HDR brachytherapy for the reirradiation of cervical and vaginal cancer: analysis of efficacy and dosage delivered to organs at risk.

OBJECTIVE: To evaluate the efficacy and toxicity of HDR brachytherapy (BT) for the reirradiation of cervical or vaginal cancer arising within a previously irradiated area with a special focus on dosage delivery to organs at risk. METHODS: Twenty consecutive patients with cervical (N = 19) or vaginal (N = 1) cancer were reirradiated with curative intent using BT with or without external beam irradiation and hyperthermia. The median biologically equivalent dose in 2 Gy fractions (EQD2), assuming α/ß = 10, for reirradiation was 48.8 Gy (range: 16.0-91.0 Gy), and the median cumulative EQD2 (for primary treatment and reirradiation) was 133.5 Gy (range: 96.8-164.2 Gy). The median follow-up after retreatment was 31 months (range: 6-86 months). RESULTS: The 3-year overall survival (OS) rate was 68% (95% confidence interval [CI]: 44%-91%). The 3-year disease-free survival (DFS) rate was 42% (95% CI: 19%-65%). The 3-year local control (LC) rate was 45% (95% CI: 22%-69%). For nine patients who received 3D treatment planning, the median cumulative EQD2 to 2 cm(3) of rectum was 94.4 Gy (range: 67.1-118.8 Gy) and to 2 cm(3) of bladder was 99.3 Gy (range: 70.4-122.3 Gy). Grade 3 late toxicity was observed in 3 patients (15%). An interval between primary RT and reirradiation of ≤ 12 months and a tumor diameter >3 cm were significant prognostic factors adversely affecting OS, DFS and LC. CONCLUSIONS: HDR BT is a valuable method for the reirradiation of cervical cancer. A cumulative EQD2 of approximately 100 Gy was safely delivered to 2 cm(3) of the bladder and the rectum.

Determinants of model of renarrowing after beta radiation for in-stent restenosis.

UNLABELLED: It is unknown whether model of renarrowing after beta-radiation for in-stent restenosis (ISR) is influenced by the type of geographic miss (GM). METHODS: In 166 ISR treated with Galileo, serial quantitative coronary angiographic analysis was done. Minimal lumen diameters and lengths were measured for (1) stent, (2) peri-stent subsegments subjected to angioplasty with/without irradiation, and (3) irradiation margins. GM was defined as: (Type 1) edge injury within the 32P source dose fall-off: 2.0 mm inside and outside the source end marker or (Type 2) overt, nonirradiated injury: beyond the outer 2.0-mm long dose fall-off zone. RESULTS: Restenosis rate was 28.3% at 8.9+/-4.5 months with 60% located exclusively outside the stent. Type 1 GM was present in 24.7% of proximal edges, whereas Type 2 in 18.1%. Respective percentages for distal edges were 23.5% and 15.7%. Regardless of presence and type of GM, significant late lumen loss occurred only outside the stent. However, the biggest late lumen loss at the proximal edge was induced by the Type 1 GM (0.65+/-0.79, p<0.001), while proximal Type 2 GM was not associated with edge renarrowing (-0.04+/-0.48, p=NS). Both reference lumen diameter and proximal Type 1 GM influenced restenosis independently (OR 0.47; 95%CI 0.24-0.90; p=0.023 and OR 2.46; 95%CI 1.12-5.40; p=0.025). CONCLUSIONS: Regardless of presence and type of geographic miss, late lumen loss after beta-radiation occurs only outside the stent. However, injury within the proximal 32P dose fall-off but not overt edge injury is associated with the biggest late lumen loss at the respective edge, triggering recurrent restenosis.

Acute lumen overdilation improves outcome after brachytherapy of in-stent restenosis.

BACKGROUND: The aim of our study was to test the impact of acute lumen overdilation on neointimal hyperplasia and late lumen size after vascular brachytherapy for in-stent restenosis (ISR). METHODS: Forty-seven ISR lesions located in 47 coronary arteries in 44 consecutive patients underwent beta brachytherapy with serial intravascular ultrasound studies. Vessel, lumen, and stent cross-sectional area were measured at 1-mm steps. Based on an interpolated reference cross-sectional area, each cross section was assessed as overdilated (lumen cross-sectional area>interpolated reference cross-sectional area) or not overdilated (lumen cross-sectional area

Optimization of dose prescription protocol and its impact on delivered dose and vascular response after beta-radiation for in-stent restenosis. A randomized trial with serial volumetric intravascular ultrasound and dose volume histograms.

AIM: The incidence of restenosis within stented segment after intravascular brachytherapy with recommended dose prescription protocols is up to 25%. Therefore, we designed a randomized trial comparing recommended dose prescription protocol with dosing adjusted for the source-to-target distance. METHODS: Fifty-one in-stent restenosis (ISR) lesions in 48 patients underwent centered source beta-irradiation with serial intravascular ultrasound. Patients randomly received 20 Gy at 1 mm either beyond lumen surface [n=25, standard group (S)] or external elastic membrane [n=26, dosing-adjusted (DA) group]. Minimum dose absorbed by 90% of adventitia (DV(90%Adv)) was calculated. RESULTS: DV(90%Adv) was higher for the DA group than for the S group (21.63+/-5.67 vs. 12.05+/-4.88 Gy, P<.001). After 8.9+/-4.5 months there was complete lumen preservation in DA vs. lumen decrease subsequent to neointimal hyperplasia (NIH) in S group (0.10+/-1.20 vs. -0.61+/-1.29 mm3/mm, P<.05). Vessel volume increased significantly in the DA group and was unchanged in S group (+1.73, P=.002 vs. 0.14 mm3/mm, P=NS). DV(90%Adv) correlated inversely with NIH volume and positively with vessel volume change (r=-.405, P=.007 and r=.363, P=.017, respectively). CONCLUSION: For beta-irradiation of ISR, dosing adjusted for the source-to-target distance leads to significant increase in target delivered doses, which is associated with complete NIH inhibition and induction of positive vessel remodeling.

Effectiveness and determinants of the long-term beta intracoronary brachytherapy results.

BACKGROUND: Effectiveness evaluation and search for the factors determining long-term results of beta intracoronary brachytherapy (ICBT) are of a special importance in an upcoming era of drug-eluting stents usage for a wide range of clinical indications: de novo and in-stent restenosis lesions. METHODS: One hundred forty eight consecutive patients (59.6+/-9.6 years, 72% men) treated with beta ICBT for in-stent restenosis (ISR) or de novo lesions were studied. There were 135 ISR in 121 patients and 31 de novo lesions in 27 patients. Follow-up coronary angiography was performed in all patients after a mean of 8.9+/-4.5 months. Detailed qualitative and quantitative angiographic analysis of pre-, peri- and postprocedural as well as follow-up angiograms was performed. RESULTS: Forty five percent of patients treated for de novo lesions were diabetic. Thirty five percent of all targets were located in vessels with a reference vessel diameter <2.5 mm. Furthermore, 77% of ISR lesions were in Class 1 according to the Mehran classification. The mean length of an irradiated segment was 37.6 mm. The overall recurrent restenosis rate was 28.3%. Multivariate analysis revealed that the reference vessel diameter and the presence of edge injury within the proximal 32P source dose-fall off were the only independent predictors of recurrent restenosis after ICBT (OR 0.46; 95%CI 0.24-0.89; p=0.021 and OR 2.55; 95%CI 1.23-5.25; p=0.011, respectively). CONCLUSIONS: Recurrent restenosis after beta intracoronary brachytherapy treatment is negatively associated with the target vessel size. Presence of edge injury within the proximal 32P source dose-fall increases the frequency of recurrent renarrowing after ICBT. Our results indicate that target vessel size should be taken into account in optimising interventional strategy for ISR treatment: drug eluting stents versus intracoronary brachytherapy. Avoidance of edge injury within the proximal 32P source dose fall-off is strongly recommended while ICBT application.

[New radiotherapy techniques in the treatment of patients with craniopharyngioma: a report of two cases]. / Zastosowanie nowoczesnych technik radioterapii w leczeniu chorych na czaszkogardlaka na przykladzie 2 przypadków.

The authors report two cases of adult patients with craniopharyngioma recurrence after surgery. In both these patients radiotherapy resulted in a complete regression of the neoplasms, confirmed both by clinical examination and MR imaging. In both cases modern radiotherapy techniques were used so as to spare healthy tissues surrounding the tumor. Case 1. A 56-year-old man was admitted with an extensive (3.5 x 4.0 x 4.0 cm) recurrent craniopharyngioma 3 years after the initial surgery and 3 months after a surgery for relapse. Conformal 3-D planned fractionated radiotherapy to the total dose of 54 Gy in 30 fractions was delivered encompassing the tumor with 5 mm margins. Four months after radiotherapy MR imaging demonstrated a complete regression of the neoplasm and the patient recovered totally from his endocrine deficiency and neurological symptoms. Case 2. A 29-year-old man was irradiated 10 months after the initial surgery when a relapse of craniopharyngioma was found in MR imaging. The largest diameter of this recurrent tumor was 18 mm. The patient was subjected to fractionated stereotactic radiotherapy to the total dose of 54 Gy in 27 fractions. Two months after the treatment his complete recovery was confirmed by MRI. Benefits resulting from the use of more recent radiotherapy techniques in the management of craniopharyngioma are discussed.

Surgery combined with brachytherapy in patients with retroperitoneal sarcomas.

PURPOSE: The primary aim of this work was to analyze feasibility of combined treatment of retroperitoneal sarcomas (RS): surgery (S) and intraoperative brachytherapy (IOBRT). The secondary aim was to analyze results and complications after this treatment. MATERIAL AND METHODS: 84 patients with retroperitoneal sarcomas were qualified for combined treatment (S and IOBRT) between June 1998 and September 2006. 65 of the patients (77.4%) had local recurrences. Sarcomas with intermediate and high grade of histological malignancy (G2, G3 - 76.2%) were the most frequent within the all surgically treated patients. Resection ability (R0/R1) in analyzed group of patients was estimated as 85% (74 cases). After intraoperative evaluation, 57 (67.8%) patients were qualified for IOBRT. Since 2000, in 34 patients (60%) an adjuvant postoperative external beam radiation therapy (EBRT) in dose of 50 Gy was applied. Median follow-up of the surviving patients was 40 months. RESULTS: On the basis of the univariate analysis, relevant aspects negatively influencing overall survival rate within the RS group treated with IOBRT were as follows: surgery of sarcoma recurrence (p = 0.002), higher grade of histological malignancy (p = 0.05), histological type different than liposarcoma (p = 0.05) as well as no adjuvant EBRT (p = 0.05). On the basis of multivariate analysis one can ascertain that relevant factors negatively influencing LRFS in RS patients treated with IOBRT were: surgery due to recurrence of sarcoma (p = 0.008) and lack of EBRT (p = 0.01). CONCLUSIONS: Combined treatment (surgery and brachytherapy) was possible to be carried out on 68% of RS patients. The overall number of complications was quite high, however acceptable, taking into consideration the application of extensive, multi-organ treatments in case of sarcoma recurrences in this localization. The results suggest that the method of treatment will improve the final outcome when most of patients will be qualified for treatment of primary sarcomas in experienced centre.

Combined therapy: surgery and intraoperative HDR brachytherapy for locally advanced and recurrent rectal cancer. Practical experience of Brachytherapy Department in Warsaw.

PURPOSE: Patients with locally advanced and recurrent rectal cancer have a dismal prognosis. The aim of proposed combined therapy - surgery and intraoperative brachytherapy, is to improve results of already applied methods and to define optimal group of patients for this treatment. We introduce practical experience of Brachytherapy Department in Cancer Centre - Institute in Warsaw. MATERIAL AND METHODS: Patients with primary T4NxM0 rectal cancer and isolated local pelvic recurrence were qualified for therapy. Between January 2005 and September 2008, 13 patients were included: 4 with primary cancer and 9 with recurrence, median age of 56. After surgical resection intraoperative radiotherapy was delivered with boost of high dose rate brachytherapy of 20Gy dose to the tumor bed. RESULTS: Primary point of the study is to evaluate impact of applied therapy on local control (LC), overall survival (OS) and disease free survival (DFS). Median follow-up is 16 months. Four of the patients died and 3 survivors are disease-free. There was no case of perioperative mortality. CONCLUSIONS: A multimodality approach, using surgical resection with intra operative brachytherapy improves local control as well as patients survival in comparison with historical treatment group. Combined therapy is related to high morbidity, but low mortality. The preliminary observations seem to correspond with other authors data.

HDR brachytherapy as a solution in recurrences of locally advanced prostate cancer.

PURPOSE: The object of this study was to analyze the outcome of salvage HDR brachytherapy treatment after local failure, for patients with prostate specific antigen (PSA) failure without distant metastasis, after external beam radiation and HDR brachytherapy treatment, or after radical prostatectomy, with or without hormonal therapy. MATERIAL AND METHODS: The group of 115 patients, without distant metastasis, after local failure and external beam radiation, followed by HDR brachytherapy treatment, or after radical prostatectomy, with hormonal therapy and without, have been enrolled to salvage HDR brachytherapy (SBR). All patients had minimum 3 months androgen deprivation therapy before salvage brachytherapy, which was continued until the next 9 months after SBR. Brachytherapy was administered in three 10 Gy fractions with 3 weeks gap between them. Each session of SBR was supported by trans-rectal USG real time pictures. The treatment planning was done on the base of Abacus system from Sauerwein® or with SWIFT system from Nucletron®. The following data were collected: Gleason score, clinical staging, the volume of the prostate, PSA before and after the initial treatment and periodically during the follow-up period. Also the time during which the PSA stays at the nadir level, patient's age and toxicity of treatments were taken into consideration. RESULTS: Doses from external radiotherapy or from HDR brachytherapy were recalculated to equivalent biological dose (EBD). The independence from biochemical progression in our group of patients after retreatment was 46% for patients with PSA ≤ 6 and 18% for patients with PSA > 6. Overall survival for patients with PSA ≤ 6 was 86% and 48% for patients with PSA > 6, respectively. CONCLUSIONS: Salvage prostate brachytherapy (SBR) can be safely performed with acceptable biochemical control and toxicity.

Surgery combined with intraoperative brachytherapy in the treatment of retroperitoneal sarcomas.

BACKGROUND: The purpose of this study was to analyze the results of treatment of retroperitoneal soft tissue sarcomas (RSTS) by surgery combined with intraoperative brachytherapy (IOBRT). METHODS: Seventy adult patients with RSTS were considered for combined treatment (surgery plus IOBRT) between June 1998 and February 2004. There were 64 (91%) recurrent tumors, and 93% of tumors exceeded 5 cm. IOBRT was performed with high-dose-rate Gammamed 12 with iridium 192 (IOBRT time range, 20-87 minutes; median, 56 minutes). RESULTS: After intraoperative re-evaluation, 24 patients (34%) were found to be ineligible for IOBRT because of multiple intraperitoneal recurrences, macroscopically nonradical resection, poor general condition, and technical aspects. Thirty-seven patients underwent IOBRT immediately after surgery during the same general anesthesia procedure. Nine patients underwent delayed IOBRT within 1 to 3 days after the primary operation. Ten (21.5%) of 46 patients underwent reoperation because of surgical complications. One patient died in the postoperative period. After IOBRT, 24 patients (52%) underwent adjuvant external beam radiotherapy (EBRT) to a total dose of 50 Gy. Over a median follow-up time of 20 months, the estimated 5-year overall survival and local recurrence-free survival rates in IOBRT patients were 55% and 51%, respectively. Application of adjuvant EBRT showed a favorable local control rate. CONCLUSIONS: The scheduled combined treatment (surgery plus IOBRT) was possible to perform in 66% of RSTS cases that received surgical treatment. The complication rate was high, but we consider it acceptable because of the necessity for extensive aggressive surgical treatment in regionally advanced RSTS. EBRT seems to be an indispensable part of treatment that provides better local control.

Angiographic restenosis following intravascular beta-brachytherapy does not correlate with delivered dose: a study with dose volume histograms. Recurrence of in-stent restenosis after brachytherapy.

INTRODUCTION: Vascular brachytherapy reduces recurrence after treatment of in-stent restenosis. However, there are still failures. The aims of the study were to investigate the relationship between two distinct dose prescriptions and the calculated dose delivered versus binary angiographic restenosis. METHODS AND MATERIALS: Fifty-five lesions in 47 patients underwent catheter-based beta-brachytherapy with a (32)P source. Doses delivered were calculated using intravascular ultrasound (IVUS) measurements. Patients randomly received 20 Gy either at 1 mm beyond mean reference lumen or 1 mm beyond mean reference external elastic membrane. Using subsequent off-line volumetric IVUS measurements, dose volume histograms (DVHs) for the adventitia were determined. RESULTS: There were 13 restenotic lesions including four total occlusions. All recurrences localized within stented segment. The frequency of restenosis was similar between dosimetry groups (20% vs. 28%; P=.5). DVH calculations were similar in restenotic versus restenosis-free lesions. However, postprocedural IVUS minimal lumen area was significantly smaller for lesions that recurred (5.03+/-1.19 mm(2) vs. 6.13+/-1.7 mm(2); P=.042). CONCLUSIONS: Calculated cumulative doses delivered to the tissues do not correlate with clinical outcome. However, an adequate lumen may be important to accommodate even a small amount of recurrent intimal hyperplasia to limit restenosis and need for target lesion revascularization.