Subir Nag

A simple method of obtaining equivalent doses for use in HDR brachytherapy

PURPOSE To develop a simple program that can be easily used by clinicians to calculate the tumor and late tissue equivalent doses (as if given in 2 Gy/day fractions) for different high-dose-rate (HDR) brachytherapy regimens. The program should take into account the normal tissue sparing effect of brachytherapy. METHODS AND MATERIALS Using Microsoft Excel, a program was developed incorporating the linear-quadratic (LQ) formula to calculate the biologically equivalent dose (BED). To express the BED in terms more familiar to all clinicians, it was reconverted to equivalent doses as if given as fractionated irradiation at 2 Gy/fraction. Since doses given to normal tissues in HDR brachytherapy treatments are different from those given to tumor, a normal tissue dose modifying factor (DMF) was applied in this spreadsheet (depending on the anticipated dose to normal tissue) to obtain more realistic equivalent normal tissue effects. RESULTS The spreadsheet program created requires the clinician to enter only the external beam total dose and dose/fraction, HDR dose, and the number of HDR fractions. It automatically calculates the equivalent doses for tumor and normal tissue effects, respectively. Generally, the DMF applied is < 1 since the doses to normal tissues are less than the doses to the tumor. However, in certain circumstances, a DMF of > 1 may need to be applied if the dose to critical normal tissues is higher than the dose to tumor. Additionally, the alpha/beta ratios for tumor and normal tissues can be changed from their default values of 10 Gy and 3 Gy, respectively. This program has been used to determine HDR doses needed for treatment of cancers of the cervix, prostate, and other organs. It can also been used to predict the late normal tissue effects, alerting the clinician to the possibility of undue morbidity of a new HDR regimen. CONCLUSION A simple Excel spreadsheet program has been developed to assist clinicians to easily calculate equivalent doses to be used in HDR brachytherapy regimens. The novelty of this program is that the equivalent doses are expressed as if given at 2 Gy per fraction rather than as BED values and a more realistic equivalent normal tissue effect is obtained by applying a DMF. Its ease of use should promote the use of LQ radiobiological modeling to determine doses to be used for HDR brachytherapy. The program is to be used judiciously as a guide only and should be correlated with clinical outcome.

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

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

125Iodine brachytherapy for colorectal adenocarcinoma recurrent in the pelvis and paraortics.

PURPOSE To evaluate the results of 125I brachytherapy in colorectal cancers recurrent in the pelvis and paraortics. METHODS AND MATERIALS From September 1989 to January 1997, 29 patients with colorectal adenocarcinoma recurrent in the pelvis or the paraortic nodes were treated intraoperatively with permanent 125iodine seed implantation at the James Cancer Center of The Ohio State University (OSU). All patients had undergone prior surgery; 72% had prior EBRT. The implanted residual tumor volume was microscopic in 38% and gross in 62%. The implanted area (median 25 cc) received a median minimal peripheral dose of 140 Gy to total decay. An omental pedicle was used to minimize irradiation of the bowel. Five patients received additional postimplant EBRT (20-50 Gy; median 30 Gy). RESULTS The 1-, 2-, and 4-year actuarial local-regional control rates were 38%, 17%, and 17%, respectively, with a median time to local failure of 11 months (95% CI 10-12 months). The first manifestation of disease progression in 52 % of the patients was local-regional. In addition, 22 patients (75%) developed distant metastases. The 1-, 2-, and 4-year actuarial overall survival rates were 70%, 35%, and 21%, (median = 18 months; 95% CI: 14-22 months). Overall survival was better for patients smaller volume implants (p = 0.007), with a lower total activity implanted (p = 0.0003), with a smaller number of implanted sites (p = 0.004), and with microscopic residual disease (p = 0.01). Patients receiving additional EBRT also had a better prognosis (p = 0.005). Local tumor progression was the cause of death in 34% of the patients who have died at the time of this report and 56% died of distant metastases. Of the patients, 13 (45%) experienced 15 toxic events, including 3 patients (10%) with enteric fistula. Neuropathy was not observed. CONCLUSIONS 125I brachytherapy can be successfully used for salvage in patients with recurrent colorectal cancer. Patients with isolated, microscopic, or minimal gross residual disease requiring small-volume implants and those receiving additional EBRT have a better prognosis. Postimplant EBRT is now routinely added, even for previously irradiated patients, in an attempt to improve local control. Compared to IOERT and IOHDR, 125I brachytherapy is not associated with clinical neuropathy, probably due to the continuous low dose rate irradiation delivered by the 125I seeds.

Feasibility of intraoperative high-dose rate brachytherapy to boost low dose external beam radiation therapy to treat pediatric soft tissue sarcomas

PURPOSE To determine if a single intraoperative high-dose-rate brachytherapy (IOHDR) dose can be used in conjunction with low dose external beam radiation therapy (EBRT) to treat soft tissue malignancies in children with reduced morbidity. METHODS From March 1992 to February 1995, six pediatric patients (4 boys, 2 girls; ages ranging from 4-13 years; median 10.5 years) were treated with IOHDR in conjunction with EBRT, chemotherapy, and radical surgery at nine sites not treatable by standard intraoperative electron beam radiation therapy techniques. The IOHDR dose was 10 Gy (at 7 sites with microscopic residual disease) or 12.5 Gy (at 2 sites with minimal gross residual disease) prescribed at 0.5 cm depth. The treatment volume varied from 9-96 cc (mean 30.3 cc). IOHDR was used in these patients because the tumor locations prevented positioning and insertion of conventional intraoperative electron beam applicators. The EBRT dose was limited to 27-30.6 Gy (median dose 27.4 Gy) postoperatively in all patients to minimize growth retardation or altered organ function. The median initial EBRT field size was 211 cm2 (range 25-483), with a median of two fields per patient (range 1-2). RESULTS After a median follow-up of 40 months (range 22-62 months), all the patients were alive, five of them without evidence of disease. The other patient, with stage IV undifferentiated synovial sarcoma developed regrowth of pulmonary metastases at 14 months and local failure at 34 months. Toxicity was seen in two patients. One patient developed recurrent urinary infections and ureteral stenosis after 6 months and required a left nephrectomy. Another developed mild to moderate loss of visual acuity and impaired orbital growth after 6 months. CONCLUSIONS Use of IOHDR in conjunction with low dose EBRT to obtain local control and long-term disease-free survival in pediatric soft tissue sarcomas is feasible with acceptable toxicity. Tumor beds not treatable with standard electron beam intraoperative radiation therapy could be satisfactorily encompassed with IOHDR.

Intraoperative high dose rate brachytherapy in recurrent or metastatic colorectal carcinoma

AbstractBackground: The survival of patients with recurrent or metastatic colorectal cancer usually is less than 12 months. In an attempt to improve this dismal prognosis, we investigated the role of intraoperative high dose rate brachytherapy (IOHDR) in the management of these patients. Methods: From April 1992 to December 1996, 26 patients with locally recurrent or metastatic colorectal carcinoma were treated with maximal surgical resection and IOHDR. Intraoperative radiation dose ranged from 10 to 20 Gy, prescribed at 0.5 cm depth. The residual tumor irradiated was microscopic in 16 patients (62%) and gross residual in 10 patients (38%). Six patients received postoperative external beam radiation therapy. Results: After a median follow-up of 28 months (range 6 to 54 months), seven of 15 evaluable patients (47%) failed in the area treated with IOHDR. The median time to local failure was 21 months (range 4 to 52 months). The median survival was 23 months (microscopic 24 months; gross 17 months), with a 4-year actuarial survival rate of 36%. Major morbidity was observed in 7 patients (47%) and usually was surgery-related. Conclusion: The use of IOHDR in association with radical resection increases local control in patients with recurrent or metastatic colorectal cancer. Patients with microscopic residual disease achieved a better result than do those with gross residual disease. Future strategies include the addition of limited EBRT dose to IOHDR, even for previously irradiated patients.

SIMPLIFIED NON-LOOPING FUNCTIONAL LOOP TECHNIQUE FOR HDR BRACHYTHERAPY

The loop technique has been employed in interstitial implantation of head and neck cancers for decades. However, cable-driven afterloading sources may be unable to negotiate the curve of the loop. The technique allows separate afterloading of each catheter ensuring a good dose distribution to the surface of the implanted structure.

Intraoperative high-dose-rate brachytherapy for paranasal sinus tumors

PURPOSE Advanced and recurrent tumors of the paranasal sinuses can be difficult to irradiate to high doses with standard external beam radiotherapy (EBRT), conventional brachytherapy, or intraoperative electron beams. We, therefore, explored the role of intraoperative high-dose-rate brachytherapy (IOHDR) as a boost to EBRT in primary tumors or as sole adjuvant treatment in recurrent disease. METHODS AND MATERIALS Between 1992 and 1998, 34 patients with locally advanced tumors arising in the paranasal sinuses were treated with IOHDR after maximal surgical excision. Twenty-seven patients with new primaries underwent gross resection and 10-12.5 Gy IOHDR followed by 45-50 Gy EBRT. Seven previously irradiated (45-63 Gy) patients with recurrent disease were treated with 15-20 Gy of IOHDR alone after gross excision. Local control and overall survival were analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS After a mean follow-up of 6 years (range 34-120 months), the 1-, 3-, and 5-year actuarial survival rate was 80%, 62%, and 44%, respectively. The overall local control rate at 1 and 5 years was 75% and 65%, respectively, and distant failure was documented in 44% of patients. Subgroup analysis revealed that the presence of gross disease after surgical resection was the strongest prognosticator, with a 5-year survival and local control rate of 17% and 50%, respectively, compared with 60% and 68%, respectively, for microscopic disease. The local control rates of patients with new primaries were similar to those of patients treated for recurrent disease (63% vs. 71%), probably because gross residual disease occurred only in the group of patients with new primaries. The addition of EBRT to IOHDR increased the 5-year disease-free survival rate from 27% to 44% but had no effect on local control (64% vs. 65%). CONCLUSION IOHDR can be safely used to deliver a high radiation dose to locally advanced and recurrent tumors in the paranasal sinuses. In an attempt to improve outcome, we are now adding limited-dose EBRT (20-30 Gy) after 17.5 Gy of IOHDR in previously irradiated patients and increasing the EBRT dose for both microscopic (50-54 Gy) and gross residual disease (60-65 Gy) after 15 Gy of IOHDR in previously unirradiated patients. Chemosensitization should also be considered in previously irradiated patients and in those with gross residual disease. Interstitial boosting techniques, which can deliver higher doses at depth, should also be considered in patients with gross residual disease.

Review article: Biliary tree malignancies

Radiation therapy is used as definitive treatment for unresectable bile duct tumors, or as adjuvant therapy after resection. External beam irradiation of 45–50 Gy is generally given whenever feasible. Intraluminal brachytherapy is a useful technique to deliver higher doses of radiation to the tumor while respecting the tolerance of the surrounding normal tissues. Brachytherapy can be given at a high dose rate or low dose rate via an in‐dwelling biliary drainage catheter to boost external beam doses. Brachytherapy alone is reserved for palliative therapy. Techniques should be implemented with care to make them not only effective but safe. The long‐term efficacy and morbidity of this mode of radiation should be studied further. Only large prospective trials can lead to resolution of some of the questions yet unsolved in treatment of these challenging malignancies. J. Surg. Oncol. 1998;67:203–210.

Brachytherapy for pediatric tumors

PURPOSE Pediatric tumors are generally managed with a multi-modality treatment program that includes surgery, chemotherapy, and teletherapy. The use of teletherapy in young children can result in significant long-term toxicity (especially retardation of growth of bones and organs). The use of brachytherapy is an attractive alternative because brachytherapy irradiates small volumes and can thus potentially minimize complications. METHODS AND MATERIALS The brachytherapy techniques used are similar to those used in adults. Low-dose-rate brachytherapy with manually-afterloaded removable 192Ir is commonly used though it is associated with some radiation exposure hazards. Low energy radionuclides and remote afterloading technology have been used to reduce the radiation exposure hazards. Teletherapy is often added in the treatment of more extensive tumors, especially in older children. RESULTS Brachytherapy (as the sole radiation modality) to small volumes in conjunction with chemotherapy and surgery has produced good local control with growth preservation and acceptable late complications in selected patients with localized tumors. CONCLUSION Brachytherapy increases local control with a decrease in the probability of late complications (especially altered bone and organ growth) in comparison to EBRT. Low energy radionuclides and remote afterloading technology (HDR, IOHDR, and PDR) have been used to extend treatment to infants and younger children while reducing the radiation exposure to patients, family, and medical personnel.

Intraoperative high-dose-rate brachytherapy

Although several modalities have been discussed, a comprehensive intraoperative program should have IOERT, IOHDR, and perioperative brachytherapy facilities available to treat all sites. Interstitial brachytherapy is preferable for the treatment of gross residual tumor; IORT (IOERT for accessible sites and IOHDR for poorly accessible sites) is added to irradiate intraoperatively the surrounding margins after gross resection; and fractionated EBRT could be used in moderate doses post-operatively to irradiate the entire area of potential microscopic disease. Depending on the volume and location of the tumor, and the available expertise and equipment, IOERT, IOHDR, or perioperative brachytherapy could be used along with EBRT and surgery for the optimal management of malignancies. Finally, the best results of IOHDR are obtained when used as a conformal boost to the tumor bed after resection in conjunction with supplementary EBRT.