Intraluminal Irradiation Research Articles

Combined external and intraluminal radiotherapy in the treatment of advanced oesophageal cancer

Background and purpose: Oesophageal cancer still has a dismal prognosis. Radical surgery is by far the most successful treatment but most patients are not operable at the time of diagnosis and for these patients external beam radiotherapy with or without concurrent chemotherapy offers the best choice for cure or palliation. In patients with advanced oesophageal cancer, intraluminal brachytherapy has been proposed as a complementary method to increase local control. Patients and methods: Between 1989 and 1999, 40 patients with inoperable oesophageal cancer were treated with combined external and intraluminal radiation therapy in Turku University Central Hospital. The external radiation was performed with a median total dose of 40 Gy given in 20 fractions. On the average a week after the external radiation a median total dose of 10 Gy intraluminal radiation therapy was given in 4 fractions. Results: The intraluminal brachytherapy could be performed without technical difficulties and no major complications were seen. In many cases (16 out of 40 patients, 40%), the symptoms could be relieved immediately and in most cases the progression of the disease could be delayed as evidenced by post-treatment serial endoscopy. No major complications were encountered. The 1- and 2-year survival rates were 30 and 17.5%, respectively. All patients alive at 2 years can be considered as long-term survivors. Median follow-up was 86 months. Conclusions: Intraluminal brachytherapy is a safe and efficient treatment modality which offers a potential means of cure for selected patients with oesophageal cancer.

A multicenter European REgistry of intraluminal coronary beta brachytherapy using the NOvoste system

While intravascular brachytherapy (VBT) is now an established mode of therapy to prevent restenosis following percutaneous intervention (PCI), there are only very few data available concerning its use outside the framework of randomized controlled trials. The RENO registry was therefore designed to assess feasibility, safety and effectiveness of VBT in routine clinical practice, as well as to determine the predictors of major adverse cardiac events (MACE) following the procedure. Between April 1999 and September 2000, 1098 consecutive patients treated in 46 European centres by intraluminal irradiation using a Sr/Y90 source train (BetaCath™, Novoste, GA) were included in RENO, and follow-up data were obtained for 98.8 % of them after 6.3 ± 2.4 months. 840 (76.5 %) patients were males, and mean age was 62.0 ± 10.2 years. 271 (26.9 %) had unstable angina, and 256 (23.5 %) were diabetics. 913 lesions (77.7 %) were in-stent restenosis, 208 (17.7 %) de novo lesions and 48 (4.1 %) non-stented restenotic lesions. Mean estimated reference diameter was 3.2 ± 0.5 mm and mean estimated lesion length was 19.0 ± 11.8 mm. The prescribed radiation dose was 18.8 ± 3.2 Gy. Multivessel irradiation was done in 6.2% of cases, and a new stent was implanted in 29.6 % of cases. Most patients received 6 or 12 months of combined aspirin and thienopyridin treatment after the procedure. Technical success was obtained in 95.9 % of treated lesions, and the in-hospital MACE rate was 1.8 %. At follow-up, the MACE rate was 18.7 % (1.9 % death of all causes, 2.6 % AMI, 13.3 % TVR by PCI and 3.3 % TVR by CABG). Using multivariate analysis, 7 independent significant predictors of MACE at follow-up could be identified. These were younger patient age, unstable angina, target lesion in a saphenous vein graft, longer lesion length, smaller reference diameter, failure to use a cutting balloon and implantation of a new stent at the time of VBT. The major current application of VBT is the treatment of in-stent restenosis. The good results of VBT observed in recent randomized controlled trials can be reproduced in clinical practice.

Palliation of advanced/recurrent esophageal carcinoma with high-dose-rate brachytherapy

Purpose: The aim was to assess the improvement in swallowing status, complication rate, and overall survival. Patients and Methods: Fifty-eight patients with advanced/recurrent esophageal carcinoma were treated for palliation with high-dose-rate intraluminal brachytherapy (HDR-ILRT) with a remote afterloading microSelectron unit ( 192Ir source) with or without external radiation from November 1994 to May 2000 at the Tata Memorial Hospital. The mean age was 64 years. The mid-third of the esophagus was involved in 38 patients (66%). The group was comprised of 37 previously untreated patients (29 with ≤50% Karnofsky performance status and old age, 4 with metastatic disease, and 4 with second primary esophageal lesions) and 21 patients with post-treatment recurrent tumors. Thirty-eight patients (65%) received intraluminal brachytherapy alone, whereas the remaining 20 patients (35%) received a combination of external and intraluminal radiation therapy. All patients received 2 fractions of HDR-ILRT 1 week apart with 600 cGy per fraction at 1 cm off axis. Results: Overall improvement in swallowing status was seen in 22 patients (48%), and 24 (41%) maintained pretreatment swallowing status. Median dysphagia-free survival was 10 months. Overall complication rates were 30%, with stricture seen in 9 patients (15%), ulceration in 6 (10%), and tracheo-esophageal fistula in 3 patients (5%). Complication rates were higher in the post-treatment group (38%) than in the previously untreated group (27%) ( p = 0.29). The median overall survival for the entire group was 7 months. Median survival was better, although not significantly, for the previously untreated cohort: 7.8 months vs. 6 months for the post-treatment group ( p = 0.77). Conclusion: HDR-ILRT brachytherapy achieves good palliation with acceptable complications in advanced/recurrent esophageal carcinoma.

Safety and Efficacy of Concurrent Cisplatin and Radiotherapy in Inoperable or Metastatic Squamous Cell Esophageal Cancer

Between August 1996 and May 1999, 50 consecutive, previously untreated patients with carcinoma of the esophagus and who were inoperable for various reasons were treated with weekly doses of cisplatin (35 mg/m 2 , maximum 7 cycles) concurrent with either 66 Gy/33 fractions external beam radiotherapy (EBRT) (n=42) or 50 Gy/25 fractions EBRT and two insertions of high-dose-rate intraluminal radiotherapy of 6 Gy each, spaced a week apart (n=8). Eighty-two percent (41/50) of the patients received the stipulated radiotherapy (RT) dose. Seventy-six percent (38/50) received at least 6 cycles of chemotherapy. Neutropenia in the form of WHO grade II-12% (6/50) and grade III-2% (1/50) was observed. Grade III emesis was seen in 8% (4/50). Improvement in the swallowing status was seen in 84% (42/50). Median duration of dysphagia relief was 6 months. The median overall survival was 9 months with 17% estimated to be alive after 4 years. Combined treatment with single agent cisplatin and definitive radiotherapy for inoperable cancer of the esophagus is safe, well tolerated and reasonably efficacious.

Therapeutic effects of simultaneous intraluminal irradiation and intraluminal hyperthermia on oesophageal carcinoma

An applicator enabling simultaneous intraluminal radiotherapy and intraluminal hyperthermia delivery was developed to improve the treatment results for locally advanced oesophageal carcinoma. Eight inoperable cases were treated by this method. Six cases received 40 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (3 Gy and 4 Gy in three cases each) once weekly for 3 weeks; the remaining two cases received 50 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (4 Gy) once weekly for 2 weeks. Hyperthermia was delivered by a radiofrequency current thermotherapy instrument for 30 min at an output that raised the oesophageal mucosal surface temperature to 42-43 degrees C. Intraluminal radiotherapy was delivered with a microSelectron to a submucosal depth of 5 mm after the first 15 min of hyperthermia. Four cases achieved complete response, with all demonstrating local control. Partial response was obtained in four cases, and three of these patients died of local recurrence. There were no significant adverse side effects apart from fistula in one case. In conclusion, simultaneous intraluminal radiotherapy and hyperthermia may improve the current treatment results for locally advanced oesophageal carcinoma.

External irradiation and intraluminal irradiation using middle-dose-rate iridium in patients with roentgenographically occult lung cancer

Purpose: Therapeutic results were analyzed in 39 patients with roentgenographically occult lung cancer (ROLC), and the significance and optimal dose of this therapy were evaluated. Methods and Materials: The subjects were 39 patients who underwent intraluminal irradiation between May 1987 and August 1999. Radiotherapy was performed by combining external irradiation with intraluminal irradiation using middle-dose-rate iridium (four 370-MBq wires) through a catheter with a spacer, which held the source in the center of the bronchus. The doses of radiation were 22–66 Gy (median value 45 Gy) by external irradiation and 10–46 Gy (median value 28 Gy) by intraluminal irradiation. Results: The therapeutic effect was CR in 38 patients and PR in 1, and local recurrence was observed in a PR case and 3 of the 38 patients who showed CR. The 3-year and 5-year relapse-free survival rates were both 87%. No severe radiation injury was observed. Conclusions: Considering that ROLC often occurs as multiple cancers and that many patients with ROLC have reduced lung function, radiation therapy by a combination of intraluminal irradiation and external irradiation is expected to replace surgery as the first choice for the treatment of this disease in the twenty-first century.

129 oral Combined Intraluminal and external irradiation of oesophageal cancer a curative option?

129 oral Combined Intraluminal and external irradiation of oesophageal cancer a curative option?

116Combined intraluminal and external irradiation of oesophageal cancer, a curative option?

116Combined intraluminal and external irradiation of oesophageal cancer, a curative option?

Clinical and quality of life outcomes in the first United Kingdom randomized trial of endobronchial brachytherapy (intraluminal radiotherapy) vs. external beam radiotherapy in the palliative treatment of inoperable non-small cell lung cancer

Background and purpose: A randomized controlled trial was designed to evaluate the clinical and quality of life (QL) outcomes of patients receiving endobronchial brachytherapy (EBT) or external beam radiotherapy (XRT) as a primary palliative treatment in advanced lung cancer. Materials and methods: Ninety-nine patients presenting de novo with lung cancer were randomized to receive EBT or XRT. Eleven key symptoms or clinical signs were assessed by clinicians and patient ratings using self-assessment questionnaires were obtained at the same time. The primary endpoints were a comparison of EBT and XRT for symptom relief and acute and late side-effects (palliation) and their effect on patients’ functional status and patient-rated QL outcomes. A secondary objective was a comparison of clinician assessments with patient self-reported symptoms. Results: Both treatments produced good levels of symptom relief. They were better for XRT at the expense of more acute morbidity. Late side-effects were similar. The functional status of patients was well maintained and changed similarly with time in both groups. XRT gave a better duration of palliation. Twenty-eight percent of XRT patients required EBT (at a median time of 304 days) whereas 51% of EBT patients subsequently had XRT (at a median of 125 days). There was a significant modest gain in median survival with initial XRT (287 vs. 250 days). When clinician and patient assessments were compared, doctors were found to underestimate the severity of breathlessness, anorexia, tiredness and nausea. Conclusions: Fractionated XRT is preferred to EBT as an initial treatment in better performance patients because it provides better overall and more sustained palliation with fewer retreatments and a modest gain in survival time. QL assessment is required in the evaluation of palliative treatments because clinicians frequently underestimate the incidence and severity of key symptoms.

Late esophageal toxicity using a combination of external beam radiation, intraluminal brachytherapy and 5-fluorouracil infusion in carcinoma of the esophagus.

One hundred patients with potentially curable squamous cell carcinoma of the esophagus were treated using a combination of external beam radiation, medium-dose intraluminal brachytherapy (ILBT), and 5-fluorouracil infusion (as a radiosensitizer) from January 1990 to December 1993. The main objective was to determine late toxicity and optimization of the dose of intraluminal radiation. All patients had external radiation of 50 Gy over 5 1/2 weeks, followed by ILBT of 20 Gy for 50 patients (group 1) and 15 Gy for a subsequent 50 patients (group 2), using a dose rate of 315-330 cGy/h with the prescription at 1 cm off axis. The 5-fluorouracil infusion was 500 mg/m2 administered 12 h prior to ILBT. The treatment-related complications among groups 1 and 2 were strictures 24% vs. 8% (p = 0.029), ulceration 30% vs. 28% (p = 0.8), and tracheoesophageal fistulae 12% for both groups. The overall survival for groups 1 and 2 was 8% and 23% at 5 years. The development of life-threatening complications is a major concern and extreme caution is urged before selecting patients for a combination of ILBT and 5-fluorouracil treatment.

The treatment results of 40 patients with localized endobronchial cancer with external beam irradiation and intraluminal irradiation using low dose rate 192Ir thin wires with a new catheter

Background and purpose: While bronchial intraluminal irradiation is valued highly as a useful palliative treatment for lung cancer, its role as a curative treatment is unclear. The treatment results of 40 localized enbobronchial tumors (including tracheal cancer) who underwent external beam irradiation (EBR) and intraluminal irradiation (IR) as a curative treatment is reported, and the role of combined EBR and IR as a curative potential treatment is examined. Materials and methods: Forty patients, including 22 with roentgenographically occult lung cancer (ROLC), 14 (18 lesions) with postoperative recurrent lung cancer (PORLC) and four with tracheal cancer, who underwent EBR and IR from February 1987 to August 1996, were studied. IR was conducted using low dose rate (1.48 GBq) 192Ir thin wires at a bronchial mucosal dose of 4–6 Gy per fraction, with a total dose of 10–57 Gy (median 28 Gy). All patients were also given combined external Linac X-ray irradiation for a total dose of 30–77 Gy (median 52 Gy). Results: As for the primary effect, complete response (CR) was obtained in all 22 ROLC cases; CR was obtained in 12 (16 lesions), partial response (PR) in one and minor response (MR) in one of the PORLC cases; and CR was obtained in three and PR in one of the tracheal cancer cases. The 3-year and 5-year local control rate by Kaplan–Meier method was 75 and 65%, respectively. Twenty-two patients survived for 3 years or longer. Complications included one case each of fatal tracheal hemorrhage, bronchial mucosal ulcer and bronchial stenosis. Conclusions: Combined EBR and IR is useful as a curative potential treatment, and long-term survival can be expected in ROLC, tracheal cancer and a portion of PORLC cases.

Treatment of endobronchial metastases with intraluminal radiotherapy

Metastasis to the lung occurs quite commonly from certain types of extrapulmonary primary carcinoma. Spread to the bronchial lumen is relatively rare. When this does occur, symptoms resembling those of primary bronchial carcinoma are often present, in association with partial or complete obstruction of the bronchial lumen. Palliation of such symptoms is possible with the use of intraluminal radiotherapy (ILT). Between 1990 and 1998, 37 patients with endobronchial metastases were treated using this modality; a single fraction of radiation was delivered by the remote afterloading high dose rate microSelectron system. Data regarding these patients' characteristics and outcome are presented, following a retrospective review of case notes.The commonest symptoms were dyspnoea, cough and haemoptysis; the commonest primary tumour sites were breast, colorectum, oesophagus and kidney. Twenty-four (64·9%) patients had some improvement in symptoms following treatment. Mean overall survival was 280 days, range 9–1145 days. No serious adverse effects occurred. ILT is a relatively simple, safe and effective treatment in the palliation of symptoms due to endobronchial metastases.

High dose rate brachytherapy to prevent recurrent benign hyperplasia in lung transplant bronchi: theoretical and clinical considerations

Background: Significant anastomotic stenosis and malacia is reported to affect 7% to 15% of lung transplant recipients. Laser debridement, dilation and stenting can be used effectively to treat the majority of these patients. However, persistent, as well as reactive hyperplastic tissue reaction, will occur in some of these patients, requiring multiple bronchoscopic interventions. The experience of 2 patients who received intraluminal brachytherapy irradiation to prevent recurrence of hyperplastic tissue causing airway obstruction is reported. Both had failed multiple attempts of local control, including wall stent, laser ablation and balloon dilation. They suffered from shortness of breath and progressive decrease in quality of life because of airway obstruction. Methods Two patients received intraluminal irradiation immediately following removal of severe post-lung transplant obstruction. Both patients developed airway obstruction 3 to 4 months after left lung transplantation. High Dose Rate (HDR) brachytherapy ( 192Ir). Afterloader was used to treat Patient 1 on two occasions. Patient 2 required a single treatment. The radiation dose of 3Gy/fraction was calculated at 1 cm from the catheter for all applications. Results Follow up for both patients included bronchoscopy at 3 weeks, 3 months and 6 months after radiation therapy. Follow up for Patient 1 is 7 months, and patient 2 is 6 months. Each patient had an initial complete response after radiation. There were no treatment-related complications, and both patients experienced significant improvement in respiratory function. Conclusions Symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal radiation therapy. Patients who develop recurrent benign granulation tissue after stent and laser therapy may be considered for this type of treatment.

Endobronchial Metastasis From Osteosarcoma of Bone: Treatment With Intraluminal Radiotherapy

Lung parenchymal metastases are common manifestations in patients with osteosarcoma; however, spread to the major airway itself is extremely rare. We present a young man who had been previously treated with surgical resection following preoperative chemotherapy and immediate postsurgical adjuvant chemotherapy for proximal tibial osteosarcoma. He developed metastasis to the major airways. The patient was treated with intraluminal radiotherapy (ILT) for the endobronchial metastasis. This is the first report of an endobronchial osteosarcoma that was treated with ILT with a complete endoscopic response. ILT provided excellent palliation in this particular case.

Preoperative radiotherapy for advanced lower rectal cancer-combination of external and high-dose-rate intraluminal radiotherapy

Preoperative radiotherapy for advanced lower rectal cancer-combination of external and high-dose-rate intraluminal radiotherapy

Intraluminal Irradiation for TIPS Stenosis: Preliminary Results in a Swine Model

To evaluate the ability of 32phosphorus intraluminal irradiation to reduce pseudointimal hyperplasia in a transjugular intrahepatic portosystemic shunt (TIPS). TIPS were successfully placed in 11 swine with normal portal pressures. Six animals received 15.2 Gy intraluminal irradiation to the hepatic parenchyma and venous outflow tract at the time of TIPS placement with use of a NA32P-filled balloon angioplasty catheter. Five control animals underwent TIPS and balloon angioplasty with saline. All animals were followed up for 28 days, at which time percutaneous portography was performed, the animals were killed, and the tissue around the TIPS stent was processed for histologic analysis. Maximum pseudointimal hyperplasia as a percentage of estimated TIPS diameter was calculated for each animal. At the time of euthanasia, all five control TIPS and all but one irradiated TIPS were occluded. Histologic analysis demonstrated considerable variability in the degree of pseudointimal hyperplasia within each TIPS and between animals. No statistically significant difference was found in the maximum pseudointimal hyperplasia, measured as a percentage of stent radius, between control (80.2%+/-17.4%) and irradiated animals (69.2%+/-25.2%). Irradiation of TIPS with 15.2 Gy 32P delivered at the time of TIPS placement did not significantly improve TIPS patency or reduce the degree of pseudointimal hyperplasia in swine with normal portal pressures.

Review of endovascular brachytherapy physics for prevention of restenosis

Intraluminal irradiation of coronary and peripheral arteries has been shown to reduce neointimal hyperplasia following balloon angioplasty, thereby inhibiting restenosis. Several irradiation techniques are being investigated, including temporary intravascular insertion of high activity gamma- or beta-emitting seeds and wires; inflation of dilatation balloon catheter with radioactive liquid or gas; insertion of miniature x-ray tubes via coronary catheters; permanent implantation of radioactive stents; and postangioplasty fractionated external beam irradiation. Unlike conventional brachytherapy, intravascular treatment of restenosis requires accurate knowledge of dose at distances of 0.5–5 mm from the radioactive source. This requirement presents special problems with regard to source calibration and dose specification, because dose gradients at such close distances from a radioactive source are extremely large. This makes it virtually impossible to define the characteristics of an ideal radiation source without some knowledge of the location and radiosensitivity of the target tissues, plus the radiotolerance of normal tissues. Hence, the current debate over whether beta or gamma sources are to be preferred. Imprecise knowledge of dose–volume effects for coronary arteries, plus uncertainties in the biological time sequencing of restenosis fuel a second debate on whether external beam treatments may be efficacious, and whether or not permanent radioactive stents may prove superior to high dose, single fraction brachytherapy. We review here the dosimetric properties of the various irradiation techniques and isotopes that have been proposed, including aspects of radiation safety, dose homogeneity, and practical aspects of source delivery.

Irradiation for the Treatment of Intimal Hyperplasia

Intimal hyperplasia represents a serious complication limiting the long-term benefits of vascular interventions such as balloon angioplasty and stent placement. Although pharmacological interventions have attempted to curtail restenosis, they have not been shown to be effective to date. Radiotherapy is one alternative that has shown promise as an inhibitor of intimal hyperplasia in several animal models. Irradiation causes cell death by producing irreparable damage to DNA. This is believed to be the mechanism of inhibition of VSMC proliferation. Delivery of irradiation can be either intraluminal via an angiographically directed catheter or extraluminal using an external radiation source such as an x-ray device. Intraluminal irradiation has generally utilized either gamma or beta-emitting sources. Both have been effective in producing a dose response, although some studies advocate the use of beta-type irradiation as a safer, more efficient means of delivery. Extraluminal irradiation also has been an effective inhibitor of intimal hyperplasia. Studies suggest that this form of irradiation provides a more even-dose distribution to vessel walls than an intravascular delivery system. The use of radiotherapy has more recently been extended to clinical trials, and initial studies have shown promising results. The success of irradiation must be balanced with its potential complications including radiation-induced arteritis, coronary artery stenosis, and secondary development of malignancy. Although these have been associated with irradiation, the dose used in these cases was often considerably higher than those used in the treatment of intimal hyperplasia. Finally, with the advent of gene therapy, irradiation may provide an additional means of supplementing this new type of therapy through radiation-inducible gene therapy.

A Pilot Study of Intracavitary Hyperthermia Combined with Radiation in the Treatment of Oesophageal Carcinoma

Twenty—five patients with primary squamous cell carcinoma of the oesophagus were treated with intracavitary hyperthermia combined with external beam radiation and intraluminal radiation at Nanjing Jinling Hospital, China. External beam radiation was given with a 6-MV X-ray; 1.8–2.0 Gy per fraction and five fractions per week; this brought the total dose to 60 Gy. Two weeks later, hyperthermia was applied with 915 MHz microwave intracavitary applicators, which were designed at the City of Hope. Temperature measurements were obtained while moving fibreoptic temperature sensors at 1.0 cm intervals in each of the six peripheral channels of the applicator. Hyperthermia was applied for 1 h before and after the intraluminal radiation. Intraluminal radiation was provided by low dose-rate iridium-192 ribbons in the same intracavitary applicator, giving 30 Gy at 0.75 cm from the applicator surface. The 3-month post-treatment responses showing complete response, partial response, no change and progressive disease were 60% (15/25), 24% (6/25), 8% (2/25) and 8% (2/25) respectively. The median follow-up time was 17 months (range 4–29 months). The 1- and 2-year overall survival rates were 72% (18/25) and 32% (8/25) respectively, and disease-free survival rates were 47 and 30% respectively. The median overall survival and disease-free survival periods were 17 and 10 months respectively. Fourteen patients had local recurrence (either at the primary site or in the lymph node) or had local progression, and five developed metastases. The median duration of the onset of local recurrence or of local progression was 9.5 months (range 0–20 months); the median of distant metastases was 8 months (range 2–16 months). Seventeen patients died. Of these, 15 died of cancer: six with local recurrence alone, four with local progression primary cancer alone, three with distant metastases alone, and two with both local and distant failure. Two patients with complete response of the primary disease died of other diseases. The toxicity was mild. According to the mucous reaction scoring criteria of the Radiation Therapy Oncology Group, the acute toxicity grades I, II, III and IV were 0% (0/25), 20% (5/25). 48% (12/25) and 32% (8/25) respectively. The major late complication was a mild oesophagus fibrosis and difficult swallowing. No serious side effects (grade IV), fistulas or perforations were seen. These results indicate that this method is safe and feasible for treating oesophageal carcinoma.

Preoperative radiotherapy for advanced lower rectal cancer-combination of external and high-dose-rate intraluminal radiotherapy

Preoperative radiotherapy for advanced lower rectal cancer-combination of external and high-dose-rate intraluminal radiotherapy