Long-term results of treatment for prostate carcinoma by staging pelvic lymph node dissection and definitive irradiation using low-dose rate temporary iridium-192 interstitial implant and external beam radiotherapy.

BACKGROUND: The objective of this study was to evaluate long-term treatment outcome of definitive irradiation by using temporary interstitial implant and limited dose of external beam radiotherapy in treatment of localized prostate carcinoma. METHODS: In total, 536 patients with biopsy-proven adenocarcinoma of the prostate, classification T1-T3, underwent staging pelvic lymph node dissection and brachytherapy delivering an average tumor dose of 30 grays (Gy), supplemented by external beam radiation therapy for an additional dose of 36 Gy delivered over 4 weeks. One hundred of 536 (18%) patients had pathologic D1 disease. A total of 181 patients had undergone transurethral prostatectomy before the treatment. Repeat prostate biopsy was performed on 132 patients 18 or more months after treatment. None of the patients received neoadjuvant or adjuvant hormone therapy. RESULTS: Cumulative disease free survival (DFS) including biochemical DFS at 10 and 15 years for classification T1B,C was 78% and 72%; for T2A, 78% and 78%; for T2B,C, 68% and 66%; and for T3A-C, 45% and 45%, respectively. Cause specific survival for the entire group at 10 and 15 years was 89% and 87%, respectively. Severe complications occurred only in the early developmental phase of the study. CONCLUSIONS: In univariate analysis, the clinical stage, histologic grade, pretreatment PSA level, lymph node status, and results of repeat posttreatment biopsy were all independently significant prognostic factors. However, the authors' study indicates that in multivariate analysis, only two factors emerged with statistical significance-the status of pelvic lymph nodes and the results of posttreatment biopsy. This signifies the importance of local tumor control to achieve ultimate cure and the importance of assessment of pelvic lymph nodes before definitive local therapy other than radical prostatectomy, especially in the high-risk group.

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma.

PURPOSE: To develop recommendations for use of high-dose-rate (HDR) brachytherapy in patients with head-and-neck cancer. METHODS: A panel consisting of members of the American Brachytherapy Society (ABS) performed a literature review, added information based upon their clinical experience, and formulated recommendations for head-and-neck HDR brachytherapy. RESULTS: The ABS recommends the use of brachytherapy as a component of the treatment of head-and-neck tumors. However, the ABS recognizes that some radiation oncologists are reluctant to employ brachytherapy in the head-and-neck region because of the complexity of the postoperative management and concerns about radiation safety. In this regard, HDR eliminates unwanted radiation exposure and thereby permits unrestricted delivery of clinical care to these brachytherapy patients. The ABS made specific recommendations for previously untreated and recurrent head-and-neck cancer patients on patient selection criteria, implant techniques, target volume definition, and HDR treatment parameters (such as time, dose, and fractionation schedules). Suggestions were provided for treatment with HDR alone and in combination with external beam radiation therapy. It should be recognized that only limited experiences exist with HDR brachytherapy in patients with head-and-neck cancers. Therefore, some of these suggested doses have not been extensively tested in clinical practice. Hence, these guidelines will be updated as significant new outcome data are available. Any clinician following these guidelines is expected to use clinical judgment to determine an individual patient's treatment. CONCLUSIONS: Little has been published in the clinical literature on HDR brachytherapy in head-and-neck cancer. Based upon the available information and the clinical experience of the panel members, general and site-specific recommendations were offered. Areas for further investigations were identified.

Primary invasive carcinoma of the vagina: treatment with interstitial brachytherapy.

BACKGROUND: Because primary carcinoma of the vagina comprises less than 2% of all gynecologic malignancies, the reported experience in the treatment of large numbers of patients is available only from a few major centers and most often encompasses a variety of differences in treatment selection and technique. The objective of this study was to assess the long term results of an interstitial iridium-192 afterloading implant technique using the Syed-Neblett dedicated vaginal plastic template. METHODS: Patients who were treated from 1976 to 1997 were examined retrospectively. RESULTS: Seventy-one patients underwent interstitial implantation with (n = 61 patients) or without external beam radiotherapy. The median age was 59 years (range, 16-86 years). Patients were staged according to the International Federation of Gynecology and Obstetrics system and included Stage I (n = 10 patients), Perez modification Stage IIA (n = 14 patients), Perez modification Stage IIB (n = 25 patients), Stage III (n = 15 patients), and Stage IV (n = 7 patients). Each implant delivered an approximately 20-gray (Gy) minimum tumor dose, with the total tumor dose reaching 80 Gy with integrated external beam radiotherapy. Local control was achieved in 53 patients (75%). The median follow-up was 66 months (range, 15-163 months), and the 2-year, 5-year, and 10-year actuarial disease free survival rates are 73%, 58%, and 58%, respectively. By stage, 5-year disease free survival rates included Stage I, 100% of patients; Stage IIA, 60% of patients; Stage IIB, 61% of patients; Stage III, 30% of patients; and Stage IV, 0% of patients. The factors disease stage and primary lesion size independently influenced the survival rates. Significant complications occurred in 9 patients (13%) and included necrosis (n = 4 patients), fistulae (n = 4 patients), and small bowel obstruction (n = 1 patient). CONCLUSIONS: Interstitial irradiation can effect local control in the majority of patients with primary carcinoma of the vagina with acceptable morbidity. Long term cure is demonstrable in patients with Stage I-III disease.

Brachytherapy for primary and recurrent nasopharyngeal carcinoma: 20 years' experience at Long Beach Memorial.

PURPOSE: We evaluated treatment outcomes of patients with mostly locally advanced primary and recurrent cancer of the nasopharynx managed with interstitial and intraluminal brachytherapy. METHODS AND MATERIALS: This is a retrospective analysis of 56 patients with cancer arising from the nasopharynx treated with interstitial and intracavitary afterloading brachytherapy from 1978 to 1997. Patients were divided into three treatment groups: 15 patients with primary cancer (Group 1), 34 patients with recurrent or persistent disease (Group 2), and 7 patients with cancer in the nasopharynx who had history of previous definitive radiation therapy to the nasopharynx for head and neck cancer (Group 3). Fifty-three percent of patients in Group 1 had 1992 AJCC Stage IV disease, and 49% of patients in Groups 2 and 3 had extensive disease (defined as T3, T4, or parapharyngeal extension). Group 1 received megavoltage radiation to 50-60 Gy followed by a boost to the primary site and neck (in cases of persistent neck disease) with a combination of interstitial and intracavitary brachytherapy (mean dose 33-37 Gy). Five patients received chemotherapy, and 6 patients received hyperthermia. Groups 2 and 3 patients were treated with brachytherapy implants (mean dose 50-58 Gy) without external beam radiation. Twenty-five patients received chemotherapy either before or during radiation, and 21 patients received hyperthermia. RESULTS: The overall survival at 2, 5, and 10 years for patients in Group 1 was 79%, 61%, and 61%, respectively, and for patients in Groups 2 and 3 combined was 48%, 30%, and 20%, respectively. Cause-specific survival at 2, 5, and 10 years was 87%, 74%, and 74%, respectively, for patients in Group 1; and 82%, 60%, and 60%, respectively, for patients in Groups 2 and 3. Local control at 2, 5, and 10 years was 93%, 93%, and 77%, respectively, for patients in Group 1; and 81%, 59%, and 49%, respectively, for patients in Groups 2 and 3. Control in the neck at 2, 5, and 10 years was achieved in 93%, 93%, and 93% of patients, respectively, in Group 1; and 88%, 81%, and 81%, respectively, for patients in Groups 2 and 3. Disease-free survival was 87%, 74%, and 62%, respectively, for patients in Group 1, and 56%, 41%, and 34%, respectively, for patients in Groups 2 and 3. There were 4 peri-operative deaths. One death (2%) was attributable to the development of late complications. Forty-five percent of patients experienced some form of late complications. CONCLUSION: Interstitial afterloading brachytherapy can provide effective treatment for nasopharyngeal cancers, especially for locally persistent/recurrent and locally extensive lesions.

Needle displacement during HDR brachytherapy in the treatment of prostate cancer.

PURPOSE: We used clinical patient data to examine implant displacement between high dose rate (HDR) brachytherapy fractions for prostate cancer to determine its impact on treatment delivery. MATERIALS AND METHODS: We analyzed the verification films taken prior to each fraction for 96 consecutive patients treated with HDR brachytherapy boosts as part of their radiation therapy for definitive treatment of organ-confined prostate cancer at our institution. Patients were treated with 18-24 Gy in 4 fractions of HDR delivered in 40 hours followed by 36-39.6 Gy external beam radiation to the prostate. We determined the mean and maximum displacement distances of marker seeds placed in the prostate and of the implanted needles between HDR fractions. RESULTS: Mean and maximum displacement distances between fractions were documented up to 7.6 mm and 28.5 mm, respectively, for the implant needles and 3.6 mm and 11.4 mm, respectively, for the gold marker seeds. All displacement of implant needles occurred in the caudal direction. At least 1 cm caudal displacement of needles occurred prior to 15.5% all fractions. Manual adjustment of needles was required prior to 15% of fractions, and adjustment of the CLP only was required in 24%. Most of the displacement for both the marker seeds and needles occurred between the first and second fractions. CONCLUSIONS: There is significant caudal displacement of interstitial implant needles between HDR fractions in our prostate cancer patients. Obtaining verification films and making adjustments in the treatment volume prior to each fraction is necessary to avoid significant inaccuracies in treatment delivery.

Initial brachytherapy in the breast conservation approach to breast cancer.

The outcome of 100 consecutive newly diagnosed breast cancer patients treated between 1975 and 1985 within a protocol of planned segmental mastectomy and radiation therapy that included an initial brachytherapy boost is reported. Margins were not routinely inked in this study and the tumor bed was determined with the operating surgeon at the time of brachytherapy. There were 30 T1 tumors, 61 T2, and 9 T3. Segmental mastectomy was followed 2 weeks later by an interstitial implant with iridium-192 sources given as initial boost dose to the tumor bed, at the time of axillary dissection. All patients received at least 20 Gy as boost dose followed by external beam radiation to a total dose of 45-50 Gy to the breast and regional nodes delivered over a period of 4-5 weeks. With a median follow-up of 7 years a total of 3 (3%) breast recurrences were detected (1/30 in T1 tumors, 2/61 in T2 tumors). Only one of the three recurrences was at the initial tumor bed. None of the nine T3 patients included in this series recurred locally. There were 4 severe complications (2 soft tissue necroses and 2 osteonecroses) occurring in 2/30 T1 and in 2/61 T2. Cosmetic results were good to excellent in 77% of the cases and fair to poor in 23%. The actuarial local control and survival probability rate were, respectively, 95% and 85% at 5 years and 93% and 73% at 10 years. Initial brachytherapy boost to a target volume accurately determined with the operating surgeon followed by subsequent external beam radiotherapy achieved excellent local control in the breast even for lesions larger than 2 cm (70% of the reported cases).

Limited external beam and interstitial 192iridium irradiation in the treatment of carcinoma of the base of the tongue: a ten year experience.

A total of 70 patients with histologically proven diagnosis of carcinoma of the base of the tongue were treated with primary irradiation between May 1974 through April 1984. Fifty-eight (83%) of these patients had locally advanced tumors (Stage T3, T4, N2, N3). Fifty-one of the 70 (73%) patients had clinically palpable neck nodes at first presentation. All patients received a combination of external and interstitial irradiation. The dose of external irradiation was limited to 45-50 Gy over 4 1/2-5 1/2 weeks. Interstitial volume implants were performed 2-3 weeks after completion of external irradiation. The primary site as well as the vallecula, epsilateral pharyngeal wall, glossopalatine sulcus, tonsillar bed, and pillars were routinely implanted to encompass contiguous spread of the disease. The doses of implant varied according to the stage of disease, that is, 2000-2500 cGy for T1 and T2 lesions, 3000-4000 cGy for T3 and T4 lesions, with typical dose rates of 50-60 cGy per hour. The neck nodes were also separately implanted to deliver additional doses of 2000-4000 cGy in 50-80 hours. Overall, local tumor control was observed in 58 of 70 (83%) patients at minimum follow-up of 2 years. An absolute 3-year disease-free survival of the entire group was 67.0%. Treatment related complications such as soft tissue necrosis and/or osteoradionecrosis occurred in 8 of the 70 (11.4%) patients. The salvage of neck failures and the local failures was feasible in 74% and 46% of the patients, respectively either by surgery or by re-irradiation using interstitial 192iridium implant alone. This treatment region is well tolerated and it preserves the functional and asthetic integrity in most patients.

Iridium-192 implants in the treatment of tonsillar region malignancies.

A total of 127 patients with histologically proved diagnosis of carcinoma of the tonsillar region and soft palate were treated over the past ten years utilizing interstitial iridium-192 implants. Eighty patients were treated for primary tumors and 47 patients for either recurrent or persistent tumors after definitive irradiation and/or surgery. All patients with primary tumors were treated by a combination of external megavoltage irradiation and interstitial iridium-192 implants, whereas patients with recurrent tumors were treated by interstitial implants alone. In the primary group, 95% of patients with T1 and T2 lesions and 79% with T3 and T4 lesions achieved complete local tumor control. The three-year absolute disease-free survival rate was 72%. Seventy-five percent local tumor control was obtained in patients with recurrent disease, with two-year absolute disease-free survival of 42%. Treatment-related complications such as soft-tissue necrosis or osteoradionecrosis occurred in 6% of patients in the primary group and 23% in recurrent group. This treatment regimen offers an excellent locoregional control with no significant functional or esthetic impairment. Most patients with primary lesions who fail this regimen can be salvaged by surgery or reirradiation using interstitial implants. Reirradiation with interstitial implants is feasible and offers a good chance of long-term local tumor control in the selected group of patients with recurrent disease for whom external irradiation and/or surgery had not been successful.

Limited external irradiation and interstitial 192iridium implant in the treatment of squamous cell carcinoma of the tonsillar region.

Between January 1976 and March 1982, 80 patients with histologically proven diagnosis of squamous cell carcinoma of the tonsillar region were treated with definitive radiotherapy. Sixty-five (81%) of these patients had locally advanced tumors (Stage III and IV); 49% of patients had clinically palpable cervical lymphadenopathy. All patients received a combined external megavoltage and interstitial irradiation. The dose of external irradiation was limited to 4500-5000 cGy over 41/2 to 51/2 weeks. This was followed by interstitial 192iridium implants to doses of 2000-2500 cGy in 50-60 hours for T1, T2 lesions and 3000-4000 cGy in 60-100 hours for T3 , T4 lesions. The neck masses were also separately implanted to deliver additional doses of 2000-4000 cGy in 50-80 hours. Overall local tumor control was observed in 84% of patients with a minimum follow-up period of 2 years. An absolute 3-year disease free survival of the entire group was 72%. Treatment related complications such as soft tissue necrosis or osteoradionecrosis occurred in 6% (5/80) of patients. The salvage of neck failures and local failures was possible in 78 and 38% of patients, respectively, either by surgery or by re-irradiation employing interstitial 192iridium implants. Functional and esthetic integrity was well preserved in most cases.

Combined external and interstitial irradiation in the treatment of stage III breast cancer.

One hundred six patients with locally advanced carcinoma of the breast underwent definitive radiation therapy for loco-regional control following incisional and/or needle biopsy. Doses of external and interstitial irradiation were 5000 rad (50 Gy) in 5 to 6 weeks, and 3000 to 4000 rad (30-40 Gy) in 60 to 80 hours, respectively. Forty-eight of 106 patients (45%) also received adjuvant systemic chemotherapy. Loco-regional control was observed in 93 of the 106 patients (88%), with five-year disease-free survival of 47%. Distant metastases developed in 59 of the 106 patients (56%). Good to satisfactory cosmetic results were obtained in the majority of these patients; morbidity was at an acceptable level. Locally advanced breast cancer can be treated adequately and satisfactorily without mastectomy by a combination of external and interstitial irradiation.

Primary irradiation in the management of early and locally advanced carcinoma of the breast.

Between September 1, 1974, and July 31, 1979, we have treated 142 patients with a diagnosis of carcinoma of the breast by a combination of megavoltage external irradiation and interstitial iridium-192 implant. Sixty-four patients had T1 and T2 lesions and 78 patients had T3 and T4 lesions of the breast. Since June 1977, pre- and perimenopausal patients with T1 and T2 lesions have undergone axillary node dissection in addition to excisional biopsies of the breasts. All patients received external irradiation to the breast and regional lymph nodes and an interstitial implant boost to the primary site and residual axillary nodes. Most of the patients with positive axillary nodes, and those with locally advanced disease, received systemic chemotherapy. Sixty-two of 64 patients (97%) with T1 and T2 lesions and 72 of 78 (92%) patients w ith T3 and T4 lesions achieved ultimate loco-regional control. The minimum follow-up period was 48 months.

Interstitial iodine-125 implant in the management of unresectable pancreatic carcinoma.

Eighteen patients with locally advanced adenocarcinoma of the head, body and tail of the pancreas were treated by a combination of biliary bypass, external and interstitial irradiation at Southern California Cancer Center of California Hospital Medical Center, Los Angeles, and Memorial Hospital Medical Center of Long Beach, Long Beach, CA, from July 31, 1975 to December 31, 1980. A dose of 3000 to 5000 rad was delivered to the pancreas and regional lymph nodes by external irradiation utilizing megavoltage units and 10,000 to 15,000 rad to the pancreas and metastatic lymph nodes by permanent Iodine-125 implants. In this group of 18 patients with unresectable carcinoma of the pancreas, excellent palliation of pain, jaundice and vomiting was achieved, with a median survival of 14 months.

Re-irradiation with interstitial implant for recurrent pelvic malignancies.

Forty patients with a diagnosis of recurrent pelvic malignancy from various primary sites with no clinical evidence of distant metastasis were re-irradiated with interstitial implant. Removable after-loading 192Ir sources or permanent 125I seeds or a combination of both were used. Twenty-six of these patients received interstitial implant at the time of exploratory laparotomy. A complete local control of implanted pelvic tumors was achieved in 27 of the 40 patients (67%). Thirteen of the 40 patients (33%) remained alive and disease-free to a minimum follow-up period of two years. Serious complications such as soft tissue necrosis and fistulae occurred in 15% of the patients.

Definitive treatment of extensive anorectal carcinoma by external and interstitial irradiation.

Forty-patients with locally extensive carcinoma of the anorectum were treated by a combination of external and interstitial irradiation from April 1, 1974 to January 30, 1979. Twenty-eight patients (70%) achieved complete local tumor control and two more patients with residual tumor were salvaged by surgery. Twenty-four patients remain alive with local control for an average follow up period of three years. The overall complication rate has been 20%.