Journal of Cancer Research and Therapeutics Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI) ISSN: 0973-1482 EISSN: 1998-4138 Vol. 7, Num. 2, 2011, pp. 174-179

Journal of Cancer Research and Therapeutics, Vol. 7, No. 2, April-June, 2011, pp. 174-179

Original Article

Computerized tomography-guided percutaneous high-dose-rate interstitial brachytherapy for malignant lung lesions

Daya Nand Sharma¹, Goura Kisor Rath¹, Sanjay Thulkar², Amit Bahl¹, Subhash Pandit¹, Parmod Kumar Julka¹

¹ Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi-110 029, India
² Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi-110 029, India
Correspondence Address: Daya Nand Sharma, F-39, Ansari Nagar, New Delhi-110 029, India, sharmadn@hotmail.com

Code Number: cr11040

PMID: 21768706
DOI: 10.4103/0973-1482.82914

Abstract

Keywords: CT guided, high dose rate, interstitial brachytherapy, lung malignancies

Introduction

Malignant lung lesions (MLL) can be primary or metastatic tumors. Surgical resection is the standard treatment for MLL, ^[1],[2] but alternative options have to be considered for medically inoperable patients and those who refuse surgery. The various non-surgical options for such patients are three dimensional conformal radiation therapy (3D-CRT), stereotactic body radiation therapy (SBRT), and various thermoablative procedures such as radiofrequency ablation (RFA). ^[3] High-dose-rate interstitial brachytherapy (HDRIBT) for MLL is relatively a new and less studied technique. It consists of the percutaneous placement of an IBT needle through the intercostals space under CT scan guidance; and precise delivery of a large single dose of radiation (about 20 Gy) in the target lesion and a minimal dose to the surrounding lung parenchyma and other critical tissues. ^[4],[5],[6] It has many advantages over other thermoablative methods: (1) It is free from the heat-sink effect, unlike RFA; (2) there is measurable dose deposition in the tumor and the surrounding normal tissues; (3) there is lesser risk of procedure-related acute complications such as pneumothorax, hydrothorax, and so on. ^[4]

As compared to the external beam radiation therapy (EBRT) techniques such as three dimensional conformal RT (3D-CRT) and SBRT; HDRIBT can potentially provide better dosimetery, as tumor movement due to breathing, unlike EBRT, does not affect dose distribution. Limited experience through small studies ^{[4],[5],[6],[7]} exists in the literature regarding the role of HDRIBT in MLL. We conducted a prospective trial to study the feasibility of HDRIBT in MLL at our institute. The endpoints of study were acute perioperative complications and short-term (six months) lesion control.

Materials and Methods

From June 2007 to December 2008, eight patients with MLL (primary non-small-cell lung carcinoma (NSCLC), two; solitary lung metastases, six) were recruited in this prospective trial. All the patients had either refused surgery or were found ineligible for surgery due to comorbidities and had consented for inclusion in the study. For primary NSCLC diagnosis, histopathological proof was mandatory. For metastatic lesions, biopsy from the primary site was essential and the lung metastases were either radiologically evident (CT scan) or proved by aspiration cytology in difficult cases. Exclusion criteria included pediatric patients, centrally located lesions, and metastases from Wilm′s tumor, choriocarcinoma, seminomas or other chemosensitive tumors. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) imaging was done for all patients as the baseline imaging, for determining the disease extent and post treatment response assessment.

Brachytherapy Implant Procedure

All the patients were admitted one day prior to the procedure. No specific premedication was advised. The procedure was done in the CT scan room (Four-slice multidetector, CT Volume Zoom Scanner, Siemens Medical System, Erlanger, Germany) under local anesthesia. The patient was placed in either a supine or prone position, depending upon the tumor location. Under CT scan guidance the tumor was localized and a skin mark placed over the corresponding intercostal space to guide the needle insertion. The patient was given local anesthesia using Injection Lignocaine (2%). A single IBT stainless steel blind end needle (17 gauge) for lesions up to 4 cm and two needles for lesions up to 6 cm in diameter were inserted percutaneously through the marked intercostal space. Caution was taken not to introduce the needle during the breathing movement in order to avoid a pleural tear. The needle tip was advanced 5 mm beyond the lesion, as the needle tip was blind. The position of the needle was verified again on the CT scan [Figure - 1]. The needles were secured with screws.

Brachytherapy Planning and Treatment Delivery

Computed tomography scan images were acquired with a slice thickness of 2.5 mm. The images were transferred to the treatment planning system (Plato Treatment Planning System, Nucletron), and the target lesion and organs at risk (OAR) were contoured on each slice. The implant needles were also marked in order to reconstruct the needle length. Using source dwell positions at a distance of 2.5 - 5.0 mm within the target area, a plan was generated for a dose of 20 Gy prescribed at the periphery of the lesion [Figure - 1]. The most peripheral point of the target lesion lying perpendicular to the needle was selected as the dose prescription point. Usually the dwell positions within the target volume were activated, however, the plan was optimized in order to cover the target adequately and restrict the OAR dose to the tolerance limits. The skin dose was kept below 10 Gy. The volume of normal lung receiving 5 Gy was kept below 50%. After plan approval, the patient was taken to the brachytherapy suite (Microselectron HDR remote after loading unit) for treatment delivery. The needle was removed in the breath hold position immediately after the completion of treatment and the puncture site was sealed. An X-ray of the chest, after two hours, to rule out pneumo / hemothorax was done. The patients were kept in the indoor unit overnight for observation.

Assessment of perioperative complications

Complications occurring during the procedure and within one week of the procedure were taken as perioperative complications. Major perioperative complications were defined as those resulting in a life-threatening condition requiring prolonged hospitalization (beyond 24 hours) and emergency interventional therapies like chest tube insertion, blood transfusion, and endotracheal intubation. Complications like pneumothorax, hemothorax, severe hemoptysis, and thromboembolic events were labeled as major perioperative complications. Minor complications included minimal hemo / pneumothorax and blood tinged sputum, which did not require any active or resuscitative measures.

Follow-up and response assessment

Patients were followed up every month, for a period of six months. Chest CT scan at one month and an FDG PET-CT scan at three and six months of the procedure were done to assess the status of the treated lesion [Figure - 2]. The response criteria were: (1) Complete Response (CR): complete disappearance of tumor on CT scan or absence of FDG uptake on PET scan; (2) Partial Response (PR): more than 50% regression in the maximum diameter of the lesion; (3) No Response (NR): less than 25% regression in the lesion, and (4) Progressive Disease (PD): more than 25% increase in the size of lesion. Tumor control rate was defined as more than 50% reduction in the tumor size (combined CR + PR).

Results

Clinical characteristics of the patients are given in [Table - 1]. There were six males and two females with a median age of 55 years (range 30 - 59 years). The median size of the lesion was 4 cm (range 3.0 - 5.5 cm). A single IBT needle was used in seven patients and two parallel needles were used in one patient who had lesion diameter of 5.5 cm. The active length of the needle at treatment varied from 3.0 - 5.0 cm. The target volume receiving 95% of the prescribed dose ranged from 5.8 cc to 69.9 cc. The mean percent lung volume receiving > 20 Gy was less than 5%. The mean V5 (volume of lung receiving 5 Gy) was 9 - 22%. An average volume of 4.2 cc within the PTV received 200% of the prescribed dose. The average time for the entire IBT procedure (Needle insertion to needle removal) was 50 minutes (range of 40 - 65 minutes). All patients could complete the prescribed treatment dose of 20 Gy. [Table - 2] shows the various perioperative complications encountered with the procedure. None of the patients had fatal complications. All the patients were discharged from the hospital within 24 hours of the procedure . Two of the eight patients (25%) had minor complications, but did not require any active intervention. Of these two patients, one had blood tinged sputum and one had minimal pleural effusion, which resolved within 24 hours. [Table - 3] shows the response rates observed during the first six months of follow-up. During the first month follow-up, none of the patients had CR; and four had PR. At six months, two patients showed PD in the treated lesions and were subsequently taken for RFA. Both these patients had stable disease in the RF ablated lesion, however, the patient who had solitary lung metastases from the chest wall STS, showed bilateral lung metastases later, during the follow-up. The remaining six patients had the lesions under control (CR or PR). At a median follow-up of eight months, all the patients were surviving.

There was no significant delayed radiation toxicity in any of the patients. All six patients who had CR / PR, had lung fibrosis in the treated area, but the PET scan did not show FDG uptake in the fibrosed area [Figure - 3]. One patient had black pigmentation of the skin, 8 mm in diameter, around the needle entry mark, along with mild persisting pain.

Discussion

Presently, RFA and SBRT are the two main non-surgical treatment options for medically inoperable MLL. ^[3] Percutaneous HDRIBT for such patients is a less experienced treatment option, although it has good therapeutic potential. According to the existing literature, the frequency and severity of the complication rates seem to be higher with RFA as compared to SBRT and HDRIBT. Results of our study have shown that HDRIBT is a safe and feasible non-surgical option for MLL.

Although RFA is being studied increasingly ^{[8],[9],[10],[11]} with encouraging results, it has some limitations. It is not suitable for lesions that are more than 5 cm in size, located near blood vessels (due to the heat sink effect), diaphragm and central structures like bronchi, mediastinum, and so on. HDRIBT has no limitation regarding the neighboring vessels; however, it is avoided in the centrally located lesions, due to the risk of injury. Relatively larger lesions have been treated with HDRIBT as compared to RFA, although the number of patients is too small to compare the two techniques on the basis of lesion size. Even though the applicator sizes are similar in RFA and HDRIBT, the perioperative complication rates seem to be higher with RFA (5 - 63% versus 0 - 30%). The overall mortality to the lung, ranging from 0 - 5.6%, has been reported after RFA. ^[3] Pneumothorax is commonly observed after this treatment, which requires chest tube insertion. Pennathur et al., ^[9] have reported a 63% pneumothorax rate requiring active intervention. None of the patients in our study have had pneumothorax. Frequency of mild hemoptysis is reported to be about 11% with RFA. ^[11] We encountered almost the same frequency (12.5%) of mild hemoptysis in our present study. Systemic air embolism has been reported as a rare complication, but may prove fatal. ^[12],[13] None of the HDRIBT studies, including ours, has encountered this complication.

Stereotactic body radiation therapy is other contemporary treatment option for MLL. ^{[3],[14],[15]} It is a form of EBRT, which delivers highly conformal large ablative doses of radiation (generally more than 10 Gy per fraction in five or fewer fractions). Only small targets can be treated (typically < 5 cm), and the accuracy and reproducibility of treatment is essential. Unlike, RFA and HDRIBT, it is a noninvasive method of treatment because it does not require needle insertion. ^{[3],[14],[15]} Compared to conventional EBRT, SBRT may reduce the safety margin significantly; the uncertainty is still about 1 cm in most patients, due to breathing movements. ^[16] In HDRIBT, the breathing motion is not a limiting factor, as the catheter has a constant position, relative to the target, without further specific preparations. Recent reports ^[17],[18] have shown higher than expected skin, chest wall, and rib toxicity, including one report ^[18] with a 48% actuarial two-year risk of rib fracture. Long-term results are necessary for a better understanding of SBRT.

Currently, there are no clinical studies comparing image-guided brachytherapy with SBRT. However, theoretical considerations favor brachytherapy, because the tolerance dose of the lung has a strong volume dependency, and the interstitial technique provides the largest potential for concentrating large doses into a small volume. Additionally, due to dose optimization tools with HDRIBT, dose distribution can be further improved.

Although Brach et al., ^[4] reported the use of percutaneous HDRIBT for the first time in MLL, they had combined it with EBRT. They treated 20 patients with MLL using 66 Gy EBRT followed by 10 - 20 Gy by HDRIBT. They reported significant pneumothorax in 30% of the patients and tumor control (more than 50% reduction in tumor measurements) in 75% of the patients.

Thus far, there are only three published studies ^[5],[6],[7] available in the literature regarding the use of HDRIBT alone (without EBRT) for MLL and ours is the fourth such study. The results of our study are comparable to these three series.

Ricke et al., ^[5] reported a prospective trial of 15 patients with 30 malignancies (28 lung metastases and two NSCLC). Their lesion size ranged from 0.6 cm to 11 cm (median 1.5 cm) with three patients having tumors more than 5.5 cm. In one patient with a 11 cm tumor diameter, they had inserted nine HDRIBT catheters. The minimal dose within the tumor margin was 20 Gy in all 30 tumors treated. Except for one patient who complained of nausea on the following day of the procedure, they observed no short-term adverse events. There were no pneumothoraces, hemoptysis or abscesses. Thus, their major and minor complication rates were 0 and 7%, respectively. Peters et al., ^[6] conducted a prospective trial with 30 patients having 83 lesions. The mean diameter was 2.5 cm. They prescribed a dose of 20 Gy to the target lesion. With a median follow-up of nine months, the tumor control rate was 91% at 12 months. The major and minor complication rates were 2 and 12% respectively. The same figures in our study were 0 and 25%, respectively. The tumor control rates in these two studies were more than 90% as compared to 75% in our study. This could be due to the smaller lesion size in both studies (median size 1.5 and 2.5 cm) as compared to ours (median size 4 cm). Imamura et al., ^[7] reported a series of 12 patients of peripheral NSCLC treated with HDR brachytherapy. Five of them were treated by percutaneous HDRIBT (20 Gy) and the remaining seven were treated by transbronchial HDR brachytherapy (12.5 Gy x 2). They reported a local control rate of 88.9% for T1 tumors with mild complications.

As per the Paris system ^[19] of dosimetry, multiple needles should be used for adequate coverage of lesions greater than 1.5 cm in diameter. We have used only one needle for lesions up to 4 cm in diameter and accepted the inhomogeneous dosimetry in the tumor. Such an inhomogeneity, which is not usually acceptable in routine HDRIBT procedures like breast and prostate brachytherapy, actually proves advantageous in lung tumors. First, the central hypoxic area of the tumor, which is closer to the needle, definitely receives a much higher dose (> 50 Gy) as compared to the peripheral portion (20 Gy). ^[20] This may result in higher tumor control. Second, multiple needles will definitely enhance the risk of complications especially pneumothorax. A very low complication rate (0% pneumothorax) and decent tumor control rate (75%) in our study, thus, justifies the use of a single needle for lesions up to 4 cm in diameter.

Jain et al., ^[21] have suggested, based on their experience in three patients, the combined use of RFA and HDRIBT in the same session of treatment. The rationale for this combination is to have greater damage to the central hypoxic portion of the tumor, which is usually radio-resistant.

The appropriate method of response assessment during the follow-up after HDRIBT remains to be defined. Unlike surgical intervention, complete radiographic disappearance of a tumor is not typically seen following HDRIBT. The tumor may persist or show slow regression on the CT scan, without any viability, as a single large dose of HDRIBT may induce inflammation / fibrosis changes. Radiobiologically, larger dose single fraction treatments may take a longer time to eradicate the tumor. PET may be a better imaging device for response assessment. In our study the response rates in the first month were slow [Table - 3]. Even after six months the CT continued to show a persistent mass, but the FDG-PET did not show any uptake [Figure - 2]. We found the PET scan to be very useful for response assessment.

Delayed radiation toxicity associated with HDRIBT for MLL has not been well-studied, due to short-term data. Both studies ^[5],[6] have a median follow-up of less than one year. The toxicity might be the same with SBRT and HDRIBT, as both use a large dose per fraction. Therefore, a growing experience with SBRT, which is relatively more popular, will provide better information about the long-term toxicity. As with every hypofractionated treatment, late effects are generally more. However, this may be clinically insignificant with HDRIBT, as these effects may be restricted to a very small volume.

Conclusion

Our study has consolidated the safety aspects of HDRIBT for MLL. The HDRIBT studies (including ours), cannot be strictly compared with other SBRT and RFA series, due to the smaller sample size. Yet the short-term results have proven that CT-guided percutaneous HDRIBT is a safer treatment option for MLL in medically inoperable patients. Thus far, short-term tumor control rates are encouraging and apparently comparable to SBRT and RFA series. It is worth conducting randomized controlled studies with a larger population of patients, with a longer duration follow-up. Additionally, based on our present experience, we recommend the use of FDG-PET scan at a minimum of three months follow-up, for response assessment, in all future studies on HDRIBT.

References

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