Remote Afterloading Technique Research Articles

Cervical Cancer, Different Treatments and Importance of Bile Acids as Therapeutic Agents in This Disease.

Cervical cancer can be cured, because it has a long preinvasive period. Early diagnosis and treatment of cervical cancer at women are crucial for reducing of rate mortality. Today, there are many methods for detecting premalignant lesions and one of them is a conventional Papanicolaou test. Cervical cancer develops through a series of changes in the epithelium called cervical intraepithelial neoplasia (CIN). The biological and genetic characteristics of the cells at cancer in situ are irreversibly altered and abnormal cells have the potential to metastasize to others anatomical regions. Infection with human Papillomavirus, which is transmitted sexually, is considered the main cause and represent the necessary, but not the only factor for the development of cervical cancer. Types of high risk human Papillomavirus are often associated with invasive cervical cancer. The carcinogenic types of HPV 16 and 18 are responsible for 70% of cervical cancer and about 50% of CIN 3. Primary prevention of cervical cancer is aimed at reducing incidence, control of causes and risk factors. In this scientific work, in addition to explaining the various treatments necessary for the treatment of cervical carcinoma, we were discussed about the anticancer effects of the synthetic derivative of ursodeoxycholic acid, such as HS-1183, and synthetic derivatives of chenodeoxycholic acid such as HS-1199 and HS-1200. Also, the effects of bile acid complexes with metals such as platinum, zinc, nickel, and copper were considered in the effective treatment of cervical cancer.KEY POINTS• Lymphogenic spreading of cervical cancer occurs relatively early in the regional lymph nodes, while this sort of progression of cervical cancer is rarer in the juxtaregional (paraaortic), mediastinal and supraclavicular nodes.Clinically proven supraclavicular metastases are not a rarity. In stages IIb and IIIa with metastases in paraaortal nodes occur a 20% metastases at the neck lymph nodes.Hematogenic metastases are relatively rare and occur in the posterior phase. Distant metastases are detected in the lungs and liver.Preinvasive and microinvasive stages of cervical cancer are without symptoms. With deeper invasion of the strome, certain clinical symptoms such as prolonged menstruation, increased vaginal secretions, vaginal bleeding between the two periods, contact bleeding (after coitus), unilateral pelvic pain with spreading in hip joint (infiltration of the pelvic nerve plexus), dysuric disturbance, anemia, islet of the lower extremities.In order to diagnose the level spreading of primary lesion of cervical cancer most commonly are used the supplemental searches such as cytoscopy, rectoscopy, urography, irigography, lung and bone radiography, scintigraphy of the liver, kidney and bone, lymphography, CT (MR) of abdomen and pelvis, as well as laboratory analysis.Surgical treatment consists of transvaginal hysterectomy, transabdominal removal of the uterus (via laparotomy), bilateral adenectomy (removal of the ovaries and the fallopian tubes), upper and middle third of the vagina and lymphonodectomy of the regional lymph nodes. The most commonly used radiotherapy, intracavitary brachytherapy, manual afterloading technique and remote afterloading techniques.The synthetic derivatives of ursodeoxycholic acid and chenodeoxycholic acid such as HS-1183, HS-1199, and HS-1200 are used to treat cervical cancer. These derivatives of chenodeoxycholic acid and ursodeoxycholic acid are capable of inhibiting cell proliferation and inducing apoptosis in SiHa human cells of cervix.Platinum compounds are used as catalysts in cervical cancer therapy. Clinical use of platinum complexes for which the bile acids bind is based on the desire to achieve the death of tumor cells and the spectrum of drug activity in the treatment of cervical cancer.Bisursodeoxycholate (ethylenediamine) platinum (II) [Pt(UDC)2(en)] is characterized by important cytotoxicity against HeLa cervical carcinoma cells and this effect already being clearly detectable after 24 h.

A Dosimetric Analysis of the Rectal Doses in Intracavitary Brachytherapy of Carcinoma Cervix: A Prospective Study from a Single Institute.

Introduction:Carcinoma cervix is a common gynecologic malignancy in India and is treated with radical chemoradiation where intracavitary brachytherapy (ICR) is an integral part. In ICR of cervix, the two-dimensional (2D) point-based dosimetry cervix is the most common method used in high-volume centers with rectal dose calculation at modified ICRU rectal point with rectal wire placement. The rectal dose measurement using this method underestimates the dose to the rectum, and rectal dose also varies with the type of applicator used. The aim of our study is to compare the rectal dose calculated by ICRU 38 method versus rectal dose calculated by the rectal wire method using Henschke applicator.Materials and Methods:This is a single-institute, dosimetric comparison study done prospectively. Fifty patients were planned for ICR after 2D orthogonal radiograph-based, computer planning by iridium 192 high-dose rate remote afterloading technique after placing the appropriate Henschke applicator. The vaginal packing was done using sterile gauze with contrast material for defining the ICRU 38 rectal point, and a rectal wire was placed for the modified ICRU rectal point. Rectal doses were calculated by both the methods and compared.Results:The modified ICRU rectal point recorded a lower rectal dose (mean of 25%) compared to ICRU 38 rectal point in the study patients. There were ten patients (20%) with either too much or too little contrast material which made the visualization of the rectal point and radiation planning difficult. P value by paired t-test method was 0.0001, which was statistically significant.Conclusion:The modified ICRU rectal point is easier to visualize than ICRU 38 method (100% vs. 80%) for dosimetry, but it underestimates the rectal doses when compared to ICRU 38 rectal point. There needs to be a correction factor applied (25% in our study for Henschke applicator) when evaluating the rectal doses calculated by rectal wire method, to reduce the rectal toxicity.

Dosimetry of indigenously developed (192)Ir high-dose rate brachytherapy source: An EGSnrc Monte Carlo study.

Clinical application using high-dose rate (HDR) 192Ir sources in remote afterloading technique is a well-established treatment method. In this direction, Board of Radiation and Isotope Technology (BRIT) and Bhabha Atomic Research Centre, India, jointly indigenously developed a remote afterloading machine and 192Ir HDR source. The two-dimensional (2D) dose distribution and dosimetric parameters of the BRIT 192Ir HDR source are generated using EGSnrc Monte Carlo code system in a 40 cm dia × 40 cm height cylindrical water phantom. The values of air-kerma strength and dose rate constant for BRIT 192Ir HDR source are 9.894 × 10−8 ± 0.06% UBq−1 and 1.112 ± 0.11% cGyh−1U−1, respectively. The values of radial dose function (gL(r)) of this source compare well with the corresponding values of BEBIG, Flexisource, and GammaMed 12i source models. This is because of identical active lengths of the sources (3.5 mm) and the comparable phantom dimensions. A comparison of gL(r) values of BRIT source with microSelectron-v1 show differences about 2% at r = 6 cm and up to 13% at r = 12 cm, which is due to differences in phantom dimensions involved in the calculations. The anisotropy function of BRIT 192Ir HDR source is comparable with the corresponding values of microSelectron-v1 (classic) HDR source.

Clinical Investigations Biological effective dose evaluation and assessment of rectal and bladder complications for cervical cancer treated with radiotherapy and surgery

PurposeThis study aims to retrospectively evaluate dosimetric parameters calculated as biological effective dose in relation to outcome in patients with cervical cancer treated with various treatment approaches, including radiotherapy with and without surgery.Material and methodsCalculations of biological effective dose (BED) were performed on data from a retrospective analysis of 171 patients with cervical carcinoma stages IB-IIB treated with curative intent, between January 1989 and December 1991. 43 patients were treated only with radiotherapy and 128 patients were treated with a combination of radiotherapy and surgery. External beam radiotherapy was delivered with 6-21 MV photons from linear accelerators. Brachytherapy was delivered either with a manual radium technique or with a remote afterloading technique. The treatment outcome was evaluated at 5 years.ResultsThe disease-specific survival rate was 87% for stage IB, 75% for stage IIA and 54% for stage IIB, while the overall survival rates were 84% for stage IB, 68% for stage IIA and 43% for stage IIB. Patients treated only with radiotherapy had a local control rate of 77% which was comparable to that for radiotherapy and surgery patients (78%). Late complications were recorded in 25 patients (15%). Among patients treated with radiotherapy and surgery, differences in radiation dose calculated as BED10 did not seem to influence survival. For patients treated with radiotherapy only, a higher BED10 was correlated to a higher overall survival (p = 0.0075). The dose response parameters found based on biological effective dose calculations were D50 = 85.2 Gy10 and the normalized to total dose slope of the dose response curve γ = 1.62 for survival and D50 = 61.6 Gy10 and γ = 0.92, respectively for local control.ConclusionsThe outcome correlates with biological effective dose for patients treated with radiation therapy alone, but not for patients treated with radiotherapy and surgery. No correlations were found between BED and late toxicity from bladder and rectum.

Brachytherapy for Head and Neck Cancer.

Brachytherapy is a useful addition to external beam irradiation in the treatment of patients with head and neck cancer. Removeable implants are especially important in the treatment of neoplasms of the oral cavity (tongue, floor of mouth, buccal mucosa), orophrynx (tonsil, palate, and base tongue) and nasopharynx (intracavitary boosts). The most commonly used isotope for removable implants is irdium 192. The remote afterloading technique is applicable to both interstitial and intracavitary removable implants. Permanent placement of iodine 125 and palladium 103 radioactive sources may be performed for recurrent nasophayngeal malignancies, for palliation of accessible recurrences of primary sites in the oral cavity, oropharynx, and hypopharynx, or for cervical lymph node metastases. With brachytherapy, high radiation doses may be delivered to the volume of interest, while at the same time protecting adjacent normal tissues. Such implantations, if carefully performed, are effective, safe, and have a low risk of complications.

Preliminary experience of high dose rate (HDR) brachytherapy following video assisted thoracoscopic surgery (VATS) based sublobar resection in patients with peripheral non-small cell lung cancer and poor pulmonary functions

7269 Background: To describe the initial experience of delivering adjuvant radiotherapy following sublobar resection using HDR brachytherapy after VATS resection of lung lesions. Methods: Between March and November 2004, 14 patients were treated with VATS sublobar resection and HDR brachytherapy to 16 peripheral lung lesions that were pathologically proven to be non-small cell lung carcinoma. Intraoperatively, brachytherapy catheters were sutured and anchored over the stapled line and to the chest wall. Brachytherapy planning was done using a CT-based planning system. A remote afterloading HDR unit was used for treatment. A median dose of 2,450 cGy was given at 350 cGy per fraction over 7 fractions twice a day, 6 hours apart, over 4 days as inpatient. Dose was prescribed to 1 cm deep to the stapled line. Biologically, this dose is approximately 5,000 cGy and above (180 cGy per fraction equivalent) at the depth of 5 mm in reference to the resection margin. Results: At median and average followup times of 3 months and 4 months respectively, patients tolerated the postoperative brachytherapy well with no pneumonitis or excess complication. Average hospital stay was one week. There was one case of empyema which may or may not be related to radiation treatment. There were 2 incidents of catheter migration due to inadvertent catheter movement during wound care. Consequently, re-planning was needed in order to continue accurate radiation delivery for these patients. Conclusions: Low dose rate brachytherapy has been described in literature for this subgroup of patients for improving local control rate. This is a first report of using HDR brachytherapy with VATS. In our initial experience, patients tolerate this method of brachytherapy well with no significant acute side effect. HDR technique complements with VATS efficiently and does not prolong hospital stay. Remote afterloading technique allows no radiation exposure to staff members or others. Further data are needed to determine the clinical impact of HDR brachytherapy in this subgroup of patients. No significant financial relationships to disclose.

GEC/ESTRO-EAU recommendations on temporary brachytherapy using stepping sources for localised prostate cancer

Background and purposeThe aim of this paper is to present the GEC/ESTRO-EAU recommendations for template and transrectal ultrasound (TRUS) guided transperineal temporary interstitial prostate brachytherapy using a high dose rate iridium-192 stepping source and a remote afterloading technique. Experts in prostate brachytherapy developed these recommendations on behalf of the GEC/ESTRO and of the EAU. The paper has been approved by both GEC/ESTRO steering committee members and EAU committee members. Patients and methodsInterstitial brachytherapy (BT) to organ confined prostate cancer can be applied as a boost treatment in combination with external beam radiation therapy (EBRT) using a proper number of BT fractions in curative intent. Temporary transperineal BT alone or in combination with EBRT are feasible as a palliative/salvage treatment modality because of local recurrence, however, without large clinical experience. The use of temporary BT as a monotherapy is subject of ongoing clinical research. ResultsRecommendations for pre-treatment investigations, patient selection, equipment and facilities, the clinical team, the implant procedure (treatment planning and needle implantation) dose and fractionation, reporting, management of side effects and follow-up are given. ConclusionsThese recommendations are intended to be technically and advisory in nature, but the ultimate responsibility for the medical decision rests with the treating physician. Although, this paper represents the consensus of an interdisciplinary group of experts, TRUS and template guided temporary transperineal interstitial implants in prostate cancer are a constantly evolving field and the recommendations are subject to modifications as new data become available.

Radiation injury to intestine following hysterectomy and adjuvant radiotherapy for cervical cancer

Objective.To evaluate the risk factors for nonrectal radiation-induced intestinal injury (NRRIII) following adjuvant radiotherapy (RT) for cervical cancer using a retrospective review of medical records. Methods.From September 1992 to December 1998, 164 patients with uterine cervical cancer that had completed their allocated adjuvant radiotherapy at the Chinese Medical University Hospital were enrolled for NRRIII analysis. The patients were classified into two groups according to the extent of surgery. Group A consisted of 110 patients (International Federation of Gynecology and Obstetrics [FIGO] stage: IB, n = 87; IIA, n = 21; IIB, n = 2) undergoing radical hysterectomy and bilateral pelvic lymph node dissection, while Group B was composed of 54 analogs receiving adjuvant radiotherapy following incident extrafascial hysterectomy. Treatment consisted of external beam radiotherapy (EBRT) and high-dose-rate intravaginal brachytherapy (HDRIVB). Initially, the whole pelvis was treated with 10 MV X-rays. After irradiation (44 Gy in 22 fractions over 4–5 weeks), the field was limited to the true pelvis and a further 10–20 Gy delivered in 5–10 fractions. For 21 patients in group A without pelvic lymph node metastasis or lymphovascular invasion, the radiation field was confined to the lower pelvis, with a prescribed dose of 50–58 Gy delivered over 5–6 weeks. HDRIVB was performed using an Ir-192 remote after-loading technique at 1-week intervals. A total of 159 patients (97%) received two insertions, while 5 had only one. The standard prescribed HDRIVB dose was 7.5 Gy to the vaginal surface. Logistic regression analysis was performed for assessment of the factors associated with NRRIII. Results.After 38–119 months of follow-up (median, 60), 22 patients (13.4%) developed Radiation Therapy Oncology Group (RTOG) grade 2 or greater NRRIII at a median latency of 18 months (range, 5–48). Four patients were diagnosed as grade 3 complications requiring surgery and three had expired. The independent factors for NRRIII were radical hysterectomy (P = 0.04, relative risk 2.45), lower-pelvic dose >54 Gy (P = 0.0001, relative risk 10.27), and age over 60 years (P = 0.001, relative risk 5.45). The incidence of NRRIII for patients receiving whole and lower-pelvic irradiation was 14.5% and 10.6%, respectively (P = 0.45). Although there was no statistical significance comparing the two external beam irradiation strategies in terms of NRRIII, all four patients with grade 3 NRRIII underwent whole pelvic irradiation. Conclusion.This study identifies three predictive factors for the development of NRRIII following adjuvant radiotherapy for cervical cancer. Limiting the EBRT dose to less than 54 Gy, meticulous patient selection in the elderly, careful planning of the irradiated field, and the constraint of vaginal brachytherapy are four approaches to optimization of postoperative adjuvant radiotherapy.

Postoperative radiotherapy for patients with invasive cervical cancer following treatment with simple hysterectomy.

This study aimed to investigate the survival and complications of patients who received adjuvant radiotherapy for invasive cervical cancer following inadvertent simple hysterectomy. From September 1992 through to December 1998, 54 patients who had received simple hysterectomies for benign lesions, but were incidentally found with invasive carcinoma of the cervix in the surgical specimen, were referred to our department for postoperative irradiation. They were categorized into two groups according to pathological findings. Group A consisted of 25 patients whose specimen showed microinvasion alone, with the depth of stromal invasion <5 mm. Group B consisted of 29 patients whose pathological findings included deep stromal invasion, tumor emboli in cervix, lymphovascular permeation, positive or close resection margin, endometrial or myometrial invasion and vaginal involvement. After external beam irradiation dose of 44 Gy in 22 fractions over 4-5 weeks to the whole pelvis, the radiation field was reduced to true pelvis for a further 10 Gy in five fractions. Brachytherapy was performed using an Ir-192 remote after-loading technique for 1-2 courses. The prescribed dose for each treatment was 7.5 Gy to the vaginal surface. A retrospective analysis was conducted to compare radiation-therapy outcomes for these 54 patients. After 37-102 months of follow-up (median, 58 months), 47 patients were alive without evidence of disease; five patients in Group B died of the disease (three with distant metastasis, one with local relapse, one with both). Two patients died of other concurrent diseases. The 5-year actuarial survival (AS) and disease-free survival (DFS) rates for all patients were 88 and 90%, respectively. The respective 5-year AS and DFS rates for Group A/B were 95/82% (P = 0.07) and 100/83% (P = 0.03). Ten patients (18.5%) developed RTOG Grade 1-4 rectal complications. Five patients (9.3%) developed RTOG Grade 3-4 bladder complications. Eight patients (14.8%) had RTOG Grade 1-4 non-rectal gastrointestinal complications. For patients with invasive cervical cancer following inadvertent simple hysterectomy, external beam radiotherapy combined with one or two fractions of intravaginal brachytherapy could achieve satisfactory disease control. It is recommended to select a high-risk group for intensive adjuvant treatment. Further optimization of the irradiation strategy is also imperative to decrease the incidence of complications.

High dose-rate brachytherapy for elderly patients with uterine cervical cancer.

The need for radiotherapy (RT) in cancer treatment for the elderly patient is growing. The purpose of this study was to analyze the efficacy and complication rate for radiotherapy, using external-beam irradiation (EBRT) and high dose-rate intracavitary brachytherapy (HDRICB), for patients aged 70 years or older with carcinoma of the uterine cervix. From September 1992 to December 1997, 295 patients diagnosed with uterine cervical cancer completed RT at the Shin Kong Memorial Hospital and China Medical College Hospital. Two hundred and fifty-eight patients [International Federation of Gynecology and Obstetrics (FIGO) stage distribution: 35 Ib, 26 IIa, 122 IIb, 10 IIIa, 58 IIIb, 7 IVa] who had undergone at least two courses of HDRICB and a minimum of 3 years of follow-up, were evaluated. A retrospective analysis was conducted to compare the outcome of radiation therapy for the 179 patients under 70 years of age (younger group) and the 79 patients aged 70 years or older (older group). The RT consisted of EBRT followed by HDRICB. After a total EBRT dose of 40-45 Gy/20 in 25 fractions, irradiating the whole pelvis over 4-5 weeks, dosage for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease was boosted to 54-58 Gy, with central shielding. HDRICB was administered at 1-week intervals using an Ir-192 remote after-loading technique. Ninety-nine patients (38.4%) received three fractions of HDRICB, while 156 patients (60.5%) had four fractions. Total prescribed Point A dosages (EBRT + HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while for larger lesions (stage IIB-IVA) analogous dosages were 59-75.6 Gy (median, 65.6 Gy). Median follow-up durations for the older and younger groups were 56/55 months, respectively. The respective 5-year actuarial survivals (AS) for the older and younger groups were 82/85% for stage Ib, 65/65% for IIa, 61/71% for IIb and 35/59% for IIIa-b. The 5-year cause-specific survivals (CSS) for the older and younger groups were 100/95% for stage Ib, 85/75% for IIa, 78/72% for IIb and 42/61% for IIIa-b. The 5-year pelvic relapse-free survivals (PRFS) for the older and younger groups were 100/100% for stage Ib, 91/93% for IIa, 91/90% for IIb and 67/80% for IIIa-b. The 5-year distant metastasis-free survivals (DMFS) for older and younger groups were 100/100% for stage Ib, 92/88% for IIa, 84/73% for IIb and 55/75% for IIIa-b. There was no statistically significant survival difference on comparing the two groups according to stage. The gross tumor-free ratios after EBRT (NRT) for the older and younger groups were 44.3/24.5% (P = 0.001). The 5-year CSS for the 35 NRT patients was 88% for the older group, while for the 44 patients diagnosed with gross residual tumor after EBRT (GRT) it was 64% (P = 0.001). Twelve (15.0%) of the 79 older patients and 14 (7.8%) of the 179 younger patients developed RTOG grade 3-4 rectal complications (P = 0.12), while seven (8.9%) of the 79 older patients and 10 (5.6%) of the 179 younger patients developed RTOG grade 3-4 small bowel complications (P = 0.34). Radiation therapy, consisting of a combination of EBRT and three or four fractions of HDRICB, proved to be effective for older patients. Further optimization of treatment policy is essential by changing the HDRICB fractionation strategy, shortening the treatment time and designing combination drug regimens that are both effective and tolerable during radiotherapy.

High dose rate brachytherapy for early stage oral tongue cancer.

High dose rate (HDR) interstitial brachytherapy of the oral tongue is a new treatment modality. Our study evaluates the outcomes of patients with early stage oral tongue cancer as treated by HDR interstitial implant. We reviewed the records of 19 patients who were seen between 1994 and 2000 with carcinoma of the oral tongue and whose primary tumors were treated solely with interstitial implant using HDR remote afterloading technique. Ten patients had T1 N0 disease, and the remaining 9 had T2 N0 disease. Elective neck treatment was withheld for 12 patients. The remaining seven patients had ipsilateral elective neck dissection. The male-female ratio was 1:0.9, and the median age was 60 years (range, 32-81 years). The median follow-up time was 43 months (range, 6-78 months). The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Fifteen patients had single planar implants, and the remaining four had double planar implants. The median number of catheters inserted was 5 (range, 4-9). The median dose given was 55 Gy in 10 fractions over 6 days. The minimal interfraction interval was 7 hours for the first 7 patients and was extended to 8 hours for the other 12. Mandibular shields were inserted before treatment. The mucositis lasted for 6 to 20 weeks (median, 9 weeks). One patient had local failure, and the 4-year local failure-free survival rate was 94.7%. Three of the 12 patients without elective neck treatment had ipsilateral regional failure develop. They were salvaged by neck node dissection and regionally remained in control. One patient with multiple nodal metastases and extracapsular spread had biopsy-proven liver metastases and died 6 months after implant. One of the seven patients who were treated with elective neck dissection had multiple nodal metastases and extracapsular spread. She was treated with postoperative radiotherapy to the neck. She died 30 months after implant with evidence of regional and distant failure. One patient treated with double planar implant had grade II necrosis of the soft tissue and bone develop. The necrosis resolved with conservative treatment. Another four patients had small area of soft tissue deficit of the tongue attributed to aggressive debulking or biopsy before brachytherapy. Our experience in treating early stage tongue cancer with HDR remote afterloading technique is encouraging, because it gives a local control rate of 94.7% at 4 years with acceptable morbidity. Further studies are eagerly awaited to delineate the optimum schedule for this new treatment modality.

Fractionated high-dose-rate brachytherapy in the management of uterine cervical cancer.

It is well known that intracavitary radiotherapy (ICR), either alone or in combination with external-beam radiotherapy (EBRT) is an essential component of the radiation treatment of uterine cervical cancer. Although low-dose-rate (LDR) brachytherapy has been successfully applied to the management of such patients, several radiation oncologists have experience of using high-dose-rate (HDR) brachytherapy with promising clinical results over the past 4 decades. However, there has been a considerable reluctance by radiation oncologists and gynecologists in North America to employ the HDR remote afterloading technique instead of the more firmly established LDR treatment modality. In contrast, the HDR-ICR system is rapidly gaining acceptance in Korea since the introduction of the Ralstron, remotely controlled afterloading system using HDR Co-60 sources, at the Yonsei Cancer Center in 1979. According to brachytherapy statistics reported by the Korean Society of Therapeutic Radiology and Oncology, in 1997, brachytherapy was performed upon 1,758 Korean patients with uterine cervical cancer, of whom approximately 83% received HDR brachytherapy. In this review, we present our experiences of HDR-ICR for the treatment of uterine cervical cancer. In addition, we discuss the controversial points, which are raised by those considering the use of HDR-ICR for uterine cervical cancer; these issues include physical and radiobiological considerations, and the prospect of future technical improvements.

New Frontiers in Brachytherapy

Brachytherapy gives a high dose to a tumor (better cell kill) because the sources are close to or within the tumor. Because of the location of the source (usually within target volume), the surrounding normal tissues are spared, resulting in lower morbidity. In the past, radiation exposure hazard to caregivers was a major disadvantage of brachytherapy; however, this concern has been reduced with the use of low energy isotopes and remote controlled afterloading techniques. The need for surgical exposure and its associated trauma has been overcome by using percutaneous, image-guided brachytherapy techniques. Use of brachytherapy to treat prostate and intravascular sites can be expected to increase.

Relative dose uniformity assessment in interstitial implants

Purpose: Two new indices, the peak index (PI) and the new geometry index (NGI), that quantify implant dose uniformity and quality are presented. Their advantages include independence to absolute treatment dose and high sensitivity compared with other adopted dose-uniformity measures. The applicability of these indices were evaluated through computer simulations and several clinically executed implant cases. Target coverage is assumed to be properly observed and will not be discussed herein. Methods and Materials: The natural volume–dose histogram serves as the basis of our investigation. The PI and NGI definitions are based on parameters derived from the histogram. Two computer-simulated implants and 12 clinically executed implants, using high-dose rate remote afterloading techniques, are studied. Various indices that quantify the dose uniformity of the implant, namely the quality index (QI), geometry index, as well as the PI and NGI, are computed, and the results are compared. Results: The PI demonstrated significantly increased sensitivity (up to 5 times) to dose-uniformity evaluation, compared with the QI. The deduced parameter NGI may thus offer a better measure of implant qualities, allowing a more meaningful assessment and correlation between implant qualities to the treatment results. The PI system also offers a guideline to the design of optimal implant geometry. Conclusion: The PI overcomes some of the shortcomings of the QI in that it provides more information about the peaking of the natural dose–volume histogram of a particular implant. The PI and NGI may offer better, more sensitive means to assess implant dose uniformity, independent of prescription dose, than other measures.

Technical hints for high dose rate interstitial tongue brachytherapy

High dose rate (HDR) interstitial tongue brachytherapy is a new treatment modality. This study describes important technical details required for its successful use. Thirteen patients with carcinoma of the oral tongue were treated solely with interstitial brachytherapy using HDR remote afterloading techniques during the years 1994–1997. The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Custom-made mandibular lead shields were inserted prior to treatment. Special reusable Tuen Mun Hospital (TMH) lead buttons were made for improved radiation protection. The median dose given was 55 Gy in ten fractions over 6 days. The interfraction interval was 7 hours for the first seven patients treated and was extended to 8 hours for the other six. Shrinking field techniques were employed and the treatment length of the last fraction was reduced by 5 mm. Commencing with the second patient treated with double planar implants, the medial plane was treated with eight fractions while the lateral plane received ten fractions. To reduce further the potential risk of tract seeding, additional coverage to the implantation tracts was given for the last four patients, with the resultant isodose curves resembling a ‘comb rake/brush’. The mean and median measured doses on the inner face of the mandibular shields were 113% and 93% of the reference dose respectively (range 77–247). The dose to the corresponding sites on the gingival surface can be reduced by 75% if the 3 mm thick lead shield is placed successfully. With the use of the TMH button, the transmitted dose to the tissue in direct contact can be reduced by one-third. With the ‘comb rake/brush’ dose distribution, the high dose volume of the single planar implants could be reduced by 44%, compared with the low dose rate technique, if loading to just 5 mm short of the submandibular skin was required. The mean doses for the combination of eight double planar plus two single planar implants, and ten double planar implants, are on average 29% and 37% greater than the reference dose respectively. An 8% reduction in absolute dose in the region between the planes of the catheters would lead to an even greater magnitude of reduction in morbidity to late responding tissue The prerequisite for the success of HDR interstitial implants is to develop a good technique in positioning the afterloading catheters and protection of the normal tissue. Its importance merits special attention if HDR remote afterloading interstitial tongue brachytherapy is to realize its full potential.

High dose rate brachytherapy for carcinoma of the oral tongue

The purpose of this study is to assess the feasibility of treating early-staged tongue cancer with high dose rate (HDR) remote afterloading technique. Furthermore, a new figure of merit, the Geometry Index (GI), is introduced to quantify the quality of the implants. Between 1994 and 1995, eight patients with carcinoma of the oral tongue were treated solely with interstitial implant using the HDR remote afterloading technique. Five patients had T1 N0 disease and the remaining three had T2 N0 disease. Elective neck treatment was withheld. The male-to-female ratio was 1:1, and the mean age 60 years (range: 32-72 years). The median follow-up time was 26 months (range: 6-30 months). The afterloading catheters were positioned through the submandibular approach with the assistance of templates. Six patients had single planar implant and the remaining two had double planar implant. The median number of catheters inserted was 5 (range: 4-9). The median dose given was 60 Gy in 10 fractions over 6 days. The interfraction interval was 7 h. Mandibular and maxillary shields were inserted prior to treatment. Thomadsen et al. introduced the use of Implant Quality Index (QI). We introduce a new parameter, GI, which is defined as ratio of the QI of the nonoptimized executed implant to the corresponding QI value of the nonoptimized idealized implant. The mucositis lasted for 6 to 20 weeks (median: 10 weeks). There was no local failure up to a median follow-up of 26 months. Two patients developed ipsilateral neck node metastases at 2 and 4 months following implant, respectively. One patient had involvement at level II and the other failed at level I to III. Both patients were salvaged by neck node dissection and regionally remained in control. One patient with multiple nodal metastases and extracapsular spread developed biopsy-proven liver metastases and succumbed 6 months following implant. One patient treated with double planar implant developed Grade 3 necrosis of the soft tissue and bone. This complication is largely preventable now, as we have acquired more technical expertise. The mean GI values for the single and double planar implants were 0.88 (range: 0.84-0.91) and 0.8, respectively. This correlates with our practical experience that it is more difficult to maintain a good geometry as double planar implant is required. The GI gives a better view of the geometry of implant as it compares the nonoptimized QI of the executed implant with its ideal counterpart. The failure to achieve a high GI in double planar implants is presumed to relate to technical difficulties rather than variation in individual performance. Our preliminary experience in treating early-staged tongue cancer with the HDR remote afterloading technique is inspiring, as it gives a local control rate of 100% with acceptable morbidity. Further studies are eagerly awaited to delineate the optimum schedule for this modality of treatment. It is hoped that the GI values, which represents the skills of insertion, could be routinely reported so that treatment results between different centers could be compared in a more precise manner.

A system for nonradiographic source localization and real-time planning of intraoperative high dose rate brachytherapy.

We have developed a system for source localization and real-time planning of interstitial volume implants for intraoperative radiation therapy (IORT) using high dose rate remote afterloading techniques. Source localization is realized by using an electromagnetic tracking device, which consists of a transmitter coil, a receiver coil, and a signal processing unit, to generate the coordinates and orientation of the receiver. A drawback of the device is its sensitivity to adjacent metallic objects. Localization accuracy was evaluated in an operating room environment, where the metallic objects closest to the receiver are surgical retractors (that, incidentally, preclude radiographic localization). For achievable separation distances, we found an rms error of 0.7 mm in determining the distance between points 2 cm apart, thereby demonstrating the feasibility of the method. The receiver is mounted on a plastic block from which projects a long stylet and the transmitter is located at about 50 cm from the receiver. The stylet is inserted sequentially into source catheters to obtain the location and orientation data that serve as input to treatment planning software. The planning program optimizes source dwell time to make calculated dose conform to the dose prescribed on an ellipsoidal surface to an extent consistent with a certain level of dose uniformity inside the target volume. A least squares method is used that involves minimizing the objective function by a matrix method (nonnegative least squares). We have demonstrated that dwell time optimization can be performed in a short time and that the approach is adequate for the IORT application.

Combined treatment with temporary short-term high dose rate Iridium-192 brachytherapy and external beam radiotherapy for irradiation of localized prostatic carcinoma

Purpose: To evaluate the treatment outcome after radical radiotherapy of localized prostate cancer in 50 patients (38 patients with stage T1–2 and 12 patients with stage T3) after a median follow-up time of 45 months (range 18–92 months). Methods: The treatment was given by combination of external beam radiotherapy (50 Gy) and brachytherapy (2 × 10 Gy). The brachytherapy was given using TRUS-guided percutaneously inserted temporary needles with a high dose rate remote afterloading technique with Ir-192 as the radionuclide source. Three target definitions and dose levels inside the prostate gland were used. Local control was evaluated by digital rectal examination, TRUS-guided biopsies and serum PSA evaluations. Results: Clinical and biopsy verified local control was achieved in 48 of the 50 (96%) patients; for stage T1–2 in 37 of 38 (97%) patients and for stage T3 in 11 of 12 (92%) patients. A posttreatment serum PSA level ≤1.0 ng/ml was seen in 42 (84%) patients, values from >1.0 to ≤2.0 ng/ml were seen in four (8%) patients and values exceeding 2.0 were seen in four (8%) patients. The late toxicity was minimal. Conclusion: The local control results and the minimal toxicity after the combined radiotherapy treatment are promising. However, long term results are necessary before general use.

Postoperative high dose-rate intravaginal brachytherapy combined with external irradiation for early stage endometrial cancer: A long-term follow-up

Purpose: To evaluate the long-term control of disease and cure rate, complications, second malignancy, and survival of early-stage endometrial cancer patients treated with surgery, high dose-rate brachytherapy, and external beam radiation therapy. Methods and Materials: From 1969 through 1979, 300 patients with clinically staged Stage I–II endometrial cancer underwent total abdominal hysterectomy and bilateral salpingo-oopherectomy, followed by high dose-rate intravaginal radiation, 7 Gy × 3 to 0.5 cm from the mucosal surface, using a remote afterloading technique. External beam radiation therapy, 40 Gy to midplane in 4 weeks, was delivered to high risk patients through AP/PA and lateral fields. Results: The patients were followed for 5–24 years (median 12). The actuarial progression-free survival rate was 96.6%. Post-treatment grade 1–2 actuarial complication rate was 9.5%, including cystitis (4.5%), vaginal stenosis (2.5%), proctitis (1.5%), vaginal necrosis (0.5%), and partial bowel obstruction (0.5%). Neither grade 3–4 complications nor additional late complications were observed in any of our patients. Relapse rate was only 3.7%, of which 45.5% were local, 45.5% were distant, and 9% were mixed. All the patients with relapse were postmenopausal, age range of 58–77 years, with tumor grade 2–3 in 64%. Second primary cancer rate was 12.8% (mostly breast and colon). Factors that were associated with improved prognosis were young age, premenopausal, low grade, no extrauterine disease, and a histology of adenoacanthoma (adenocarcinoma with squamous metaplasia). Conclusion: High dose rate intravaginal radiation therapy combined with surgery and external beam radiation therapy achieved a high cure rate and small number of minor complications. No long-term treatment-related complications were noted in any of the patients. This treatment combination may be safely applied to patients with early stage endometrial cancer.

High dose rate afterloading intraluminal brachytherapy in malignant airway obstruction of lung cancer

Purpose : This is a retrospective study to review the palliation rate, survival rate and complications of high dose rate (HDR) intraluminal brachytherapy in the treatment of malignant airway obstruction of lung cancer. Methods and Materials : A total of 225 high dose rate (HDR) brachytherapy treatments were delivered to 76 patients with symptomatic malignant airway obstruction by remote afterloading technique. An average of 7 Gy at a radius of 1 cm from the center of the source was delivered by Iridium-192 (Ir-192) sources. The majority of the patients received 3 fractions at 2 week intervals. Fifty-four patients received HDR brachytherapy as part of their initial treatment; 20 patients presented as symptomatic endobronchial recurrence. Two patients received YAG laser photoresection to open up the obstruction to allow insertion of the brachytherapy catheter. Fifty-nine patients received concurrent external beam irradiation. Forty-two patients were given 60–70 Gy in 6–7 weeks with curative intent. Seventeen patients were given 20–59 Gy in 2–5 weeks as a palliative measure. Nine patients received a radiosensitizer. One patient received concurrent chemotherapy. Results : The symptomatic response rates are as follows: dyspnea had an 87% response rate (59% partial response, 28% complete response), cough had a 79% response rate (47% partial response, 32% complete response), hemoptysis had a 95% response rate (38% partial response, 57% complete response), and postobstructive pneumonia had an 88% response rate (53% partial response, 35% complete response). Sixty-six patients had follow up endoscopic examination (1–3 months after brachytherapy). Their total response rate was 87% (52% partial response and 35% complete response). There were four acute complications: three cases of massive hemoptysis and one of mild hemoptysis. There are five late complications: three cases of radiation pneumonitis and two of esophagitis. At the time of this study, 55 patients have died with the maximum survival duration 113 months (9.4 years) from diagnosis date and 18 months from first HDR treatment. Twenty-one patients are still alive with a mean follow-up duration of 20 months from diagnosis date and 7.8 months from the first HDR treatment. Conclusion : HDR brachytherapy is an excellent modality for palliating symptomatic malignant airway obstruction with an acceptable complication rate; however, no definitive increase of survival rate was observed. Prospective clinical trials are needed to better define its merit regarding survival. This paper also includes a literature review and discussion of HDR brachytherapy on bronchogenic cancer.