Tag Archives: radiofrequency ablation

Cancer Survivors With Low Volume Metastases May Benefit From Radiotherapy

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“Precisely targeted radiation therapy can eradicate all evidence of disease in selected patients with cancer that has spread to only a few sites, suggests the first published report from an ongoing clinical trial. … Six of the 29 [21%] initial patients had lasting tumor control, with no detectable evidence of disease 15 months after treatment. Many patients had a complete response in at least one tumor. Thirty-one of the 56 treated tumors (55%) completely disappeared. Two tumors (4%) had a partial response, defined as reduction in tumor volume of more than 30 percent. Only three of the 56 tumors progressed (5%), growing in size by 20 percent or more during the treatment phase … Crucial to this approach is careful patient selection, distinguishing between patients who have a treatable number of tumors and those who have widespread metastasis, including multiple tumors too small to detect. Currently, there are no known genetic “signatures” to differentiate between widespread cancer versus oligometastasis, the authors point out.”

Image-Guided Radiation Therapy Used To Treat "Oligometastasis"

Image-Guided Radiation Therapy (IGRT) Used To Treat "Oligometastasis"

“Precisely targeted radiation therapy can eradicate all evidence of disease in selected patients with cancer that has spread to only a few sites, suggests the first published report from an ongoing clinical trial.

In the August 15, 2008, issue of Clinical Cancer Research, (published online August 12) researchers from the University of Chicago Medical Center report that targeted radiation therapy had completely controlled all signs of cancer in 21 percent of patients who had five or fewer sites of metastatic disease.

‘This was proof of principle in patients who had failed the standard therapies and had few, if any, remaining options,’ said the study’s senior author, Ralph Weichselbaum, MD, professor and chairman of radiation and cellular oncology at the University of Chicago Medical Center. “We had encouraging results, including several long-term survivors, in patients with stage-IV cancers that had spread to distant sites.’

In 1994, Weichselbaum and colleague Samuel Hellman proposed that there was an intermediate state between cancer that had not spread at all and cancer that had spread extensively. They named this phenomenon “oligometastases,” meaning cancer that had spread to a few distant sites.

In some cases, surgeons have successfully treated such limited cancer spread, producing long-term survival by removing the primary cancer and one or two distant tumors, off-shoots of the original cancer–usually in the lung or liver. However, some patients are not fit for surgery or have cancer that is inoperable.

Recent improvements in tumor detection and precise image-guided radiation therapy, however, have made simultaneous treatment of multiple tumor sites with radiation feasible. So in 2004, Weichselbaum organized a clinical trial to test the ability of local radiation therapy to control a limited number of related tumors which colleague Joseph Salama, MD, assistant professor of radiation oncology at the University of Chicago has directed since 2005.

Patients with stage-IV cancer with one to five distant metastases and no tumors bigger than 10 centimeters (about four inches) in diameter were eligible to participate in the study either before or after chemotherapy treatment.

Each patient received three doses, separated by at least two days, of precisely targeted radiation therapy focused on each metastatic tumor. Treatment was usually completed within one week. The first patients in the study received lower doses. As few side effects were seen, radiation doses were gradually increased in subsequent groups of patients.

‘Previous studies determined the maximal radiotherapy doses for single organs,’ said Salama, lead author of the study, ‘but this technique has not been tested for simultaneous use on multiple organs. So we designed a dose-escalation trial to determine the optimal dose, starting with fairly low levels and increasing the dose in later groups of patients.’

From November 2004 through February 2008, 29 patients, with a total of 56 cancerous lesions, enrolled in the trial. Of the 29 patients, 24 had progressed after at least one round of systemic chemotherapy. For the other five, there was no promising choice of therapy.

Six of the 29 initial patients had lasting tumor control, with no detectable evidence of disease 15 months after treatment.

Many patients had a complete response in at least one tumor. Thirty-one of the 56 treated tumors (55%) completely disappeared. Two tumors (4%) had a partial response, defined as reduction in tumor volume of more than 30 percent. Only three of the 56 tumors progressed (5%), growing in size by 20 percent or more during the treatment phase.

Tumor control improved as the radiation dose increased. Thirty-nine percent of the 31 tumors treated with 24 gray of radiation met the criteria for tumor control–a complete or partial response. That increased to 79 percent for the 19 tumors treated with 30 gray, and to 83 percent for the six tumors treated with 36 gray.

‘This suggests that the initial doses were too low,’ said Salama. ‘We have seen improved response rates with higher radiation doses without an increase in side effects yet.’

Typical treatment doses for a patient with breast cancer, for example, are in the range of 50 to 60 gray, spread over 20-30 sessions. The trend however, is toward delivering higher doses in fewer sessions.

Patients tolerated the treatment, the authors write, with ‘limited difficulty.’ All had some fatigue but few had serious side effects. The most severe included one patient being treated for abdominal tumors who developed vomiting that required hospitalization. One lung cancer patient developed a severe cough. One patient had gastrointenstinal [sic] bleeding three months after treatment that required blood transfusion and laser treatment.

Crucial to this approach is careful patient selection, distinguishing between patients who have a treatable number of tumors and those who have widespread metastasis, including multiple tumors too small to detect. Currently, there are no known genetic “signatures” to differentiate between widespread cancer versus oligometastasis, the authors point out. This is one area of active research. Only five of the 29 patients treated so far, however, had tumor progression in more than five sites.

The technique could also be applied after chemotherapy, the authors suggest, in cases where the drugs had eliminated most the smaller cancer, leaving only a few larger tumors behind.

The trial is still underway. ‘We now have about 50 patients,’ said Weichselbaum, ‘and several of them remain disease-free, one of them three years after treatment.’

The Ludwig Center for Metastasis Research and the University of Chicago Cancer Research Center funded this study. Additional authors include Steven Chmura, Neil Mehta, Kamil Yenice, Walter Stadler, Everett Vokes, Daniel Haraf and Samuel Hellman, of the University of Chicago Medical Center.”

Quoted Source: Targeted Radiation Therapy Can Control Limited Cancer Spread, Press Release, The University of Chicago Medical Center, August 15, 2008 (summarizing the findings of An initial report of a radiation dose-escalation trial in patients with one to five sites of metastatic disease; Salama JK et. al., Clin Cancer Res. 2008 Aug 15;14(16):5255-9. (” … RESULTS: Twenty-nine patients with 56 metastatic lesions were enrolled from November 2004 to March 2007, with a median follow-up of 14.9 months. Two patients experienced acute (radiation pneumonitis and nausea) and one experienced chronic (gastrointestinal hemorrhage) grade >/=3 toxicity. Fifty-nine percent of patients responded to protocol therapy. Twenty-one percent of patients have not progressed following protocol treatment. Fifty-seven percent of treated lesions have not progressed at last follow-up. Progression was amenable to further local therapy in 48% of patients. CONCLUSIONS: Patients with low-volume metastatic cancer can be identified, safely treated, and may benefit from radiotherapy.”))

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Radiofrequency Ablation Effective in Treatment of Primary Lung Cancer & Metastatic Lung Disease

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“… Our study shows that percutaneous CT-guided radiofrequency ablation yields high proportions of sustained [complete responses] in properly selected patients with primary or secondary lung malignancies, and is associated with acceptable morbidity,’ write the authors.”

“Treatment options are limited for patients with non-small-cell lung cancer (NSCLC) who are not surgical candidates, and surgery is frequently not feasible for patients with secondary lung malignancies. However, according to new data published online June 17 in the Lancet Oncology, radiofrequency ablation could be an option for patients who are unable to undergo surgery, radiotherapy, or chemotherapy.

Percutaneous radiofrequency ablation is a relatively new and minimally invasive technique that has been used to treat solid tumors. In particular, it is becoming a viable option for unresectable liver malignancies. Although the use of radiofrequency ablation is at an early stage of clinical application for other types of solid tumors, recent studies have shown that it has potential in the treatment of lung, bone, and renal malignancies. The authors note that several single-institution case series have suggested that radiofrequency ablation is a feasible option for patients with unresectable or medically inoperable pulmonary tumors.

In this study, Riccardo Lencioni, MD, associate professor of radiology in the department of oncology, transplants and advanced technologies in medicine at the University of Pisa, in Italy, and colleagues designed a prospective single-group multicenter clinical trial to evaluate the feasibility, safety, and effectiveness of percutaneous computed tomography (CT)-guided radiofrequency ablation in the treatment of NSCLC. The study also included patients with metastatic disease to the lungs.

A series of 106 patients, with a total 183 lung tumors measuring 3.5 cm or smaller in diameter, were enrolled in the study. Of this group, 33 patients had been diagnosed with NSCLC, 53 had metastasis from colorectal carcinoma, and 20 patients had metastasis from other primary malignancies. All of the patients were deemed unsuitable for surgery, radiotherapy, or chemotherapy.

The primary end points were technical success, safety, and confirmed complete response of tumors. The authors defined technical success as the correct placement of the ablation device in all target tumors with completion of the planned ablation protocol. Secondary end points of the study included overall survival, cancer-specific survival, and quality of life.

Study participants underwent radiofrequency ablation in accordance with standard rules for CT-guided lung biopsy. Follow-up visits were scheduled at 1 and 3 months after the procedure, and then at 3-month intervals for up to 2 years.

A total of 137 procedures were performed, and treatment was successfully completed in 105 of 106 patients (99%). From this group, it was possible to assess the primary end point of a confirmed complete response in 85 patients (80%). The researchers noted a confirmed complete response of all targeted tumors that lasted for at least 1 year after treatment in 75 of 85 patients (88%), with incomplete ablation and evidence of local progression in at least 1 treated tumor in the remaining patients. There was no difference in tumor responses to ablation between patients with NSCLC and those with metastatic lung disease.

Overall and Cancer-Specific Survival

Patient Subgroup Overall Survival at 1 Year Overall Survival at 2 Years Cancer-Specific Survival at 1 Year Cancer-Specific Survival at 2 Years
NSCLC 70% 48% 92% 73%
Stage 1 NSCLC n/a 75% n/a 92%
Colorectal metastases 89% 66% 91% 68%
Metastases from other sites 92% 64% 93% 67%

Although there was no procedure-related mortality, 27 of the procedures were complicated by a large or symptomatic pneumothorax that required drainage. A second major complication was the occurrence of pleural effusion in 4 procedures, which also necessitated drainage.

‘Our study shows that percutaneous CT-guided radiofrequency ablation yields high proportions of sustained [complete responses] in properly selected patients with primary or secondary lung malignancies, and is associated with acceptable morbidity,’ write the authors.

They note that the rate of overall survival was greatly affected by the recruitment of patients with severely impaired pulmonary function, with substantial comorbidities, or both. All participants were deemed unsuitable for surgery, radiotherapy, or chemotherapy, or they had exhausted conventional treatment options. Under these circumstances, it was not possible to reliably compare radiofrequency ablation survival curves and those achieved with other treatments.

‘Additionally, the patient population was heterogeneous and included patients with NSCLC and patients with pulmonary metastases from different primary malignancies, and the study was not designed to provide evidence of survival benefits,’ they write. ‘A randomized controlled trial comparing radiofrequency ablation versus standard treatment options is now warranted to prove the clinical benefit of this approach.’”

[Quoted Source: Radiofrequency Ablation Offers Promise in Treatment of Lung Cancer (access requires free Medscape registration), by Roxanne Nelson, Medscape Medical News, MedscapeToday, June 19, 2008 (summarizing the Lancet Oncology article entitled, Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study); Lencioni, R. et. al., Lancet Oncology DOI:10.1016/S1470-2045(08)70155-4 (early publication on-line), June 18, 2008).

Comment: The Lancet study findings indicate that radiofrequency ablation is a fairly safe and very effective treatment for lung metastases up to 3.5 cm in size. Importantly, the Lancet study findings indicate that there was no difference in tumor response to ablation between patients with primary lung cancer and those with secondary metastatic lung disease caused by another form of cancer originating outside of the lungs.  Any women with ovarian cancer metastatic lung disease should show this study to her doctor to determine if she is eligible for radiofrequency ablation. As noted under the “Additional Studies, Clinical Trials & Other Information” section below, a 2007 U.S. study found pulmonary radiofrequency ablation for inoperable lung cancer safe and effective. Moreover, a 2006 U.S. study found radiofrequency ablation safe and effective for the treatment of ovarian cancer metastasis. Accordingly, percutaneous radiofrequency ablation can be effective in the treatment of ovarian cancer metastatic lung and liver disease for select women.

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