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Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors.

ABSTRACT: Malignant tumors are considered "unresectable" if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120?nm, to form (103)Pd@Au nanoseeds. The therapeutic efficacy of (103)Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of (103)Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

SUBMITTER: Moeendarbari S

PROVIDER: S-EPMC4745015 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors.

Moeendarbari Sina S Tekade Rakesh R Mulgaonkar Aditi A Christensen Preston P Ramezani Saleh S Hassan Gedaa G Jiang Ruiqian R Öz Orhan K OK Hao Yaowu Y Sun Xiankai X

Scientific reports 20160208

Malignant tumors are considered "unresectable" if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unres ...[more]

PMID: 26852805

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Project description:BackgroundSelective internal radiotherapy is widely used for liver dominant diseases of solid tumors. However, data about sequential treatment and prognostic factors are lacking.MethodsWe consecutively included all 209 patients who received a selective internal radiotherapy intervention between January 2015 and May 2019. A retrospective analysis of their electronic patient records was performed regarding diagnosis of cancer, previous therapies and applied radioactive activity. A multicenter follow-up at least 6 weeks after intervention to assess radiological response and irregular subsequent follow-ups to asses disease progression were conducted. In addition, subgroup analyses were carried out.ResultsThe most frequently treated indications were hepatocellular carcinoma (37%), colorectal cancers (14%), neuroendocrine tumors (9%), and breast cancer (8%). In hepatocellular carcinoma, selective internal radiotherapy was most performed without prior systemic therapy (40%), and for the remaining indications, most often after surgery with systemic therapy in sequence. Local radiological response, defined as either regression or stable disease, was assessed at least 6 weeks after intervention and showed 52% across all indications. Hepatocellular carcinoma (59%) and breast cancer (67%) showed an excellent, colorectal cancers (29%) a particularly poor response rate. Neuroendocrine tumors showed the third longest median post-selective internal radiation therapy (SIRT) survival with 12.4 months and the second longest median progression-free time with 5.2 months. Hepatocellular carcinoma showed even better results with a post-SIRT survival of 15.7 months and a median progression-free time of 5.3 months. Pancreatic neuroendocrine tumors showed significantly worse outcomes than other neuroendocrine tumors, regarding median post-SIRT survival and median progression-free time. No relevant SIRT related differences among sexes were detected.ConclusionsPatients with neuroendocrine tumors, breast cancer in late therapy lines and early-stage hepatocellular carcinoma seem to show better responses to SIRT than other entities. Colorectal cancers were mainly treated with SIRT in a second or third therapy line but with considerably weaker results than other entities.

Project description:PurposeBoth external beam radiation therapy (EBRT) and selective-internal radiation therapy (SIRT) are implemented to treat unresectable intrahepatic cholangiocarcinoma (iCCA). The present study aimed to evaluate the efficacy of EBRT and SIRT in managing iCCA through a systematic review and meta-analysis.MethodsPubMed and Cochrane database were queried to search for studies published from January 2000 toJune 2020 without language restrictions. Median survival time, overall survival, and radiological response were extracted. Secondary outcomes such as complication rates, predictors of survival, and downstage to surgery were pooled. Patient-level survival data were obtained to generate Kaplan-Meier survival graph. Pooled outcomes were analyzed with a random-effect model.ResultsTwenty-nine and 20 studies including 732 and 443 patients from the SIRT and EBRT groups were included in the present study. From initial radiation treatment, the median survival time for patients who underwent SIRT and EBRT were 12.0 (95% confidence interval [CI]: 10.8-14.6) and 13.6 (95% CI: 11.1-16.0) months, respectively. As first-line therapy, the median survival time was 36.1 (95% CI: 20.6-39.5) months for SIRT and 11.0 (95% CI: 9.3-13.6) months for EBRT. Both radiation modalities were effective in downstaging initially unresectable iCCA to surgery (SIRT: 30.5%; EBRT: 18.3%). Patients in the SIRT group encountered more post-embolization abdominal pain (6.9 vs. 2.2%), ulcer (1.0 vs. 0.5%), nausea (1.6 vs. 0.7%), anorexia (5.9 vs. 0%), thrombocytopenia (7.3 vs. 6.0%), hyperbilirubinemia (5.2 vs. 2.1%), and hypoalbuminemia (13.2 vs. 3.3%), whereas EBRT was associated with higher rates of anemia (0.6 vs. 7.5%) and neutropenia (6.5 vs. 11.0%).ConclusionsBoth EBRT and SIRT were safe and effective in treating unresectable iCCA. However, available evidence was highly heterogeneous regarding patient population, limiting fair comparison between 2 radiation modalities. Future high-quality comparative studies are warranted.

Project description:PurposePatients with oligometastatic colorectal cancer have demonstrated excellent clinical outcomes with surgical resection of hepatic and pulmonary metastases. Stereotactic ablative radiation therapy (SABR) has emerged as an alternative local therapy for nonsurgical candidates. Herein, we report the oncologic and patient-reported quality-of-life (PR-QoL) outcomes for a subset of patients with oligometastatic colorectal cancer who were treated in a prospective phase 2 multicenter clinical trial.Methods and materialsPatients with a pathologically proven diagnosis of oligometastatic colorectal cancer were enrolled as part of a prospective study. SABR dose and fractionation schedules were dependent on the lesion location and size. Patient follow-up occurred 6 weeks after completion of SABR and at 3-month intervals for the following 3 years. Patients received the Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up visit to assess PR-QoL. The total Functional Assessment of Cancer Therapy-General questionnaire scores were compared with those from baseline using the Wilcoxon signed rank test. Overall survival, local progression-free survival (PFS), and distant PFS were calculated using the Kaplan-Meier estimation to the date of the last follow-up visit/death or local/distant failure.ResultsA total of 31 patients with oligometastatic colorectal cancer with 1 (71.0%), 2 (16.1%), 3 (3.2%), 4 (3.2%), or 5 (6.5%) metastatic lesions were identified. After a median follow-up time of 50.1 months, the median OS from the time of completion of the SABR was 53.9 months (95% confidence interval, 23.2-84.6), and the 5-year OS, local PFS, and distant PFS were 45%, 83%, and 27%, respectively. Acute grade 2+ toxicity was 9.7% (pain, nausea, fatigue) and late grade 3+ toxicity (small bowel obstruction) was 3.2% with no significant change in PR-QoL in the year after SABR.ConclusionsThis subset analysis of a prospective phase 2 study demonstrates that SABR is a safe and effective treatment option for patients with unresectable oligometastic colorectal cancer. In addition, SABR of oligometastatic disease preserves PR-QoL.

Project description:IntroductionSelective internal radiation therapy (SIRT) is a targeted method of treatment for unresectable liver tumors in which radiation therapy is directly delivered to the tumor(s) via the hepatic vasculature. Successful outcomes with SIRT are dependent on the specific vasculature of the liver and tumor, and the patient therefore needs to attend a "work-up" to map the hepatic vasculature prior to the SIRT procedure. Recent advances in SIRT delivery have enabled same-day or same-stay work-up and procedure, requiring only one hospital visit rather than two. We aimed to evaluate the economic, travel time, and transport-related environmental impact of a new brachytherapy device delivery program, the order-map-treat (OMT) program, in patients with unresectable hepatocellular carcinoma (HCC) in England.MethodsA healthcare resource group (HRG)-based analysis of costs from a national payer (Department of Health and Social Care, DHSC) perspective was conducted assuming that, with OMT, patients would have to attend hospital only once for both the SIRT work-up and procedure versus twice without OMT. Patient travel time and CO2 emissions were then estimated by identifying the SIRT center closest to the centroid of each clinical commissioning group (CCG) and calculating straight-line distances with a "detour index" to capture the effect of indirect routes via road or rail.ResultsIt was estimated that 856 patients per annum would be eligible for SIRT treatment for unresectable HCC in England. OMT would be anticipated to save GBP 2842 per patient versus performing SIRT without OMT. Furthermore, across all patients with HCC eligible for SIRT in England, OMT would avoid 74,500 km of travel, 2299 h of travel time, and 13.9 metric tons of patient transport-related CO2 emissions annually.ConclusionOMT reduces the number of hospital visits required for SIRT by 50%, resulting in financial savings from the DHSC perspective, time savings from the patient perspective, and reduced CO2 emissions arising from patient transport.

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Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors.

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Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors.

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