Liver and Lung mets

[beach sunrise]

Laser Ablation
Since 1996, Alex Rolle, MD, Chief of Thoracic and Vascular Surgery in Coswig/Dresden, Germany has been performing aggressive laser ablations of lung metastases. He has removed an average of 10 nodules apiece from 328 patients, using laser ablation (with a 1318 nm Nd:YAG laser). In 93% of cases, a precision laser resection was achieved. Five-year survival after complete resection was 55 percent for solitary nodules, 41 percent for all patients, 28 percent for those having 10 metastases, and 26 percent for those who had 20 or more metastases resected. Outcome was much poorer after incomplete resection (7 percent). No 30-day mortality was observed. Major postoperative complications included prolonged air leaks (2 cases), intrapleural bleeding (2 cases), and late pneumothorax (2 cases); all of these were treated successfully with a chest tube.

(Rolle A, Pereszlenyi A, Koch R, Richard M, Baier B. Is surgery for multiple lung metastases reasonable? A total of 328 consecutive patients with multiple-laser metastasectomies with a new 1318-nm Nd:YAG laser. J. Thorac. Cardiovasc. Surg. 2006;131:1236-1242; Rolle A, Pereszlenyi A, Koch R, Bis B, Baier B. Laser resection technique and results of multiple lung metastasectomies using a new 1,318 nm Nd:YAG laser system. Lasers Surg Med. 2006;38:26-32; Rolle A, Koch R, Alpard SK, Zwischenberger JB. Lobe-sparing resection of multiple pulmonary metastases with a new 1318-nm Nd:YAG laser–first 100 patients. Ann. Thorac. Surg. 2002;74:865-869)
Like other surgeons, before proceeding, Rolle requires that the lung be the only site of active cancer at the time of treatment.

(Venuta F, Rolle A, Anile M, et al. Techniques used in lung metastasectomy. J Thorac Oncol. 2010;5:S145-150)
These reports are excellent and might even justify a trip to Germany to obtain this treatment, if you cannot get it in your home country. We’ve had clients go there when no one else would treat them in the United States and they felt they had great success. Although his Web site is only in German, he speaks English and American patients have gone there successfully.

(Rolle A, Koch R, Alpard SK, et al. Lobe-sparing resection of multiple pulmonary metastases with a new 1318-nm Nd:YAG laser–first 100 patients. Ann Thorac Surg. 2002;74:865-869; Rolle A, Koch R, Alpard SK, et al. Lobe-sparing resection of multiple pulmonary metastases with a new 1318-nm Nd:YAG laser–first 100 patients. Ann Thorac Surg. 2002;74:865-869; 1Wang D, Xu Z, Yu H, et al. Treatment of metastatic breast cancer by combination of chemotherapy and photothermal ablation using doxorubicin-loaded DNA wrapped gold nanorods. Biomaterials. 2014;35(29):8374-8384. doi:10.1016/j.biomaterials.2014.05.094)
Cyberknife for Lung Metastases
In patients for whom RFA, laser-induced thermoablation or stereotactic radiotherapy are impossible, due to their invasiveness, an image-guided, highly selective, robot-based radiotherapy could be effective. With this technique, we are told, “metastases may be treated in an outpatient single-treatment setting.”

(Rentsch M, Winter H, Bruns CJ, et al. [Cyberknife surgery with a radio-scalpel: a new treatment option for patients with unresectable metastases]. Zentralbl Chir. 2010;135:175-180; Snider JW, Oermann EK, Chen V, et al. CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Single Peripheral Lung Metastases. Frontiers in oncology. 2012;2:63)
Image-Guided Percutaneous Tumor Ablation
Image-guided ablation is a technique that uses ultrasound to guide a needle-like probe through the skin (‘percutaneously’) and into a tumor. Once in place, the probe can be used to deliver either thermal energy or cytotoxic agents directly into the tumor. When ethanol (alcohol) is used as the toxic agent this is called percutaneous ethanol injection (PEI). Heat-based tumor ablation can be delivered using one of several heat sources: radio waves (as in radiofrequency ablation (RFA), which is otherwise known as RITA, or radiofrequency interstitial tumor ablation), microwaves, laser or ultrasound, to name just the most familiar techniques.

(Lin S. Recent advances in radiofrequency ablation in the treatment of hepatocellular carcinoma and metastatic liver cancers. Chang Gung Med J. 2009;32:22-32; Carrafiello G, Mangini M, Fontana F, et al. Radiofrequency ablation for single lung tumours not suitable for surgery: seven years’ experience. La Radiologia medica. 2012)
Radiofrequency Ablation (RFA)
Percutaneous radiofrequency ablation (RFA) is a relatively new and important FDA-approved technique for destroying liver tumors, liver metastases, lung metastases, solid renal (kidney) masses, adrenal tumors, as well as other forms of cancer. It has a great deal of promise, although there are restrictions on who can be a candidate for this treatment.

(Lin S. Recent advances in radiofrequency ablation in the treatment of hepatocellular carcinoma and metastatic liver cancers. Chang Gung Med J. 2009;32:22-32; Giorgio A. Percutaneous radiofrequency ablation of hepatocellular carcinoma on cirrhosis: state of the art and future perspectives. Recent Pat Anticancer Drug Discov. 2010;5:69-76; Iannuccilli JD, Dupuy DE, Mayo-Smith WW. Solid renal masses: effectiveness and safety of image-guided percutaneous radiofrequency ablation. Abdom Imaging. 2012;37(4):647–658; Mayo-Smith WW, Dupuy DE. Adrenal neoplasms: CT-guided radiofrequency ablation–preliminary results. Radiology. 2004;231(1):225–230)
RFA is described as an image-guided minimally invasive strategy for the treatment of focal malignant disease.

(Dupuy DE, Goldberg SN. Image-guided radiofrequency tumor ablation: challenges and opportunities—part II. J Vasc Intervent Radiol. 2001;12:1135-1148)
A 2010 review from Massachusetts General Hospital, Boston, calls it a “promising” modality.

(Flanders VL, Gervais DA. Ablation of liver metastases: current status. J Vasc Interv Radiol. 2010;21(8 Suppl):S214-222)
RFA uses electromagnetic radio waves in the 10 kHz to 2.59 GHz range to heat tumors to at least 100 degrees Celsius (= 212º Fahrenheit); at this temperature tumor cells are essentially melted away. Most doctors will not consider using RFA in patients who have active cancer anywhere else in the body in addition to the liver. But by using RFA, doctors are able to destroy accessible tumors in a minimally invasive way, without surgery. Some surgeons prefer to do this procedure using what is called an open approach. This is accomplished through a small incision in the abdominal wall, since it allows the doctors to visually inspect the liver and the abdominal cavity, at which time the presence of any extra-hepatic disease (i.e., outside the liver) can then be double-checked.

RFA is very useful in selected cases such as those in which there is a solitary tumor that is not amenable to surgical resection. Clinical experience has shown that local tumor control can be achieved in 85 to 90 percent of cases provided the tumor is solitary and no larger than 2.5 centimeters (i.e., 1 inch). Indeed, RFA is now being used in the treatment of a variety of cancers including early lung cancer, breast cancer (in support of lumpectomy) and extensive bone metastases. In the latter role it has shown itself extremely effective in reducing both the size of some bone lesions and the pain they cause.

In 2009, Japanese scientists compared RFA vs. a microwave technique known as percutaneous microwave coagulation therapy (PMCT). They found both techniques equally effective in destroying tumors in the liver. RFA had the advantage, however, of requiring fewer treatment sessions. Both RFA and PMCT were found in this study to have major complications in relatively few cases.

(Ohmoto K, Yoshioka N, Tomiyama Y, et al. Comparison of therapeutic effects between radiofrequency ablation and percutaneous microwave coagulation therapy for small hepatocellular carcinomas. J. Gastroenterol. Hepatol. 2009;24:223-227; Shibata T, Iimuro Y, Yamamoto Y, et al. Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy. Radiology. 2002;223:331-337)
It is my belief that RFA is a very useful technique that is presently underutilized as a substitute for open surgery in many situations.

A 2011 evidence-based practice review of pulmonary RFA from Ireland calls RFA “a promising treatment for pulmonary malignancy in carefully selected patient populations.”

(Chan VO, McDermott S, Malone DE, Dodd JD. Percutaneous radiofrequency ablation of lung tumors: Evaluation of the literature using evidence-based techniques. J Thorac Imaging. 2011;26:18-26)
RFA and Lung Cancer
In 2008 the results of a large Italian study on the RFA of lung metastases were published in Lancet Oncology. This was arguably the largest and more rigorous study of the topic done so far. It consisted of a series of 106 patients with 183 lung tumors that were 3.5 centimeter (cm) in diameter or smaller. Patients were enrolled in a prospective, intention-to-treat, single-arm, multicentre clinical trial from seven centers in Europe, the US, and Australia. Every tumor was confirmed as malignant through biopsy prior to start of treatment.

Completion of therapy was achieved in 99 percent of patients; correct placement of the probe could not be achieved in only one small tumor. The major findings were as follows:

There were no treatment-related deaths.
Eighty-eight (88) percent of patients achieved a complete disappearance of cancer at the site of the RFA, and this lasted for at least one year.
Overall survival at one year was 70 percent, 89 percent, and 92 percent, respectively, for patients with non-small cell lung cancer (NSCLC), patients with lung metastases from colorectal cancer, and those with metastases from other sites.
Overall survival at two years was 48 percent, 66 percent, and 64 percent, respectively, for patients with NSCLC, those with lung metastases from colorectal cancer, and those with metastases from other sites.
Only 8 percent of patients diagnosed with Stage I NSCLC (stage at which the cancer has not spread outside the lung) died from their cancer at two years.
(Lencioni R, Crocetti L, Cioni R, et al. Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE Study) Lancet Oncology. 2008;9:621-628)
In an earlier study at John Wayne Cancer Institute in California, 84 patients with a total of 231 tumors were treated with RFA. Eight percent of the patients suffered non-fatal complications ranging from third degree burns to liver abscesses and hemorrhage. In three cases, the complications were fatal. After a follow-up of 9 months, 18 percent of patients had developed recurrences.

(Wood TF, Rose DM, Chung M, et al. Radiofrequency ablation of 231 unresectable hepatic tumors: indications, limitations, and complications. Ann Surg Oncol. 2000;7:593-600)
The authors of this study explicitly stated their conclusions that they did not favor the use of RFA as an alternative to liver surgery, whose efficacy and safety are well established. Instead, they saw RFA as an adjunct to surgery, cryotherapy and/or hepatic artery infusion. But by using RFA in conjunction with cryotherapy they were able to significantly reduce the complications associated with cryotherapy alone. RFA is useful as a primary modality, they said, in cases where surgery is impossible (ibid.).

Needle Track Metastases
As a result, RFA should not be seen as a technique without complications or adverse (side) effects. There are indeed some negative effects and potential complications. One such is the development of metastatic tumors in the track, or path, of the RFA probe. In a Canadian study 8 patients out of 200 (4 percent) developed needle track metastases (i.e., metastatic cancer due to the ‘seeding’ of cancer cells into the path of the electrode probe that was inserted into the liver). The authors concluded:

“Neoplastic seeding may occur after RFA of liver tumors. The results show that the frequency of this complication is not insignificant, and are at the upper end of rates reported in the literature of 0.5 percent to 2.8 percent. Specific risk factors identified in this study include treatment of subcapsular lesions, patients treated in multiple sessions, and lesions requiring more than one electrode placement.”
(Jaskolka JD, Asch MR, Kachura JR, et al. Needle track seeding after radiofrequency ablation of hepatic tumors. J Vasc Interv Radiol. 2005;16(4):485-91; Liu SY, Lee K, Lai PB. Needle track seeding: a real hazard after percutaneous radiofrequency ablation for colorectal liver metastasis. World J Gastroenterol. 2009;15:1653-1655)
The results obtained with these methods are comparable to those obtained by surgery, i.e., up to 65 percent five-year survival in the most favorable cases (solitary lesions less than three centimeters—one and a half inches—in diameter). Indeed, some clinicians have claimed an 80-90 percent success rate using RFA to control small, solitary lesions.

(Gillams AR, Lees WR. Survival after percutaneous, image-guided, thermal ablation of hepatic metastases from colorectal cancer. Dis Colon Rectum. 2000;43:656-661)
To find a doctor who uses radiofrequency ablation (RFA) for liver metastases try contacting the Society of Interventional Radiology (SIR). Look at their website, www.sirweb.org, for many interesting articles and ideas. There is a directory of members, broken down by US state on their Web site (look for the “doctor finder”). I am sure that there are many excellent and capable interventional radiologists whose names are obtainable at this site. One of the challenges is to find interventional radiologists who are willing to “push the envelope” and use RFA for sites other than the liver (e.g., the breast and lungs). You may need to call around to find one.

Some leading clinicians who have been used by our readers are:

Damien Dupuy, MD, of the Division of Tumor Ablation of John Williams Hospital, Providence, Rhode Island;
David Nielson, MD, of San Antonio, Tx (for lung metastases);
Allan Siperstein, MD, at the Cleveland Clinic, Cleveland, OH;
Stephen Solomon, MD of Memorial Sloan-Kettering Cancer Center, NY; and
Professor Nagy A Habib ChM, Professor of Hepato-biliary Surgery at Hammersmith Hospital, London and Imperial College, London.
(See discussion of Alex Rolle, elsewhere on our site)

Liver Transplantation
This has been performed for some cases of primary liver cancer. It is not advisable for liver metastases, however, since metastatic tumor cells are usually spread throughout the body and will most likely recur and reseed the new liver as well as other organs. In some selected cases a surgical resection of liver metastases makes sense. This is generally when there are no more than three tumors, no sign of disease outside the liver, and at least a 10 millimeters margin of normal tissue that can be removed around the tumor itself. In other cases, cryosurgery may benefit patients who are not candidates for surgery. The use of either systemic or HAI chemotherapy will increase the chance of remission. But there is at present no proof that such treatments increase overall survival.

(Mendizabal M, Reddy KR. Current management of hepatocellular carcinoma. Med Clin North Am. 2009;93:885-900)
Pulmonary (Lung) Metastases

Since the entire output of the heart and the lymphatic system passes through the lungs, it stands to reason that blood-borne clusters (also called tumor emboli) of malignant cells can reach the lungs in large numbers; once they reach the lungs they can lodge in small capillaries and begin to grow and invade surrounding lung tissue. Indeed, metastasis to the lungs is a relatively common phenomenon: lungs are the second most common site for metastases to appear. Lung is the sole site of metastasis in about 20 percent of cases.

(Willis R. The spread of tumors in the human body. In: Pathology of Metastases. Boston: GK Hall, 1978;167-183).
It is estimated by Roswell Park that between 25 and 30 percent of all cancer patients develop lung metastases at some point, although these many only show up at autopsy. The rate is even higher for some specific kinds of cancer, such as sarcoma.

(Davidson RS, Nwogu CE, Brentjens MJ, and Anderson TM. The surgical management of pulmonary metastasis: current concept. Surg Oncol 2001;10:35–42)
Virtually any primary cancer can metastasize to the lungs. However, some forms of cancer do so preferentially, particularly those kinds of tumors that have rich venous drainage, such as melanomas, bone and other sarcomas and kidney cancers.

(Welter S, Grabellus F, Bauer S, et al. Growth patterns of lung metastases from sarcoma: prognostic and surgical implications from histology. Interactive cardiovascular and thoracic surgery. Virchow’s Arch. 2011 Aug;459:213-219)
Kidney cancers are particularly prone to migrate to the lungs. So do choriocarcinomas, which are rare cancers of the placenta. Bone cancers and germ cell cancers also show a predilection for metastasizing to the lungs.

Metastatic disease in the lungs usually takes the form of ‘nodules’, that is, multiple discrete spherical lesions scattered throughout the lung, arising from tumor clusters (emboli) that have lodged in the small blood vessels of the lung.

However, another form of metastatic lung lesion, lymphangitis carcinomatosis (LC), should also be mentioned, even though only around 7 percent of lung metastases are of this kind. This type of metastatic disease, sometimes also called interstitial metastatic disease, is different from the nodular form of metastasis in that it occurs within the lymphatic channels that drain the lung tissue, and quickly causes an obstruction of the lymphatic flow, resulting in an accumulation of fluid in the lung.

As a technical point, I should tell you that the types of cancer known as adenocarcinoma—that is, tumors arising from secreting or glandular tissue—are particularly prone to forming lymphangitis carcinomatosis (LC). Breast, stomach, pancreas and prostate cancers can also give rise to LC. In general, LC has a poorer prognosis (outlook) than nodular metastases.

(Donington, Jessica S. Metastatic cancer to lung. In: Chang AE, Ganz PA, Hayes DF, et al. Oncology: An Evidence-Based Approach. New York: Springer, 2006, p. 1626)
The first surgical resection of a pulmonary metastasis was performed in 1855. The first en bloc removal of a sarcoma with lung metastasis (by Weinlecher) occurred in 1882. But J. Alexander and C. Haight published the first series of pulmonary metastasectomies in 1946. They demonstrated 3-year survival in 24 patients who underwent resection of their metastatic lung lesions. This highly optimistic report stimulated interest in the surgical treatment of patients with pulmonary metastases and is considered the modern-day turning point for the field.

(Alexander J, Haight C. Pulmonary resection for solitary metastatic sarcomas and carcinomas. Univ Hosp Bull. 1946;12:117)
At one time, it was thought that treating lung metastases was futile. However, it is now widely believed that some patients can achieve prolonged survival through treatment of their lung metastases. As with other sites of metastatic spread, though, to address the metastases alone while ignoring the primary cancer elsewhere makes no sense therapeutically, although treatment of the metastases alone is often done for palliative purposes—that is, to make a patient more comfortable rather than in an attempt to prolong life.

If the primary cancer is one of those that tends to migrate to the lungs, physicians are usually on the lookout for chest symptoms and chest X rays are generally given every three to four months for the first two to three years after treatment.

Usually, lung metastases cause no symptoms in the early stages. Less than a quarter of patients are first seen with a cough, chest pain, sputum production, fever, etc. Such symptoms usually do not appear until late in the process and thus are generally not useful for diagnosis. Nor is bronchoscopy or sputum cytology (analysis of sputum under the microscope) useful in detecting lung metastases. For these reasons, X rays are still the standby for making an accurate diagnosis or following the course of the metastases.

Treatment of Lung Metastases
Depending on the sensitivity of the particular primary tumor to chemotherapy, systemic chemotherapy can prove useful in shrinking lung metastases with consequent improvement in symptoms. Primary tumors such as testicular cancer and choriocarcinoma tend to be much more chemosensitive than tumors such as prostate cancer. In general, though, while chemotherapy is used as a way of “mopping up” small clusters of cells after surgery, and radiation can palliate symptoms, surgery is still the main potentially curative treatment available to oncologists.

The lungs are the most common sites for metastases, after the regional lymph nodes and the liver. The first lung “metastasectomy” (i.e., surgical removal of metastases) was performed by the Viennese professor of surgery Josef Weinlechner, MD (1829-1906) in 1882.

(Weinlechner J. Tumoren an der Brust und deren Behandlung: Resektion der Rippen, Eröffnung der Brusthöhle, partielle Entfernung der Lunge. Wien Med Wochenschr 1882:20-21)
The first such US operation took place in 1934, on a patient who had a large lung metastasis from a primary in the kidney. He subsequently underwent removal of the kidney and lived 23 years, before dying of an unrelated cause. This well publicized case gave some impetus to the idea of operating on isolated metastases, especially in cases of metastatic kidney cancer. However, the procedure was slow to develop. For instance, from 1940 through 1965, only 25 such ‘metastasectomies’ were performed at Memorial Sloan-Kettering Cancer Center, NY.

(Barney J.D., Churchill E.J. Adenocarcinoma of the kidney with metastasis to the lung: cured by nephrectomy and lobectomy. J Urol. 1939;42:269-276; Rusch VW. Pulmonary metastasectomy: current indications. Chest. 1995;107:322S-31S)
While it has been shown in many retrospective reviews that the surgical removal of lung metastases can prolong survival, there are a number of major considerations that will decide whether or not a surgeon should in fact operate. First of all, has the primary tumor been completely and cleanly removed? It is believed that patients whose tumors have not been completely resected are unlikely to derive significant benefit from this further operation.

(Todd TR. Pulmonary metastectomy. Current indications for removing lung metastases. Chest. 1993;103:401S-403S)
Another consideration is the natural history of the tumor, i.e., whether or not it metastasizes primarily to the lung. Primary cancers such as kidney cancer are a good example. If you can remove the primary kidney tumor and if the lung metastasis is solitary (i.e., there is just one metastasis, isolated and in a surgically accessible position) you might actually “cure” the patient, or at least provide a meaningful extension in overall survival. On the other hand, if the primary cancer is one (such as breast cancer) that often has simultaneously metastasized to bone, removing the lung metastases makes little sense from the point of view of survival.

In colorectal cancer, the lungs are the second most common sites of metastatic disease. (The liver is the most common.) Lung metastases are in fact seen in about 10 to 20 percent of patients with colorectal cancer. In most of these cases, the lung metastases form part of a more disseminated disease process. However in about 10 percent of these cases (i.e., 2 to 4 percent of the total number of colorectal cancer patients) the lung metastases are of the isolated, nodular type, and are relatively slow-growing. Such metastases can often be successfully operated upon. The five-year survival rate following such surgery ranges from 13 to 42 percent.

The general health of the patient must also be considered, and this includes an assessment of whether he or she has what is called “cardiopulmonary reserve.” In other words, can patient’s heart and lungs stand the strain of such an operation.

There is another consideration: some kinds of cancer are considered highly responsive to chemotherapy, and some of them actually can be cured. In that case, chemotherapy will be used to knock out both what remains of the primary tumor and the various metastases. A good case in point is germ cell cancer. This type of cancer is one of the few that can often be truly cured (rather than “cured”, in the sense the word is used in oncology—i.e., to imply a prolonged remission rather than a real, permanent disappearance of the disease) through chemotherapy. It would be foolish to start operating on isolated lung metastases from a germ cell tumor before first trying chemotherapy.

To summarize, then, there are five main questions that must be asked to in order to establish who will be a good candidate for lung metastasis removal (metastasectomy):

Has the primary tumor been controlled? Is there any extrapulmonary (outside the lungs) disease that is still active?
Are the x-ray findings consistent with metastases (as opposed to a second primary lung tumor or another disease)?
Are there any metastases outside the lung itself?
Are the lung metastases surgically accessible and removable?
Can the patient withstand the rigors of the operation itself?
NOTE: Although about 30 percent of cancer patients develop lung metastases, only about a third of those meet the above five criteria. Thus, about one in ten cancer patients is actually a candidate for such surgery. Solitary lung metastases are uncommon: only about 2-10 percent of patients have solitary nodules.

In addition to pulmonary metastasectomy there are a number of new and evolving treatments for this condition. These include

Isolated lung perfusion;
Inhalation therapy;
Radiofrequency ablation;
Stereotactic radiosurgery; and
Laser therapy.
Isolated Lung Perfusion
This technique increases drug concentrations in the lung tissue and decreases systemic toxicity.

(Müller H, Guadagni S. Regional chemotherapy for carcinoma of the lung. Surg Oncol Clin N Am. 2008;17:895-917)
The evidence for the effectiveness of this procedure has been variable. There were five small publications between 1995 and 2000. None of them had more than 16 patients. Two of them showed a 0% response rate. The best results, in a total of 15 patients, was a combination of tumor necrosis factor (TNF) and interferon (a kind of immunotherapy). There was a 33 percent response rate but at the same time a 20 percent complication rate.

(Pass HI, Mew DJ, Kranda KC, Temeck BK, Donington JS, Rosenberg SA. Isolated lung perfusion with tumor necrosis factor for pulmonary metastases. Ann Thorac Surg. 1996;61:1609-1617)
Inhalation Therapy
This has been used most frequently in cases of lung metastases from kidney (renal cell) cancer. Inhaled interleukin-2 (IL-2) has been given in doses of 18 to 36 million IUs, either alone or in combination with other systemic therapies. The main toxicity was a dose-related cough. There was a decrease in the progression of such metastases. (Huland E, Heinzer H, Huland H, Yung R. Overview of interleukin-2 inhalation therapy. Cancer J Sci Am. 2000;6 Suppl 1:S104-112; Del Monte G, Ferroni P, Mariotti S, et al. Interleukin-2 inhalation therapy in renal cell cancer: a case report and review of the literature. In Vivo. 2008;22:481-488)

Radiofrequency Ablation
RFA is increasingly being used for pulmonary metastasectomy (removal of metastatic lesions from the lung) in patients who are not candidates for traditional surgical resection.

(Soga N, Yamakado K, Gohara H, et al. Percutaneous radiofrequency ablation for unresectable pulmonary metastases from renal cell carcinoma. BJU Int. 2009;104(6):790-794; Jungraithmayr W, Shafer O, Stoelben E, et al. Radiofrequency ablation of malignant lung tumours. Judicious approach? Chirurg. 2005;76:887-93; Schneider T, Reuss D, Warth A, et al. The efficacy of bipolar and multipolar radiofrequency ablation of lung neoplasms – results of an ablate and resect study. Eur J Cardiothorac Surg. 2010)
There are a few clinical trials to assess the efficacy of RFA in the treatment of lung metastases. In the US, however, choices are limited. Two leading American practitioners are David Nielson and Damian Dupuy (discussed elsewhere in our writings).

Stereotactic Radiosurgery
This is an intensive radiation schedule that was developed originally for brain tumors. It is still considered a novel approach to the treatment of lung metastases, however. Treatment uses a 6-Me LIAC (i.e., a 6 megavolt linear accelerator) on a robotic arm. There was a phase I study of this technique at Stanford University Medical Center on patients who were not candidates for surgical resection. Twenty-five percent had stable disease, 40 percent had partial response and 35 percent had a complete response at a median follow-up of eight months.

(Le Q, Loo BW, Ho A, et al. Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for lung tumors. J Thorac Oncol. 2006;1:802-809)
Symptoms and Complications of Lung Metastases
Perhaps surprisingly, the vast majority of patients with lung metastases, even multiple metastases, have no symptoms. The exception is the small percentage of patients with the lymphangitis carcinomatosis (LC) type of metastases. Here, shortness of breath is a common symptom, as is dry cough.

Shortness of breath (dyspnea) may develop in a patient with lung metastases of either the LC or nodular type once the tumor becomes large enough to replace a significant amount of the lung tissue (or parenchyma), so that the oxygen absorbing function of the lungs is impaired. Shortness of breath may also occur if a pleural effusion is present. Pleural effusion is an abnormal collection of fluid in the chest cavity, and it is a common occurrence in the presence of metastatic cancer. It is estimated to occur in almost one half of all cases of metastatic cancer.

In the US there are an estimated 200,000 cases of pleural effusion annually due to malignancy in the lungs. Women are more often afflicted than men (2:1) primarily because pleural effusions are often associated with breast and gynecologic cancers. Pleural effusions are also particularly commonly seen in mesothelioma, lymphomas and leukemias, as well as stomach cancer, melanoma and sarcomas.

Malignant pleural effusions can be of very large volume—up to 2 liters—and the distress associated with this condition can be very great. Fluid accumulation can result in lung collapse. The fluid can be drained by a procedure known as thoracentesis, during which a needle is inserted carefully through the chest wall.

NOTE: One useful development in the care of patients with pleural effusions is the PleurX pleural catheter, from CareFusion. This is a large company, headquartered in San Diego, CA and Switzerland, with 20,000 employees worldwide. Among other things, they market an implanted pleural catheter that enables patients to have their pleural effusion drained at home rather than in the hospital. In clinical trials this technique resulted in improved quality of life, reduction of breathlessness and improved sense of wellbeing. In half the patients treated with this device, re-adhesion was avoided. This device certainly promises an improvement in the management of the distressing and debilitating condition of pleural effusion.

The outlook for patients with pulmonary (lung) metastases who develop pleural effusions is on the whole not as good as for those patients with lung metastases who do not show signs of pleural effusion. Pleural effusions with a low glucose level and a pH less than 7.2 are also associated with a poorer outcome.

Pericardial Effusions
Pericardial effusions may also occur in patients with lung metastases, often by extension from tumors growing in the lymph nodes at the center of the chest (mediastinum) adjacent to the heart.

(Imazio M, Brucato A, Derosa FG, et al. Aetiological diagnosis in acute and recurrent pericarditis: when and how. J Cardiovasc Med (Hagerstown). 2009;10:217-230)
In this condition, fluid collects around the heart, inside the membranes that surrounds the heart (the visceral and parietal pericardium). Such fluid collections around the heart may restrict the ability of the heart to pump effectively, resulting in breathlessness and fatigue, and potentially to a condition known as cardiac tamponade, which can rapidly become life-threatening.

Perhaps surprisingly, up to 50 percent of cases of pericardial effusion are not caused by the malignancy itself, but by treatment: radiation treatment frequently causes pericardial effusion, for example. Treatment of pericardial effusion, like that of pleural effusion and ascites, involves draining off the excess fluid. This can be done by pericardiotomy (the opening and draining of the pericardial space). Administration of chemotherapy (primarily cisplatin) directly into the pericardial space has also been attempted for the treatment of recurrent pericardial effusion.

If a tumor blocks one of the airways the lung tissue beyond that blockage may collapse and/or become infected (a condition known as atelectasis), and this is obviously a situation that requires imm