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.

Interstitial low-dose-rate brachytherapy as a salvage treatment for recurrent head-and-neck cancers: long-term results.

PURPOSE: Recurrent cancers of the head and neck within previously irradiated volume pose a serious therapeutic challenge. This study evaluates the response and long-term tumor control of recurrent head-and-neck cancers treated with interstitial low-dose-rate brachytherapy. METHODS AND MATERIALS: Between 1979 and 1997, 220 patients with prior radiation therapy with or without surgery for primary tumors of the head and neck were treated for recurrent disease or new primary tumors located within previously irradiated volumes. A majority of these patients had inoperable diseases with no distant metastasis. There were 136 male and 84 female patients, and median age was 56 years. All patients had previously received radiation therapy as the primary treatment or adjuvant treatment following surgery, with a median dose of 57.17 cGy (range, 39-74 cGy). The salvage brachytherapy consisted of a low-dose-rate, afterloading Iridium(192) implant, which delivered a median minimum tumor dose of 53 Gy to a mean tumor volume of 68.75 cm(2). Sixty percent of the patients also received interstitial hyperthermia, and 40% received concurrent chemotherapy as a radiosensitizing and potentiating agent. RESULTS: At a minimum 6-month follow-up, local tumor control was achieved in 77% (217/282) of the implanted tumor sites. The 2, 5, and 10-year disease-free actuarial survival rates for the entire group were 60%, 33%, and 22%, respectively. The overall survival rate for the entire group at 5 years was 21.7%. Moderate to severe late complications occurred in 27% of the patients. CONCLUSION: It has been estimated that approximately 20-30% of head-and-neck cancer patients undergoing definitive radiation therapy have recurrence within the initial treatment volume. Furthermore, similar percentages of patients who survive after successful irradiation develop new primary tumors of the head and neck or experience metastatic neck disease. A majority of such patients cannot be treated with a repeat course of external beam irradiation because of limited normal tissue tolerance, leading to unacceptable morbidity. However, in a select group of these patients, salvage interstitial brachytherapy may play an important role in providing patients with durable palliation and tumor control, as well as a chance for cure.

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.

High-dose-rate brachytherapy in the treatment of carcinoma of the prostate.

BACKGROUND: Although radical prostatectomy for localized disease is considered as a standard of care, external-beam radiotherapy and brachytherapy are equally effective. We report on the technique and preliminary results of high-dose-rate (HDR) brachytherapy using a temporary iridium-192 implant technique. METHODS: The authors reviewed the literature on the techniques, treatment protocols, and results of HDR brachytherapy in the treatment of carcinoma of the prostate, and they report their own protocols, technique, and results. RESULTS: The combination of HDR brachytherapy and external irradiation has been well tolerated by all 200 patients in our series, with less than 3% grade 3 late complications and with 95% PSA relapse-free survival with a median follow-up of 24 months. CONCLUSIONS: HDR brachytherapy may be the most conformal type of irradiation in the treatment of carcinoma of the prostate regardless of tumor size, anatomical distortion, and organ mobility.

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.

Interstitial brachytherapy for vaginal recurrences of endometrial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. METHODS: Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. RESULTS: The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I (n = 18), Stage II (n = 7), and Stage III (n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3-119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina (n = 5) or at distant sites (n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis (n = 2), fistula (n = 2), and radiation stricture (n = 1). CONCLUSION: Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy.

Interstitial brachytherapy in the treatment of advanced and recurrent vulvar cancer.

OBJECTIVE: Our purpose was to evaluate the role of interstitial brachytherapy in vulvar cancer management. STUDY DESIGN: From 1985-1992 we performed a retrospective study of patients treated at the University of California, Irvine Medical Center, and Long Beach Memorial Medical Center. RESULTS: Eleven patients received interstitial brachytherapy, with (n = 5) or without (n = 6) external beam radiotherapy, for locally advanced (n = 5) or recurrent (n = 6) vulvar cancer. Local control was achieved in all patients. Ten patients have died of disease at a mean interval of 33 months from the time of treatment, with 9 patients having maintenance of local control at death. One patient is alive without disease after 77 months of follow-up. There were 2 cases of local necrosis (18%) and 1 case of rectovaginal fistula (9%). CONCLUSION: Local control of advanced vulvar cancer can be achieved with interstitial brachytherapy, with or without external beam radiotherapy. With improved systemic therapy this treatment modality may be used to salvage women with bulky, symptomatic tumors.

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).

Breast arterial calcification: association with coronary artery disease. Work in progress.

PURPOSE: To assess the association between mammographically detected breast arterial calcification (BAC) and coronary artery disease (CAD) and diabetes mellitus (DM). MATERIALS AND METHODS: The records of 182 women (aged 39-92 years) who underwent both mammography and coronary arteriography were retrospectively reviewed to determine BAC, CAD, and DM status. RESULTS: For women aged less than 59 years (under-59 group) (n = 54), nearly all women with BAC (n = 8) had CAD (n = 7) and also had DM (n = 6). For this group, the positive predictive value of BAC for CAD was 0.88 and the negative predictive value was 0.65 (chi 2 = 7.7, P < .05). DM was a confounding variable. The positive predictive value of DM for CAD increased from 0.62 when BAC was absent to 1.00 when BAC was present (standard error of difference, .22; P < .10). No significant association between BAC and CAD was found for women aged 59 years and older (n = 128). CONCLUSION: BAC in women aged less than 59 years may indicate an additional risk factor for CAD, particularly in diabetic patients.

Temporary iridium-192 implant in the management of carcinoma of the prostate.

The controversy about the treatment of carcinoma of the prostate has increased in the last decade, with most urologists favoring radical prostatectomy rather than primary irradiation. Several reports of persistent tumors in 50% to 90% of patients after external irradiation and permanent iodine-125 implantation of the prostate have been disturbing. From July 1977 to December 1985, 200 patients with adenocarcinoma of the prostate were treated by combining bilateral pelvic lymphadenectomy and temporary interstitial iridium-192 implantation of the prostate, followed by external irradiation. Seventy-four (36%) patients underwent biopsies of the prostate 4 months to 2 years after completion of the irradiation. Only 12 (16%) patients had persistent tumors. Complications were minimized subsequently by dose modifications.

Followup prostate biopsy in patients with carcinoma of the prostate treated by 192iridium template irradiation plus supplemental external beam radiation.

We reviewed our experience with 81 patients who had undergone followup needle biopsies of the prostate between 12 and 27 months after 192iridium template radiotherapy combined with external beam radiation therapy. When broken down by stage 82% of the patients with stage A2, 92% with B1, 95% with B2 and 55% with C disease demonstrated a negative biopsy and adequate local control of the cancer. We believe that in elderly patients, poor risk patients with early stage disease and stage C lesions this low morbidity, low mortality therapy offers a viable option to other modalities of treatment.

Endocurietherapy in pediatric oncology.

Endocurietherapy (brachytherapy) is the placing of radioactive sources directly into or near a solid tumor. This technique delivers a concentrated dose of radiation to a restricted volume while minimizing radiation effects on normal tissue. We have treated 11 patients (nine sarcomas, one carcinoma, and one Wilms') with endocurietherapy procedures as part of their multimodality treatment program. Six were treated as part of the primary management, and the other five were treated for recurrent or metastatic disease. Temporary afterloaded implants using ribbons embedded with radioactive iridium192 (Ir192) seeds delivered typical tumor doses of 4,000 cGy. Six patients, including four primary cases and two recurrent cases, are currently classified as no evidence of disease (NED) without further local regional treatment (follow-up of 11-62 months; median, 38 months), and one patient treated for metastasis also remains locally controlled. Two patients are classified as alive with disease (AWD), two died of disease (DOD), and one is now NED after surgical salvage. Special considerations were given to gonadal shielding, radioprotection techniques, and psychosocial issues in this pediatric population.

[A new multi-channel LDR/MDR-afterloading-system (Inter-Pal-C38)]. / Ein neues vielkanaliges LDR/MDR-Afterloading-System (Inter-Pal-C38).

The methods of temporary interstitial implantation of iridium-192 seed chains have been applied in Erlangen for two years in many cases of squamous cell carcinoma in the head and neck area, the cervix uteri or the anal duct. The afterloading procedure which at the beginning had to be performed manually involved partially considerable radiation-exposures of medical and nursing staff. Therefore we have developed a 38-canal machine for remote control afterloading with iridium-192 seed chains in LDR and MDR therapy which is working in a similar way as the already established methods of remote control afterloading in HDR therapy. Special technical features are the automatic afterloading procedure, the disconnecting of patient and machine for any length of time, the possibility to use the machine for several succeeding patients, and the modern computer control by an IBM PC with color monitor and alpha-numerical keyboard. The new machine is fast and easy to handle, protects the staff completely against radiation and, due to the possibility of disconnection and free mobility, makes it easier and more comfortable for the patient to stay within the radioprotection room.

Radical hysterectomy and tailored postoperative radiation therapy in the management of bulky stage 1B cervical cancer.

Ninety-two patients with Stage IB cervical cancers having a diameter equal to or greater than 4.0 cm were treated with radical surgery. Thirty-two patients received postoperative radiotherapy because of operative findings suggestive of high risk of pelvic recurrence. All 32 irradiated patients were treated with a standard pelvic field. Four patients also received paraaortic radiotherapy, and ten received intravaginal brachytherapy. Postoperative complications were seen in five patients (two nonirradiated, three irradiated). Projected 5-year survival is 79% (71% 5-year survival in irradiated patients, and 83% 5-year survival in nonirradiated patients). Preoperative evaluation of tumor volume was not found to reliably predict histologic high risk factors such as depth of stromal invasion, risk of lymph node metastases, or presence of extracervical/uterine involvement. A primary surgical approach in this group of patients with large-diameter Stage IB cervical cancers allows definition of those patients who might benefit from a combined surgical and radiotherapeutic approach to treatment based on findings at operation.

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.

Treatment of advanced and recurrent squamous carcinoma of the uterine cervix with constant intraarterial infusion of cisplatin.

Twelve patients with primary or locally recurrent squamous carcinoma of the cervix were treated with constant internal iliac artery infusion of cisplatin (CDDP) via a totally implantable chemotherapy pump. Seven previously untreated patients received standard external and interstitial radiotherapy (RT) in conjunction with CDDP infusion. Five patients with isolated pelvic recurrences received CDDP therapy only. The chemotherapy pump was refilled weekly on an outpatient basis. All nine evaluable patients developed unilateral or bilateral lower extremity pain which responded to dosage reduction. No renal or marrow toxicity was seen. Both of the evaluable patients treated for recurrent tumor died 32 and 60 weeks after initiation of treatment. The seven patients treated primarily with RT + CDDP infusion include one who expired with persistent tumor and one with no evidence of disease (NED) after exenteration for a pelvic recurrence at 48 and 85 weeks respectively. The five remaining patients are NED at 12 to 60 weeks. Constant internal iliac artery infusion of CDDP via an implantable chemotherapy pump can be performed with acceptable toxicity. The preliminary results suggest that further study in previously untreated undergoing concurrent radiotherapy is warranted.