[Rich66]

(cryotherapy, radiofrequency ablation/RFA, microwave, laser, aerosolized chemo, w/cyclo, w/vit D)



Overview of ablation techniques: http://www.cancerablation.com/procedures.html



Cancer Imaging. 2008 Apr 22;8:116-7.
Lung tumour ablation - where are we now?

Gillams A.



Abstract

Ablation of lung tumours is the fastest expanding area within interventional oncology. Radiofrequency, laser, microwave and cryotherapy have all been shown to be effective. Which of these ablation technologies becomes the preferred technique for lung tumours remains to be seen.

PMID: 18442957 [PubMed - indexed for MEDLINE]PMCID: PMC2365456Free PMC Article



Ann Surg Oncol. 2009 Dec 22. [Epub ahead of print]
Rate of Freeze Alters the Immunologic Response After Cryoablation of Breast Cancer.

Sabel MS, Su G, Griffith KA, Chang AE.
Division of Surgical Oncology, University of Michigan, Ann Arbor, MI, USA, msabel@umich.edu.
BACKGROUND: Cryoablation has garnered significant interest as a treatment for solid tumors including breast cancer for both its local effects and potential in stimulating an antitumor immune response. We sought to examine the impact that variances in technique might have on the immune response and examine the mechanism by which cryoablation may stimulate an antitumor immune response. MATERIALS AND METHODS: Balb/c mice with established 4T1 mammary carcinomas were treated by cryoablation at either a high rate of freeze or low rate of freeze, or by surgical excision, after spontaneous metastases occurred. Tumor-draining lymph nodes (TDLN) were excised at 1 week for EliSPOT assay and immunophenotyping. Mice were followed after treatment for enumeration of pulmonary metastases and survival. RESULTS: Compared with surgical excision, cryoablation using a high freeze rate resulted in a significant increase in tumor-specific T cells in the TDLN, a reduction in pulmonary metastases, and improved survival. However, cryoablation using a low freeze rate resulted in an increase in regulatory T cells, a significant increase in pulmonary metastases, and decreased survival. CONCLUSIONS: Cryoablation of breast cancer in mice can generate a tumor-specific immune response that can eradicate systemic micrometastases and improve outcome compared with surgical excision; however, the technique used to freeze the tissue may alter the immune response from stimulatory to suppressive.

PMID: 20033323 [PubMed - as supplied by publisher]




Freezing Breast Tumors Helps Stop Cancer's Spread In Mice

03 Mar 2010


LINK
Freezing a cancer kills it in its place, and also appears to generate an immune response that helps stop the cancer's spread, leading to improved survival rates over surgery, according to a new study in mice from researchers at the University of Michigan Comprehensive Cancer Center.

Researchers looked at two different cryoablation techniques, which both involve applying a cold probe to a tumor to freeze it. The study was done in mice with breast cancer. One method involves freezing the tumor rapidly, in about 30 seconds; the other freezes the tumor slowly, taking a few minutes.

Both cryoablation techniques successfully killed the breast tumor. The mice treated with the rapid freeze had fewer tumors that spread to the lungs and improved survival compared to mice treated with surgery alone or mice treated with the slower freezing technique. The study showed that the benefit from the rapid freezing is likely due to changes in the immune system that help to kill the tumor. Freezing with the slower technique appeared to make the immune system not as able to kill the tumor.

The study showed that the benefit from the rapid freezing is likely due to changes in the immune system that help to kill the tumor. Freezing with the slower technique appeared to make the immune system not as able to kill the tumor.

"Cryoablation has strong potential as a treatment for breast cancer. Not only does it appear effective in treating the primary tumor with little cosmetic concerns, but it also may stimulate an immune response capable of eradicating any cells that have traveled throughout the body, reducing both local and distant recurrence, similar to giving a breast cancer vaccine," says lead study author Michael Sabel, M.D., associate professor of surgery at the U-M Medical School.

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Cancer Cell. 2009 Aug 4;16(2):91-102.
CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages.

DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM.
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Comment in:

• Nat Rev Cancer. 2009 Sep;9(9):609.
• Cancer Cell. 2009 Aug 4;16(2):81-2.

FREE TEXT
During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we demonstrate that IL-4-expressing CD4(+) T lymphocytes indirectly promote invasion and subsequent metastasis of mammary adenocarcinomas by directly regulating the phenotype and effector function of tumor-associated CD11b(+)Gr1(-)F4/80(+) macrophages that in turn enhance metastasis through activation of epidermal growth factor receptor signaling in malignant mammary epithelial cells. Together, these data indicate that antitumor acquired immune programs can be usurped in protumor microenvironments and instead promote malignancy by engaging cellular components of the innate immune system functionally involved in regulating epithelial cell behavior.



PMID: 19647220 [PubMed - indexed for MEDLINE]


Cardiovasc Intervent Radiol. 2010 May 1. [Epub ahead of print]
Optimizing the Protocol for Pulmonary Cryoablation: A Comparison of a Dual- and Triple-Freeze Protocol.

Hinshaw JL, Littrup PJ, Durick N, Leung W, Lee FT Jr, Sampson L, Brace CL.
Department of Radiology, University of Wisconsin, Mail Code 3252, 600 Highland Ave., Madison, WI, 53792-3252, USA, jhinshaw@uwhealth.org.
Abstract

The purpose of this study was to compare a double freeze-thaw protocol to a triple freeze-thaw protocol for pulmonary cryoablation utilizing an in vivo porcine lung model. A total of 18 cryoablations were performed in normal porcine lung utilizing percutaneous technique with 9 each in a double- (10-5-10) and triple-freeze (3-3-7-7-5) protocol. Serial noncontrast CT images were obtained during the ablation. CT imaging findings and pathology were reviewed. No imaging changes were identified during the initial freeze cycle with either protocol. However, during the first thaw cycle, a region of ground glass opacity developed around the probe with both protocols. Because the initial freeze was shorter with the triple freeze-thaw protocol, the imaging findings were apparent sooner with this protocol (6 vs. 13 min). Also, despite a shorter total freeze time (15 vs. 20 min), the ablation zone identified with the triple freeze-thaw protocol was not significantly different from the double freeze-thaw protocol (mean diameter: 1.67 +/- 0.41 cm vs. 1.66 +/- 0.21 cm, P = 0.77; area: 2.1 +/- 0.48 cm(2) vs. 1.99 +/- 0.62 cm(2), P = 0.7; and circularity: 0.95 +/- 0.04 vs. 0.96 +/- 0.03, P = 0.62, respectively). This study suggests that there may be several advantages of a triple freeze-thaw protocol for pulmonary cryoablation, including earlier identification of the imaging findings associated with the ablation, the promise of a shorter procedure time or larger zones of ablation, and theoretically, more effective cytotoxicity related to the additional freeze-thaw cycle.

PMID: 20437048 [PubMed - as supplied by publisher]




J Pharmacol Exp Ther. 2009 Aug;330(2):596-601. Epub 2009 Apr 30.
Cyclophosphamide unmasks an antimetastatic effect of local tumor cryoablation.

Levy MY, Sidana A, Chowdhury WH, Solomon SB, Drake CG, Rodriguez R, Fuchs EJ.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

1. Address correspondence to:
   Dr. Ephraim J. Fuchs, 488 Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231. E-mail: fuchsep@jhmi.edu
   

Abstract

Cryoablation of a solitary tumor mass releases intact tumor antigens and can induce protective antitumor immunity but has limited efficacy in the treatment of established metastatic cancer. Cyclophosphamide (Cy), an anticancer drug, selectively depletes regulatory T cells (T_regs) and attenuates suppression of antitumor immunity. We used a BALB/c mouse model of metastatic colon cancer to investigate the systemic antitumor effects of in situ cryotherapy alone or in combination with 200 mg/kg i.p. Cy. When combined with Cy, cryoablation was significantly more effective than either surgical excision or cautery at inducing systemic antitumor immunity, resulting in the cure of a fraction of animals with established metastatic disease and resistance to tumor rechallenge. Lymphocytes from cured animals contained an expanded population of tumor-specific, interferon-γ producing T cells and transferred antitumor immunity to naive recipients. Depletion of CD8⁺ cells significantly impaired the adoptive transfer of antitumor immunity. Furthermore, treatment with Cy and cryoablation was associated with a significant decrease in the ratio of regulatory to effector CD4⁺ T cells. The combination of tumor cryoablation and Cy induces potent, systemic antitumor immunity in animals with established metastatic disease.

• Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

Cryobiology. 1983 Feb;20(1):78-82.
Cyclophosphamide pretreatment in tumor cryotherapy: a comparison with alternative drugs.

Cooper AJ, Fraser JD.
Abstract

The method of Turk and Lagrange for modulating immune responses in favor of the cell-mediated effector arm by using single high doses of cyclophosphamide 3 days before antigen has previously been shown to cause decreased rates of local tumor recurrence when adapted as an adjunctive therapy to cryosurgery in a murine model. This series of experiments compares cyclophosphamide, azathioprine, and methotrexate against cryosurgery alone in the same therapeutic protocol. Only cyclophosphamide gave enhanced numbers of cures; azathioprine caused an increase in metastases arising concurrently with local tumor recrudescence.

PMID: 6831912 [PubMed - indexed for MEDLINE]






Letrozole (Femara) alone or with Cyclophosphamide decrease Tregs, possibly helpful to Crotherapy, even in ER- tumors:

Clin Cancer Res. 2009 Feb 1;15(3):1046-51.
Immunomodulation of FOXP3+ regulatory T cells by the aromatase inhibitor letrozole in breast cancer patients.

Generali D, Bates G, Berruti A, Brizzi MP, Campo L, Bonardi S, Bersiga A, Allevi G, Milani M, Aguggini S, Dogliotti L, Banham AH, Harris AL, Bottini A, Fox SB.
Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

FREE TEXT


Abstract

PURPOSE: We have shown previously that tumor infiltration by FOXP3+ regulatory T cells (Treg) is associated with increased relapse and shorter survival of patients with both in situ and invasive breast cancer. Because estrogen regulates Treg numbers in mice and promotes the proliferation of human Tregs, we hypothesized that blocking estrogen receptor-alpha signaling would abrogate Tregs and be associated with response to hormonal therapy and increased survival. EXPERIMENTAL DESIGN: FOXP3+ Tregs were quantified in tumor samples collected at baseline by incisional biopsy and after 6 months at definitive surgery in 83 elderly breast cancer patients (T2-4 N0-1) enrolled in a randomized phase II trial based on 6 months of primary letrozole (2.5 mg/d) or 6 months of letrozole plus oral "metronomic" cyclophosphamide (50 mg/d). RESULTS: Treg number ranged from 0 to 380 (median, 30) before treatment and from 0 to 300 (median, 8) after treatment. There was a significant reduction in Tregs in letrozole and letrozole-cyclophosphamide patients (P < 0.0001 and P < 0.002, respectively) after treatment. Treg number at residual histology was inversely related with response (P < 0.03 and P = 0.50, respectively) and a greater Treg reduction was observed in responding patients (P < 0.03). CONCLUSION: This study suggests that aromatase inhibitors may have an indirect antitumor mechanism of action through reducing Tregs in breast tumors and may be of use in estrogen receptor-alpha-negative tumors in combination with immunotherapy approaches.

PMID: 19188178 [PubMed - indexed for MEDLINE]Free Article

Translational Relevance We have shown recently that high numbers of Tregs in in situ and invasive breast carcinomas give independent prognostic information even beyond 5 years when conventional pathologic factors lose their power. Because Tregs play a pivotal role in immunosuppression and tumor emergence, we performed a phase II randomized controlled trial of letrozole ± the immunomodulatory agent cyclophosphamide in breast cancer patients to assess the clinical utility of the number of Tregs in predicting the response to therapy. This question addresses second of the top 15 breast cancer research priorities determined by registrants at the San Antonio Breast and St Gallen meetings in 2005. We show a significant reduction in the numbers of Tregs in the primary tumor after treatment with an aromatase inhibitor but not by the addition of cyclophosphamide, showing that the effect is largely due to the aromatase inhibitor. Importantly, this reduction in Tregs is inversely related to the response. These novel findings suggest that letrozole has a significant immunomodulatory role and that aromatase inhibitors could be used in the future in combination with other immunotherapeutic approaches not only in patients with ER-positive but also in ER-negative tumors.

Urology. 2010 Jul 2. [Epub ahead of print]
Role of Vitamin D(3) as a Sensitizer to Cryoablation in a Murine Prostate Cancer Model: Preliminary In Vivo Study.

Kimura M, Rabbani Z, Mouraviev V, Tsivian M, Caso J, Satoh T, Baba S, Vujaskovic Z, Baust JM, Baust JG, Polascik TJ.
Duke Prostate Center and Division of Urologic Surgery, Department of Surgery, Durham, North Carolina.
Abstract

OBJECTIVES: Calcitriol has been reported to have antitumor efficacy in several cancers. In this study, we hypothesized that calcitriol may potentially function as a cryosensitizer that can enhance cryoablation, and we investigated several molecular marker changes in a murine model of prostate cancer. METHODS: Murine prostate tumors (RM-9) were grown in male C57BL/6J mice subcutaneously with neoadjuvant intratumoral injection of calcitriol followed by cryoablation. The microenvironmental changes after cryoablation alone and in combination with calcitriol were analyzed in a comparative fashion using immunohistochemistry and Western blot analyses. RESULTS: Both cryoablation and the combination group could suppress tumor growth after treatment compared with the control. At final pathologic assessment, a larger necrotic area was seen in the combination group (P = .026). Although microvessel density (CD31) and the area of hypoxia (pimonidazole) was not different between the control and combination groups, cell proliferation (Ki-67) significantly decreased in the combination treatment (P = .035). In Western blot analyses, several markers for apoptosis were expressed significantly higher with the combination treatment. CONCLUSIONS: The synergistic effect of calcitriol with cryoablation was demonstrated because of enhanced antitumor efficacy by increasing necrosis and apoptosis and reduced cell proliferation. This study suggests that calcitriol is a potentially applicable reagent as a freeze sensitizer to cryoablation. Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 20599255 [PubMed - as supplied by publisher]




Intern Med. 2010;49(5):431-3. Epub 2010 Mar 1.
Acute respiratory distress syndrome after percutaneous cryotherapy for a pulmonary metastatic lesion.

Tasaka S, Tomomatsu K, Funatsu Y, Soejima K, Ishizaka A.
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo. tasaka@cpnet.med.keio.ac.jp

Abstract

Percutaneous cryotherapy (PCT) under computed tomographic guidance is minimally invasive, with satisfactory local control of primary lung cancer and pulmonary metastatic lesions. We report a case of acute respiratory distress syndrome (ARDS) in a patient who underwent PCT for lung metastasis of recurrent esophageal cancer. The patient responded to pulse steroid therapy and recovered from severe respiratory failure. Excessive inflammatory response to necrotic debris might contribute to the development of ARDS. To the best of our knowledge, this is the first report describing the details of ARDS following PCT.

PMID: 20190478 [PubMed - indexed for MEDLINE]Free Article




Eur J Cancer. 2009 Jul;45(10):1773-9. Epub 2009 Mar 11.
The use of PTC and RFA as treatment alternatives with low procedural morbidity in non-small cell lung cancer.

Choe YH, Kim SR, Lee KS, Lee KY, Park SJ, Jin GY, Lee YC.
Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, Jeonbuk, South Korea.
Abstract

Minimally invasive percutaneous ablative therapies for treating lung cancers are currently being studied as treatment alternatives. This present study investigated the efficacies of percutaneous thoracic cryotherapy (PTC) and radiofrequency ablation (RFA) on clinical courses of pulmonary malignant tumours, especially in the setting of non-surgical candidates. Sixty-five patients with lung malignancy underwent sixty-seven sessions of RFA and nine sessions of PTC. We evaluated the results of RFA and PTC including efficacies, local progression rate, survival rate, and complications. Twenty-nine patients (43.3%) treated with RFA and six patients (66.7%) with PTC attained complete ablation. In small-sized lung mass (3 cm), complete ablation rate of RFA and PTC was increased to 76.2% and 85.7%, respectively. Additionally, we have found that the complete ablation group had significantly higher survival duration and progression free survival duration compared with the partial ablation group. Moreover, the complication profile was acceptable and the pain associated with the procedures disappeared within 1 day; 42 patients (62.7%) after RFA and all patients after PTC. This study provides evidence for the use of PTC and RFA as treatment alternatives with low procedural morbidity in the management of inoperable pulmonary malignant tumours, although the current study is limited by the small sample size and the short follow-up period.

PMID: 19285385 [PubMed - indexed for MEDLINE]




Cardiovasc Intervent Radiol. 2010 Apr 29. [Epub ahead of print]
Lung Tumor Radiofrequency Ablation: Where Do We Stand?

de Baère T.
Department of Interventional Radiology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805, Villejuif, France, debaere@igr.fr.
Abstract

Today, radiofrequency ablation (RFA) of primary and metastatic lung tumor is increasingly used. Because RFA is most often used with curative intent, preablation workup must be a preoperative workup. General anesthesia provides higher feasibility than conscious sedation. The electrode positioning must be performed under computed tomography for sake of accuracy. The delivery of RFA must be adapted to tumor location, with different impedances used when treating tumors with or without pleural contact. The estimated rate of incomplete local treatment at 18 months was 7% (95% confidence interval, 3-14) per tumor, with incomplete treatment depicted at 4 months (n = 1), 6 months (n = 2), 9 months (n = 2), and 12 months (n = 2). Overall survival and lung disease-free survival at 18 months were, respectively, 71 and 34%. Size is a key point for tumor selection because large size is predictive of incomplete local treatment and poor survival. The ratio of ablation volume relative to tumor volume is predictive of complete ablation. Follow-up computed tomography that relies on the size of the ablation zone demonstrates the presence of incomplete ablation. Positron emission tomography might be an interesting option. Chest tube placement for pneumothorax is reported in 8 to 12%. Alveolar hemorrhage and postprocedure hemoptysis occurred in approximately 10% of procedures and rarely required specific treatment. Death was mostly related to single-lung patients and hilar tumors. No modification of forced expiratory volume in the first second between pre- and post-RFA at 2 months was found. RFA in the lung provides a high local efficacy rate. The use of RFA as a palliative tool in combination with chemotherapy remains to be explored.

PMID: 20429003 [PubMed - as supplied by publisher]




Eur J Radiol. 2010 May 7. [Epub ahead of print]
Radiofrequency ablation of pulmonary tumors.

Crocetti L, Lencioni R.
Division of Diagnostic Imaging and Intervention, Department of Liver Transplants, Hepatology and Infectious Diseases, Pisa University School of Medicine, Italy.
Abstract

The development of image-guided percutaneous techniques for local tumor ablation has been one of the major advances in the treatment of solid tumors. Among these methods, radiofrequency (RF) ablation is currently established as the primary ablative modality at most institutions. RF ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma when liver transplantation or surgical resection are not suitable options and is considered as a viable alternate to surgery for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer. Recently, RF ablation has been demonstrated to be a safe and valuable treatment option for patients with unresectable or medically inoperable lung malignancies. Resection should remain the standard therapy for non-small cell lung cancer (NSCLC) but RF ablation may be better than conventional external-beam radiation for the treatment of the high-risk individual with NSCLC. Initial favourable outcomes encourage combining radiotherapy and RF ablation, especially for treating larger tumors. In the setting of colorectal cancer lung metastases, survival rates provided by RF ablation in selected patients, are substantially higher than those obtained with any chemotherapy regimens and provide indirect evidence that RF ablation therapy improves survival in patients with limited lung metastatic disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PMID: 20452739 [PubMed - as supplied by publisher]






Interact Cardiovasc Thorac Surg. 2010 Apr;10(4):650-1. Epub 2010 Jan 26.
Parietal tumor recurrence of lung metastasis after radiofrequency ablation.

Guihaire J, Verhoye JP, de Latour B, Leguerrier A.
Department of Cardiovascular and Thoracic Surgery, Pontchaillou Hospital, Rennes, France.



Abstract

Metastasis is the most common form of malignant lung tumor. Radiofrequency ablation (RFA) is a new treatment for single pulmonary tumors. However, RFA can be complicated by iatrogenic and parietal recurrence. We report the case of a 67-year-old man with a single pulmonary metastasis from colorectal cancer diagnosed two years previously and locally controlled by left hemi-colectomy. The metastasis was treated by RFA. Four months after the procedure, a positron emission tomography scan revealed parietal chest contamination. Surgical resection enabled the diagnosis of parietal tumor expansion and confirmed successful treatment of the initial metastasis. This case highlights the risk of iatrogenic parietal contamination after RFA. To our knowledge no similar case has been published to date. The most appropriate steps to prevent this type of complication still have to be defined.
PMID: 20103508 [PubMed - in process]Free Article




J Transl Med. 2010 Jul 29;8:73.
Low temperature of radiofrequency ablation at the target sites can facilitate rapid progression of residual hepatic VX2 carcinoma.

Ke S, Ding XM, Kong J, Gao J, Wang SH, Cheng Y, Sun WB.
Department of Hepatobiliary Surgery, West Campus, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China.


FREE TEXT

Abstract

BACKGROUND: Rapid progression of residual tumor after radiofrequency ablation (RFA) of hepatocellular carcinoma has been observed increasingly. However, its underlying mechanisms remain to be clarified. The present study was designed to determine whether low temperature of RFA at the target sites facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms.
METHODS: The residual VX2 hepatoma model in rabbits was established by using RFA at 55, 70 and 85 degrees C. Rabbits that were implanted with VX2 hepatoma but did not receive RFA acted as a control group. The relationship between rapid progression of residual hepatic VX2 carcinoma and low temperature of RFA at the target sites was carefully evaluated. A number of potential contributing molecular factors, such as proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and Interleukin-6 (IL-6) were measured.
RESULTS: The focal tumor volume and lung metastases of RFA-treated rabbits increased significantly compared with the control group (P < 0.05), and the greatest changes were seen in the 55 degrees C group (P < 0.05). Expression of PCNA, MMP-9, VEGF, HGF and IL-6 in tumor tissues increased significantly in the RFA-treated groups compared with the control group, and of the increases were greatest in the 55 degrees C group (P < 0.05). These results were consistent with gross pathological observation. Tumor re-inoculation experiments confirmed that low temperature of RFA at the target sites facilitated rapid progression of residual hepatic VX2 carcinoma.
CONCLUSIONS: Insufficient RFA that is caused by low temperature at the target sites could be an important cause of rapid progression of residual hepatic VX2 carcinoma. Residual hepatic VX2 carcinoma could facilitate its rapid progression through inducing overexpression of several molecular factors, such as PCNA, MMP-9, VEGF, HGF and IL-6.

PMID: 20667141 [PubMed - in process]PMCID: PMC2917410Free PMC Article







J Aerosol Med Pulm Drug Deliv. 2008 Mar;21(1):61-70.
Aerosolized chemotherapy.

Gagnadoux F, Hureaux J, Vecellio L, Urban T, Le Pape A, Valo I, Montharu J, Leblond V, Boisdron-Celle M, Lerondel S, Majoral C, Diot P, Racineux JL, Lemarie E.
Département de Pneumologie, CHU, Angers, France. frgagnadoux@chu-angers.fr
Regional chemotherapy has been proposed as a treatment modality in a number of cancer settings. In primary or metastatic lung cancer, administration of chemotherapy via inhalation could increase exposure of lung tumor to the drug, while minimizing systemic side effects. Several proof of concept studies in animal models of metastatic or primary lung cancer have demonstrated the safety, pharmacokinetic advantage, and antitumor effect of aerosol administration of several chemotherapeutic agents including doxorubicin, gemcitabine and liposome-encapsulated formulations of paclitaxel and 9-nitrocamptothecin (9-NC). Recent phase I studies have demonstrated the feasibility of aerosol delivery of doxorubicin and liposomal formulations of 9-NC and cisplatin in patients with primary and metastatic lung cancer with a limited pharmacokinetic profile consistent with the observed low systemic toxicity. Further studies integrating safety, pharmacokinetic, and efficacy considerations are required to determine whether there is a place for local administration of chemotherapy via inhalation in lung cancer.

PMID: 18518832 [PubMed - indexed for MEDLINE]



Cancer. 1987 Feb 15;59(4):688-9.
Nasally administered buserelin inducing complete remission of lung metastases in male breast cancer.

Vorobiof DA, Falkson G.
A 60-year-old man with bilateral lung metastases from breast cancer was treated with the gonadotropin-releasing hormone analogue, buserelin, given as an intranasal spray. Androgen deprivation and complete remission of lung metastases were achieved with minimal side effects. Androgen deprivation by means of nasally administered buserelin offers an easy and efficient alternate approach in the treatment of metastatic male breast cancer.

PMID: 3100015 [PubMed - indexed for MEDLINE]


Cancer Treat Res. 2010;152:203-15.
Non-Surgical Treatment of Pulmonary and Extra-pulmonary Metastases.

Anderson P.
Children's Cancer Hospital, University of Texas MD Anderson Cancer Center, Unit 87, Pediatrics, 1515 Holcombe Blvd., Houston, TX, 77030-4009, USA, pmanders@mdanderson.org.
Studies have demonstrated that chemotherapy alone is usually unsuccessful as exclusive therapy for osteosarcoma (Cancer 95:2202-2201, 2002). Information will be presented for situations where non-surgical alternatives could be considered as useful, if not necessary, adjuncts to chemotherapy. In the thorax these include treatment of pleural effusions, chest wall lesions, central lung or mediastinal osteosarcoma, as well as recurrences in patients with limited pulmonary reserve. Other situations include too many metastases to easily resect, axial osteosarcomas, bone metastases, liver and brain metastases.Non-surgical local control measures include radiation with chemotherapy for radiosensitization, bone-seeking radioisotopes (e.g., (153)Sm-EDTMP, (223)Ra), bisphosphonates, heat (radiofrequency ablation), freezing and thawing (cryoablation), and intracavitary or regional (aerosol) therapy. Because of the predictable and common pattern of pulmonary metastases in osteosarcoma, aerosol therapy also offers an attractive regional treatment strategy. Principles and use of aerosol cytokines (e.g., GM-CSF, IL-2), and aerosol chemotherapy with gemcitabin will be discussed. Individual cases illustrating strategy and techniques will be presented.

PMID: 20213392 [PubMed - in process]




Cardiovasc Intervent Radiol. 2010 Mar 16. [Epub ahead of print]
Bronchopleural Fistula After Radiofrequency Ablation of Lung Tumours.

Cannella M, Cornelis F, Descat E, Ferron S, Carteret T, Castagnède H, Palussière J.
Department of Interventional Radiology, Institut Bergonié, Regional Cancer Center, 229 cours de l'Argonne, 33076, Bordeaux Cedex, France.
The present article describes two cases of bronchopleural fistula (BPF) occurring after radiofrequency ablation of lung tumors. Both procedures were carried out using expandable multitined electrodes, with no coagulation of the needle track. After both ablations, ground-glass opacities encompassed the nodules and abutted the visceral pleura. The first patient had a delayed pneumothorax, and the second had a recurrent pneumothorax. Both cases of BPF were diagnosed on follow-up computed tomography chest scans (i.e., visibility of a distinct channel between the lung or a peripheral bronchus and the pleura) and were successfully treated with chest tubes alone. Our goal is to highlight the fact that BPF can occur without needle-track coagulation and to suggest that minimally invasive treatment is sufficient to cure BPFs of this specific origin.

PMID: 20232201 [PubMed - as supplied by publisher]