Osteogenic Sarcoma of the Head and Neck: Is Chemotherapy Needed?

OPINION STATEMENT: Head and neck osteosarcoma (HNOS) is a rare subtype of sarcoma that most commonly arises in the mandible or maxilla. Treatment for HNOS typically involves a multidisciplinary and multimodal approach depending on the size, grade, and histological subtype. Surgery by sarcoma-experienced head and neck surgeons and orthopedic oncologists remains a crucial component of treatment in all subtypes of HNOS, particularly for those with low-grade histology, which can be treated definitively with surgical resection if negative margins are obtained. Negative surgical margins are of utmost prognostic importance, and neoadjuvant or adjuvant radiation should be considered in patients with positive (or anticipated positive) margins/residual postoperative disease. Current data favors the use of (neo)adjuvant chemotherapy in patients with high-grade HNOS to improve overall survival but must be individualized to weigh benefits and risks of the short- and long-term effects of treatment. Our center uses a multidisciplinary treatment plan and notes anecdotal improvement in treatment outcomes with a combined surgical and ifosfamide-containing chemotherapeutic approach with radiotherapy for local control if positive margins. Large volume cohorts and adequate randomized control trials assessing the efficacy of chemotherapy in HNOS are scant and additional research and multi-institutional collaboration are needed to study polychemotherapeutic and radiation treatment regimens and outcomes more adequately.

For Hepatocellular Carcinoma Treated with Yttrium-90 Microspheres, Dose Volumetrics on Post-Treatment Bremsstrahlung SPECT/CT Predict Clinical Outcomes.

In transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) with Yttrium-90 (Y-90) microspheres, recent studies correlate dosimetry from bremsstrahlung single photon emission tomography (SPECT/CT) with treatment outcomes; however, these studies focus on measures of central tendency rather than volumetric coverage metrics commonly used in radiation oncology. We hypothesized that three-dimensional (3D) isodose coverage of gross tumor volume (GTV) is the driving factor in HCC treatment response to TARE and is best assessed using advanced dosimetry techniques applied to nuclear imaging of actual Y-90 biodistribution. We reviewed 51 lobar TARE Y-90 treatments of 43 HCC patients. Dose prescriptions were 120 Gy for TheraSpheres and 85 Gy for SIR-Spheres. All patients underwent post-TARE Y-90 bremsstrahlung SPECT/CT imaging. Commercial software was used to contour gross tumor volume (GTV) and liver on post-TARE SPECT/CT. Y-90 dose distributions were calculated using the Local Deposition Model based on post-TARE SPECT/CT activity maps. Median gross tumor volume (GTV) dose; GTV receiving less than 100 Gy, 70 Gy and 50 Gy; minimum dose covering the hottest 70%, 95%, and 98% of the GTV (D70, D95, D98); mean dose to nontumorous liver, and disease burden (GTV/liver volume) were obtained. Clinical outcomes were collected for all patients by chart and imaging review. HCC treatment response was assessed according to the modified response criteria in solid tumors (mRECIST) guidelines. Kaplan-Meier (KM) survival estimates and multivariate regression analyses (MVA) were performed using STATA. Median survival was 22.5 months for patients achieving objective response (OR) in targeted lesions (complete response (CR) or partial response (PR) per mRECIST) vs. 7.6 months for non-responders (NR, stable disease or disease progression per mRECIST). On MVA, the volume of underdosed tumor (GTV receiving less than 100 Gy) was the only significant dosimetric predictor for CR (p = 0.0004) and overall survival (OS, p = 0.003). All targets with less than CR (n = 39) had more than 20 cc of underdosed tumor. D70 (p = 0.038) correlated with OR, with mean D70 of 95 Gy for responders and 60 Gy for non-responders (p = 0.042). On MVA, mean dose to nontumorous liver trended toward significant association with grade 3+ toxicity (p = 0.09) and correlated with delivered activity (p < 0.001) and burden of disease (p = 0.05). Dosimetric models supplied area under the curve estimates of > 0.80 predicting CR, OR, and ≥grade 3 acute toxicity. Dosimetric parameters derived from the retrospective analysis of post-TARE Y-90 bremsstrahlung SPECT/CT after lobar treatment of HCC suggest that volumetric coverage of GTV, not a high mean or median dose, is the driving factor in treatment response and that this is best assessed through the analysis of actual Y-90 biodistribution.

Utilization of a Modified Roux-en-Y Anastomosis as an Access point for Percutaneous Transjejunal Cholangioplasty of Recurrent Biliary Strictures.

INTRODUCTION: Biliary duct injuries pose a significant management challenge due to the propensity for recurrent biliary strictures. Development of a modified Roux-en-Y hepaticojejunostomy known as a Hutson-Russell Pouch (HRP) provides a point of entry for repetitive access to the biliary tree. We aim to highlight the effectiveness of using the HRP as an access point for the long-term management of anastomotic and distal biliary strictures, thereby showcasing the value in potential widespread adoption of this modification to a standard surgical procedure. MATERIALS AND METHODS: IRB-approved retrospective study of 36 patients (10 M, 26 F; mean age 55.19 ± 13.94; 15-83) underwent a total of 110 transjejunal cholangiograms. Indications for cholangiogram included cholangitis (n = 38), surveillance (n = 36), and elevated liver enzymes (n = 36). Technical success was defined by the ability to access and intervene in the biliary tree via HRP access. In case of stenosis, the ability to successfully dilate (< 30%) residual stenosis was considered a technically successful procedure. Clinical success was defined by normalization of the liver function tests or resolution of cholangitis. RESULTS: Technical success was achieved in 83/110 (75.45%) of the cases, and clinical success was achieved in 102/110 (98.2%). Transhepatic access was needed in 27/110 (24.5%) of the cases. Interventions performed included balloon cholangioplasty in 104/110 (94.5%), biliary stone removal in 2/110 (1.8%), biliary stent placement in 2/110 (1.8%), and biliary drain placement in 4/110 (3.6%). There were a total of 9/110 complications (8.2%). CONCLUSION: The HRP was an effective access point in the management of recurrent benign biliary strictures in this cohort.

Colorectal Liver Metastasis: Overview of Treatment Paradigm Highlighting the Role of Ablation.

OBJECTIVE: The objective of this article is to discuss the current treatment options for colorectal cancer (CRC) liver metastases and the role of ablation. CONCLUSION: A randomized control trial of ablation combined with chemotherapy showed improved overall survival compared with chemotherapy alone. Local recurrence rates are comparable to those associated with resection when ablative margins of more than 5 mm are achieved and target lesions are smaller than 3 cm. In patients with unresectable disease, ablation for curative intent should be considered.

Percutaneous Image-Guided Irreversible Electroporation for the Treatment of Unresectable, Locally Advanced Pancreatic Adenocarcinoma.

PURPOSE: To describe safety and effectiveness of percutaneous irreversible electroporation (IRE) for treatment of unresectable, locally advanced pancreatic adenocarcinoma (LAPC). MATERIALS AND METHODS: This retrospective study included 50 patients (23 women, 27 men; age range, 46-91 y; median age, 62.5 y) with biopsy-proven, unresectable LAPC who received percutaneous computed tomography (CT)-guided IRE. The primary objective was to assess the safety profile of the procedure; the secondary objective was to determine overall survival (OS). All patients had prior chemotherapy (1-5 lines, median 2), and 30 (60%) of 50 patients had prior radiation therapy. Follow-up included CT at 1 month and at 3-month intervals thereafter. RESULTS: There were no treatment-related deaths and no 30-day mortality. Serious adverse events occurred in 10 (20%) of 50 patients (abdominal pain [n = 7], pancreatitis [n = 1], sepsis [n = 1], gastric leak [n = 1]). Median OS was 27.0 months (95% confidence interval [CI], 22.7-32.5 months) from time of diagnosis and 14.2 months (95% CI, 9.7-16.2 months) from time of IRE. Patients with tumors ≤ 3 cm (n = 24) had significantly longer median OS than patients with tumors > 3 cm (n = 26): 33.8 vs 22.7 months from time of diagnosis (P = .002) and 16.2 vs 9.9 months from time of IRE (P = .031). Tumor size was confirmed as the only independent predictor of OS at multivariate analysis. CONCLUSIONS: Percutaneous image-guided IRE of unresectable LAPC is associated with an acceptable safety profile.

Unresectable Hepatocellular Carcinoma: Radioembolization Versus Chemoembolization: A Systematic Review and Meta-analysis.

BACKGROUND: Transarterial radioembolization (TARE) has emerged as a newer regional therapy to transarterial chemoembolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). The aim of this study is to compare clinical outcomes of both the techniques. METHODS: Online search for studies comparing TARE to TACE from 2005 to present was performed. Primary outcome was overall survival rate for up to 4 years. Secondary outcomes included post-treatment complications and treatment response. Quality of included studies was evaluated by STrengthening the Reporting of OBservational studies in Epidemiology criteria. Relative risk (RR) and 95 % confidence intervals (CI) were calculated from pooled data. RESULTS: The search strategy yielded 172 studies, five met selection criteria and included 553 patients with unresectable HCC, 284 underwent TACE and 269 underwent TARE. Median ages were 63 and 64 years for TACE and TARE, respectively. Meta-analysis showed no statistically significant difference in survival for up to 4 years between the two groups (HR = 1.06; 95 % CI 0.81-1.46, p = 0.567). TACE required at least one day of hospital stay compared to TARE which was mostly an outpatient procedure. TACE had more post-treatment pain than TARE (RR = 0.51, 95 % CI 0.36-0.72, p < 0.01), but less subjective fatigue (RR = 1.68, 95 % CI 1.08-2.62, p < 0.01). There was no difference between the two groups in the incidence of post-treatment nausea, vomiting, fever, or other complications. In addition, there was no difference in partial or complete response rates between the two groups. CONCLUSION: TARE appears to be a safe alternative treatment to TACE with comparable complication profile and survival rates. Larger prospective randomized trials, focusing on patient-reported outcomes and cost-benefit analysis are required to consolidate these results.

Percutaneous Approach to Irreversible Electroporation of the Pancreas: Miami Protocol.

Despite advances in the treatment of unresectable locally advanced pancreatic cancer, outcomes remain poor. Irreversible electroporation is a nonthermal ablative modality whose role in the management of locally advanced pancreatic cancer is being studied. This review highlights patient selection, preparation, and follow-up as well as discusses the techniques to achieve safe and effective tumor ablation in this challenging location.

Liver Function Tests Following Irreversible Electroporation of Liver Tumors: Experience in 174 Procedures.

Irreversible electroporation (IRE) is a relatively new ablation modality that uses electric currents to cause cell death. It is commonly used to treat primary and secondary liver tumors in patients with normal liver function and preexisting cirrhosis. Retrospective analysis of 205 procedures sought to evaluate changes in liver function after IRE. Liver function tests (LFTs) results before and after IRE were evaluated from 174 procedures in 124 patients. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALKP), and total bilirubin levels were analyzed. The study was Health Insurance Portability and Accountability Act compliant and institutional review board approved. Informed consent was waived. Changes in LFT results after IRE were compared with baseline and were followed up over time to see if they resolved. Changes were compared with volume of ablation. The greatest perturbations were in transaminase levels. The levels increased sharply within 24 hours after IRE in 129 (74.1%) procedures to extreme levels (more than 20 times the upper limit of normal in one-third of cases). Resolution occurred in 95% and was demonstrated to have occurred by a mean of approximately 10 weeks, many documented as early as 7 days after procedure. ALKP levels elevated in 10% procedures, was slower to increase, and was less likely to resolve. Total bilirubin level demonstrated 2 different patterns of elevation--early and late--and similar to ALKP, it was more likely to remain elevated. There was no increased risk in patients with cirrhosis or cholangiocarcinoma. There was no correlation of levels with volume of ablation. IRE results in significant abnormalities in LFT results, but in most of the cases, these are self-limiting, do not preclude treatment, and are similar to the changes seen after radiofrequency and cryoablation in the liver.

Irreversible Electroporation of Hepatic and Pancreatic Malignancies: Radiologic-Pathologic Correlation.

Irreversible electroporation (IRE) is a novel therapy that has shown to be a feasible and promising alternative to conventional ablative techniques when treating tumors near vital structures or blood vessels. The clinical efficacy of IRE has been evaluated using established imaging criteria. This study evaluates the histologic and imaging response of hepatic and pancreatic malignancies that were surgically resected after IRE. In total, 12 lesions ablated with IRE were included, including 3 pancreatic carcinomas, 5 primary tumors of the liver, and 4 metastatic tumors of the liver. The rate of complete response to IRE was 25% based on the histologic evaluation of the resected tumors. Although treatment-related vessel wall changes were noted in several cases in histologic findings, there was no evidence of vascular luminal narrowing or obliteration in any of the specimens. The imaging response to IRE before surgical resection usually resulted in underestimation of disease burden when compared with the histologic response seen on the resected specimens.

Proximal Splenic Artery Embolization in Chemotherapy-Induced Thrombocytopenia: A Retrospective Analysis of 13 Patients.

PURPOSE: To determine if proximal splenic artery embolization (PSAE) provides a safe and effective alternative to alleviate chemotherapy-induced thrombocytopenia (CIT), allowing patients with cancer to resume chemotherapy regimens. MATERIALS AND METHODS: Thirteen patients (9 men, 4 women; mean age, 63 y) with underlying malignancy (pancreatic adenocarcinoma, n = 6; cholangiocarcinoma, n = 5; other, n = 2) complicated by CIT underwent PSAE. Mean platelet counts were calculated before the initiation of chemotherapy, at the nadir that resulted in discontinuation of chemotherapy before the PSAE procedure, at peak values after the procedure, and at a mean follow-up of 9.2 months. The time to reinitiation of chemotherapy after PSAE was calculated. RESULTS: Baseline platelet count before initiation of chemotherapy was 162 × 10(9)/L (range, 90-272 × 10(9)/L). The platelet count nadir resulting in cessation of chemotherapy was 45 × 10(9)/L (range, 23-67 × 10(9)/L), and the pre-PSAE platelet count was 88 × 10(9)/L (range, 49-131 × 10(9)/L). The post-PSAE peak platelet count improved significantly (to 209 × 10(9)/L; range, 83-363 × 10(9)/L) compared with the nadir counts and the pre-PSAE counts (P < .01) at a mean short-term follow-up of 35 days (range, 7-91 d). The counts at follow-up to 9.2 months (range, 3-15 mo) were 152 × 10(9)/L (range, 91-241 × 10(9)/L). All patients became eligible to resume chemotherapy. The time to initiation of chemotherapy after PSAE averaged 22 days (range, 4-58 d) in 12 patients; one patient declined chemotherapy. CONCLUSIONS: Proximal splenic artery embolization appears to be safe and effective in alleviating CIT, allowing resumption of systemic chemotherapy. Further studies may help guide patient selection by identifying characteristics that allow a sustained improvement in thrombocytopenia.

Safety and efficacy of the PleurX catheter for the treatment of malignant ascites.

BACKGROUND: Malignant ascites is a common complication seen in association with various types of neoplastic processes. Due to high recurrence rates, patients may require multiple paracenteses, which have associated complications such as increased risk of bleeding, infection, pain, and volume and electrolyte depletion. OBJECTIVE: This study evaluated the management of malignant ascites by placement of the PleurX® tunneled catheter system at a single center. METHODS: This was a retrospective study of 38 patients who underwent PleurX catheter placement for refractory malignant ascites between February 2006 and March 2012 at our institution. Pretreatment characteristics and outcome measures were reported using descriptive statistics. RESULTS: The population included 21 males and 17 females with a mean age of 60.6 years (range, 36-79 years) diagnosed with metastatic disease from a variety of primary malignancies, the most common of which was pancreatic cancer (10 patients). In 84% of patients (32/38) who were not lost to follow-up, mean survival time was 40.7 days (range 4-434 days). Technical success rate of catheter placement was 100%. CONCLUSIONS: The PleurX catheter can be used to manage malignant ascites in severely ill patients with metastatic cancer, with a high rate of procedural success and a low incidence of potentially serious adverse events, infections, or catheter-related complications.