Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: A phase I study

Order, Stanley E.; Siegel, Jeffry A.; Principato, Robert; Zeiger, Louis S.; Johnson, Elizabeth; Lang, Patricia; Lustig, Robert A.; Wallner, Paul E.

doi:10.1016/s0360-3016(96)00484-1

Cited by 43 publications

(29 citation statements)

References 9 publications

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“…Mixed results seen in current clinical uses of radionuclide therapy modalities may be further evidence of the results described in this work. In the past, nonresectable pancreatic cancer patients have been treated with a direct interstitial tumor infusion technique using colloidal 32 P. 35 Patients received av- erage tumor doses from 235 to 17 000 Gy, ablative dose levels unheard of in EBRT modalities due to toxicity issues. However, median survival was only improved to 12 months compared to 8-10.4 months seen with EBRT of 60 or [35][36][37][38][39][40] Gy with concomitant 5-fluorouracil.…”

Section: Discussionmentioning

confidence: 99%

Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

Hrycushko

Goins

et al. 2011

Medical Physics

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Purpose: Focused radiation therapy by direct intratumoral infusion of lipid nanoparticle ͑liposome͒-carried beta-emitting radionuclides has shown promising results in animal model studies; however, little is known about the impact the intratumoral liposomal radionuclide distribution may have on tumor control. The primary objective of this work was to investigate the effects the intratumoral absorbed dose distributions from this cancer therapy modality have on tumor control and treatment planning by combining dosimetric and radiobiological modeling with in vivo imaging data. Methods:99m Tc-encapsulated liposomes were intratumorally infused with a single injection location to human head and neck squamous cell carcinoma xenografts in nude rats. High resolution in vivo planar imaging was performed at various time points for quantifying intratumoral retention following infusion. The intratumoral liposomal radioactivity distribution was obtained from 1 mm resolution pinhole collimator SPECT imaging coregistered with CT imaging of excised tumors at 20 h postinfusion. Coregistered images were used for intratumoral dosimetric and radiobiological modeling at a voxel level following extrapolation to the therapeutic analogs, 186Re / 188Re liposomes. Effective uniform dose ͑EUD͒ and tumor control probability ͑TCP͒ were used to assess therapy effectiveness and possible methods of improving upon tumor control with this radiation therapy modality. Results: Dosimetric analysis showed that average tumor absorbed doses of 8.6 Gy/MBq ͑318.2 Gy/mCi͒ and 5.7 Gy/MBq ͑209.1 Gy/mCi͒ could be delivered with this protocol of radiation delivery for 186 Re / 188Re liposomes, respectively, and 37-92 MBq ͑1-2.5 mCi͒/g tumor administered activity; however, large intratumoral absorbed dose heterogeneity, as seen in dose-volume histograms, resulted in insignificant values of EUD and TCP for achieving tumor control. It is indicated that the use of liposomes encapsulating radionuclides with higher energy beta emissions, dose escalation through increased specific activity, and increasing the number of direct tumor infusion sites improve tumor control. For larger tumors, the use of multiple infusion locations was modeled to be much more efficient, in terms of activity usage, at improving EUD and TCP to achieve a tumoricidal effect. Conclusions: Direct intratumoral infusion of beta-emitting radionuclide encapsulated liposomes shows promise for cancer therapy by achieving large focally delivered tumor doses. However, the results of this work also indicate that average tumor dose may underestimate tumoricidal effect due to substantial heterogeneity in intratumoral liposomal radionuclide distributions. The resulting intratumoral distribution of liposomes following infusion should be taken into account in treatment planning and evaluation in a clinical setting for an optimal cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

Hrycushko

Goins

et al. 2011

Medical Physics

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“…Colloidal 32 P has been used for the treatment of intracavitary malignancies. The retention of radioactivity of colloidal 32 P at the site of a solid tumor required the infusion of macroaggregated albumin (19). An alternative method to aid radioactivity retention at the tumor site has been to use labeled, nontoxic and undegradable microcarriers such as phosphorus-32 glass microspheres (20).…”

Section: Discussionmentioning

confidence: 99%

“…There have been few animal studies (20, 28 -30) and clinical trials (15,19,31,32) on intratumoral brachytherapy in hepatocellular carcinoma and pancreatic carcinoma. These have either used glass microspheres as a vehicle or infusional maccroaggregated albumin as a means to aid radioactivity retention at the tumor site.…”

Section: Discussionmentioning

confidence: 99%

“…In the trial by Firusian et al (32), only 3 of the 17 patients had hepatocellular carcinoma but good responses were recorded in all three cases. A clinical study using infusional macroaggregated albumin in combination with external beam radiation and chemotherapy in unresectable pancreatic adenocarcinoma similarly reported good response with complete remission (19,33).…”

Section: Discussionmentioning

confidence: 99%

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Complete Tumor Response Following Intratumoral 32P BioSilicon on Human Hepatocellular and Pancreatic Carcinoma Xenografts in Nude Mice

Zhang¹,

Loong

Connor³

et al. 2005

Clinical Cancer Research

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Purpose:32 P BioSilicon is a new, implantable, radiological medical device that comprises particles of highly pure silicon encapsulating 32 phosphorus ( 32 P) for the treatment of unresectable solid tumors. Prior to administration, the device particles are suspended in a formulant which provides an even suspension of the intended dose for implantation. The primary objective of this animal trial study was to investigate the effects of intratumoral injection of 32 P BioSilicon on human hepatocellular (HepG2) and pancreatic carcinoma (2119) xenografts implanted in nude mice (BALB/c). A secondary objective was the histopathologic examination of the tumor foci and surrounding tissue during the study. Methods: Cultured human carcinoma cells (HepG2 and 2119) were injected s.c. into the gluteal region of nude mice.When the implanted tumors were f1cm in diameter, 32 P BioSilicon (0.5, 1.0, and 2.0 MBq) or formulant was injected into the tumors. Implanted tumor size was measured once a week for 10 weeks. At study termination, the tumor and surrounding normal tissue were collected and fixed in 10% formalin and processed for histopathologic analysis. Results:32 P BioSilicon produced a reduction in HepG2 tumor volume when compared with formulant control, and complete response was observed among tumors in the 1.0 and 2.0 MBq treatment groups after week 8. There was also significant reduction in 2119 tumor volume in all treated groups, with the complete response rate of 67% in the 2.0 MBq group. Conclusion:32 P BioSilicon suppressed the growth of both human hepatocellular and pancreatic carcinoma xenografts implanted in nude mice and complete responses were also observed in tumors at higher radiation doses.

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“…The high incidence of complications associated with resection of advanced pancreatic cancer and the significant gastrointestinal toxicity of external−beam radiation limit their usefulness (Yao et al, 2002). Other series of intraoperative iodine−125 implantation have been associated with mortality ranging from 0% to 16% and major morbidity of 18% (Order et al, 1996). Sun S et al reported (Sun et al, 2006), there was no significant immediate complications, such as significant bleeding or infection.…”

Section: Wwwintechopencommentioning

confidence: 99%

Clinical Application of Image-Guided Iodine-125 Seed Implantation Therapy in Patients with Advanced Pancreatic Cancer

Wang¹,

Chen²

2011

Current Cancer Treatment - Novel Beyond Conventional Approaches

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Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: A phase I study

Cited by 43 publications

References 9 publications

Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

Complete Tumor Response Following Intratumoral 32P BioSilicon on Human Hepatocellular and Pancreatic Carcinoma Xenografts in Nude Mice

Clinical Application of Image-Guided Iodine-125 Seed Implantation Therapy in Patients with Advanced Pancreatic Cancer

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