High Dose Rate Intraluminal Brachytherapy Research Articles

Intraluminal High Dose Rate Brachytherapy for Palliation of Dysphagia in Cancer of the Oesophagus

Intraluminal High Dose Rate Brachytherapy for Palliation of Dysphagia in Cancer of the Oesophagus

Reirradiation of head and neck cancer with high-dose-rate brachytherapy: A customizable intraluminal solution for postoperative treatment of tracheal mucosa recurrence

Purpose Delivering adequate dose to tracheal mucosa recurrence after multiple prior courses of surgery and radiation presented a challenge for radiation delivery. Tumor bed location and size, combined with previous doses to surrounding areas, complicated the use of external beam therapy with either photons or electrons. High-dose-rate (HDR) brachytherapy was explored to provide sufficient dose coverage. Methods and Materials A 45-year-old gentleman presented with recurrent head and neck cancer. After undergoing additional excision of gross tumor in the tracheal region, radiation was recommended to improve local control. The region of residual tumor was confined to a small superficial lesion at the posterior–superior aspect of the trachea, involving mucosa located along the bend of the trachea, immediately deep to the stoma. External beam treatment was discussed but was not recommended based on recurrence location in the prior radiation field and patient’s flexed chin position. HDR technique with a custom applicator was preferred. Results A three-dimensional HDR plan based on computed tomography used a single catheter optimized to cover gross tumor volume as delineated by physician. Prescribed dose was 5 Gy/fraction for six fractions (two fractions/wk). The applicator position was verified daily with computed tomography and physician setup approval before treatment. The patient was positioned on a wing board to allow access to the stoma. HDR brachytherapy was well tolerated. Conclusions Intraluminal HDR brachytherapy is a viable option for providing dose to region inside tracheal stoma. Advantages over photon and electron beam therapy include reduced dose to surrounding tissues previously irradiated, skin dose, and reproducibility of treatment delivery.

High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers

To determine the feasibility and safety of high dose rate intraluminal brachytherapy (HDR-ILBT) boost during preoperative chemoradiation for rectal cancer. Between 2008 and 2009, thirty-six patients with locally advanced rectal cancer (≥ T3 or N+), were treated initially with concurrent capecitabine (825 mg/m(2) oral twice daily) and pelvic external beam radiotherapy (EBRT) (45 Gy in 25 fractions), then were randomized to group A; HDR-ILBT group (n = 17) to receive 5.5-7 Gy × 2 to gross tumor volume (GTV) and group B; EBRT group (n = 19) to receive 5.4 Gy × 3 fractions to GTV with EBRT. All patients underwent total mesorectal excision. Grade 3 acute toxicities were registered in 12 patients (70.6%) in group A and in 8 (42.1%) in group B. Complete pathologic response of T stage (ypT0) in group A was registered in 10 patients (58.8%) and in group B, 3 patients (15.8%) had ypT0 (P < 0.0001). Sphincter preservation was reported in 6/9 patients (66.7%) in group A and in 5/10 patients (50%) in group B (P < 0.01). Overall radiological response was 68.15% and 66.04% in Group A and B, respectively. During a median follow up of 18 mo, late grade 1 and 2 sequelae were registered in 3 patients (17.6%) and 4 patients (21.1%) in the groups A and B, respectively. HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers, with higher response rates, downstaging and with manageable acute toxicities.

High-dose-rate afterloading intraluminal brachytherapy for advanced inoperable rectal carcinoma

Purpose High-dose-rate (HDR) intraluminal brachytherapy for advanced or inoperable tumors of the rectum has been used both palliatively and to dose escalate after chemoradiation for curative treatment. Methods Between 1993 and 2007, 79 patients were treated with HDR afterloading brachytherapy for rectal cancer; 70 patients had adenocarcinoma of the rectum; and 9 patients had squamous cell carcinoma of the anal canal. Fifty-two patients had localized disease but were unfit for major surgery and received radiotherapy with radical intent. Twenty-seven patients with advanced or metastatic disease received palliative treatment. The median age was 82 years (range, 33–97). Radical treatment comprised either chemoradiation followed by intraluminal brachytherapy delivering 12 Gy at 1 cm in two fractions or radical monotherapy delivering up to 36 Gy at 1 cm in six fractions two to three times weekly. Palliative HDR brachytherapy schedules were predominantly 10 Gy at 1 cm single dose. Results Objective local tumor response was seen in 41 of 48 assessable patients (85%); of whom, 28 patients (58%) had a complete response and 13 (27%) had a partial response. The most common symptom was rectal bleeding, which was controlled with a complete response rate of 63%. The median duration of the symptom response was 3 months (range, 1–73), and the median survival of the palliative patients was 6 months (range, 1 week–37 months). The median survival for patients treated with radical intent was 18.5 months (range, 2–119). Six patients reported late toxicity with three cases of rectal ulcer, two strictures, and one fistula. Conclusions Intraluminal HDR brachytherapy is effective as local treatment in both the radical and palliative setting, with high tumor and symptom response rates, and acceptable late toxicity.

Intraluminal brachytherapy in the management of squamous carcinoma of the esophagus

Intraluminal high dose rate brachytherapy (ILHDR BT) is one of several effective modalities for palliation of advanced esophageal cancer. Thirty patients with endoscopic-proven, mostly locally advanced, squamous cell carcinoma of the esophagus, not involving the gastroesophageal junction and without distant metastases, were included in this analysis. Twenty-nine patients received two ILHDR BT sessions of 8 Gy within a week and one patient received only one session. All patients were followed monthly. Outcomes included quality of life (QOL), symptoms control: dysphagia, regurgitation, odynophagia, and chest or back pain, as well as, overall survival. Through 4 months of follow-up, QOL was statistically improved (having lowered scores) in regards to feelings (P= 0.013), sleeping (P= 0.032), eating (P= 0.020), and social life (P= 0.002). The most significantly improved symptom was dysphagia (P < 0.006), with a reduction of 0.52 units or one-half grade. Regurgitation, odynophagia, and pain were lower during follow-up but were not statistically significant. The median overall survival from death of any cause was 165 days (with a 95% confidence interval of 128-195 days). In conclusion, ILHDR BT of advanced squamous esophageal cancer consisting of two out-patient procedures is very successful in achieving the primary objectives of the patients to reduce dysphagia and improve QOL.

Endoscopic brachytherapy for obstructive colorectal cancer

Purpose Palliation of obstructive colon cancer is often challenging. Treatment options include Yttrium aluminum garnet (YAG) laser, stent placement, and surgical intervention. High-dose-rate intraluminal brachytherapy (HDRILBT) has been used to relieve obstructive symptoms due to rectal, bronchial, and esophageal cancers. In this case report, we document the combined use of YAG laser and HDRILBT for the palliation of obstructive colon cancer at the hepatic flexure, not previously reported in the literature. Methods and Materials The patient in this case report had a large colonic tumor at the hepatic flexure causing near complete obstruction. Stent insertion and surgery were not feasible. YAG laser was used once and 11 days later, two fractions of HDRILBT were given 1 week apart. Under endoscopic vision and fluoroscopic guidance, a 150-cm Teflon catheter was passed through the lumen of the partially obstructed bowel for purposes of HDRILBT. A total dose of 10 Gy was delivered at 1 cm from the center of the source axis using a high-dose-rate afterloader. Results After treatment with the first fraction of HDRILBT, the tumor size decreased and the colonic lumen was significantly more patent. The patient's symptoms were significantly relieved after two fractions. Her weight increased and she was medically fit enough to undergo further chemotherapy. Further HDRILBT was not indicated. The calculated biological effective dose for the total HDRILBT treatments was well below the dose tolerances for acute effects for normal colonic tissue. Conclusion HDRILBT should be considered as a possible treatment option for obstructive colon cancers when stent placement or surgery is not possible.

In Vitro Survival of Nonsmall Cell Lung Cancer Cells Following Combined Treatment with Ionizing Radiation and Photofrin‐mediated Photodynamic Therapy

It has been suggested that combination high dose rate (HDR) intraluminal brachytherapy and photodynamic therapy (PDT) in nonsmall cell lung cancer (NSCLC) may improve efficacy of treatment, reduce toxicity and enhance quality of life for patients. To provide a cellular basis for this we examined the in vitro sensitivity of MRC5 normal lung fibroblasts and four NSCLC cell lines following HDR radiation, PDT and combined HDR radiation and PDT. HDR radiation was cobalt-60 gamma rays (1.5-1.9 Gy min(-1)). For PDT treatment, cells were exposed to 2.5 microg mL(-1) Photofrin for 18-24 h followed by light exposure (20 mW cm(-2)). For combined treatment cells were exposed to Photofrin and then either exposed to light and 15-30 min later exposed to HDR radiation or exposed to HDR radiation and 15-30 min later exposed to light. D(37) values calculated from clonogenic survival curves indicated a six-fold difference in HDR radiation sensitivity and an eight-fold difference in PDT sensitivity. The effect of combined treatment was not significantly different from an additive effect of the individual treatment modalities for the NSCLC cells, but was significantly less than additive for the MRC5 cells. These results suggest an equivalent tumor cell kill may be possible at reduced systemic effects to patients.

Intraluminal high-dose rate brachytherapy (HDR) with or without external radiotherapy in patients with unresectable hilar cholangiocarcinoma

Intraluminal high-dose rate brachytherapy (HDR) with or without external radiotherapy in patients with unresectable hilar cholangiocarcinoma

Value of Chemotherapy with ECF in Advanced Esophageal Cancer Treated with Endoscopic Guided High Dose Rate Intraluminal Brachytherapy (EGHDRILBT)

Value of Chemotherapy with ECF in Advanced Esophageal Cancer Treated with Endoscopic Guided High Dose Rate Intraluminal Brachytherapy (EGHDRILBT)

Second Line Palliative Endobronchial Radiotherapy with HDR Ir 192 in Recurrent Lung Carcinoma

PurposeTo observe the efficiency of reirradiation with high dose rate intraluminal brachytherapy in symptomatic palliation of recurrent endobronchial tumors.Materials and MethodsBetween January 1994 and June 1998, 21 patients diagnosed with recurrent endobronchial tumors following external beam radiotherapy were treated palliatively with high dose rate intraluminal irradiation at Hacettepe University Oncology Institute. A single fraction of 10 Gy was prescribed to the specified area in 9 patients and 15 Gy to 12.ResultsEndobronchial treatment improved the performance and reduced symptomatology in 17 (81%) patients. Ten dyspneic patients (10/14, 71%) recovered clinically with an accompanying radiological downstaging. The median symptomatic palliation was 45 days (range, 0 - 9 months), and the overall median survival was 5.5 months (range, 4 - 12 months). The palliative intrabronchial brachytherapy was well tolerated, with the exception of in one patient with a fatal hemorrhage, and another with medically salvaged bronchospasm and intrabronchial edema.ConclusionRecurrent patients with a history of previous thoracic external beam irradiation can be effectively palliated with high dose rate endobronchial reirradiation if the symptoms are directly related to the endobronchial tumor.

Endoscopic intraluminal brachytherapy and metal stent in malignant hilar biliary obstruction: a pilot study

Malignant hilar biliary obstruction carries a poor prognosis, as the disease is often unresectable at the time of diagnosis. Various palliative measures as surgical/radiological/ endoscopic drainage with or without radiotherapy/chemotherapy have been tried with dismal outcome. We prospectively studied the effect of unilateral metal stent with intraluminal high dose rate (HDR) brachytherapy in patients with type II malignant hilar biliary obstruction. Eight patients with type II malignant hilar biliary obstruction were treated with contrast-free unilateral metal stenting followed by endoscopic intraluminal brachytherapy (ILBT). A retrospectively analyzed group of 10 patients treated only with contrast-free unilateral metal stenting served as historical controls. A successful drainage was achieved in all, cholangitis occurred in none and no patient died within 30 days in both groups. The mean (+/-SD) patency of metal stent was 305 (+/-183.96) days and 143.9(+/-115.11) days in patients with and without intraluminal brachytherapy, respectively (P=0.03). Mean (+/-SD) survival of these patients was 310 (+/-192.68) days and 154.9 (+/-122.51) days in patients with and without intraluminal brachytherapy, respectively (P=0.05). Kaplan-Meier analysis showed estimated median survival of 225 (95% CI; 169.5, 280.4) days in brachytherapy and 100 (95%CI; 94.1, 105.8) days in control group (P=0.025). No major complications related to metal stent or ILBT were observed. Contrast-free unilateral metal stenting with HDR ILBT in type II malignant hilar biliary obstruction is a safe and effective method of palliation and appears to prolong patient survival as well as patency of stent in these patients, however, a larger, randomized trial is required to validate the same.

2177: Treatment of Esophageal Cancer Using High Dose Rate Intraluminal Brachytherapy Alone Or In Combination With Other Modalities

2177: Treatment of Esophageal Cancer Using High Dose Rate Intraluminal Brachytherapy Alone Or In Combination With Other Modalities

Concomitant Chemotherapy and External Radiotherapy plus Brachytherapy for Locally Advanced Esophageal Cancer Results of a Retrospective Multicenter Study

In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable. Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients. At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pT0) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy. For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.

Randomized prospective study on the role of high dose rate intraluminal brachytherapy (HDRILBT) in palliation of symptoms in advanced non small cell lung cancer (NSCLC) treated with radiation alone

Randomized prospective study on the role of high dose rate intraluminal brachytherapy (HDRILBT) in palliation of symptoms in advanced non small cell lung cancer (NSCLC) treated with radiation alone

Randomized prospective study on the role of high dose rate intraluminal brachytherapy (HDRILBT) in palliation of symptoms in advanced non small cell lung cancer (NSCLC) treated with radiation alone

Randomized prospective study on the role of high dose rate intraluminal brachytherapy (HDRILBT) in palliation of symptoms in advanced non small cell lung cancer (NSCLC) treated with radiation alone

57 Randomized prospective study on the role of high dose rate intraluminal brachytherapy (HDRILBT) in palliation of symptoms in advanced non small cell lung cancer (NSCLC) treated with radiation alone

57 Randomized prospective study on the role of high dose rate intraluminal brachytherapy (HDRILBT) in palliation of symptoms in advanced non small cell lung cancer (NSCLC) treated with radiation alone

Randomized prospective study comparing high-dose-rate intraluminal brachytherapy (HDRILBT) alone with HDRILBT and external beam radiotherapy in the palliation of advanced esophageal cancer

Purpose HDRILBT is one of the best methods of palliation for advanced esophageal cancer (AEC) by improving dysphagia-free survival (DFS) and overall survival (OS). This study examines if the addition of EBRT would further improve the outcome by improving DFS in AEC. Methods and materials Patients with inoperable AEC were entered into a randomized prospective study. HDRILBT of 16 Gy/2 fractions/3 days was given initially to all patients. Following treatment, patients were randomized to receive no further treatment (Group A) or additional EBRT of 30 Gy/10 fractions/2 weeks (Group B) and were followed for 1 year. Statistical analysis of the data was done using the SAS statistical software package (SAS Institute, Cary, NC). Prognostic variables were analyzed using the χ 2 and log-rank tests and survival curves were drawn using the Kaplan–Meier method. Multivariate survival analysis was done using the Cox proportional hazards model. Results Sixty patients were entered into the study. Patient and tumor characteristics were comparable among the groups. Of 30 patients in Group B, 2 refused additional EBRT (no dysphagia). At 6 months, >50% had DFS in both groups and this was comparable. There was no difference statistically (p >0.05) in the DFS and OS between the two groups at the end of 12 months. Median survival for Group A was 7.23 months and 7.5 months for Group B. Additional EBRT did not improve DFS or OS. Eleven patients developed strictures related to radiotherapy and were dilated successfully (Group A, 7; Group B, 4; p >0.05). Four patients had progressive luminal disease which progressed to fistula (Group A, 3; Group B, 1; p >0.05). There was no effect of any patient or treatment parameter on DFS. Presenting weight and ECOG score had an impact on OS. Conclusions From the preliminary analysis, additional EBRT to HDRILBT does not improve DFS or outcomes in inoperable AEC.

Palliative treatment by high–dose-rate intraluminal brachytherapy in patients with advanced esophageal cancer

Purpose The aim of this work was to analyze the results of palliative HDR brachytherapy in patients with advanced esophageal cancer. Methods and materials Ninety-one patients with unresectable, advanced esophageal cancer were treated palliatively by HDR brachytherapy. All patients received a total dose of 22.5 Gy in three fractions per week. Remissions of dysphagia and other clinical and radiological factors were assessed in the first month posttreatment, and then in the third, sixth, and twelfth months. The survival rate was compared with some chosen clinical factors using a log-rank test and the Kaplan–Meier method. Results The median survival time among all patients was 8.2 months. The median survival time according to the obtained remission was 14.6, 7.2, and 3.8 months (log-rank p = 00001, F Cox p = 0.00001) for complete remission (CR), partial remission (PR), and lack of remission (NR), respectively. A longer median survival time was observed when tumor size was less then 5 cm (12.1 months), than between 5 and 10 cm (7.8 months), or longer than 10 cm (6.4 months) (log-rank p = 0.002). Longer median survival times were observed in clinical stage II (14.1 months), compared with clinical stage III (7.7 months) and IV (7.2 months) (log-rank p = 0.01). Significant correlations were found between survival and the Karnofsky Performance Status, grade of dysphagia, and age. Conclusions HDR brachytherapy for advanced esophageal cancer allowed for improvement of dysphagia in most patients. The complete or partial remission, the older age of patients, and the lower grade of dysphagia observed in first month posttreatment were the most important prognostic factors allowing for prolonged survival (confirmed by a multivariate analysis). In the univariate analysis, important prognostic factors for prolonged survival were: a higher Karnofsky Performance Status, a lower clinical stage and a small tumor size.

Randomized prospective study comparing high dose rate intraluminal brachytherapy (HDRILBT) alone to HDRILBT and external beam radiotherapy (EBRT) in the palliation of advanced esophageal cancer

Purpose/Objective: Previous studies have shown that HDRILBT is the best method of palliation for advanced esophageal cancer offering lasting palliation by improving dysphagia-free survival (DFS) in more than 60% of cases for prolonged periods of time. This, in turn, improves the overall survival (OS) in patients with advanced disease with a good quality of life. Encouraged by the results of HDRILBT alone in palliation of advanced cases, a study was designed to determine if the addition of EBRT would further improve the outcome in terms of DFS for advanced esophageal cancers. Materials/Methods: Patients with advanced inoperable esophageal cancer were entered into a randomized prospective study at the Johannesburg Hospital, University of the Witwatersrand, South Africa. All patients were initially investigated and found to be inoperable due to advanced lesions (extra esophageal spread or long lesions) by our surgical colleagues. Chemoradiotherapy was not considered as a suitable option in these patients as all these patients had lost more than 30–40% of their body weight in the past 6 months, and had presented to us with severe dehydration and wasting which precluded them from undergoing aggressive chemoradiotherapy regimes successfully. Selection criteria included lesion in the thoracic esophagus, inoperable advanced disease, histologically proven squamous cell carcinoma, no evidence of distant metastasis, no involvement of the tracheo-bronchial tree on bronchoscopy and/or barium swallow and an ECOG performance score of 0 or 1 or 2. HDRILBT of 16 Gy in 2 fractions over 3 days was prescribed at 1 cm from the center of the source axis and a margin of 2 cm was given proximal and distal to the tumor. Following treatment, patients were randomized to either receive no further treatment (Group A) or additional EBRT of 30 Gy in 10 fractions over 2 weeks (Group B). Following treatment all patients were followed up for a year. Statistical analysis of the data was done using the SAS statistical software package (SAS Institute, Cary, NC). Prognostic variables were analyzed using the chi square and log rank tests and survival curves were drawn using the Kaplan Meier method. Multivariate survival analysis was done using the Cox proportional hazards model. Results: Sixty patients were entered into the study. The mean length was 8.06 cm and the mean weight 46.15 kg. Of the 30 patients, who received initial HDRILBT and were then randomized to receive additional EBRT, two refused additional EBRT as they did not have any dysphagia. These two patients were therefore excluded from the survival analysis and their outcome is mentioned separately. At 6 months more than 50% had dysphagia-free survival in the two groups and this was comparable. There was no difference statistically (p> 0.05) in the dysphagia free survival between the two groups at the end of 12 months. The overall survival amongst the two groups was also similar (p>0.05). The median survival for Group A was 7. 23 months while for Group B it was 7. 5 months. The addition of additional EBRT did not improve the dysphagia free or overall survival in the preliminary analysis. Eleven patients developed strictures related to radiotherapy and all were dilated successfully (Group A-7, Group B- 4, p>0.05). Four patients had progressive luminal disease, which progressed, to fistula (Group A- 3, Group B- 1, p>0.05). There was no effect of age, sex, race, location of tumor, grade of tumour, pain, presenting dysphagia scores, mean length and protocol of treatment on dysphagia free or overall survival on univariate and multivariate analysis. Presenting weight and ECOG score had an impact on overall survival but not on DFS. Conclusions: From the preliminary analysis, it appears that additional EBRT to HDRILBT does not improve dysphagia free survival and outcomes in advanced inoperable esophageal cancer.

211 Intraluminal high dose rate brachytherapy in the treatment of carcinomas of the subhepatic region

The −863 C/A polymorphism in the tumor necrosis factor-α (TNF-α) promoter has been suggested to influence TNF-α expression. Here we elucidated the molecular mechanisms underlying the allele-specific regulation of TNF-α gene expression under basal and LPS-stimulated conditions in THP-1 cells and in human primary macrophages. We show that the binding of two NF-κB complexes, the p50/p50 homodimer and the p50/p65 heterodimer, was upregulated upon LPS stimulation. Both complexes bound to the C-allele whereas the A-allele only bound the p50/p65 complex. Two DNase I hypersensitive sites appeared in the TNF-α promoter after LPS stimulation of THP-1 cells. DNase I hypersensitivity of the TNF-α promoter was also analyzed in human monocytes prepared from individuals of different −863C/A genotype. Hypersensitivity was increased in the promoter harboring the mutant A-allele, particularly after LPS stimulation. In summary, binding of transcription factor NF-κB to the TNF-α promoter is associated with allele-specific remodeling of chromatin structure.