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Pulmonary Metastases: Further Treatment Options
compiled by doctordee
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VATS [Video Assisted Thoracoscopic Surgery]

VATS is like laparascopic [or keyhole] surgery, but in the chest. It is a useful choice for surgical removal of lung metastases.

For further information go to VATS page on this website
and to Comparison of VATS, RFA, and thoracotomy

RFA [Radio Frequency Ablation]
What is Radio Frequency Ablation?
Written by Beth C, November 2001
Updated by doctordee November 2003

Radio Frequency Ablation (RFA) is a procedure that can be used to destroy tumors in the liver, lungs, bone, kidney, pancreas, and adrenal gland, as well as other locations. RFA is carried out by an Interventional Radiologist, who is a medical doctor who has specialized in this field.

RFA works by passing radio frequency energy through the tumor. Heat is generated at the site of the tumor through agitation caused by this energy. This heat produces coagulation and cellular destruction --necrosis -- resulting in destruction of the lesion or tissue. The electrode is heated on the way out, sterilizing the track, to prevent local recurrences due to implantation seeding of tumor cells.

Radio Frequency Ablation is a specialized technique, and should be carried out in a specialized treatment center.

How does it work?
Using conventional imaging methods -- ultrasound, CT scan, or MRI -- an electrode is positioned strategically within the lesion. The electrode is then connected to a radiofrequency generator and the energy is delivered into the tissue. As the cells are heated, they are destroyed. The mechanism of RFA is similar to that of a microwave oven, heating from the inside out. The tissue reabsorbs the destroyed cells over a period of time.

For fuller information about RFA, please see the RFA page on this website
as well as the following:


1. Search Pubmed for RFA and Lung
As of November 2003, there are 28 articles listed in this search.

2. Effect of Radio Frequency Ablation on Lung Cancer.
ASCO [ 1342 - 2001]

3.Percutaneous imaging-guided radio frequency ablation (RFA) of metastatic colorectal cancer (CRC) in lung
ASCO [2216 - 2002]

4. Percutaneous Imaging-Guided Radio Frequency Ablation (RFA) of Secondary Colorectal Cancers (CRC) in Lung.
ASCO [2203 - 2001]

5. Radio Frequency Ablation (Rfa) of Metastatic Lesions in Adrenocortical Cancer (Acc)
ASCO [609N - 2000]

6. Chest
Radiofrequency thermal ablation of a metastatic lung nodule
..."This case illustrates the use of RF ablation in a patient in whom surgical resection was no longer possible and where chemotherapy was unlikely to produce benefit. This technique may offer a viable method of cytoreduction when other treatments have not succeeded."
Abstract

7. European Radiology Issue: Volume 12, Supplement 3 December 2002 Pages: S166 - S170
Radiofrequency thermal ablation of a metastatic lung nodule
Abstract

8. NOTE: There are open clinical trials for RFA, some of which are for pulmonary metastases.
RE-Resection [Reoperate]
Repeated Resections of Pulmonary Metastases

If pulmonary metastases are completely resected with clear surgical margins, survival time is extended significantly. Resection of RECURRENT pulmonary metastases, again with clear margins, also extends survival time significantly. See articles described below.

Search Pubmed for Sarcoma and Pulmonary Metastasectomies
See the Web Page Metastasectomies


Selected Medical Journal Annotated References


J Am Coll Surg 2000 Aug;191(2):184-90; discussion 190-1 Comment in: J Am Coll Surg. 2000 Aug;191(2):193-5
Repeat resection of pulmonary metastases in patients with soft-tissue sarcoma.
Weiser MR, Downey RJ, Leung DH, Brennan MF.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

...Even after an apparent complete resection of sarcomatous pulmonary metastases, 40% to 80% of patients will re-recur in the lung. The benefit of subsequent re-resection is poorly defined. This study examines patient survival after repeat pulmonary exploration for re-recurrent metastatic sarcoma at a single institution.
... Between July 1982 and December 1997, data on 3,149 adult in-patients with soft tissue sarcoma were prospectively gathered. Of these, pulmonary metastases were present or developed in 719 patients and 248 underwent at least one resection. Of the patients relapsing in the lung after an apparently complete resection, 86 underwent reexploration. Disease-specific survival (DSS) after re-resection was the end point of the study....
* The median DSS after re-resection for all patients undergoing at least two pulmonary resections was 42.8 months with an estimated 5-year survival of 36%.
* The median DSS[Disease Specific Survival] in patients with complete reresection was 51 months (n = 68) compared with 6 months in patients with an incomplete re-resection (n = 16, p<0.0001).
* Patients with one or two nodules at re-resection (n = 39) had a median DSS of 51 months compared with 20 months in patients with three or more nodules (n = 40, p = 0.003).
* Patients in whom the largest metastasis re-resected was less than or equal to 2 cm (n = 33) had a median DSS of 44 months compared with 20 months in patients with metastasis greater than 2 cm (n = 43, p = 0.033).
* Patients with primary tumor high-grade histology (n = 75) had a median DSS of 32 months and patients with low-grade histology (n = 11) had a median DSS that was not reached (p = 0.041).
* Three independent prognostic factors associated with poor outcomes may be determined preoperatively: > or =3 nodules, largest metastases > 2 cm, and high-grade primary tumor histology.
* Patients with either zero or one poor prognostic factor had a median DSS > 65 months and patients with three poor prognostic factors had a median DSS of 10 months.
* ...Re-exploration for recurrent sarcomatous pulmonary metastases appears beneficial for patients who can be completely re-resected.
* Outcomes are described by factors that may be determined preoperatively, including metastasis size, metastasis number, and primary tumor histologic grade.
* Patients who cannot be completely re-resected or those with numerous, large metastasis and high-grade primary tumor pathology have poor outcomes and should be considered for investigational therapy.
Fetch PMID: 10945362


Am J Surg 2000 Feb;179(2):122-5
Importance of the control of lung recurrence soon after surgery of pulmonary metastases.
Maniwa Y, Kanki M, Okita Y.
Department of Surgery, Division II, Kobe University School of Medicine, Kobe, Japan.

...In this study, we investigated factors that determined prognosis in patients who underwent surgery for metastatic lung tumors, focusing on early relapse of metastatic lung lesions after surgery, and considered countermeasures for improving long-term results based on this study. ...This study was performed in patients with metastatic lung tumors who underwent surgery during the 22 years after November 1975 in this department. ... The 1-year, 3-year, and 5-year survival rates in all patients were 70%, 42%, and 37%, respectively. On comparison among the groups, there were no significant differences by gender, age, organ with the primary lesion, disease-free interval, number of metastases, or surgical procedure. However, prognosis was significantly poorer in patients with recurrent metastatic lung lesions. Prognosis was especially poor in patients with recurrence within 6 months after pneumonectomy, and this was an important factor that worsened the surgical results. ... As the mechanism of early recurrence of lung metastasis after surgery for metastatic lung tumor, multiple micrometastases (dormancy) that cannot be detected during surgery for metastatic lung tumor may be present in the lung. Establishment of a method of controlling an increase in dormant metastasis may lead to improvement of surgical results of metastatic lung tumors. [Adjuvant antiangiogenic treatment might be somewhat effective here. Ed.]
Fetch PMID: 10773147


Nippon Geka Gakkai Zasshi 1998 Dec;99(12):855-60
[Surgical management of pulmonary metastases].[Article in Japanese]
Hara S, Otsuka H, Hirohata T, Nishi K, Yasutomi M.
First Department of Surgery, Kinki University School of Medicine, Osakasayama, Japan.

The results of surgical resection for pulmonary metastases from ..., soft tissue sarcoma, and osteosarcoma are reviewed. The number of pulmonary metastases, the presence of hilar or mediastinal involvement, and extrapulmonary foci are discussed in terms of surgical treatment. The size of pulmonary tumors or tumor doubling time has no significant effect on survival, while the number of metastatic foci does.... Higher relapse rates have been reported in patients with soft tissue sarcoma and osteosarcoma, although patients with these metastases can achieve long-term survival after a second metastasectomy. VATS is not be recommended for metastatic cancer surgery, because intraoperative identification of metastatic foci is often difficult. Publication Types: Review
Fetch PMID: 10063499


Ann Thorac Surg 1998 Apr;65(4):909-12 Comment in: Ann Thorac Surg. 1998 Sep;66(3):989
Long-term results after repeated surgical removal of pulmonary metastases.
Kandioler D, Kromer E, Tuchler H, End A, Muller MR, Wolner E, Eckersberger F.
Department of Cardio-Thoracic Surgery, University of Vienna Medical School, Austria
.
... Although surgical resection is accepted widely as first-line therapy for pulmonary metastases, few data exist on the surgical treatment of recurrent pulmonary metastatic disease. In a retrospective study, we analyzed patients who were operated on repeatedly for recurrent metastatic disease of the lung with curative intent over a 20-year period. ... From 1973 to 1993, 396 metastasectomies were performed in 330 patients. The study population included patients with any histologic tumor type who had undergone at least two (range, 2 to 4) complete surgical procedures because of recurrent metastatic disease. Surgical and functional resectability of the recurrent lung metastases and control of the primary lesion served as objective criteria for reoperation. A subgroup of 35 patients that included patients with histologic findings such as epithelial cancer and osteosarcoma then was analyzed retrospectively to calculate prognosis and define selection criteria for repeated pulmonary metastasectomy. ... The 5- and 10-year survival rates after the first metastasectomy were 48% and 28%, respectively. The overall median survival was 60 months. A mean disease-free interval (calculated for all intervals, with a minimum of two) of greater than 1 year was significantly associated with a survival advantage beyond the last operation. Univariate analysis failed to show size, number, increase or decrease in number or size, or distribution of metastases as factors related significantly to survival. ...Although patients with different histologic tumor types were included, the study population appeared to be homogeneous in terms of survival benefit and prognostic factors, and it probably represented the selection of biologically favorable tumors in which histology, size, number, and laterality are of minor importance. We conclude that patients who are persistently free of disease at the primary location but who have recurrent, resectable metastatic disease of the lung are likely to benefit from operation a second, third, or even fourth time.
Fetch PMID: 9564899


Eur J Cardiothorac Surg 1997 Nov;12(5):703-5
Survival after surgical treatment of recurrent pulmonary metastases.
Groeger AM, Kandioler D, Mueller MR, End A, Eckersberger F, Wolner E.
Department of Cardio-Thoracic Surgery, University of Vienna, Austria.

...Resection of lung metastases is a generally accepted therapeutic strategy today. This retrospective study was performed in order to estimate the value of an aggressive surgical approach in recurrent metastatic disease of the lung. ... The survival rates of 42 patients undergoing repeated resectional treatment for recurrent lung metastases (group A) were compared to the outcome of a total of 288 patients after a single surgical intervention for lung metastases (group B). Survival rates and the relative effects of the various prognostic factors were calculated according to Kaplan-Maier and Mantel Cox or Wilcoxon test. Histology of the primary tumors in group A consisted of 18 carcinomas, 22 sarcomas and two melanomas, in group B the distribution was 64% carcinoma, 27% sarcoma and 9% melanoma. The mean follow-up period was 88.5 months for group A and 27 months for group B.... The overall survival rate for group A was 48% at 5 years and 30% at 10 years, the survival rate for group B was 34% at 5 years. ... Long-term survival rates superior to those after single resectional treatment for lung metastases encourage an aggressive surgical approach for this disease.
Fetch PMID: 9458139


Am J Respir Crit Care Med 1994 Feb;149(2 Pt 1):469-76
Surgical resection of pulmonary metastases. Up to what number?
Girard P, Baldeyrou P, Le Chevalier T, Lemoine G, Tremblay C, Spielmann M, Grunenwald D. Department of Thoracic Surgery, Centre Medico-Chirurgical de la Porte de Choisy, Paris, France.

Specific results on the surgical resection of a large number of pulmonary metastases (PM) are currently unavailable, and the risk-benefit ratio of this aggressive approach may appear questionable. A systematic review of the records of 456 adult patients who underwent thoracic surgery for PM between 1979 and 1990 led to the identification of 44 patients who underwent at least one resection of eight or more PM (range eight to 110), of whom 33 (75%) had PM from osteogenic or soft tissue sarcoma. These 44 patients underwent a total of 77 operations, of which 47 (61%) were bilateral and nine (12%) incomplete resections. The 3- and 5-yr probabilities of survival after the first resection of eight or more PM were 36 and 28%, respectively, and were not significantly different from those of the 412 other patients who underwent surgery for PM over the same period. In this small group of patients, only the quality of resection (complete or incomplete) was found to be a highly significant prognostic factor (p < 0.01). A critical analysis of the reported data supports the view that, at least in patients with osteogenic or soft tissue sarcoma, the prognostic value of the number of PM seems to be more dependent on associated resectability than on the number per se and that, after careful preoperative patient selection, PM that can be resected should be resected, whatever their number.
Fetch PMID: 8306048

Chemotherapy
Metastases & Chemotherapy

If the pulmonary metastases are operable, but there are other tumor deposits which are inoperable.....
Or if the pulmonary metastases are inoperable and not ablatable....
Then systemic chemotherapy might be the treatment of choice.


For further discussion of chemotherapy and chemotherapy agents, see the Chemotherapy Section of this website.

Pulmonary Metastases & Chemotherapy
Selected Medical Journal Annotated References



Gan To Kagaku Ryoho 1998 Sep;25(11):1701-6
[Chemotherapy for pulmonary metastases of soft tissue sarcoma]. [Article in Japanese]
Kito M, Umeda T.
Dept. of Orthopedic Surgery, National Cancer Center Hospital East.

The role and value of chemotherapy for soft tissue sarcomas remain unclear. Seventeen patients with pulmonary metastatic soft tissue sarcomas underwent treatment with chemotherapy, and the clinical efficacy and prognosis were studied. ... [3 patients had LMS] The chemotherapy agents were ifosfamide in 10 cases, combination of ifosfamide and adriamycin in 5 cases, or cisplatin and adriamycin in 2 cases. Of the 17 patients, seven had partial responses radiographically and five had pulmonary metastases from synovial sarcoma. Eight patients underwent resection of pulmonary metastases following chemotherapy.... Twelve of the patients died of disease at 6-108 months (median, 30 months) from the time of the initial therapy, and five patients have survived from 1-53 months (median, 30 months). The absolute three-year survival rate, ..., for all 17 patients was 39%. In the two cases with no change and progressive disease, all patients were dead within 2 years, while in the seven partial response cases, two patients were dead, four were alive with pulmonary metastases, and only one case was disease-free at this writing. The survival rate for patients with partial response was significantly higher than for patients with no response. Although the cure rate of pulmonary metastatic soft tissue sarcomas is still low, the combination of chemotherapy and surgery has been shown to result in prolonged survival.
Fetch PMID: 9757195

J Surg Oncol 1993 May;53(1):54-9
Selected benefits of thoracotomy and chemotherapy for sarcoma metastatic to the lung.
Mentzer SJ, Antman KH, Attinger C, Shemin R, Corson JM, Sugarbaker DJ.
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115.

To determine the benefit of aggressive surgical therapy, we studied 77 consecutive patients presenting to our sarcoma registry with pulmonary metastases. Detailed follow-up was available on all patients; the median follow-up of the 13 long-term survivors was 72 months from the date of diagnosis of the primary tumor. Survival of these 77 patients with metastatic disease was independent of the size, location, and histology of the primary tumor. Once metastases developed, survival of patients with pulmonary metastases was not influenced by the extent of surgical resection of the primary tumor or by the use of radiation therapy.

Pulmonary metastases were initially treated with thoracotomy and metastasectomy in 34 patients. The median survival after thoracotomy was 26 months. Seven patients were alive more than 4 years after their diagnosis. Pulmonary metastases were treated with chemotherapy alone in 43 patients. Although the survival was shorter (median survival 14 months) in patients treated with chemotherapy, an objective response to chemotherapy was obtained in 13 (30%) patients. Four of these patients were alive 4 years after their diagnosis. These data demonstrate that both thoracotomy and chemotherapy are associated with long-term survival of patients with sarcoma metastatic to the lung.

Fetch PMID: 8479198

Chemoembolization

Embolization or chemoembolization could be of use for unresectable lung metastases. Also, this regional therapy may offer new hope for those sarcoma patients who have lung metastases resistant to combination systemic chemotherapy, either for downgrading of tumors prior to surgical resection, or for palliation. Embolization or chemoembolization is not curative by itself, and additional therapy is required to eradicate residual disease.

Blood is delivered to tumors by means of arteries. Anticancer drugs mixed with some 'embolic' particles such as polyvinyl alcohol and gelatin powder can be injected selectively in the arteries that feed tumors. This causes clotting in those arteries, and infarcts tumors [kills tumor cells by removing their blood supply]. Additionally the anticancer drugs work on the tumor. Their work is enhanced by their not being quickly washed away by the blood circulation [which has been clotted or slowed]. Radio-opaque contrast media can also be present in the mixture, and the progress of the mixture monitored radiologically.

Chemoembolization causes massive shrinkage due to ischemia [loss of blood supply], and increases the local drug intensity and drug exposure.

The feeding artery is reached by advancing a catheter from the femoral or other artery. The catheter can be advanced into the artery that feeds the majority of the tumor blood supply, and the embolization material is injected, followed by the chemotherapy regimen previously decided upon, until the feeder artery no longer transports liquid.

Side Effects and Complications are the obvious ones: local trauma, artery rupture, infection, abscess, reaction to the injected materials, the side effects due to the injected materials, fever, pain, misdirected drainage of the injected material resulting in damage to other structures.

For more information, Search Pubmed for lung metastases and chemoembolization


Annotated Medical Journal Articles


J Surg Res. 2002 Oct;107(2):159-66.
Temporary unilateral microembolization of the lung-a new approach to regional chemotherapy for pulmonary metastases.
Schneider P, Foitzik T, Pohlen U, Golder W, Buhr HJ.
Department of Surgery, University Hospital Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30, Germany.

BACKGROUND: Except in patients with resectable disease, treatment of pulmonary metastases is still disappointing. Regional chemotherapy may be a suitable method for delivering more effective doses to regionally confined tumors while minimizing systemic toxicity. We propose an unilateral chemoembolization of the lung applicable by endovascular method.
MATERIALS AND METHODS: An unilateral microembolization of the lung with degradable starch microspheres (DSM) alone (group 1) and combined with carboplatin (group 2) was performed on Sprague-Dawley rats (n = 12). Microcirculatory parameters were studied by in vivo videomicroscopy and radiological pattern on pulmonary angiogram.
RESULTS: After injection of DSM,... [there was] neither altered permeability nor pulmonary edema. Pulmonary angiogram confirmed patency of the central pulmonary artery.
CONCLUSION: For the first time unilateral microembolization of the lung could be established in an experimental model. By injection of DSM, reversible embolization on arteriolar and capillary level could be demonstrated without occlusion of the main branches of the pulmonary arteries. Alveolar-capillary membrane disorder as symptom of early toxicity could not be detected even with additional application of carboplatin.
Fetch PMID: 12429171


Clin Cancer Res. 2002 Jul;8(7):2463-8.
Chemoembolization of the lung improves tumor control in a rat model.
Schneider P, Kampfer S, Loddenkemper C, Foitzik T, Buhr HJ.
Department of Surgery, Benjamin Franklin Medical Center, Freie Universitat Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany.

PURPOSE: The novel method of organ-specific drug application we present here is unilateral chemoembolization of the lung by injecting the pulmonary artery with degradable starch microspheres and cytotoxic drugs to improve tumor control in lung metastases.
EXPERIMENTAL DESIGN: In a solitary metastasis rat model (CC531 adenocarcinoma), we studied the clinical and histological tumor response as well as subacute toxicity of the lung. Fourteen days after tumor induction, animals were randomized into five groups. Groups I and II served as controls. Group III received carboplatin i.v. (45 mg/kg). Isolated lung perfusion with buffered starch solution and carboplatin (15 mg/kg) was installed in group IV. Chemoembolization with carboplatin (15 mg/kg) was performed in group V.
RESULTS: Seven days later, the difference in the tumor volume before and after treatment was +422 mm(3) (+/-226) in group I, +697 mm(3) (+/-423) in group II, +70 mm(3) (+/-31) in group III, -8 mm(3) (+/-17) in group IV, and -17 mm(3) (+/-16) in group V (P < 0.05 groups IV and V versus groups I, II, and III). No pleural spread was observed in groups IV and V. Histologically, the area of tumor necrosis was largest in group IV. Mild alveolar cell hyperplasia, pulmonary edema, and hemorrhage without subacute fibrotic changes were noted in all groups. CONCLUSION: This is the first study to perform chemoembolization of the lung. Compared with i.v. therapy, chemoembolization was more effective without serious toxicity. Its efficacy was comparable with that of isolated lung perfusion but less stressful for a possible clinical application.
Fetch PMID: 12114454


Cancer. 1984 Dec 1;54(11 Suppl):2751-65.
Infusion-embolization.
Wallace S, Charnsangavej C, Carrasco CH, Bechtel W.

Transcatheter intra-arterial therapy for the cancer patient encompasses infusion of chemotherapy and embolization. Intra-arterial infusion of chemotherapeutic agents has been resurrected because of the availability of new drugs, combinations of drugs, and the capability of percutaneous selective catheter placement. Intra-arterial infusion has been effective in patients with carcinomas of the liver, bladder, prostate, uterus, ovary, and lung and in bone and soft tissue sarcomas, melanomas, and tumors of the brain. Embolization of the arterial supply, creating ischemia of the neoplasm, has been employed in the therapeutic management of patients with primary and secondary neoplasms of the liver, kidney, and bone. The median survival of 100 patients with neoplasms of the liver from the time of hepatic artery embolization was 11.5 months. In 100 patients with pulmonary metastases from carcinoma of the kidney, 28 experienced a response to renal artery embolization, a therapeutic delay of 4 to 7 days, nephrectomy, and Depo-Provera (medroxyprogesterone). Seven of 12 patients with giant cell tumor of the pelvis and lumbar spine responded to arterial embolization after all other therapy failed. Chemoembolization, the combination of arterial infusion of chemotherapy and embolization, can be accomplished by the use of microencapsulated agents, liposomes, and particulate emboli with drugs. This approach integrates the advantages of infusion and occlusion, and has considerable potential. Intra-arterial immunotherapy has been initiated with bacillus Calmette-Guerin (BCG) administration into renal neoplasms in patients with metastatic disease.
Fetch PMID: 6093984
Isolated Lung Perfusion

Unquestionable indications are for Surgical Resection For non-resectable lung metastases other treatments must be explored [RFA, conventional chemotherapy, and so on.]. Where conventional systemic chemotherapy is chosen, but is ineffective, there are alternative methods of delivering the chemotherapy agent that maximizes tumor exposure.

Chemoembolisation can provide the tumor with high drug concentrations without provoking systemic side effects. These procedures do not prevent the appearance of extra-regional recurrence or metastases.

Isolated lung perfusion is a regional treatment technique that delivers high dose chemotherapy, biologic agents, and hyperthermia via a completely isolated vascular recirculating perfusion circuit as a means of regionally treating tumors. . The chemotherapy and other agent[s] are injected into the lung circulation, but do NOT get into the rest of the body's circulation. The lung's blood circulation is ISOLATED from the rest of the body. After perfusing the lung for an hour with the high concentration chemotherapy agent[s], the lung is given a 'washout' and then reconnected to the systemic circulation. This allows higher concentration of toxic chemicals to be given to the lung, and spares the rest of the body the side effects.

Search Pubmed for Isolated Lung Perfusion


Pulmonary Metastases & Isolated Lung Perfusion
Selected Medical Journal Annotated References



Anticancer Res 1998 Sep-Oct;18(5D):3899-905
TNF alpha in isolated perfusion systems: success in the limb, developments for the liver credits, debits and future perspectives.
Eggermont AM.
University Hospital Rotterdam, Daniel den Hoed Cancer Center, The Netherlands. eggermont@chih.azr.nl

The clinical applicability of Tumor Necrosis Factor-a pi (TNF) is under renewed investigation because of its successful use in the isolated limb perfusion in patients with irresectable soft tissue extremity sarcomas. The high response rate of > 80% with a similarly successful limb salvage rate in this patient population has led to the submission of TNF for registration for this indication in Europe. Similarly, the agent has been shown to be successful in the isolated limb perfusion setting for tumors other than sarcomas, e.g. melanoma, carcinomas. This has caused renewed interest in TNF alpha and in its application in isolated organ perfusions, such as isolated hepatic perfusion. At the Rotterdam Cancer Center a preclinical-clinical interactive development program has been established dedicated to isolated limb, kidney, liver and lung perfusions and the application of new drugs such as TNF and TNF-mutants in these systems. Moreover a program dedicated to reduce the magnitude of surgical procedures by using occlusion balloon catheters is investigating the techniques and pharmacokinetics of procedures such as balloon catheter mediated hypoxic pelvic perfusions (HPP) and isolated hypoxic hepatic perfusions (IHHP). Here we present an overview of these developments. Publication Types: Review Review, tutorial
Fetch PMID: 9854502


J Thorac Cardiovasc Surg 1995 Aug;110(2):368-73
Lung perfusion with chemotherapy in patients with unresectable metastatic sarcoma to the lung or diffuse bronchioloalveolar carcinoma.
Johnston MR, Minchen RF, Dawson CA.
Division of Thoracic Surgery, Mt. Sinai Hospital, Toronto, Canada.

Eight patients with metastatic sarcoma to the lung (n = 4) or diffuse bronchioloalveolar carcinoma of the lung (n = 4) underwent isolated lung perfusion with chemotherapy in a pilot study. Ages ranged from 18 to 60 years and half were female. The left lung was perfused in three patients (single lung perfusion) and both lungs in five patients (total lung perfusion). Perfusions ranged from 45 to 60 minutes at ambient or normothermic temperatures. One patient received perfusion at moderate hyperthermia (40 degrees C). Escalating doses of doxorubicin (1 to 10 micrograms/ml perfusate) was used in six patients, whereas two received cisplatin (14 and 20 micrograms/ml perfusate). There were two major complications and no objective responses. The isolated perfusion systems gave excellent separation between systemic and pulmonary circulations with zero to 15% of the measured peak drug concentration of the pulmonary perfusate detected in the systemic circulation. `Drug concentrations in normal lung and tumor generally increased with higher drug dosages and drug was detectable in mediastinal lymph nodes of three out of four patients in whom sampling was done. Isolated lung perfusion with chemotherapy can be done safely in patients with lung malignancies and evidence suggests that higher drug dosages should be well tolerated. Publication Types: Clinical trial
Fetch PMID: 7637354


Verh K Acad Geneeskd Belg 1999;61(4):517-50
Isolated lung perfusion for the treatment of pulmonary metastases an experimental study in the rat.
Van Schil P, Hendriks J. Department of Surgery, University Hospital of Antwerp, Edegem.

The lung is a common site of metastatic involvement and 5-year survival rates after complete surgical resection of lung metastases vary between 16 and 42%. As isolated limb or liver perfusion, isolated lung perfusion offers a new therapeutic option to deliver high-dose chemotherapy with minimal systemic side-effects ..... Clinical studies are necessary to determine its effect on pulmonary metastases in man, especially in case of unresectable disease or possibly as adjuvant therapy after surgical resection.
Fetch PMID: 10500475


Cancer 1993 May 15;71(10):2962-70
In situ lung perfusion with cisplatin. An experimental study. [ed. in PIGS.]
Ratto GB, Esposito M, Leprini A, Civalleri D, De Cian F, Vannozzi MO, Romano P, Canepa M, Zaccheo D. Department of Patologia Chirurgica, University of Genoa, Italy.

....This study provides the pharmacokinetic rationale for the application of lung perfusion to patients with pulmonary metastases.
Fetch PMID: 8490824


J Surg Res 1991 Feb;50(2):124-8
Pharmacokinetics and toxicity of isolated perfusion of lung with doxorubicin.
Baciewicz FA Jr, Arredondo M, Chaudhuri B, Crist KA, Basilius D, Bandyopadhyah S, Thomford NR, Chaudhuri PK.
Department of Surgery, Medical College of Ohio, Toledo 43699-0008.

The treatment of pulmonary metastases from soft tissue sarcomas with chemotherapy has an overall response rate of less than 30%, and the majority of these responses are short lived. It is postulated that increased drug delivery to the pulmonary metastases may improve the outcome of these patients. An isolated perfusion system would have the ability of delivering increased levels of drug to target tissue without the systemic toxic effect of the drug. The purpose of this study was to establish the pharmacokinetics of doxorubicin delivery, lung toxicity, and the ideal dose for clinical application in an in vivo isolated perfusion model. Our results suggest that normothermic isolated perfusion of the lung with doxorubicin using a dose level up to 6 micrograms/ml in the perfusate can be accomplished without histologic lung injury, systemic toxicity, or adverse clinical outcome. Perfusate concentration of greater than 7 micrograms/ml caused significant histologic injury and adverse clinical outcome without systemic toxicity. The technique may be utilized in selective settings to improve treatment in mesenchymal tumors metastatic to the lung.
Fetch PMID: 1990216

Radiotherapy
Radiotherapy and Lung Metastases

We have seen radiotherapy used with really large pulmonary tumors. Radiation was then used along with a sensitizing chemotherapy agent like gemcitabine, to downsize the tumor so it would be operable.

We have also seen very focal radiation, proton beam irradiation, used to treat a tumor recurrent from a previous RFA procedure, while the person was being irradiated for an inoperable tumor in the collar/neck area.

However, generally radiation therapy is not used on lung tissue because of the problems from the irradiation, as well as there being no proven benefit in LMS for adjuvant radiotherapy.

Search Pubmed for Radiotherapy and Sarcoma Pulmonary Metastases


Eur J Cardiothorac Surg. 1999 Apr;15(4):456-60.
Surgical treatment of primary pulmonary sarcomas.
Bacha EA, Wright CD, Grillo HC, Wain JC, Moncure A, Keel SB, Donahue DM, Mathisen DJ.
Thoracic Surgical Unit, Massachusetts General Hospital, Boston 02114, USA.

OBJECTIVE: We sought to identify the long-term prognosis after surgical treatment for primary pulmonary sarcoma.
METHODS: Twenty-three patients were retrospectively identified as having been treated surgically for primary pulmonary sarcoma between 1981 and 1996. The records of all patients were reviewed, and the histopathology reexamined by a pathologist.
RESULTS: Fifteen patients were male and eight female; their ages ranged from 20 to 78 (mean 51) years. Tumors measured between 0.9 and 12.0 (mean 5.2) cm across the greatest diameter. The histologic diagnoses were malignant fibrous histiocytoma (8, three grade 1 or 2, two grade 3), synovial sarcoma (4), malignant schwannoma (3), leiomyosarcoma (3), and one case each of angiosarcoma, intimal sarcoma, epitheloid hemangioendothelioma, fibrosarcoma and primitive neuroectodermal tumor. Three patients were found to be unresectable. All three underwent radiation and chemotherapy. Lobectomies or bilobectomies were performed in 13 patients including two sleeve resections, one carinal resection, and one chest wall resection. Four patients underwent radical pneumonectomies. Three patients with invasion of the pulmonary artery, pulmonary veins or atrial wall underwent extended resections with the use of cardiopulmonary bypass. In two, a homograft was used to reconstruct the right ventricular outflow tract. Of the resected patients, six had a positive resection margin, and four had at least one positive lymph node in the specimen. Three patients underwent repeat pulmonary resections for recurrences. Eleven patients received postoperative chemotherapy and eight had radiation therapy. Follow-up was available on 22 patients, and ranged from 2 to 183 (mean 48) months; 14 patients are disease free, six died of disease, one died of surgical complications (operative mortality 5%), and two are alive with disease. Actuarial 3- and 5-year survival of the resected patients was 69%. Size and grade were not found to be correlated with significantly increased survival, but completeness of resection was (P<0.05).
CONCLUSIONS: Resection of primary pulmonary sarcomas can produce an acceptable survival rate if the resection is complete. Cardiopulmonary bypass can be a useful adjunct when tumors involve a resectable area of the heart or great vessels.
Fetch PMID: 10371121

Cryotherapy

For more information on cryotherapy itself,
see About Cryotherapy
and Cryo FAQs
Search Pubmed for Cryoablation and Lung Metastases for the latest information.


Annotated Medical Journal Abstracts


Zhonghua Wai Ke Za Zhi. 1995 Oct;33(10):639-40.
[Cryosurgical resection of pulmonary metastases (experience of twenty years)] [Article in Chinese]
Xiang J, Xie D, Qiu J.
Cancer Hospital, Shanghai Medical University.

Cryosurgical resection of pulmonary metastases was performed in 112 patients from 1973 to 1993. The cumulative 1, 3, 5, 10 year survival rate was 80.37%, 41.81%, 28.01% and 17.28%. One patient died of respiratory failure after operation. Thirty-day mortality rate was 0.89%. The disease-free interval (DFI) between the control of primary tumor and appearance of metastases was significantly correlated with post-thoracotomy survival. The multiple factor analysis also demonstrated that DFI was the most important prognostic factor for patients after cryosurgical resection of pulmonary metastatic lesions. The overall 5 year survival rate of patients treated with cryosurgery in our report was higher than that of those treated by local resection of pulmonary metastases reported by other authors. Our results indicated that cryosurgical resection of pulmonary metastases was effective and safe, the survival time of most patients could be prolonged and some patients could be cured.
Fetch PMID: 8731905


Minerva Med 1986 Nov 30;77(45-46):2159-62
[Cryotherapeutic destruction of invasive tracheo-bronchial tumors. Personal case histories]. [Article in Italian]
Astesiano A, Aversa S, Ciotta D, Galietti F, Gandolfi G, Giorgis GE, Oliaro A, Scappaticci E, Pepino E.

Data are presented on 15 cases of invasive tracheobronchial tumours subjected to cryotherapy in 1984-85. The technique is indicated in patients who cannot be given surgical or radiation treatment ad in cases of asphyxial syndrome requiring faster deobstruction than is obtainable with radiation treatment.
Fetch PMID: 3025779


Cancer. 1994 Aug 15;74(4):1253-60.
Conservative surgery for giant cell tumors of the sacrum. The role of cryosurgery as a supplement to curettage and partial excision.
Marcove RC, Sheth DS, Brien EW, Huvos AG, Healey JH.
Orthopaedic Surgery Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.

BACKGROUND. Giant cell tumors (GCTs) of the sacrum are a difficult clinical problem. Wide excision (total sacrectomy) is associated with high morbidity and pelvic/spinal instability. Curettage with or without supplemental radiotherapy is associated with a high recurrence rate. In view of the proven effectiveness of cryosurgery as an adjunct to curettage for extremity GCT, cryosurgery was used for treatment of GCTs of the sacrum.
METHODS. Seven patients with GCTs of the sacrum were treated at our institution by conservative surgery from 1973 to 1992. Four patients presented with recurrent tumors after failing previous radiation treatment (dose, 5040 cGy). Four patients were treated with curettage with cryosurgery and three with limited excision with cryosurgery. In the latter procedure after limited excision of the caudal (below S2) part of the tumor, the upper sacral segments were treated with curettage and cryosurgery. This spared the important upper sacral roots and maintained the skeletal integrity.
RESULTS. At a median follow-up of 12.25 years (range, 2-14.2 years), all patients were disease free. Local recurrence developed in two patients. Both of these underwent repeat curettage and cryosurgery and have since remained disease free. Two patients had positive second look biopsy with microscopic tumor. Both of these were treated with repeat cryosurgery and have remained disease free. Two patient who developed solitary pulmonary metastases, underwent wedge resection and are alive without disease. No patient suffered neurologic deterioration.
CONCLUSION. Conservative surgery (curettage or partial excision) with adjunct of cryosurgery is our preferred technique for the treatment of GCT of the sacrum. Satisfactory local control could be obtained by close observation, second look biopsy and repeat cryosurgery. The chief advantages of this method include preservation of pelvic and spinal continuity, speed and ease of surgical procedure and less potential blood loss. We recommend it over more radical sacrectomy due to low morbidity and less resultant neurologic deficits.
Fetch PMID: 8055446


Eksp Onkol. 1984;6(3):55-7.
[Effect of cryodestruction of Lewis lung carcinoma in mice on the development of metastases] [Article in Russian]
Mosienko VS, Kuz'menko AP, Rikberg AB, Trushina VA.

The effect of the primary tumour cryodestruction on a degree of metastatic spreading in the lungs was investigated in experiments with C57B1/6 mice with Lewis carcinoma of the lungs. It is found that after the tumour cryosurgery there was a less quantity of metastases as compared with operated animals (surgical removal of the tumour or amputation of the limb with the tumour) or with untreated animals. A regular correlation is observed between the degree of metastatic spreading and the efficiency of the primary tumour treatment. The relapse after cryosurgery or surgical removal of the tumour led to an increase in the quantity of pulmonary metastases.
Fetch PMID: 6499741


Schweiz Med Wochenschr. 1981 Sep 5;111(36):1303-6.
[Current state of surgery in the treatment of lung metastases][Article in German]
Metzger U, Uhlschmid G, Largiader F.

64 resections and 51 instances of cryosurgical treatment in 102 patients with pulmonary metastases are reported. Under clearly established conditions, parenchyma-saving resection is often the only curative treatment for pulmonary metastases. Survival rates are 72% after one year and 35% after 5 years. Resection is also indicated after a short interval between the treatment of the primary tumor and onset of lung secondaries. Prognostic factors are histology of the primary tumor and progress of pulmonary metastases, measurable by tumor doubling time and the onset of new secondaries during a given short time interval. Cryosurgery for multiple metastases or local inoperable tumor has a one-year survival rate of 48% and a 5-year survival rate of 26%. While systemic therapy will change the role of surgery, its importance will increase as a factor in combined treatment modalities.
Fetch PMID: 7302532


Schweiz Rundsch Med Prax. 1980 Dec 16;69(50):1865-71.
[Pulmonary metastases in adults, what can be done? (author's transl)] [Article in German]
Geroulanos S, Pouliadis G, Aberle HG, Metzger U, Uhlschmid G, Largiader F, Martz G, Hahnloser P, Schwarz H.
Fetch PMID: 7196581


Cryobiology. 1979 Apr;16(2):171-8.
Cryosurgery of pulmonary metastases.
Uhlschmid G, Kolb E, Largiader F.
Fetch PMID: 477364


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