Comparative Efficacy and safety of new targeted therapies and immunotherapies for metastatic triple negative breast cancer: a network meta-analysis.

BACKGROUND: Several therapies directed at novel targets and also immunotherapies have recently shown promising results in advanced or metastatic TNBC. We aimed to compare the efficacy and safety of these new regimens for advanced or metastatic TNBC (mTNBC). METHODS: The PubMed, Embase, and Cochrane Library electronic databases were searched for phase III randomized trials. We conducted a network meta-analysis to compare the efficacy and safety of new targeted and immunotherapy regimens. Trial quality was assessed using the GRADE method. The comparative outcomes were progression-free survival, overall survival, and G3-4 adverse drug events (ADEs). RESULTS: Thirteen phase III randomized controlled trials were identified in the network meta-analysis. Olaparib significantly improved PFS in comparison with the pembrolizumab plus chemotherapy 1, atezolizumab plus nab-paclitaxel and pembrolizumab regimens. Sacituzumab yielded a significant improvement in OS over immunotherapies, veliparib, and chemotherapy alone, but no significantly superiority over pembrolizumab, olaparib, and talazoparib. The risk of ≥grade 3 ADEs associated with olaparib was significantly lower than the risks associated with the other regimens. CONCLUSION: For mTNBC, sacituzumab had a better effect on overall survival, with comparatively high risk of SAE, whereas olaparib improved progression-free survival with a lower risk of SAE, particularly in those patients with BRCA mutations.

Cost-effectiveness of trastuzumab biosimilar combination therapy and drug wastage as first-line treatment for HER2-positive metastatic breast cancer.

BACKGROUND: The rising cost of cancer drug therapy threatens the long-term sustainability of Taiwan National Health Insurance. Cost savings can be achieved through various strategies, e.g., using smaller vial sizes, sharing vials, weight-based dosing, or switching to biosimilars. Here we aimed to examine the cost-effectiveness of a trastuzumab biosimilar combined with docetaxel (TDbiol) for treatment-naïve HER2+ metastatic breast cancer (MBC), and the financial impact of drug wastage. METHODS: A Markov model with three health states was developed to assess the cost-effectiveness of trastuzumab biosimilars plus docetaxel over a 40-month time horizon in patients with HER2+ MBC. Based on the literature and our expert opinion, we assumed similar efficacy between the trastuzumab biosimilar and its reference product. The primary clinical input for the biosimilar was the same as for the reference product in the Catastrophic Patient Database (HV). Health state utilities were derived from the literature, and direct medical costs were obtained from the National Health Insurance Administration (NHIA). RESULTS: In the base-case scenario, the incremental cost-effectiveness ratio (ICER) was NTD 811,050 per QALY gained. One-way sensitivity analyses showed that the model was sensitive to utilities and transition probabilities, but not particularly sensitive to the wastage assumption. In scenario analyses, the ICER was higher when applying the price for trastuzumab reference biologic (branded), than for trastuzumab biosimilar. CONCLUSION: The trastuzumab biosimilar combination regimen is cost-effective and offers significant drug cost savings in Taiwan.

Cecal lipoma with subclinical appendicitis: A case report.

BACKGROUND: Colonic lipomas are rare, slow-growing benign tumors. Colonic lipomas are generally asymptomatic and are found incidentally. Although cases of cecal lipoma have been sporadically reported in the literature, the disease has not been systematically reviewed. CASE SUMMARY: We present a 44-year-old man who underwent a routine physical check-up during which colonoscopic examination revealed an asymptomatic 1.5-cm cecal mass at the appendiceal orifice. Laparoscopic exploration was performed that also demonstrated a congested and erythematous appendix. En bloc resection of both the cecum and vermiform appendix was performed because of the suspicion of malignancy. Histopathological examination revealed a cecal lipoma composed of mature adipose tissue, and the appendix showed subclinical inflammation. Our procedures and findings were discussed, along with relevant English literature that was retrieved from the PubMed database from 2000 to 2017. Twenty-six cases, including ours, were reported. Consistent with the findings of the literature, it is difficult to obtain a definitive diagnosis by colonoscopic biopsy. CONCLUSION: Surgery remains the treatment of choice for this condition. Intraoperative frozen pathological sectioning helped the surgeon decide the extent of surgery, and radical surgery was avoided. Excision of benign lesions occupying the appendiceal orifice may be indicated for the prevention of later development of acute appendicitis. The prognosis is generally good, with only one of the 26 reported patients complicated with acute appendicitis, who subsequently succumbed due to severe comorbidities and sepsis.

Topical treatment with oxaliplatin for the prevention of port-site metastases in laparoscopic surgery for colorectal cancer.

BACKGROUND: The development of port-site metastases following laparoscopic resection of various malignancies continues to be a disturbing issue for laparoscopic surgeons. Previous studies revealed promising results with oxaliplatin, a third-generation platinum compound, as a first-line treatment in advanced colorectal cancer. This study evaluates the effect of topical application of oxaliplatin on the development of port-site metastases in an experimental murine model. METHODS: Nineteen female BDIX rats (immunocompetent, 6 weeks old) underwent a sham laparoscopic operation after 1 x 10(7) viable rat colon carcinoma viable cells (LMCR) had been injected into their peritoneal cavities. Three trocars (1 central camera port and 2 additional lateral ports) were introduced into the abdomen, and a pneumoperitoneum was created with carbon dioxide. Ten minutes after LMCR, cells were injected into the peritoneal cavity, the 2 lateral trocars were removed and carbon dioxide insufflation was maintained for an additional 5 minutes to allow for tumor cell seeding. Oxaliplatin (0.198 mg/kg) was then topically applied to 1 trocar site intramuscularly, while the other site was left untreated. One week later, the animals were euthanized, and the port sites were histologically examined for evidence of metastases. RESULTS: The rate of tumor implantation at the muscle layer in control sites was 68% (13/19) compared with 37% (7/19) at oxaliplatin-treated sites (P = 0.1). Also, no significant differences were detected in port-site metastasis rates in other untreated layers of the abdominal wall. CONCLUSION: Intramuscular topical application of oxaliplatin may not decrease the incidence of port-site metastasis in a syngeneic animal model of colon cancer. Nevertheless, we can see the tendency of declination. Further studies are needed to better determine its possible therapeutic role in high-risk humans undergoing laparoscopic resection of colorectal malignancies.

Systemic administration of attenuated Salmonella choleraesuis in combination with cisplatin for cancer therapy.

Some anaerobic and facultative anaerobic bacteria have been employed as anticancer agents. Previously, we have demonstrated tumor-targeting and antitumor activities of attenuated Salmonella choleraesuis carrying antiangiogenic genes. Here we exploited S. choleraesuis as a single-agent therapy and as part of a combination therapy with low-dose cisplatin for syngeneic murine lung tumor and hepatoma. Systemically injected S. choleraesuis preferentially accumulated within tumors for at least 4 weeks and the bacteria accumulated preferentially in not only subcutaneous but also orthotopic tumors over livers and spleens at ratios ranging from 1000:1 to 100,000:1. S. choleraesuis was capable of delaying tumor growth and enhancing survival in both subcutaneous tumor and experimental metastasis models. More strikingly, the combination of S. choleraesuis plus cisplatin acted additively to retard tumor growth and extensively prolong the survival time of the mice bearing hepatomas or lung tumors. Such combination treatment also increased infiltrating neutrophils and CD8+ T cells, as well as apoptotic cells, in the tumors, compared with S. choleraesuis or cisplatin treatment alone. These findings suggest that S. choleraesuis in combination with cisplatin, which exerts oncolytic effects and enhances antitumor immune responses, represents a promising strategy for the treatment of primary and metastatic tumors.

A review of obturator hernia and a proposed algorithm for its diagnosis and treatment.

The aim of this article is to provide a review of six patients with the various stages of obturator hernia and a diagnostic and therapeutic strategy in suspected cases. Obturator hernia is relatively rare and is a diagnostic challenge. It is a significant cause of intestinal obstruction, especially in emaciated elderly women with chronic disease. A palpable groin mass is not common in these patients because the hernia mass is usually concealed beneath the pectineus muscle. The high mortality is directly related to the delayed recognition, with resultant ruptured gangrenous bowel, and to the high incidence of patients with concurrent medical illness. A total of six patients with obturator hernias were treated at this hospital between 1994 and 2004, and one of these patients was diagnosed and treated by elective laparoscopy. We reviewed these six cases and examined the clinical presentation, age, body weight, associated medical conditions, preoperative diagnosis, operative findings, complications, and outcome in this retrospective study. We concluded that we cannot shorten the time from onset of symptoms to admission, but what we can do is to make a rapid evaluation and surgical intervention to reduce the morbidity and mortality from obturator hernia. The approaches to different presentation of obturator hernia and diagnostic role of CT scan are also discussed.

Oncolysis of multifocal hepatocellular carcinoma in the rat liver by hepatic artery infusion of vesicular stomatitis virus.

Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and few effective treatments, as well as ever-increasing frequencies in the Western world. Viruses that replicate selectively in cancer cells hold considerable promise as novel therapeutic agents for the treatment of malignancy. Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with intrinsic oncolytic specificity due to significantly attenuated antiviral responses in many tumor cells. The aim of this study was to evaluate the potential of VSV, administered via the hepatic artery, as an effective and safe therapeutic agent for treating "multifocal" HCC in the rat liver. Recombinant VSV vector expressing beta-galactosidase (rVSV-beta-gal) was generated by reverse genetics and infused into the hepatic artery of Buffalo rats bearing orthotopically implanted multifocal HCC. Access by the virus to multifocal HCC lesions in the liver, as well as the kinetic profiles of intratumoral viral replication and spread, was established by X-gal staining of liver and tumor sections. Plaque assays were also performed to determine the infectious viral yields in tumor and normal liver tissues. Pharmacotoxicology studies, including serum chemistries and proinflammatory cytokine production, as well as organ histopathology, were performed. Buffer- or vector-treated tumor-bearing rats were followed for survival and the results were analyzed by the Kaplan-Meier method and the log-rank test. Hepatic arterial infusion of rVSV-beta-gal at the maximum tolerated dose in tumor-bearing rats resulted in efficient viral transduction of multifocal HCC lesions in their livers, tumor-selective viral replication, and extensive oncolysis. Importantly, no significant vector-associated toxicities were noted and, in particular, no damage to the hepatic parenchyma was seen. Finally, survival of vector-treated rats was substantially prolonged over that of animals in the control treatment group (p < 0.028). Thus, hepatic arterial administration of VSV is both effective and safe in an orthotopic animal model of multifocal HCC. The results suggest that oncolytic VSV can be developed into an effective and safe therapeutic modality for patients with multifocal HCC in the future.