Intraoperative interstitial microwave-induced hyperthermia and brachytherapy

Intra-operative placement of 11-gauge nylon catheters into deep-seated unresectable tumors for interstitial brachytherapy permits localized heating of tumors (hyperthermia) using microwave (915 MHz) antennas which are inserted into these catheters. Four preliminary cases are described where epithelial tumors at various sites were implanted with an antenna array and heated for 1 hour, both before and after the iridium-192 brachytherapy. Temperatures were monitored in catheters required for the appropriate radiation dosimetry but not required for the interstitial microwave antenna array hyperthermia (IMAAH) system. Additional thermometry was obtained using nonperturbed fiberoptic thermometry probes inserted into the catheters' housing antennas. No significant complications, such as bleeding or infection, were observed. This approach to cancer therapy is shown to be feasible and it produces controlled, localized hyperthermia, with temperatures of 50 degrees C or more in tumors. This technique may offer a therapeutic option for pelvic, intra-abdominal and head and neck tumors.     

Interstitial brachytherapy for carcinomas of the lower lip. Results of treatment.

From 1973 to 1988 47 patients with previously untreated T1 and T2 squamous cell carcinomas of the lower lip received a definitive course of interstitial brachytherapy by iridium 192 wires. The disease stage was T1 in 21 cases (44.7%) and T2 in 26, and N0 in all cases except 2 of N1. Radiation therapy dose ranged between 6000 and 8000 cGy. Local control was obtained in 44 patients (93.6%). Treatment failure in the neck was observed in 3 patients (6.7%). The 5- and 10-year actuarial disease-free survival rates were 92% and 85%, respectively. A surgical salvage was attempted in 3 patients, with postoperative definitive control of the disease in 2. The 10-year actuarial overall survival was 95%. The incidence of complications was acceptable (10.6% of mucosal necrosis). An excellent or good cosmetic result was obtained in 91.7% of patients.     

Interstitial brachytherapy and hyperthermia for malignant gliomas

Interstitial brachytherapy has well-known radiobiological and radiophysical advantages that has made delivery of high doses of radiation to malignant brain tumors a possibility [1]. Over the past 10 years a great deal of clinical information attesting to the usefulness of brachytherapy in the treatment of malignant gliomas has been accrued.     

Interstitial brachytherapy of peri-orificial skin carcinomas on the face]

Purpose. - To analyse outcomes after interstitial brachytherapy of facial periorificial skin carcinomas. Patients and methods. - We performed a retrospective analysis of 97 skin carcinomas (88 basal cell carcinomas (BCCs), 9 squamous cell carcinomas (SCCs)) of the nose, periorbital areas and ears from 40 previously untreated patients (group 1) and 57 patients who had undergone surgery (group 2). The average dose was 55 Gy [50-65] in group 1 and 52 Gy [50-60] in group 2 (mean implantation times: 79 and 74 hours respectively). We calculated survival rates and assessed functional and cosmetic results de visu. Results. - Median age was 71 years [17-97]. There were 29 T1, 8 T2, 1 T3 and 2 Tx tumors in group 1. Tumors were<2 cm in group 2. Local control was 92.5% in group 1 and 88% in group 2 (median follow-up: 55 months [6-132]). Five-year disease-free survival was better in group 1 (91% [75-97]) than in group 2 (80% [62-90]), P=0.23. Of the 34 patients whose results were re-assessed, eight presented pruritus or epiphora. One group 2 patient had an impaired eyelid aperture. Cosmetic results were better in group 1 than in group 2, with respectively 72% (8/11) vs 52% (12/23) of good results and 28 (3/11) vs. 43% (10/23) of fair results. Conclusion. - Brachytherapy provided a high level of local control and good cosmetic results for facial periorificial skin carcinomas that pose problems of surgical reconstruction. Results were better for untreated tumors than for incompletely excised tumors or tumors recurring after surgery.     

放射性粒子种植治疗前列腺癌

随着放射性粒子、计算机软件系统及植入设备的发展,放射性粒子种植治疗前列腺癌取得较大进展.现就放射性粒子种植治疗前列腺癌的常用方法、临床适应证、所需设备、可能的并发症及疗效评价方式等作一综述.     

Interstitial hyperthermia and interstitial iridium 192 implantation: a technique and preliminary results

A simple technique using interstitial hypertbermia in combination with interstitial Iridium 192 implantation is described in detail. This technique was initially tested on swine and later successfully tested on seven patients. The preliminary results of the City of Hope Interstitial Hyperthermia Pilot protocol are stated. The authors feel that this simple technique could be used by any radiation oncologist while performing interstitial implants in selected sites.     

Interstitial microwave hyperthermia and brachytherapy for malignancies of the vulva and vagina. I: Design and testing of a modified intracavitary obturator.

A vaginal obturator was fabricated to be used in combination with implanted catheters to provide microwave hyperthermia and brachytherapy to the vulva and vaginal wall. This site is difficult to heat or irradiate solely with interstitial techniques. The obturator was modified to provide grooves for the mounting of interstitial catheters into the outer wall and was matched with a template for circumferential implants. Power deposition tests were done using arrays of three microwave antenna designs: dipole (hA = hB = 3.9 cm), helical (3.9 cm coil, shorted), and modified dipole (1.0 cm helix on dipole tip) to test the performance of the obturator. The obturator and four non-obturator catheters were positioned in muscle-equivalent phantom. Two obturator catheters along with two free-standing catheters formed the obturator array. Four freestanding catheters formed the non-obturator array. Power deposition or specific absorption rate (SAR) measurements were made along the central axis, bisect, and diagonal transect of each array. SAR results showed that antennas in the obturator wall radiated as dipole theory predicts, although with less power density when compared to antennas in the same catheters spaced 1.8 cm from the obturator. This could be compensated for by increasing the power to the antennas in the obturator by 42%. Adjacent pairs of antennas were placed 90 degrees out of phase for 0.25 sec and rotated around the array. Phase rotation demonstrated that the central array SAR peaks could be lowered from 100% to 50% SAR, with dipole antennas thus resulting in lowered peak temperatures and the ability to heat larger volumes by improving the distribution of power. With helical antennas, there was 50% SAR at the array center when operated coherently without phase rotation. Three patients were treated with the obturator and a custom-made template using dipole antennas, and temperatures were measured in five obturator catheters. Therapeutic heating was measured in the catheters on the obturator between antennas in contact with the vaginal mucosa.     

Superficial microwave-induced hyperthermia in the treatment of chest wall recurrences in breast cancer

Our study concerns 42 patients with chest wall recurrences from breast cancer: 17 Stage 1 (less than 4 cm in diameter), 11 Stage 2 (more than 4 cm), seven Stage 3 (skin ulceration whatever tumor size), and seven Stage 4 (neoplastic lymphangitis and/or skin nodules covering chest wall beyond midline). All the patients were treated with 2450 MHz microwaves by means of a generator with 4 magnetrons (250 to 300 W) and arterial applicators delivering 5 to 10 W/cm2. Each applicator is coupled with an infrared thermometer allowing an atraumatic temperature control processed by a PC-compatible computer using a Turbo Pascal program. A temperature of 41.5 degrees C to 42.5 degrees C was maintained for 45 minutes from the skin surface to a 2.5-cm depth within tissues. Hyperthermia alone was done in four patients; hyperthermia was combined with chemotherapy in four patients, and with electrontherapy (2 X 450 cGy or 3 X 350 cGy/week) in 34 patients: tumor dose under 3000 cGy in seven patients and over 3000 cGy in 27 patients. We observed a complete response in 22 patients (52.3%), a partial response (greater than 50%) in 11 patients (26.1%), and no response in nine patients (21.4%). No complete response was observed in patients treated with hyperthermia alone or in conjunction with chemotherapy. The local control was demonstrated to be improved only in patients treated with hyperthermia and radiotherapy. The results were correlated with tumor stage: ten complete responses out of 12 Stage 1, and one complete response out of four Stage 4. We noted nine side effects completely reversible within a month with no late skin reaction. Our results show that hyperthermia can give improved local control without any morbidity in treating chest wall recurrences of breast cancer.     

Intraluminal brachytherapy in the treatment of bile duct carcinomas

Patients with carcinoma of the biliary tract have a poor prognosis because the disease is often unresectable at diagnosis. Intraluminal brachytherapy has been reported as an effective treatment for localized cholangiocarcinoma of the biliary tract. The purpose of our study was to analyse the survival of patients treated with brachytherapy and make some recommendations regarding its use. Fifteen patients underwent brachytherapy via a trans-hepatic approach at the Royal Prince Alfred Hospital from 1983 to 1993. Eleven patients had low-dose rate brachytherapy and four patients had high-dose rate treatment. There were nine males and six females. The median age was 64 years. Other treatment included bypass procedures in two patients, endoscopic stents in 14 patients and external beam irradiation in one patient. The median survival was 12.5 months and 47% of the patients survived 1 year. The only complication reported was cholangitis which was seen in one patient. There did not seem to be any difference in survival or complications between low- and high-dose rate brachytherapy. We conclude that the addition of intraluminal brachytherapy after biliary drainage prolongs survival and is a safe and effective treatment, but patients still have a high rate of local failure, and further studies will be needed to address this problem.     

Interstitial brachytherapy of periorificial skin carcinomas of the face: a retrospective study of 97 cases

PURPOSE: To analyze outcomes after interstitial brachytherapy of facial periorificial skin carcinomas. PATIENTS AND METHODS: We performed a retrospective analysis of 97 skin carcinomas (88 basal cell carcinomas, 9 squamous cell carcinomas) of the nose, periorbital areas, and ears from 40 previously untreated patients (Group 1) and 57 patients who had undergone surgery (Group 2). The average dose was 55 Gy (range, 50-65 Gy) in Group 1 and 52 Gy (range, 50-60 Gy) in Group 2 (mean implantation times: 79 and 74 hours, respectively). We calculated survival rates and assessed functional and cosmetic results de visu. RESULTS: Median age was 71 years (range, 17-97 years). There were 29 T1, 8 T2, 1 T3, and 2 Tx tumors in Group 1. Tumors were <2 cm in Group 2. Local control was 92.5% in Group 1 and 88% in Group 2 (median follow-up, 55 months; range, 6-132 months). Five-year disease-free survival was better in Group 1 (91%; range, 75-97) than in Group 2 (80%; range, 62-90; p = 0.23). Of the 34 patients whose results were reassessed, 8 presented with pruritus or epiphora; 1 Group 2 patient had an impaired eyelid aperture. Cosmetic results were better in Group 1 than in Group 2 with, respectively, 72% (8/11) vs. 52% (12/23) good results and 28 (3/11) vs. 43% (10/23) fair results. CONCLUSIONS: Brachytherapy provided a high level of local control and good cosmetic results for facial periorificial skin carcinomas that pose problems of surgical reconstruction. Results were better for untreated tumors than for incompletely excised tumors or tumors recurring after surgery.     

Long duration mild temperature hyperthermia and brachytherapy.

Combining long duration mild temperature hyperthermia (LDMH) and low dose-rate (LDR) brachytherapy to enhance therapeutic killing of cancer cells was proposed many years ago. The cellular and tumour research that supports this hypothesis is presented in this review. Research describing LDMH interaction with pulsed brachytherapy and high dose-rate brachytherapy using clinically relevant parameters are compared with LDMH/LDR brachytherapy. The mechanism by which LDMH sensitizes LDR has been established as the inhibition of sublethal damage repair. The molecular mechanisms have been shown to involve DNA repair enzymes, but the exact nature of these processes is still under investigation. The relative differences between LDMH interactions with human and rodent cells are presented to help in the understanding of possible roles of LDMH in clinical application. The role of LDMH in modifying tumour blood flow and its possible role in LDR sensitization of tumours is also presented. The positive aspects of LDMH-brachytherapy for clinical application are sixfold; (1) the thermal goals (temperature, time and volume) are achievable with currently available technology, (2) the hyperthermia by itself has no detectable toxic effects, (3) thermotolerance appears to play a minor if any role in radiation sensitization, (4) TER of around 2 can be expected, (5) hypoxic fraction may be decreased due to blood flow modification and (6) simultaneous chemotherapy may also be sensitized. Combined LDMH and brachytherapy is a cancer therapy that has established biological rationale and sufficient technical and clinical advancements to be appropriately applied. This modality is ripe for clinical testing.     

Interstitial iridium 192 for cutaneous carcinoma of the external nose

Several implantation techniques useful for nasal skin carcinoma have been developed at the Henri Mondor Hospital in Créteil, France and are described in detail. Iridium 192 wires, 0.3 mm in diameter, are afterloaded into either supple plastic tubes or rigid needles implanted according to the rules of the Paris system. Dosimetry is performed by computer, based on either direct measurements of active lengths and spacing, orthogonal films or a tomogram oriented in the central plane of the implant. According to a recent review by the European Curietherapy Group of 468 implants, the optimal dose is 60 Gy. The overall failure rate was 2.6%. Indications for implantation and choice of technique, based on tumor size, site, and gross morphology are discussed.     

Interstitial 192Ir flexible catheter radiofrequency hyperthermia treatments of head and neck and recurrent pelvic carcinomas

Since September 1983, five patients with head and neck cancers and five patients with pelvic or perineal recurrences of colorectal neoplasms received 192Ir interstitial implants through flexible afterloading catheters that were modified to allow RF hyperthermia treatments of the tumor within 1 hr pre- and post-brachytherapy. Local control in the implant volume was obtained in three of the patients with head and neck cancers (base tongue--2/4; floor of mouth--1/1) with follow-up of 9 to 42 months. Two patients had local recurrences after disease-free periods of 8 and 24 months. Two of the five patients treated for pelvic recurrences had complete responses lasting less than 3 months; prolonged stabilization (12 months) of a presacral mass in a third patient also occurred, but the neoplasm eventually regrew. Average temperatures of 39.2 degrees C to 43.7 degrees C were obtained in the implant volumes of these patients during the 45 minute heating periods which took place prior to loading, and just after removal, of the 192Ir seeds in each patient. No instances of intra or post-operative hemorrhage or necrosis of bone or soft tissues occurred in these patients. However, one individual required a permanent tracheostomy for persistent epiglottic edema after implantation as part of a base-tongue brachytherapy procedure. Interstitial RF hyperthermia in conjunction with brachytherapy appears to be a relatively safe and effective modality, but must be tested prospectively to compare its efficacy to interstitial irradiation alone.     

Interstitial brachytherapy should be standard of care for treatment of high-risk prostate cancer

High-risk prostate cancer represents a therapeutic challenge for both the urologist and radiation oncologist. Biochemical outcomes with radical prostatectomy and external-beam radiation therapy are poor in this subset of patients. These unfavorable results have led some to believe that high-risk prostate cancer is not curable with conventional treatment approaches, which has been an impetus for many of the current trials using neoadjuvant chemotherapy and prostatectomy. With the established efficacy of interstitial brachytherapy, these efforts are likely excessive. Most modern trials indicate excellent biochemical control rates among high-risk patients treated with an aggressive locoregional approach that includes brachytherapy. A thoughtful review of the literature would suggest that interstitial brachytherapy offers a therapeutic advantage over other local treatment modalities and should be considered standard treatment for aggressive organ-confined prostate cancer.     

Results of the treatment of 165 lid carcinomas by iridium wire implant

A group of 160 adult patients with epithelial tumors of the lid and/or canthi treated by iridium 192 wire implant are presented. There were 165 epithelial tumors, most of them were basocellular type (85%). In all cases, a nonradioactive procedure was used with disposable angiocatheters before introducing active wires. Respectively, 111/114 (97.4%) of "new" lesions and 48/51 (94%) of previously treated tumors were definitively cured by iridium wire implant. Among the 6 local recurrences, 4 were salvaged by a second iridium implant, and the two others by extensive surgery. Local side effects were present in 30 patients (18%): impairment of the eyelid aperture 9, stenosis of lacrymal ducts 7, eversion of the lid 7, lack of substance 7. These postherapeutic complications were significantly more frequent in treating recurrent lesions (15/48, 31.2%) than in previously untreated tumors (15/112, 13.4%). No visual complication was observed even in the early patients of this series.     

Interstitial brachytherapy for salvage treatment of vaginal recurrences in previously unirradiated endometrial cancer patients

PURPOSE: To evaluate whether interstitial brachytherapy can effectively salvage vaginal recurrence from endometrial carcinoma. METHODS AND MATERIALS: Between September 1989 and September 2000, 13 previously unirradiated patients (mean age 70 years) with isolated vaginal recurrences from endometrial adenocarcinoma were treated with interstitial low-dose-rate brachytherapy with or without additional external beam radiotherapy. Brachytherapy was delivered using a modified perineal Syed template loaded with (192)Ir. The central cylinder was loaded with high-activity (192)Ir (n = 12) or (137)Cs (n = 1). RESULTS: The patients had initially presented with FIGO Stage I (n = 11) or III (n = 2) cancer. Vaginal recurrences were diagnosed at a mean interval of 27.5 months after hysterectomy (range 2-83). The patients were followed for a median of 60 months (range 15-105). Ten patients had recurrence at the vaginal apex and three had recurrence in the lower two-thirds of the vagina. The median time to recurrence was 22 months. The tumor size ranged from 1.5 to 6 cm (mean 2.2, median 2.5). Eleven of 13 patients received 45-50-Gy pelvic external beam radiotherapy, followed by a mean interstitial brachytherapy boost of 28.3 Gy (range 18-35). The 2 other patients received brachytherapy only of 40 Gy and 50 Gy, respectively. All tumors were locally controlled. Three (23%) of 13 patients had a relapse at distant sites (two in the paraaortic region and one in the liver). The overall 8-year actuarial disease-specific survival rate was 77%. Major (Grade 3 and 4) long-term morbidity occurred in 2 patients (15%) and included Grade 3 vaginal ulceration in 1 patient, and Grade 4 colovesical fistula requiring surgical intervention in 1 patient. Additional long-term morbidity included Grade 2 proctitis in 1 patient. CONCLUSION: Interstitial brachytherapy with or without supplementary external beam radiotherapy can effectively salvage vaginal recurrence from endometrial cancer with very favorable local control and overall survival and acceptable morbidity.     

Interstitial low-dose-rate brachytherapy as a salvage treatment for recurrent head-and-neck cancers: long-term results

PURPOSE: Recurrent cancers of the head and neck within previously irradiated volume pose a serious therapeutic challenge. This study evaluates the response and long-term tumor control of recurrent head-and-neck cancers treated with interstitial low-dose-rate brachytherapy. METHODS AND MATERIALS: Between 1979 and 1997, 220 patients with prior radiation therapy with or without surgery for primary tumors of the head and neck were treated for recurrent disease or new primary tumors located within previously irradiated volumes. A majority of these patients had inoperable diseases with no distant metastasis. There were 136 male and 84 female patients, and median age was 56 years. All patients had previously received radiation therapy as the primary treatment or adjuvant treatment following surgery, with a median dose of 57.17 cGy (range, 39-74 cGy). The salvage brachytherapy consisted of a low-dose-rate, afterloading Iridium(192) implant, which delivered a median minimum tumor dose of 53 Gy to a mean tumor volume of 68.75 cm(2). Sixty percent of the patients also received interstitial hyperthermia, and 40% received concurrent chemotherapy as a radiosensitizing and potentiating agent. RESULTS: At a minimum 6-month follow-up, local tumor control was achieved in 77% (217/282) of the implanted tumor sites. The 2, 5, and 10-year disease-free actuarial survival rates for the entire group were 60%, 33%, and 22%, respectively. The overall survival rate for the entire group at 5 years was 21.7%. Moderate to severe late complications occurred in 27% of the patients. CONCLUSION: It has been estimated that approximately 20-30% of head-and-neck cancer patients undergoing definitive radiation therapy have recurrence within the initial treatment volume. Furthermore, similar percentages of patients who survive after successful irradiation develop new primary tumors of the head and neck or experience metastatic neck disease. A majority of such patients cannot be treated with a repeat course of external beam irradiation because of limited normal tissue tolerance, leading to unacceptable morbidity. However, in a select group of these patients, salvage interstitial brachytherapy may play an important role in providing patients with durable palliation and tumor control, as well as a chance for cure.