High-Dose-Rate (HDR) or Pulsed-Dose-Rate (PDR) Perioperative Interstitial Intensity-Modulated Brachytherapy (IMBT) for Local Recurrences of Previously Irradiated Breast or Thoracic Wall Following Breast Cancer

PURPOSE: In patients receiving salvage high-dose-rate (HDR) or pulsed-dose-rate (PDR) brachytherapy for a local recurrence on the chest wall or in the previously treated breast, clinical outcome and benefit were investigated. All patients had previously been treated with full-dose adjuvant external-beam irradiation (EBRT). Disease-free interval after salvage treatment, local tumor control and side effects were analyzed retrospectively. PATIENTS AND METHODS: Between 1996 and 2002, a total of 32 consecutive patients were treated. 13 patients initially treated with mastectomy and postoperative irradiation and 19 patients initially treated with breast-conserving surgery and postoperative irradiation developed a local recurrence. The mean dose of previous radiation therapy was 58 Gy (range, 42-64 Gy), applied by conventional fractionation. After implantation +/- surgery of recurrent disease and CT-based 3-D planning, 15 patients were irradiated with HDR-IMBT (intensity-modulated brachytherapy) with a mean dose of 28 Gy (range, 10-30 Gy, 2 x 2.5 Gy/day at 6-h daily interfraction interval) and 17 patients received PDR-IMBT with a mean dose 30 Gy (range, 10-45 Gy, 5 x 1 Gy/day at 2-h pulse intervals). Four patients underwent additional EBRT using a dose of 24-40 Gy electrons. Treatment was performed only on working days. RESULTS: After a mean post-implant follow-up of 19 months (range, 1-83 months), no signs of local recurrence were observed in 20 of the 32 patients. In twelve patients, local recurrence occurred after a mean follow-up of 13 months (range, 1-78 months). 20 of the 32 patients experienced an additional systemic progress. In one patient, an EORTC/RTOG grade 3 side effect (ulceration of the skin) was described, which was followed by a local recurrence 12 months posttherapeutically. CONCLUSION: Perioperative interstitial HDR/PDR-IMBT of localized breast or thoracic wall recurrences following previous full-dose EBRT appears to be a meaningful salvage treatment with acceptable toxicity.     

The feasibility of a second lumpectomy and breast brachytherapy for localized cancer in a breast previously treated with lumpectomy and radiation therapy for breast cancer

PURPOSE: With accumulating evidence supporting partial-breast irradiation, we conducted a Phase I/II study to evaluate the role of a second conservative surgery and brachytherapy for patients presenting with a local recurrence/new primary in a breast who has previously undergone a lumpectomy and external radiation therapy for breast cancer. METHODS AND MATERIALS: Fifteen patients with a localized lesion in the breast have undergone a second lumpectomy and received low-dose-rate brachytherapy on protocol. The first 6 patients received a dose of 30Gy. With no unacceptable acute toxicity observed, the brachytherapy dose was increased to 45Gy. Three patients received adjuvant chemotherapy and 8 patients are on antiestrogen therapy. RESULTS: The median time interval between the primary breast cancer diagnosis and the second cancer event in the ipsilateral breast is 94 months (range, 28-211). With a median followup of 36 months after brachytherapy, the 3-year Kaplan-Meier overall survival, local disease-free survival and mastectomy-free survival are 100% and 89%, respectively. There was no Grade 3/4 fibrosis or necrosis observed. All patients had baseline asymmetry due to the breast volume deficit from the second lumpectomy. With breast asymmetry as a given, the cosmetic result observed in all patients has been good to excellent. CONCLUSIONS: Early results suggest low-complication rates, high rate of local control and freedom from mastectomy. Additional studies are needed to establish whether a second lumpectomy and breast brachytherapy are an acceptable alternative to mastectomy for patients presenting with a localized cancer in a previously irradiated breast.     

Pulsed-dose rate brachytherapy with concomitant chemotherapy and interstitial hyperthermia in patients with recurrent head-and-neck cancer

PURPOSE: We attempted in our clinic to evaluate the efficacy and feasibility of a simultaneous application of a cis-platinum-based chemotherapy and interstitial hyperthermia to interstitial pulsed-dose rate (PDR) brachytherapy in patients with recurrent head-and-neck cancer. METHODS AND MATERIALS: Between April 1999 and September 2001, 15 patients with recurrent head-and-neck cancer were treated with PDR brachytherapy, chemotherapy, and interstitial hyperthermia. All patients had received prior radiation therapy. A dose per pulse of 0.46 to 0.55 Gy was given up to a median total dose of 55 Gy. Simultaneously to the PDR brachytherapy, chemotherapy was given with cis-platinum 20 mg/m2 as a short i.v. infusion each day and 5-fluorouracil 800 mg/m2 by continuous infusion from Day 1 to Day 5. After the PDR brachytherapy was finished, all patients were treated with a single session of interstitial hyperthermia. RESULTS: All the patients could receive the whole treatment. After treatment, only mild oral mucositis occurred. One patient developed soft tissue ulceration. None of the patients developed osteoradionecrosis. After a median follow-up of 6 months, the local tumor control rate was 80% (12 of 15), and the 2-year overall survival was 67% (10 of 15). CONCLUSIONS: The intensification of the interstitial PDR brachytherapy with chemotherapy and hyperthermia is feasible and safe, and the preliminary results are encouraging.     

Breast conservation surgery and interstitial brachytherapy in the management of locally recurrent carcinoma of the breast: the Allegheny General Hospital experience

PURPOSE: To evaluate lumpectomy followed by interstitial brachytherapy as an acceptable salvage therapy for women who have developed localized recurrence of breast cancer after conservation surgery and postoperative external radiotherapy. METHODS AND MATERIALS: Between 1/1998 and 10/2006, 21 patients with T0 or T1 in-breast recurrence of carcinoma were offered interstitial low-dose rate brachytherapy after tumor re-excision as an alternative to salvage mastectomy. All patients had failed lumpectomy followed by standard postoperative external beam radiotherapy (range, 5000-6040cGy) as treatment for the initial breast carcinoma. Seven recurred as ductal carcinoma in situ, 2 as infiltrating lobular carcinoma, and 12 as recurrent invasive carcinoma. The recurrent tumors were excised with final margins of resection free of residual disease per National Surgical Adjuvant Breast and Bowel Project definition. Tumor bed implantation was then carried out with an interstitial technique using (192)Ir with the target volume consisting of the tumor bed plus a minimum 1.0-cm clinical margin. The required minimum dose delivered to the target volume was 4500-5000cGy (range, 4500-5530). RESULTS: Twenty of 21 patients were free of local disease with a median observation time of 40 months (range, 3-69). The single patient who developed a second local recurrence was treated successfully with simple mastectomy. Two patients succumbed to systemic disease at 17 and 24 months after salvage implant therapy. One patient developed a contralateral breast cancer. Cosmetic results defined by the National Surgical Adjuvant Breast and Bowel Project cosmesis scale were acceptable. One patient developed a localized seroma requiring multiple needle aspirations before complete resolution. Two patients developed localized skin breakdown in the tumor bed. One healed after 6 months of conservative treatment. The other healed 9 months later with Grade II cosmesis. This patient also developed a concurrent postoperative wound infection. CONCLUSIONS: Repeat lumpectomy followed by brachytherapy is feasible and may be an acceptable alternative to salvage mastectomy in patients who locally fail conservation breast therapy; however, longer followup and greater patient numbers may be needed to better define the role of salvage brachytherapy.     

The role of pulsed-dose-rate brachytherapy in previously irradiated head-and-neck cancer

PURPOSE: The purpose of this prospective study was to analyze the value of interstitial pulsed-dose-rate (PDR) brachytherapy (iBT) with regard to local control and the incidence of side effects in patients with head-and-neck cancer in a previously irradiated area. METHODS AND MATERIALS: From October 1997 to September 2001, 43 patients with head-and-neck cancer in a previously irradiated area (31 patients with recurrent cancer) were treated with iBT alone or in combination with external beam radiation. Thirty-four of 43 patients received interstitial PDR brachytherapy (DREF=20-60 Gy) as part of their curative treatment regimen alone or in combination with external radiation. Nine patients were implanted for palliative purposes. The pulses were delivered 24 h/day with a time interval of 1 h between two pulses. The dose per pulse (dp) ranged from 0.4-0.7 Gy. Sixteen of 43 (37%) patients also received cisplatin or carboplatin with 5-fluorouracil during the time of the iBT. Additionally 20/43 (47%) patients were treated with interstitial hyperthermia. Thirteen of 43 (30%) patients received external beam radiation in a dose range from 20-67 Gy. A follow-up of all patients was done to analyze local control and survival, and acute and delayed toxicity. This analysis was performed after a median follow-up of 24 months (6-48 months). RESULTS: Local tumor control was achieved in 34 of a total of 43 patients (79%) and in 30/34 patients (88%) treated for curative intention. Distant metastases were observed in 5/43 (12%) patients. The 2-year local recurrence-free survival rates, disease-free survival rates, and overall survival rates according to the Kaplan-Meier method for all patients were 68%, 62%, and 49%, respectively, and for patients treated with curative intention they were 80%, 77% and 66%, respectively. There was no statistical difference in the probability of local recurrence in patients subgrouped by recurrent tumor vs. secondary primary, tumor size, grading and lymphangiosis. The application of chemotherapy or hyperthermia did not have significant influence on the therapy results. Soft tissue necrosis was the only serious side effect seen in 2/43 patients (4.7%). No other serious side effects were observed. CONCLUSIONS: Interstitial pulsed-dose-rate brachytherapy for patients with previously irradiated head-and-neck cancer is an effective therapy with minimal toxicity. The role of chemotherapy and hyperthermia in these patients remains unclear. Further randomized studies with larger patient numbers are necessary to draw a definite conclusion.     

Feasibility and Early Results of Interstitial Intensity-Modulated HDR/PDR Brachytherapy (IMBT) with/without Complementary External-Beam Radiotherapy and Extended Surgery in Recurrent Pelvic Colorectal Cancer

BACKGROUND: A new multimodality treatment concept consisting of extended resection and postoperative fractionated intensity-modulated interstitial brachytherapy (IMBT) was introduced for pelvic recurrence of colorectal carcinoma. PATIENTS AND METHODS: 46 patients received extended resection and single plastic tubes were sutured directly onto the tumor bed. IMBT was started within 2 weeks postoperatively with a median dose of 24.5 Gy (5-35 Gy). Patients were treated either with high-dose-rate brachytherapy (HDR; n = 23) or with pulsed-dose-rate brachytherapy (PDR; n = 23). 25 patients received complementary 45-Gy external-beam irradiation (EBRT) to the pelvic region after explanting the plastic tubes. RESULTS: Median follow-up was 20.6 months (7-107 months) and mean patient survival 25.7 +/- 25.8 months (median 17, range 1-107 months). After 5 years overall survival, disease-free survival and local control rate were 23%, 20% and 33%, significantly influenced by the resectional state. There was a trend in favor of PDR compared to HDR, which reached statistical significance in patients who had not received additional EBRT. CONCLUSION: The combination of extended surgery and postoperative interstitial IMBT is feasible and offers effective interdisciplinary treatment of recurrent colorectal cancer. In this small and inhomogeneous cohort of patients PDR seems to be more effective than HDR, particularly when application of complementary EBRT is not possible. None of the patients who required resection of distant metastasis survived > 2 years in this study.     

5-Year Results of Pulsed Dose Rate Brachytherapy Applied as a Boost after Breast-Conserving Therapy in Patients at High Risk for Local Recurrence from Breast Cancer

PURPOSE: The aim of this study was to evaluate effect, toxicity, and cosmesis of a prospectively applied pulsed dose rate (PDR) brachytherapy boost schedule in patients with stage I/II/IIIa invasive breast cancer. PATIENTS AND METHODS: A total of 113 patients were treated after breast-conserving surgery (BCS) and external beam radiotherapy (median 50 Gy, range 46-52). The boost dose was graded in accordance to the pathologic tumor characteristics: 20-25 Gy: incomplete resection (n = 34), vascular invasion (n = 27), close margin resection (n = 41); 15 Gy: T2G3 stage (n = 11). PDR brachytherapy (37 GBq, (192)Ir source) was carried out after geometric volume optimization with 1 Gy/pulse/h. The implantation and dose specification were performed similar to the rules of the Paris system. RESULTS: The overall local failure rate after a median follow-up of 61 months was 4.4% (5/113). The actuarial 5- and 8-year local recurrence-free survival rates were 95% and 93%, respectively. Cosmesis was rated by 90% of the patients as excellent or good. 14/113 patients experienced grade III (all caused by planar telangiectasia) and none of the patients grade IV late toxicity of the skin (RTOG/EORTC). A boost dose of 25 Gy resulted in a significantly higher rate of late toxicity (Fisher's exact test, p < 0.01). CONCLUSIONS: PDR brachytherapy is safe, effective, and provides good cosmesis. A CLDR breast boost can be replaced by PDR brachytherapy without significant loss of therapeutic ratio.     

PSA Kinetics after External Beam Radiotherapy Alone or Combined with an Iridium Brachytherapy Boost to Deliver 85 Grays to Prostatic Adenocarcinoma

PURPOSE: Increasing the dose to prostatic adenocarcinoma in conformal external beam therapy (EBT) has resulted in increased levels of PSA normalization and increased percentage of biochemical disease-free survival rates. However technical problems due to prostate motion inside the pelvis or patients' set-up make difficult the realization of the EBT boost fields above 72 Gy. Brachytherapy which overcomes these problems was investigated to deliver the boost dose to achieve 85 Gy. PSA nadir which has been identified as the strongest independent predictor of any failure in many studies has been used as the end point for early evaluation of this work. PATIENTS AND METHODS: In a retrospective way we report on 163 patients' PSA kinetics after EBT alone to 68 Gy or EBT first and a brachytherapy boost up to 75 or 85 Gy. RESULTS: At 12 months follow-up, PSA nadirs percentage < or = 0.5 or < or = 1 ng/ml increased from 7.5 and 20.7% after 68 Gy EBT to 49.8 and 71.2% after a brachytherapy boost to deliver 85 Gy (p < 0.0001). In the Cox PH model analysis, the total dose remained the most important factor for predicting PSA normalization. CONCLUSIONS: These results are in accordance with the most recent results published after conformal EBT at the same 80 Gy level of dose. If confirmed on a higher number of patients they could place brachytherapy among the most accurate methods of boosting in the radiation treatment of prostatic carcinoma.     

Die kombinierte Behandlung des lokal begrenzten Prostatakarzinoms mit HDR-Iridium-192-Nachlade-Brachytherapie und perkutaner Bestrahlung

BACKGROUND: The localized prostate cancer can be treated curatively by radiation therapy. The combined treatment of external beam irradiation and HDR-Iridium 192 remote brachytherapy allows higher radiation doses within the tumor without increasing radiation sequelae. PATIENTS AND METHODS: Patients of our clinic have been treated with this combined procedure since 1991. Between 1991 and 1994 15 patients received 2 x 9 Gy of high-dose-rate brachytherapy, followed by 36 Gy external beam irradiation (group A). Because of the frequent local failures in group A, the reference dose of external beam irradiation was increased to 50.4 Gy after brachytherapy between 1994 and 1996. RESULTS: Seven of 15 patients (47%) in group A developed a local recurrence after a median of 17 (13 to 30) months. In group B (20 patients) local failure occurred in 3 patients (15%) after 11, 16 and 32 months. CONCLUSION: The combined radiation therapy of localized prostate cancer cannot substitute radical prostatectomy completely, but it is a promising alternative in the curative treatment in selected patients.     

Role of Interstitial PDR Brachytherapy in the Treatment of Oral and Oropharyngeal Cancer

PURPOSE: To evaluate the role of pulsed-dose-rate interstitial brachytherapy (PDR IBT) in patients with head-and-neck malignancies. PATIENTS AND METHODS: From October 1997 to December 2003, 236 patients underwent PDR IBT for head-and-neck cancer at the authors' department. 192 patients received brachytherapy as part of their curative treatment regimen after minimal non-mutilating surgery, 44 patients were treated with irradiation alone. 144 patients had sole IBT (median D(REF) = 56 Gy), in 92 patients IBT procedures (median D(REF) = 24 Gy) were performed in combination with external irradiation. The pulses (0.4-0.7 Gy/h) were delivered 24 h a day with a time interval of 1 h between two pulses. The analysis of tumor control, survival and treatment-related toxicity was performed after a median follow-up of 26 months (6-75 months). RESULTS: At the time of analysis permanent local tumor control was registered in 208 of 236 patients (88%). At 5 years overall survival and local recurrence-free survival of the entire group were 82-73% and 93-83% for T1/2, and 56% and 83% for T3/4, respectively. Soft-tissue necrosis was seen in 23/236 patients (9.7%) and bone necrosis in 17/236 patients (7.2%). No other serious side effects were observed. CONCLUSION: PDR IBT with 0.4-0.7 Gy/h and 1 h between pulses is safe and effective. These results confirm that PDR IBT of head-and-neck cancer is comparable with low-dose-rate (LDR) brachytherapy - equally effective and less toxic.     

Re-irradiation with interstitial pulsed-dose-rate brachytherapy for unresectable recurrent head and neck carcinoma

PurposeTo assess the long-term results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy combined with simultaneous chemotherapy in selected patients with recurrent head and neck tumors not amenable to salvage surgery.Methods and MaterialsA total of 51 patients with recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Forty patients (78%) had salvage brachytherapy alone using a median total dose of 60 Gy. Salvage brachytherapy in combination with external beam therapy was performed in 11 patients (22%) using a median total dose of D_REF = 27 Gy. Simultaneously with the PDR brachytherapy, a concomitant chemotherapy was administered in 35/51 (69%) of patients. The analysis was performed after a median followup of 58 months.ResultsLocal control rates calculated according to Kaplan–Meier after 2 and 5 years were 71% and 57%, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 5-year local recurrence-free survival rates were 78.9% vs. 38.5% (p = 0.01), respectively. No other patient or treatment-related parameters had a significant influence on treatment results. A total of 9/51 (17.7%) and 6/51 (11.8%) patients developed soft-tissue necrosis or bone necrosis, respectively, but only 2% of patients required surgical treatment.ConclusionsPDR interstitial brachytherapy with pulse doses between 0.4 and 0.7 Gy/h/24 h with simultaneous chemotherapy is an effective and safe option for curative therapy in selected patients with head and neck cancer in previously irradiated areas, which are not suitable for salvage surgery.     

Interstitial High-Dose-Rate Brachytherapy in the Treatment of Base of Tongue Carcinoma

BACKGROUND AND PURPOSE:. To date none of the studies examined the feasibility and efficacy of interstitial high-dose-rate (HDR) brachytherapy in the treatment of carcinoma of the tongue base. Therefore the aim of this study was to contribute to this issue. PATIENTS AND METHODS:. Between 1992 and 2000 37 patients (mean age 55 years) with T1-4 and N0-3 carcinoma of the base of tongue were presented. Neck dissection was carried out in twelve cases (32%). 30 patients with advanced stage received brachytherapy boost after 50-66.5 Gy (mean, 60 Gy) locoregional external beam irradiation (EBI) and 7 patients with early stage (T1-2, N0) were managed locally with wide tumor excision and sole brachytherapy. 4 of them underwent neck dissection and the others were subjected to 50 Gy regional EBI. The mean dose of boost and sole brachytherapy was 18 Gy and 28 Gy, respectively. RESULTS:. The median follow-up time for surviving patients was 51 months. The 7 sole brachytherapy patients are living with no evidence of disease. For patients treated with EBI and brachytherapy boost, the 5-year actuarial rate of local, locoregional recurrence-free and overall survival was 60%, 52% and 46%, respectively. For all patients in univariate analysis larger tumor size (T4 vs. T1-3) was significant negative predictor of local (RR: 7.23) and locoregional control (RR: 3.87), but nodal involvement was not. Delayed soft tissue ulceration and osteoradionecrosis occurred in 4 (13%) EBI and brachytherapy treated patients. None of the sole brachytherapy patients experienced severe late radiation toxicity. CONCLUSION:. EBI combined with interstitial HDR brachytherapy boost result in acceptable local tumor control with low incidence of late side effects in patients with advanced disease. Fractionated sole HDR brachytherapy following tumor excision is a feasible treatment option for patients with early stage cancer and gives excellent local results.     

High-dose-rate interstitial brachytherapy in recurrent and previously irradiated head and neck cancers--preliminary results

PURPOSE: Although high-dose-rate brachytherapy (HDRBT) offers significant advantages over low dose rate brachytherapy, there are scant data on improved local control (LC) and treatment-related complications in patients with recurrent head and neck (H&N) cancers. We report our preliminary results in patients with recurrent H&N cancers treated with interstitial HDRBT. METHODS AND MATERIALS: Thirty patients with recurrent H&N cancers were treated with HDRBT between September 2003 and October 2005. Seventy-seven percent (23/30) of the patients had either local or regional recurrence in the area of previous external beam radiation therapy. The treatment sites were oral cavity/oropharynx (11/30), neck (10/30), face/nasal cavity (6/30), and parotid bed (3/30). Whereas 18 patients underwent surgical resection followed by HDRBT, 3 patients were treated with combined external beam radiation and HDRBT, and the remaining 9 were treated with HDRBT alone. The dose and fractionation schedules used were 3.4Gy twice per day (b.i.d.) to 34Gy for postoperative cases, 4Gy b.i.d. to 20Gy when combined with 40-50Gy external beam, and 4Gy b.i.d. to 40Gy for definitive treatment. HDRBT was initiated 5 days after catheter placement to allow for tissue healing. RESULTS: With a median followup of 12 months, 6 local recurrences were observed 1-10 months after the procedure. The 2-year LC and overall survival outcomes for the entire group were 71% and 63%, respectively. Patients treated with surgical resection and HDRBT had an improved 2-year LC compared to the patients treated with HDRBT+/-external beam radiation alone (88% vs. 40%, p=0.05). Six Grade II and four Grade III complications were noted in five patients, all observed in the postoperative HDRBT group. CONCLUSION: The preliminary results of HDRBT indicate an acceptable LC and morbidity in recurrent H&N cancers. A planned surgical resection followed by HDRBT is associated with improved tumor control in these high-risk patients. Based on these encouraging results, prospective clinical trials are warranted using HDRBT in recurrent H&N cancers to decrease late toxicity.     

Long-term results of pulsed irradiation of skin metastases from breast cancer. Effectiveness and sequelae.

PURPOSE: The concept of pulsed brachytherapy suggested by Brenner and Hall requires an unusual fractionation scheme. Effectiveness and sequelae of this new irradiation method were observed in patients with disseminated cutaneous metastases of breast cancer. PATIENTS AND METHODS: A flexible, reusable skin mold (weight 110 g) was developed for use with a pulsed dose rate (PDR) afterloader. An array of 18 parallel catheters (2 mm diameter) at equal distances of 10 or 12 mm was constructed by fixation of the catheters in a plastic wire mesh. The array is sewn between 2 foam rubber slabs of 5 mm thickness to provide a defined constant distance to the skin. Irradiations are possible up to a maximum field size of 20 x 23.5 cm using a nominal 37 GBq Ir-192 source. Pulses of 1 Gy reference dose at the skin surface are applied at a rate of 1 pulse every 1.2 hours (0.8 Gy per hour). The dose distribution is geometrically optimized to provide a homogeneous skin dose (100% +/- 10%). The 80% dose level lies at 5 mm below the skin surface. Between April 1994 and December 1997, 52 patients suffering from cutaneous metastases at the thoracic wall were treated with 54 fields and total doses of 38 to 50 Gy (median 42 Gy) applying 2 PDR courses with a pause of 4 to 5 weeks. RESULTS: Forty-six patients (48 fields) were eligible for evaluation in June 1998. The median follow-up was 16 months (range 7.1 to 46.2 months). Local control was achieved in 40 out of 48 fields (83%) or 41 of 46 patients (89%), respectively. Moist desquamation occurred in 52% of the patients. Late reactions were judged after a minimum follow-up of 6 months. Thirty-two fields had been previously irradiated with external beam therapy to doses of 40 to 60 Gy. Regardless of whether the skin was preirradiated or not all patients surviving long enough developed telangiectasia within 2 years after PDR irradiation. In preirradiated patients (n = 32) skin contractures and/or skin necrosis occurred in 12% each. In newly irradiated patients (n = 14) no contractures or skin necrosis were observed. CONCLUSIONS: Pulsed brachytherapy is an effective and time-sparing method for the treatment of cutaneous metastases from breast cancer. Skin reactions are comparable to the sequelae of orthovoltage therapy. Two sessions of approximately 20 Gy PDR were tolerated on preirradiated skin without severe sequelae.     

Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma

PURPOSE: To study the efficacy of reirradiation as salvage treatment in patients with locally recurrent nasopharyngeal carcinoma. PATIENTS AND METHODS: Between 1993 and 2000, 20 consecutive patients (twelve males and eight females) with nasopharyngeal cancer, previously irradiated in different Hungarian institutions, were reirradiated for biopsy-proven locally recurrent tumor. Histologically, 85% of the patients had WHO type III, 5% type II, and 10% type I disease. Stages I-IV (AJCC 1997 staging system) were assigned to five (25%), seven (35%), five (25%), and three (15%) patients, respectively; none of them had distant metastases, and only eight (40%) displayed regional dissemination. The median time period between termination of primary treatment and local recurrence was 30 (range, 10-204) months.Brachytherapy was the method most frequently used: in ten cases alone (especially for rT1 tumors), and in eight cases in combination with external beam therapy. Two patients with locally advanced disease underwent external beam therapy only. The median dose in the event of brachytherapy alone was 20 Gy (4 x 5 Gy or 5 x 4 Gy, range, 16-36 Gy), and the dose range for exclusive external irradiation was 30-40 Gy. In cases of combined irradiation, a median 20-Gy brachytherapy (range, 16-40 Gy) was associated with 30-40 Gy of external irradiation. Radiotherapy was supplemented by neck dissection (six patients), nasopharyngectomy (one patient), or chemotherapy (eleven patients). RESULTS: 16 patients were reirradiated once, three twice, and one patient three times, with a median equivalent dose for tumor effect of 36 Gy (mean, 44 Gy; range, 19-117 Gy; the estimated alpha/beta-ratio was 10 Gy). The median equivalent dose of reirradiation for late effect on normal tissue (with an estimated 70% delivery of the tumor dose) amounted to 30 Gy (mean, 37 Gy; range, 13-101 Gy, estimated alpha/beta-ratio 3 Gy). After a median follow-up of 37 (range, 12-72) months, the overall survival was 60% (12/20). Seven of the twelve surviving patients are currently tumor-free. After primary irradiation, xerostomy occurred in all patients as an unavoidable side effect of treatment. Following reirradiation, a severe (grade 3 or higher) late toxicity (CTC criteria, version 2) has been observed in two tumor-free patients (10%) so far (necrosis of soft palate and paresis of glossopharyngeal nerve). CONCLUSION: Retreatment of nasopharyngeal carcinoma with radiotherapy (preferably a combined modality), can result in longterm local control and survival in a substantial proportion of patients, at the price of an acceptable morbidity.     

Reirradiation for Recurrent Neck Metastases of Head-and-Neck Tumors Using CT-Guided Interstitial 192Ir HDR Brachytherapy

PURPOSE: To report the therapeutic results obtained with CT-guided interstitial high-dose-rate brachytherapy (HDR-BRT) as exclusive treatment for recurrent neck metastases of head-and-neck tumors. PATIENTS AND METHODS: Between 1995 and 1999, 49 patients with prior radiation therapy (RT) with or without surgery for primary head-and-neck tumors were treated for recurrent neck metastases located within previously irradiated volumes. All patients had fixed lymphadenopathy with a mean tumor volume of 96 cm(3) (range, 15-452 cm(3)). There were 38 males and eleven females with a mean age of 60 years (range, 28-79 years). All patients had previously received RT as primary or adjuvant treatment with a mean dose of 54 Gy (range, 45-80 Gy). 36 patients (73%) underwent surgery, and 26 (53%) received adjuvant or palliative chemotherapy. The accelerated hyperfractionated interstitial HDR-BRT (2 x 3.0 Gy/day) delivered 30 Gy in 37/49 (75%) and 36 Gy in 12/49 implants (25%). RESULTS: At a minimum 6-week follow-up, the response rate was 83% (41/49) with complete remission in 20% (10/49) and partial remission in 63% (31/49) of the implanted tumor sites. 8/49 patients (17%) did not respond to the treatment. After 19 months of median follow-up, the local control rate was 69% and a total of 15/49 patients (30%) experienced local disease progression. Of these, nine (18%) had locoregional progression and six (12%) progression within the treated volume. The median post-BRT survival was 14 months. The overall survival rate was 52% at 1 year, 31% at 2 years, and 6% at 3 years. CONCLUSION: In patients with recurrent cervical lymphadenopathy of head-and-neck tumors, exclusive interstitial HDR-BRT can provide palliation and tumor control.     

Transperineal Low-Dose Rate Iridium-192 Interstitial Brachytherapy in Cervical Carcinoma Stage IIB

PURPOSE: To assess local control, survival and complications in patients with cervical carcinoma Stage IIB treated radically with transperineal Iridium-192 low-dose rate interstitial brachytherapy following external beam radiotherapy. PATIENTS AND METHODS: 65 women (age 25-70 years, mean 47 years) with cervical carcinoma Stage IIB were initially treated with external beam radiotherapy on a telecobalt or 6 MV linear accelerator to a dose of 50 Gy delivered in 5-6 weeks. After 2-3 weeks of completing external radiation, patients received interstitial brachytherapy with Iridium-192 (activity 0.5-1 mCi/cm) using a Syed-Neblett perineal template. The median dose delivered to the implant volume was 24 Gy (range 20-32 Gy) delivered at an average dose rate of 0.70 Gy/h (range 0.40-1.20 Gy/h). A point defined at 1.5 cm lateral to the central uterine tandem at the level of os was taken as a representative for assessing the dose to the cervix. Mean doses delivered by interstitial brachytherapy to point A, cervix, point B and rectum were 38 Gy, 34 Gy, 16 Gy and 16 Gy, respectively. RESULTS: At a median follow-up of 53 months, the actuarial disease free survival and overall survival for 65 patients at both 5 and 10 years was 64% and 44%, respectively. Response to radiotherapy was a strong predictor of local control with 82% of patients continuing to have pelvic control after initial complete response. Overall, nine (14%) patients had persistent disease, ten (15%) developed a central recurrence after initial control and three patients developed distant metastasis on follow-up. No patient had any immediate treatment-related complication. Late toxicity included grade I-II rectal reactions in five patients and grade IV bladder complication (vesico-vaginal fistula) in two patients. 5 years after treatment, one patient developed intestinal obstruction, which was relieved after conservative management. Two patients developed vaginal stenosis. The 5- and 10-year disease free survival was 48% in patients aged less than 45 years as compared to 80% in patients of more than 45 years (p = 0.009). Dose to the cervical point was a prognostic indicator with 5- and 10-year disease free survival of 47% in patients who received < 35 Gy in comparison to 80% in patients who had > 35 Gy (p = 0.03). There was no difference in local control and survival in patients with minimal and moderate parametrial involvement. Bulky disease (> 4 cm) at presentation and a longer gap between external radiation and brachytherapy showed a trend towards inferior local control. CONCLUSIONS: Interstitial brachytherapy after external beam irradiation in patients with cervical carcinoma Stage IIB results in acceptable local control, survival and complication rates. Increased dose to the cervical disease results in improved local control and survival and should therefore be considered while optimizing brachytherapy treatment plans. Comparison of the results with those of standard intracavitary therapy remains to be proven in a randomized trial.     

Daytime pulsed dose rate brachytherapy as a new treatment option for previously irradiated patients with recurrent oesophageal cancer

The aim of this study was to evaluate the feasibility, effects, and toxicity of pulsed dose rate (PDR) brachytherapy for re-irradiation of oesophageal carcinoma. A total of 16 patients (median age 67 years) with inoperable recurrences from oesophageal cancer after primary radio-(chemo)-therapy (median 50 Gy) were re-irradiated using PDR brachytherapy ((192)Ir, 37 GBq). Treatment was carried out on an outpatient basis applying a weekly 5 Gy daytime schedule (0.5 Gy pulse(-1) h(-1), total dose 15-20 Gy). The dose was prescribed 10 mm from the mid-dwell position and encompassed the clipped tumour extension with 2 cm margins. The use of clips for delineation of tumour extent and catheter movement during irradiations was evaluated. All 61 PDR treatments were applied safely. The median catheter movement was 5 mm, range 2-12 mm. After a median follow-up of 8 months, three patients had a complete and five a partial remission. Body weight increased in 5 of 16 (31%) and was stable in 4 of 16 (25%) patients, respectively. The median grade 2 (RTOG/EORTC) dysphagia-free survival was 17 months. Seven patients experienced grade 1, five grade 2, and one grade 3 late toxicity. Three patients with uncontrolled locoregional disease showed grade 4 complications (oesophago-tracheal fistulae (n=2), fatal arterial bleeding (n=1). Daytime PDR brachytherapy proved to be feasible and provided effective palliation. Toxicity remains a major problem. Thus, total dose should be restricted to <15 Gy in this palliative situation.     

Hyperfractionated <Superscript>192</Superscript>Ir Brachytherapy for Recurrent Retroperitoneal Sarcoma: a Technique for Delivery of Local Tumor Boost Dose

BACKGROUND: Radical surgery is the treatment of first choice for retroperitoneal sarcoma. However, locoregional relapse is frequently observed leading to death in the majority of patients. The role of radiotherapy is not well defined in the management of retroperitoneal sarcoma. Yet, there is evidence that adjuvant irradiation does improve local tumor control. MATERIAL AND METHODS: In order to deliver sufficiently high radiation doses to the retroperitoneum, different techniques for application of a local tumor boost dose in addition to external beam treatment have been proposed. We present a technique of hyperfractionated (192)Ir brachytherapy (HFIR) of the tumor bed via intraoperatively implanted plastic catheters. Postoperative CT-based image-guided brachytherapy was performed. In two consecutive patients with recurrent retroperitoneal sarcoma, treatment was delivered twice daily with single doses of 1.5-2.0 Gy in 5-10 mm tissue depth up to a total dose of 18-32.5 Gy. RESULTS: HFIR of the tumor bed was easily accomplished facilitating delivery of high radiation doses to the retroperitoneum. No major late effects of treatment have been observed with a follow-up of 15 and 28 months, respectively. Details of the brachytherapy procedure are presented. CONCLUSION: HFIR via intraoperatively implanted catheters in the retroperitoneum is a technique suitable for application of a local tumor boost dose. Thus, sufficiently high doses of radiation mandatory for long-lasting local tumor control can be delivered in the tumor bed of the retroperitoneum without exceeding normal tissue radiotolerance in this unfavorable disease.     

High-dose-rate brachytherapy for previously irradiated patients with recurrent esophageal cancer

Purpose Our objective was to assess the feasibility, efficacy, and complications of high-dose-rate (HDR) brachytherapy for patients with recurrent esophageal cancer after external radiotherapy. Materials and methods Six patients with recurrent esophageal cancer after external radiotherapy were treated with HDR brachytherapy (Ir-192 source) from January 2003 to February 2004. The median age of the patients was 69 years. All patients had received external radiotherapy (median dose 60 Gy) before HDR brachytherapy. All patients underwent HDR brachytherapy once a week with a dose of 4 or 5 Gy per fraction in the esophageal mucosa (median total dose 20 Gy). The Kaplan-Meier method was used to calculate local control rates. Results The median overall survival period was 30.0 months. Local control was observed in five patients and residual tumor in one patient. Persistent local control was observed in two patients. No patient died of esophageal cancer, and all patients survived. We observed no severe late complications related to HDR brachytherapy. Conclusion These data suggest that HDR brachytherapy is an effective and safe treatment for patients with recurrent esophageal cancer after external radiotherapy.