-directed treatments of liver-dominant metastatic leiomyosarcoma.

PURPOSE: The purpose of this study was to determine the safety and efficacy of liver-directed therapies in patients with unresectable metastatic leiomyosarcoma to the liver. Liver-directed therapies included in this study were transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE), yttrium-90 (Y90) radioembolization, and percutaneous microwave ablation. METHODS: This is a single institution retrospective study of unresectable metastatic leiomyosarcoma to the liver treated with DEB-TACE, radioembolization, or microwave ablation. DEB-TACE was performed using 70-150 or 100-300 µ doxorubicin-loaded drug-eluting LC beads. Radioembolization was performed using Y90 glass microspheres. Electronic medical records were retrospectively reviewed to evaluate clinical and biochemical toxicities, tumor response on imaging, overall survival (OS), and liver progression-free survival (PFS). RESULTS: A total of 24 patients with metastatic leiomyosarcoma to the liver who underwent liver-directed treatment were identified (8 males, 16 females; average age, 62.8±11.4 years). Of these patients, 13 underwent DEB-TACE, 6 underwent Y90, and 5 underwent ablation. Three patients received a combination of treatments: one received Y90 followed by DEB-TACE, one received ablation followed by DEB-TACE, and one received ablation followed by Y90. Of the 24 patients, 19 received prior chemotherapy. At 3-month follow-up, grade 1 or 2 lab toxicities were found in 20 patients; 3 patients had grade 3 toxicities. A grade 3 clinical toxicity was reported in one patient. MELD score was 7.5±1.89 at baseline and 8.8±4.2 at 3 months. Median OS was 59 months (95% CI, 39.8-78.2) from diagnosis, 27 months (95% CI, 22.9-31.0) from development of liver metastasis, and 9 months (95% CI, 0-21.4) from first liver-directed treatment. Median liver PFS was 9 months (95% CI, 1.4-16.6). CONCLUSION: Treatment with liver-directed therapies for patients with unresectable metastatic leiomyosarcoma to the liver is safe and can improve overall survival, with OS after liver-directed therapy being similar to patients who underwent surgical resection.

Partial Splenic Artery Embolization in 35 Cancer Patients: Results of a Single Institution Retrospective Study.

PURPOSE: To evaluate the safety and efficacy of partial splenic embolization (PSE) in cancer patients with different etiologies of splenomegaly/hypersplenism. MATERIALS AND METHODS: The medical records of 35 cancer patients who underwent 39 PSE procedures were analyzed. The splenomegaly/hypersplenism was due to chemotherapy (n = 17), portal hypertension (n = 10), or hematologic malignancy (n = 8). After the first 11 PSEs, celiac plexus neurolysis, corticosteroids, and non-steroid anti-inflammatory drugs (NSAIDs) were included in the post-procedural management. RESULTS: PSE led to 59 ± 16% (mean ± standard deviation) splenic infarcts. The infarct volume per 1 mL 300-500 µm tris-acryl gelatin microspheres was not significantly different between the chemotherapy-induced group (264 ± 89 cm3) and the portal hypertension group (285 ± 139 cm3) but was significantly higher in the hematology group (582 ± 345 cm3). Platelet count increased from 65.7 ± 19.7 k/µl to a peak platelet count of 221 ± 83 k/µl at 2 weeks after PSE. Patients with a follow-up period of more than 1 year had the most recent platelet count of 174 ± 113 k/µl. Platelet count increase was significantly higher in the chemotherapy-induced group than the portal hypertension group. Adding celiac plexus neurolysis, corticosteroids, and NSAIDs to the post-procedural management resulted in a decreased rate of major complications from 73% to 46% and a decrease in the rate of moderate or severe pain from 92% to 20%. CONCLUSIONS: PSE improved platelet counts in cancer patients despite different etiologies of splenomegaly. The addition of celiac plexus neurolysis, corticosteroids, and NSAIDS to the post-PSE treatment protocol reduced complications. Data from this study could help to predict the amount of 300-500 µm tris-acryl gelatin microspheres required to achieve a planned infarct size.

Circulating tumor cells and γH2AX as biomarkers for responsiveness to radium-223 in advanced prostate cancer patients.

AIM: Radium-223 improves overall survival in patients with metastatic castration-resistant prostate cancer to the bone. Radium-223 causes double-strand DNA breaks and produces γH2AX, a potential biomarker for response. We examined the feasibility of tracking γH2AX positivity and numeration in circulating tumor cells. PATIENTS & METHODS: Ten patients with biopsy-confirmed symptomatic M1b castration-resistant prostate cancer received radium-223 as standard of care and were assessed for γH2AX level changes following doses 1, 3 and 6. RESULTS: Trend tests confirmed that patients with ≥50% increase in circulating tumor cells positive for γH2AX postradium-223 therapy had a lower risk of death (p = 0.035). CONCLUSION: Regular interval measurements of γH2AX are feasible. The potential correlation between γH2AX changes and overall survival warrants further investigation.

Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study.

PURPOSE: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. RESULTS: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. CONCLUSIONS: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.