Lasers Med Sci 1999, 14:136–142 © 1998 Springer-Verlag London Limited
Laser-Induced Thermotherapy (LITT) for Retreatment of Locally Advanced Recurrences of Breast Cancer M.S. Ismail1,2,3, C. Philipp1, U. Torsten2, H. Weitzel2 and H.-P. Berlien1 1 Department of Laser Medicine, Neuko¨lln Hospital, Berlin; 2Department of Gynaecology and Obstetrics, University Hospital Benjamin Franklin, Freie University, Berlin, Germany; 3Department of Gynaecology and Obstetrics, Al-Azhar University, Cairo, Egypt
Abstract. The e#ect of laser-induced thermotherapy (LITT) as a palliative method for treatment of patients with local recurrence of breast cancer is investigated. This report describes the use of interstitial laser photocoagulation to manage such lesions. The interstitial laser applications were performed in seven women with locally recurrent breast carcinoma on the chest wall after mastectomy. All patients had been heavily pretreated with conventional modes of therapy (radiotherapy, chemotherapy, hormonal therapy, surgical resection). A Nd:YAG laser with a wavelength of 1064 nm was used to heat the lesions. Heat expansion was controlled digitally and monitored by ultrasonography and colour-coded duplex sonography (CCDS). In five women this minimally invasive method enabled the precise coagulation of the subcutaneous tumour without destruction of the skin or ulceration, although these areas had been pretreated by irradiation up to 60 Gy. In two patients with extensive multiple metastases and with skin infiltration, secondary skin ulceration and delayed healing was observed. For palliative reasons, LITT under CCDS guide can aid in local control of chest wall recurrence following mastectomy in selected patients. Keywords: Colour-coded duplex sonography; Laser induced thermotherapy; Minimal invasive therapy; Recurrent breast cancer
INTRODUCTION Breast cancer is the most frequently observed cancer among women and has the highest incidence of any cancer in western Europe and North America. Worldwide, more than one million women per year will develop breast cancer by the year 2000 [1]. Locally recurrent breast carcinoma of the chest wall following mastectomy can be di$cult to eradicate. Radiotherapy, chemotherapy and hormonal therapy have shown variable e$cacy in controlling these metastases. Because not all patients are surgical candidates and not all metastases are surgically amenable, a search for new modalities for the treatment of this taxing problem is desirable. If left unchecked, discrete nodules can coalesce into larger tumour masses that may erode and ulcerate. These open, draining areas cause pain, odour, Correspondence to: Dr. med. M.S. Ismail MD, Department of Laser Medicine, Neuko¨lln Hospital, Rudower Str. 48, D-12313 Berlin, Germany.
and problems with local wound care that are cosmetically unacceptable and psychologically di$cult for the patient [2]. The superficial location of the breast and its associated lesions, plus the easy localisation, palpation and visualisation of the lesions within the breast or the chest wall area made it an ideal site for laser-induced thermotherapy (LITT). Local recurrence may be slightly more common after breast conservation surgery rather than mastectomy [3]. LITT covers the treatment modality of laser-induced hyperthermia for temperatures from 42C to 60C as well as high temperature treatment of laser-induced coagulation for temperatures above 60C. LITT was first proposed in 1983 by Bown [4] for liver metastasis, and by Ascher [5] for treatment of brain tumours. In 1984, Berlien introduced LITT for the treatment of congenital vascular malformations and haemangiomata [6,7]. LITT has already found a place in the management of isolated metastases [8] and has considerable promise for the treatment of benign prostatic hyperplasia [9], colorectal cancer secondaries
Laser-Induced Thermotherapy for Retreatment of Breast Cancer
in the liver [10], breast and brain tumours [8,11], malignancies of the female genital tract [12], uterine leiomyomata [13] and vascular disorders [14]. The goal of LITT is to apply laser radiation to pathological tissue [15]. With adequate treatment parameters and efficient monitoring procedures, the e#ects of LITT can be limited to the diseased area without destruction of the healthy surrounding tissues. This will increase the patient’s safety [15]. Several techniques for controlling LITT can be applied. Ultrasonography [16–19] and magnetic resonance imaging (MRI) [19–23] are the two main imaging modalities currently used. Studies on normal liver tissue showed a good correlation between the size of the echogenic lesion on ultrasonography and that seen on the pathological specimen at the end of the LITT and at various subsequent times [16,17]. Several studies have demonstrated a direct correlation between laser energy deposition in tissue, real time thermal profiles, MRI signal intensity changes, and subsequent histological changes [20–23]. Unfortunately, the clinically available conventional MRI sequences require several seconds to collect data for an image, which causes disturbance owing to respiratory movements in addition to the artefacts caused by movements of the patients, limited direct access to the patient as well as the high costs of this method. With these limitations of MRI in on-line monitoring of LITT, MRI cannot be recommended for LITT monitoring in breast cancer. Interest in ultrasonography in controlling the LITT process is based on the simplicity of its use, the machine being portable and the imaging performed at the same time and place as the treatment [24]. Extensively pretreated subcutaneous chest wall recurrences in seven patients su#ering from breast cancer have been treated palliatively by the LITT-method under the control of colour-coded duplex sonography (CCDS)
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Fig. 1. Chest wall with local recurrences of breast cancer: status after bilateral mastectomy, axillary lymph node dissection and irradiation.
Fig. 2. Preoperative CCDS visualisation of the anatomy of a chest wall metastasis within its surrounding tissue.
skin ulceration. LITT was performed 11 times in these patients (Figs 1 and 2). In all patients, it was not possible to treat these lesions surgically, with chemotherapy or radiotherapy, and the areas of concern had been pretreated by chest wall irradiation after mastectomy and/or systemic chemotherapy. For ethical reasons, all patients were thoroughly informed about the study and patient consent was obtained.
Imaging PATIENTS AND METHODS Patients Seven patients (age 50–84 years) su#ering from solitary or multiple subcutaneous pretreated chest wall recurrences of breast cancer were treated with LITT for palliation. The diameters of the subcutaneous metastases were in the range 3–35 mm, and the number of lesions ranged from 1 to 15. There were no cases with
Ultrasonography was used to measure the dimensions of the metastases and the largest diameter was noted. Colour-coded duplex sonography (Quantum 2000, Siemens), with a transducer frequency of 7.5 MHz, was used for both preoperative visualisation of the tumour anatomy (Fig. 2), and for control of the therapeutic coagulation e#ects. The power and the amplification of the signal was set individually according to the required application.
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expansion was intermittently controlled digitally and monitored by ultrasonography and CCDS. In cases where the metastasis was directly under the skin, the cutis above the metastasis was always protected from the laser thermal e#ect using ice.
RESULTS
Fig. 3. Puncture of a metastasis with a Teflon catheter (Abbocath G 16). The puncture site is always in the healthy skin area.
Laser Parameter A continuous wave Nd:YAG laser (wavelength 1064 nm, Martin Nd:YAG-Laser, MY 60, Tuttlingen, Germany) was used. A sterilised, single freshly cleaved 600 m fibre was used with a bare tip to deliver laser energy to the tumour (bare fibre 9M-6065, 1050 m outer diameter, Martin, Tuttlingen, Germany).
Procedure Interstitial laser treatment was performed under local anaesthesia for small metastases (diameter 10 mm), where multiple punctures were needed with a distance of more than 10 mm between lesions. Under sterile conditions and after visualisation of the diseased area with CCDS imaging (a sterile sheet was used over the ultrasound probe), the area to be treated was punctured with a Teflon catheter (Abbocath G 16; Fig. 3), which was placed within the tissue under B-scan control. The Teflon catheter was always introduced through a healthy skin area about 1 cm from the metastasis margin to avoid direct skin puncture over the lesion. In each case, a freshly cleaved bare fibre was inserted through the Teflon catheter which was pulled back for 10 mm over the fibre and laser thermal interaction with the catheter material was avoided. The Nd:YAG laser was applied with a power setting of 5 W for a time range of 120–600 s (600–3000 J). In this way it is possible to produce a coagulation zone of approximately 15 mm in diameter, which extends retrograde and in cylindrical form along the fibre. Heat
Ultrasound guidance enabled correct positioning of the catheter and bare fibre inside the metastatic lesion. After a delay of a few seconds, a gradually expanding spherical hyperechoic region appeared around the laser fibre tip. This was followed after 30 s, by a signal in CCDS imaging in the form of random mixtures of red and blue coloration. The hyperechoic area expanded to reach a peak within 100–300 s (according to laser power) and remained approximately the same size and shape until the end of therapy. Under the CCDS, and as the photocoagulation process progressed, the colour signal enlarged but it was not necessarily equal in size and position to the hyperechogenic zone. The onset of colour signals was dependent on the laser power setting. After various times depending on the irradiation parameters, these signals decreased and no further changes were observed in CCDS imaging. During further irradiation, the hyperechogenic zone under B-scan was shifted along the puncture channel towards the periphery. At this time gas bubbles passing along the Teflon catheter and appearing at its proximal end were observed. The extent of the coagulation zone was visible, using the B-scan several minutes after laser exposure. The cutis in the over-lying layers of the metastasis was always preserved without any sign of necrosis. The temperature rise throughout the treated tumour and its skin covering was detected during the digital control of the heat expansion. We also detected crepitation caused by water vapour and spread of CO2 gas in the tissues, a consequence of tissue temperature elevation. This reaction was also monitored in CCDS in the form of random noise of red and blue colouration. The colour signal alters in a reproducible pattern according to the heat distribution and the subsequently occurring degasification of the tissue. This colour signal represents the intensity of tissue reaction and gives information about the actual heat development (Figs 4 and 5). The control CCDS two weeks after the primary treatment showed all
Laser-Induced Thermotherapy for Retreatment of Breast Cancer
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Fig. 4. Colour-coded duplex sonography imaging during the treatment of subcutaneous local recurrence of breast cancer.
Fig. 6. The chest wall after one month of successful LITT. The same patient in Fig. 1.
Fig. 5. Colour-coded duplex sonography imaging: signal at the end of irradiation during the treatment of the same subcutaneous local recurrence of breast cancer as in Fig. 4.
the signs of fibrosis and reduction of vascular perfusion in these areas. In cases with subcutaneous lesions without skin infiltration, a precise coagulation of the tumour without destruction of the skin or ulceration was achieved. On completion of treatment, an immediate reaction is noted, with erythema and oedema followed by necrosis during the first week. Tumour response was complete within three weeks of treatment. With healing, there is observable shrinkage and flattening of the lesions. Over the next 4–8 weeks the only abnormalities visible after healing were small central depressed scars which gradually faded. Patients with local anaesthesia experienced minimal pain and discomfort during therapy. All patients experienced pain following treatment. For most patients mild analgesia was all that was required for pain control. The incidence of skin necrosis increased with the presence of skin infiltration (intracutaneous metastases). Two cases with skin infiltration
and multiple recurrence lesions near each other, showed skin ulceration and delayed healing up to 12 weeks. Follow-up has ranged from 3 months to 3 years. In the first 6 months follow-up period, two women died of disseminated disease. Three patients, those who had solitary metastases separated by healthy skin, are free of chest wall disease at 6 months follow-up (Fig. 6). The life quality of those patients was improved as a consequence of disappearance of the metastases and also from the psychological aspect. A residual tumour was noted in two patients after treatment.
DISCUSSION LITT has been used for several years in the treatment of subcutaneous lesions of di#erent pathological origins. The laser used is usually a continuous wave Nd:YAG laser (wavelength 1064 nm), since light within the NIR (near infrared region) wavelength range has the greatest penetration depth in biological tissue. Seven patients su#ering from subcutaneous pretreated chest wall recurrences of breast cancer were treated with LITT for palliative reasons. LITT was performed 11 times in these patients. Because of advanced disease it was no longer possible to treat these lesions surgically by a TRAM-flap or a latissimus dorsi muscle-flap. In all cases, the areas of concern
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had been pretreated by chest wall irradiation after mastectomy and/or systemic chemotherapy. The tissue changes in those treated areas could be visualised excellently with CCDS. Thus, it became possible to change the positioning of the bare fibre if necessary, and to completely coagulate the metastases. Until now only a small number of studies [1,24–28] have reported on LITT for breast cancer. In two recent studies, interstitial laser photocoagulation was used for the evaluation of tumour coagulation e$ciency prior to its surgical resection. The assessment of response to therapy was carried out with contrast enhanced MRI. It was concluded that LITT can achieve complete tumour ablation in primary breast cancer and the post-contrast MR images can define the extent of both laserinduced necrosis and residual tumour following LITT of breast cancer [28]. The same group have used LITT for treating breast fibroadenoma in 14 patients. A 40% reduction in tumour volume in all treated fibroadenomas after 8 weeks post-laser application and >90% tumour regression was seen [27]. LITT was applied in 13 patients with tumours that were well defined by mammography (6–18 mm in diameter). Total tumour ablation was achieved in nine cases [25]. To our knowledge, this is the first clinical report about the application of interstitial laser therapy as a treatment modality for the retreatment of locally advanced recurrences of breast cancer. It is also the first study using the CCDS as a controlling imaging modality whilst achieving the complete disappearance of local recurrences. Our results were not promising in achieving complete disappearance of local breast recurrences in patients with multiple, intracutaneous metastasis and with metastases near each other, as in these cases a necrotic skin ulcer with prolonged and bad healing followed laser coagulation (Fig. 7). This meant the conversion of a closed lesion into an ulcerated lesion. In those severly advanced cases, the quality of life and reduction of su#ering were not improved. LITT is ideal for cases with solitary subcutaneous lesions and when the metastases are separated from each other, enabling a good chance of healing without ulceration of the metastasis. In the two patients where skin ulceration developed, this was because the tumour infiltrated skin and in these cases the heating e#ects of laser in the skin layer could not be avoided as the avoidance of skin coagulation
M.S. Ismail et al.
Fig. 7. The chest wall of the same patient as in Fig. 3 after two weeks of LITT. There were more than 15 chest wall metastases near each other. Skin ulceration and delayed healing resulted. This patient died 2 months from metastatic disease.
would mean incomplete destruction of all the malignant cells. Perhaps in cases with intracutaneous a#ection photodynamic therapy could o#er a lower incidence of skin ulceration. For the successful application of LITT in clinical practice, development of heatsensitivity and fast imaging techniques for real-time monitoring of interstitial laser thermotherapy are required. Several modalities are currently available for imaging control of such types of laser applications including visual and digital control [29–31], ultrasonography, MRI [26,28,32] and stereotaxic systems [25]. Mumtaz et al. described the use of delayed gadolinium-enhanced MR images in defining the extent of laser-induced necrosis and residual tumour after interstitial laser photocoagulation therapy in breast cancer [1]. Each of these methods has its advantages and disadvantages and cannot satisfy all aspects of control and evaluation of the LITT procedure. A more easily applicable technique, which generates real time images of the LITT procedure and its e#ects on tissue, is required to make interstitial laser application a more widely used clinical procedure. Initial interest in ultrasonography in imaging the e#ects of LITT was based on the simplicity of its use, portability and the fact that imaging is performed at the same time and place as the treatment [24].
Development of the CCDS Imaging Method One of the major problems encountered during interstitial laser treatment is the real-time
Laser-Induced Thermotherapy for Retreatment of Breast Cancer
control of tissue e#ects. To avoid coagulation necrosis of the overlying skin, the temperature of the irradiated skin region has to be controlled. For application close to the body surface direct control by palpation of crepitation and heat development as well as visual control of the changes in the transilluminating He-Ne beam are suitable methods. During the application of LITT in the treatment of subcutaneous lesions of di#erent pathological origin, we always monitored heat expansion on the surface of the skin digitally. Using this digital control, we also detected a crepitation caused by vapour and degasification of CO2 in the tissue [29]. But this method did not satisfy all aspects of LITT control. This reaction can also be monitored in CCDS in the form of an indeterminate random noise of red and blue. The colour signal starts, changes and moves in a reproducible pattern, following the heat distribution and the subsequently occurring degasification of the tissue. This colour signal represents the intensity of tissue reaction and gives information about the actual heat development. CCDS may also be used for monitoring localization of the fibre tip. In the procedures where we used the B-scan image for puncture control, a colour signal was displayed which represented tissue movement. By means of CCDS, changes in perfusion are also detectable. The precise extent of the coagulation zone only becomes visible when using the B-scan several minutes after laser exposure. The suitability of CCDS for on-line monitoring of LITT has been investigated experimentally. Rohde et al. [31], have investigated the changes in CCDS imaging in pig liver ex vivo during laser irradiation as well as the thresholds at which the colour signal occurred and the correlation between the B-scan imaging of the damaged area with the size of coagulation in pathological evaluation. They found that CCDS is a sensitive and e$cient technique in providing information about the coagulation process and a correlation between the B-scandetermined hyperechogenic area and the macroscopically observed signs of coagulation and vaporisation.
CONCLUSION In view of the severity of the disease and the failure of other treatment modalities, LITT can play a role in treatment of repeated local recurrences of breast cancer as these lesions, if
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left inadequately treated, can cause significant local problems. These high risk patients may derive an advantage from this method, above all as far as their quality of life is concerned. Much psychological and physical comfort can be a#orded to these women if the chest wall disease is controlled. Further clinical trials are warranted. CCDS is a reliable and easy technique for pre- and postoperative real-time control of the LITT procedure.
REFERENCES 1. Mumtaz H, Hall-Craggs M, Wotherspoon A, Paley M, Buonaccorsi G, Amin Z et al. Laser therapy for breast cancer: MR imaging and histopathologic correlation. Radiology 1996; 200:651–8. 2. Shuh M, Nseyo U, Potter W, Dao T, Dougherty T. Photodynamic therapy for palliation of locally recurrent breast carcinoma. J Clin Oncol 1987; 5:1766–70. 3. Kiebert GM, de Haes JM, Van der Velde CH. The impact of breast conserving treatment and mastectomy on the quality of life. J Clin Oncol 1991; 9:1059–70. 4. Bown SG. Phototherapy of tumours. World J Surg 1983; 7:700–9. 5. Ascher PW. Interstital thermotherapy of brain tumours with Nd:YAG laser under real time MRI control. SPIE Proc 1990; 1200:242–5. 6. Berlien H-P, Waldschmidt J, Mu¨ ller G. Laser treatment of cutaneous and deep vessel anomalies. In: Waidelich W (ed) Laser Optoelectronics in Medicine. Berlin, Heidelberg: Springer-Verlag, 1990:526–8. 7. Berlien H-P, Philipp C, Fuchs B, Engel-Murke F. Therapeutische Leitlinien zur laserbehandlung. In: Berlin H-P und Mu¨ ller G (eds) Angewandte Lasermedizin, Lehr- und Handbuch fu¨ r Praxis und Klinik, ecomed, Landsberg-Mu¨ nchen-Zu¨ rich, 1992. 8. Bown SG. Clinical application. In: Mu¨ ller G and Roggan A (eds) Laser induced interstitial thermotherapy. SPIE Proc, 1995:375–6. 9. Hofstetter A. Interstitielle Thermokoagulation (ITK) von Prostatatumoren. Lasermedizin 1991; 7:179–83. 10. Amin Z, Harries S, Lees W, Bown S. Interstitial tumor photocoagulation. End Surg 1993; 1:224–9. 11. Ascher PW, Justich E, Schro¨ ttner O. A new surgical but less invasive treatment of central brain tumors with Nd:YAG laser under real time monitoring by MRI. J Clin Laser Med Surg 1991; 1:79–83. 12. Wallwiener D, Kurek R, Pollman D et al. Palliative therapy of gynecological malignancies by laser induced thermotherapy. Lasermedizin 1994; 10:44–51. 13. Chapman R. Low power interstitial photocoagulation of uterine leiomyomas by KTP/YAG laser. Laser Med Sci 1994; 9:37–46. 14. Philipp C, Poetke M, Berlien H-P. Klinik und Technik der Laserbehandlung angeborener Gefßerkrankungen. In: Berlien H-P, Muller G (eds) Angewandte Lasermedizin, Lehr- und Handbuch fu¨ r Praxis und Klinik, ecomed, Landsberg-Mu¨ nchen Zu¨ rich, 1992. 15. Van Gemert MJC. Modelling of light and heat di#usion in biological tissue. In: Mu¨ ller G, Roggan A (eds) Laser Induced Interstitial Thermotherapy, SPIE Proc 1995:83–4.
142 16. Dachman AH, Mc Gehee JA, Beam TE, Burris JA, Powell DA. US-guided percutaneous laser ablation of liver tissue in a chronic pig model. Radiology 1990; 176:129–33. 17. Bosman S, Phoa SSK, Bosma A, Van Gemert MJC. E#ect of percutaneous interstitial thermal laser ablation on normal liver of pigs: Sonographic and histopathological correlation. Br J Surg 1991; 78: 572–5. 18. Littrup PJ, Lee F, Borlaza GS, Sackno# EJ, Torp Pedersen S, Gray JM. Percutaneous ablation of canine prostate using transrectal ultrasound guidance absolute ethanol and Nd:YAG laser. Invest Radiol 1988; 23:734–9. 19. Amin Z, Donald J, Master A, Kant R, Steger AC, Bowen SG et al. Hepatic metastases: interstitial photocoagulation with real-time US monitoring and dynamic CT evaluation of treatment. Radiology 1993; 187:339–47. 20. Jolesz F, Bleier A, Jakab P, Ruenzel P, Huttl K, Jako J. MR imaging of laser tissue interations. Radiology 1988; 168:249–53. 21. Anzai Y, Lifkin R, Saxton R et al. Nd:YAG interstitial laser phototherapy guided by magnetic resonance imaging in an ex vivo model: dosimetry of laser-MR-tissue interation. Larynoscope 1991; 101: 755–60. 22. Tracz R, Wyman D, Littel P et al. Magnetic resonance imaging of interstitial laser photocoagulation in brain. Laser Surg Med 1992; 12:165–73. 23. Vogl T, Mu¨ ller P, Weinhold N et al. MR-guided laserinduced thermotherapy (LITT) of liver metastasis In: Mu¨ ller G, Roggan A (eds) Laser induced interstitial thermotherapy. SPIE Proc 1995:477–92. 24. Mumtaz H, Harris S, Hall-Craggs M, Davidson T, Lees W, Bown SG. In: Mu¨ ller G, Roggan A (eds) Laser
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25.
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induced interstitial thermotherapy, SPIE Proc 1995:426–33. Dowlatshahi K, Fan M, Bloom K, Gould V. Stereotaxically-guided interstitial laser therapy for non-palpable breast cancers. Laser Med Surg (Abstract) 1997; 8:15. Harries S, Amin Z, Smith ME, Lees WR, Bown SG. Interstitial laser photocoagulation as a treatment of breast cancer. Br J Surg 1994; 81:1617–19. Mumtaz H, Hall-Craggs M, Kissin M, Amin Z, Taylor I, Bown SG. The treatment of breast fibroadenomas using interstitial laser photocoagulation. Laser Med Surg (Abstract) 1997; 8:15. Mumtaz H, Hall-Craggs M, Lewis T, Kissin M, Taylor I, Davidson T et al. Multiple fiber interstitial laser photocoagulation for the treatment of breast cancer. Laser Med Surg (Abstract) 1997; 8:14. Philipp C, Bollow M, Krasicka-Rohde E, Fobbe F, Berlien H-P. Color-coded sonography as a new method for monitoring of laser-induced thermotherapy. Proceedings of Clinical Application of Modern Imaging Technology II SPIE 1994; 2132:287–94. Philipp C, Rohde E, Berlien H-P. Treatment of congenital vascular disorders (CVD) with laser induced thermotherapy (LITT). In: Mu¨ ller G, Roggan A (eds) Laser induced interstitial thermotherapy. SPIE Proc. 1995:443–58. Rohde E, Philipp C, Berlien H-P. Monitoring of interstitial laser induced thermotherapy (LITT) with colour-coded duplexsonography (CCDS). In: Mu¨ ller G, Roggan A (eds) Laser induced interstitial thermotherapy, SPIE Proc. 1995:267–78. Mack M, Vogl T, Mu¨ ller P, Scholz W, Weinhold N, Phillip C et al. Laserinduzierte Thermotherapie (LITT) von Kopf-Halstumoren. Fortschr Ro¨ ntgenstr 1996:164– 72.
Paper received 3 January 1998; accepted after revision 30 July 1998.
Laser-Induced Thermotherapy (LITT) for Retreatment of Locally Advanced Recurrences of Breast Cancer M.S. Ismail1,2,3, C. Philipp1, U. Torsten2, H. Weitzel2 and H.-P. Berlien1 1 Department of Laser Medicine, Neuko¨lln Hospital, Berlin; 2Department of Gynaecology and Obstetrics, University Hospital Benjamin Franklin, Freie University, Berlin, Germany; 3Department of Gynaecology and Obstetrics, Al-Azhar University, Cairo, Egypt
Abstract. The e#ect of laser-induced thermotherapy (LITT) as a palliative method for treatment of patients with local recurrence of breast cancer is investigated. This report describes the use of interstitial laser photocoagulation to manage such lesions. The interstitial laser applications were performed in seven women with locally recurrent breast carcinoma on the chest wall after mastectomy. All patients had been heavily pretreated with conventional modes of therapy (radiotherapy, chemotherapy, hormonal therapy, surgical resection). A Nd:YAG laser with a wavelength of 1064 nm was used to heat the lesions. Heat expansion was controlled digitally and monitored by ultrasonography and colour-coded duplex sonography (CCDS). In five women this minimally invasive method enabled the precise coagulation of the subcutaneous tumour without destruction of the skin or ulceration, although these areas had been pretreated by irradiation up to 60 Gy. In two patients with extensive multiple metastases and with skin infiltration, secondary skin ulceration and delayed healing was observed. For palliative reasons, LITT under CCDS guide can aid in local control of chest wall recurrence following mastectomy in selected patients. Keywords: Colour-coded duplex sonography; Laser induced thermotherapy; Minimal invasive therapy; Recurrent breast cancer
INTRODUCTION Breast cancer is the most frequently observed cancer among women and has the highest incidence of any cancer in western Europe and North America. Worldwide, more than one million women per year will develop breast cancer by the year 2000 [1]. Locally recurrent breast carcinoma of the chest wall following mastectomy can be di$cult to eradicate. Radiotherapy, chemotherapy and hormonal therapy have shown variable e$cacy in controlling these metastases. Because not all patients are surgical candidates and not all metastases are surgically amenable, a search for new modalities for the treatment of this taxing problem is desirable. If left unchecked, discrete nodules can coalesce into larger tumour masses that may erode and ulcerate. These open, draining areas cause pain, odour, Correspondence to: Dr. med. M.S. Ismail MD, Department of Laser Medicine, Neuko¨lln Hospital, Rudower Str. 48, D-12313 Berlin, Germany.
and problems with local wound care that are cosmetically unacceptable and psychologically di$cult for the patient [2]. The superficial location of the breast and its associated lesions, plus the easy localisation, palpation and visualisation of the lesions within the breast or the chest wall area made it an ideal site for laser-induced thermotherapy (LITT). Local recurrence may be slightly more common after breast conservation surgery rather than mastectomy [3]. LITT covers the treatment modality of laser-induced hyperthermia for temperatures from 42C to 60C as well as high temperature treatment of laser-induced coagulation for temperatures above 60C. LITT was first proposed in 1983 by Bown [4] for liver metastasis, and by Ascher [5] for treatment of brain tumours. In 1984, Berlien introduced LITT for the treatment of congenital vascular malformations and haemangiomata [6,7]. LITT has already found a place in the management of isolated metastases [8] and has considerable promise for the treatment of benign prostatic hyperplasia [9], colorectal cancer secondaries
Laser-Induced Thermotherapy for Retreatment of Breast Cancer
in the liver [10], breast and brain tumours [8,11], malignancies of the female genital tract [12], uterine leiomyomata [13] and vascular disorders [14]. The goal of LITT is to apply laser radiation to pathological tissue [15]. With adequate treatment parameters and efficient monitoring procedures, the e#ects of LITT can be limited to the diseased area without destruction of the healthy surrounding tissues. This will increase the patient’s safety [15]. Several techniques for controlling LITT can be applied. Ultrasonography [16–19] and magnetic resonance imaging (MRI) [19–23] are the two main imaging modalities currently used. Studies on normal liver tissue showed a good correlation between the size of the echogenic lesion on ultrasonography and that seen on the pathological specimen at the end of the LITT and at various subsequent times [16,17]. Several studies have demonstrated a direct correlation between laser energy deposition in tissue, real time thermal profiles, MRI signal intensity changes, and subsequent histological changes [20–23]. Unfortunately, the clinically available conventional MRI sequences require several seconds to collect data for an image, which causes disturbance owing to respiratory movements in addition to the artefacts caused by movements of the patients, limited direct access to the patient as well as the high costs of this method. With these limitations of MRI in on-line monitoring of LITT, MRI cannot be recommended for LITT monitoring in breast cancer. Interest in ultrasonography in controlling the LITT process is based on the simplicity of its use, the machine being portable and the imaging performed at the same time and place as the treatment [24]. Extensively pretreated subcutaneous chest wall recurrences in seven patients su#ering from breast cancer have been treated palliatively by the LITT-method under the control of colour-coded duplex sonography (CCDS)
137
Fig. 1. Chest wall with local recurrences of breast cancer: status after bilateral mastectomy, axillary lymph node dissection and irradiation.
Fig. 2. Preoperative CCDS visualisation of the anatomy of a chest wall metastasis within its surrounding tissue.
skin ulceration. LITT was performed 11 times in these patients (Figs 1 and 2). In all patients, it was not possible to treat these lesions surgically, with chemotherapy or radiotherapy, and the areas of concern had been pretreated by chest wall irradiation after mastectomy and/or systemic chemotherapy. For ethical reasons, all patients were thoroughly informed about the study and patient consent was obtained.
Imaging PATIENTS AND METHODS Patients Seven patients (age 50–84 years) su#ering from solitary or multiple subcutaneous pretreated chest wall recurrences of breast cancer were treated with LITT for palliation. The diameters of the subcutaneous metastases were in the range 3–35 mm, and the number of lesions ranged from 1 to 15. There were no cases with
Ultrasonography was used to measure the dimensions of the metastases and the largest diameter was noted. Colour-coded duplex sonography (Quantum 2000, Siemens), with a transducer frequency of 7.5 MHz, was used for both preoperative visualisation of the tumour anatomy (Fig. 2), and for control of the therapeutic coagulation e#ects. The power and the amplification of the signal was set individually according to the required application.
138
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expansion was intermittently controlled digitally and monitored by ultrasonography and CCDS. In cases where the metastasis was directly under the skin, the cutis above the metastasis was always protected from the laser thermal e#ect using ice.
RESULTS
Fig. 3. Puncture of a metastasis with a Teflon catheter (Abbocath G 16). The puncture site is always in the healthy skin area.
Laser Parameter A continuous wave Nd:YAG laser (wavelength 1064 nm, Martin Nd:YAG-Laser, MY 60, Tuttlingen, Germany) was used. A sterilised, single freshly cleaved 600 m fibre was used with a bare tip to deliver laser energy to the tumour (bare fibre 9M-6065, 1050 m outer diameter, Martin, Tuttlingen, Germany).
Procedure Interstitial laser treatment was performed under local anaesthesia for small metastases (diameter 10 mm), where multiple punctures were needed with a distance of more than 10 mm between lesions. Under sterile conditions and after visualisation of the diseased area with CCDS imaging (a sterile sheet was used over the ultrasound probe), the area to be treated was punctured with a Teflon catheter (Abbocath G 16; Fig. 3), which was placed within the tissue under B-scan control. The Teflon catheter was always introduced through a healthy skin area about 1 cm from the metastasis margin to avoid direct skin puncture over the lesion. In each case, a freshly cleaved bare fibre was inserted through the Teflon catheter which was pulled back for 10 mm over the fibre and laser thermal interaction with the catheter material was avoided. The Nd:YAG laser was applied with a power setting of 5 W for a time range of 120–600 s (600–3000 J). In this way it is possible to produce a coagulation zone of approximately 15 mm in diameter, which extends retrograde and in cylindrical form along the fibre. Heat
Ultrasound guidance enabled correct positioning of the catheter and bare fibre inside the metastatic lesion. After a delay of a few seconds, a gradually expanding spherical hyperechoic region appeared around the laser fibre tip. This was followed after 30 s, by a signal in CCDS imaging in the form of random mixtures of red and blue coloration. The hyperechoic area expanded to reach a peak within 100–300 s (according to laser power) and remained approximately the same size and shape until the end of therapy. Under the CCDS, and as the photocoagulation process progressed, the colour signal enlarged but it was not necessarily equal in size and position to the hyperechogenic zone. The onset of colour signals was dependent on the laser power setting. After various times depending on the irradiation parameters, these signals decreased and no further changes were observed in CCDS imaging. During further irradiation, the hyperechogenic zone under B-scan was shifted along the puncture channel towards the periphery. At this time gas bubbles passing along the Teflon catheter and appearing at its proximal end were observed. The extent of the coagulation zone was visible, using the B-scan several minutes after laser exposure. The cutis in the over-lying layers of the metastasis was always preserved without any sign of necrosis. The temperature rise throughout the treated tumour and its skin covering was detected during the digital control of the heat expansion. We also detected crepitation caused by water vapour and spread of CO2 gas in the tissues, a consequence of tissue temperature elevation. This reaction was also monitored in CCDS in the form of random noise of red and blue colouration. The colour signal alters in a reproducible pattern according to the heat distribution and the subsequently occurring degasification of the tissue. This colour signal represents the intensity of tissue reaction and gives information about the actual heat development (Figs 4 and 5). The control CCDS two weeks after the primary treatment showed all
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Fig. 4. Colour-coded duplex sonography imaging during the treatment of subcutaneous local recurrence of breast cancer.
Fig. 6. The chest wall after one month of successful LITT. The same patient in Fig. 1.
Fig. 5. Colour-coded duplex sonography imaging: signal at the end of irradiation during the treatment of the same subcutaneous local recurrence of breast cancer as in Fig. 4.
the signs of fibrosis and reduction of vascular perfusion in these areas. In cases with subcutaneous lesions without skin infiltration, a precise coagulation of the tumour without destruction of the skin or ulceration was achieved. On completion of treatment, an immediate reaction is noted, with erythema and oedema followed by necrosis during the first week. Tumour response was complete within three weeks of treatment. With healing, there is observable shrinkage and flattening of the lesions. Over the next 4–8 weeks the only abnormalities visible after healing were small central depressed scars which gradually faded. Patients with local anaesthesia experienced minimal pain and discomfort during therapy. All patients experienced pain following treatment. For most patients mild analgesia was all that was required for pain control. The incidence of skin necrosis increased with the presence of skin infiltration (intracutaneous metastases). Two cases with skin infiltration
and multiple recurrence lesions near each other, showed skin ulceration and delayed healing up to 12 weeks. Follow-up has ranged from 3 months to 3 years. In the first 6 months follow-up period, two women died of disseminated disease. Three patients, those who had solitary metastases separated by healthy skin, are free of chest wall disease at 6 months follow-up (Fig. 6). The life quality of those patients was improved as a consequence of disappearance of the metastases and also from the psychological aspect. A residual tumour was noted in two patients after treatment.
DISCUSSION LITT has been used for several years in the treatment of subcutaneous lesions of di#erent pathological origins. The laser used is usually a continuous wave Nd:YAG laser (wavelength 1064 nm), since light within the NIR (near infrared region) wavelength range has the greatest penetration depth in biological tissue. Seven patients su#ering from subcutaneous pretreated chest wall recurrences of breast cancer were treated with LITT for palliative reasons. LITT was performed 11 times in these patients. Because of advanced disease it was no longer possible to treat these lesions surgically by a TRAM-flap or a latissimus dorsi muscle-flap. In all cases, the areas of concern
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had been pretreated by chest wall irradiation after mastectomy and/or systemic chemotherapy. The tissue changes in those treated areas could be visualised excellently with CCDS. Thus, it became possible to change the positioning of the bare fibre if necessary, and to completely coagulate the metastases. Until now only a small number of studies [1,24–28] have reported on LITT for breast cancer. In two recent studies, interstitial laser photocoagulation was used for the evaluation of tumour coagulation e$ciency prior to its surgical resection. The assessment of response to therapy was carried out with contrast enhanced MRI. It was concluded that LITT can achieve complete tumour ablation in primary breast cancer and the post-contrast MR images can define the extent of both laserinduced necrosis and residual tumour following LITT of breast cancer [28]. The same group have used LITT for treating breast fibroadenoma in 14 patients. A 40% reduction in tumour volume in all treated fibroadenomas after 8 weeks post-laser application and >90% tumour regression was seen [27]. LITT was applied in 13 patients with tumours that were well defined by mammography (6–18 mm in diameter). Total tumour ablation was achieved in nine cases [25]. To our knowledge, this is the first clinical report about the application of interstitial laser therapy as a treatment modality for the retreatment of locally advanced recurrences of breast cancer. It is also the first study using the CCDS as a controlling imaging modality whilst achieving the complete disappearance of local recurrences. Our results were not promising in achieving complete disappearance of local breast recurrences in patients with multiple, intracutaneous metastasis and with metastases near each other, as in these cases a necrotic skin ulcer with prolonged and bad healing followed laser coagulation (Fig. 7). This meant the conversion of a closed lesion into an ulcerated lesion. In those severly advanced cases, the quality of life and reduction of su#ering were not improved. LITT is ideal for cases with solitary subcutaneous lesions and when the metastases are separated from each other, enabling a good chance of healing without ulceration of the metastasis. In the two patients where skin ulceration developed, this was because the tumour infiltrated skin and in these cases the heating e#ects of laser in the skin layer could not be avoided as the avoidance of skin coagulation
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Fig. 7. The chest wall of the same patient as in Fig. 3 after two weeks of LITT. There were more than 15 chest wall metastases near each other. Skin ulceration and delayed healing resulted. This patient died 2 months from metastatic disease.
would mean incomplete destruction of all the malignant cells. Perhaps in cases with intracutaneous a#ection photodynamic therapy could o#er a lower incidence of skin ulceration. For the successful application of LITT in clinical practice, development of heatsensitivity and fast imaging techniques for real-time monitoring of interstitial laser thermotherapy are required. Several modalities are currently available for imaging control of such types of laser applications including visual and digital control [29–31], ultrasonography, MRI [26,28,32] and stereotaxic systems [25]. Mumtaz et al. described the use of delayed gadolinium-enhanced MR images in defining the extent of laser-induced necrosis and residual tumour after interstitial laser photocoagulation therapy in breast cancer [1]. Each of these methods has its advantages and disadvantages and cannot satisfy all aspects of control and evaluation of the LITT procedure. A more easily applicable technique, which generates real time images of the LITT procedure and its e#ects on tissue, is required to make interstitial laser application a more widely used clinical procedure. Initial interest in ultrasonography in imaging the e#ects of LITT was based on the simplicity of its use, portability and the fact that imaging is performed at the same time and place as the treatment [24].
Development of the CCDS Imaging Method One of the major problems encountered during interstitial laser treatment is the real-time
Laser-Induced Thermotherapy for Retreatment of Breast Cancer
control of tissue e#ects. To avoid coagulation necrosis of the overlying skin, the temperature of the irradiated skin region has to be controlled. For application close to the body surface direct control by palpation of crepitation and heat development as well as visual control of the changes in the transilluminating He-Ne beam are suitable methods. During the application of LITT in the treatment of subcutaneous lesions of di#erent pathological origin, we always monitored heat expansion on the surface of the skin digitally. Using this digital control, we also detected a crepitation caused by vapour and degasification of CO2 in the tissue [29]. But this method did not satisfy all aspects of LITT control. This reaction can also be monitored in CCDS in the form of an indeterminate random noise of red and blue. The colour signal starts, changes and moves in a reproducible pattern, following the heat distribution and the subsequently occurring degasification of the tissue. This colour signal represents the intensity of tissue reaction and gives information about the actual heat development. CCDS may also be used for monitoring localization of the fibre tip. In the procedures where we used the B-scan image for puncture control, a colour signal was displayed which represented tissue movement. By means of CCDS, changes in perfusion are also detectable. The precise extent of the coagulation zone only becomes visible when using the B-scan several minutes after laser exposure. The suitability of CCDS for on-line monitoring of LITT has been investigated experimentally. Rohde et al. [31], have investigated the changes in CCDS imaging in pig liver ex vivo during laser irradiation as well as the thresholds at which the colour signal occurred and the correlation between the B-scan imaging of the damaged area with the size of coagulation in pathological evaluation. They found that CCDS is a sensitive and e$cient technique in providing information about the coagulation process and a correlation between the B-scandetermined hyperechogenic area and the macroscopically observed signs of coagulation and vaporisation.
CONCLUSION In view of the severity of the disease and the failure of other treatment modalities, LITT can play a role in treatment of repeated local recurrences of breast cancer as these lesions, if
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left inadequately treated, can cause significant local problems. These high risk patients may derive an advantage from this method, above all as far as their quality of life is concerned. Much psychological and physical comfort can be a#orded to these women if the chest wall disease is controlled. Further clinical trials are warranted. CCDS is a reliable and easy technique for pre- and postoperative real-time control of the LITT procedure.
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Paper received 3 January 1998; accepted after revision 30 July 1998.
