Twelve-month follow-up results of a trial utilizing Axxent electronic brachytherapy to deliver intraoperative radiation therapy for early-stage breast cancer.

BACKGROUND: Accelerated partial breast irradiation (APBI) is emerging as a valid alternative to whole-breast radiation therapy (WBRT) in breast-conserving therapy (BCT) for early-stage breast cancer. Axxent electronic brachytherapy (EBX) is a form of portable, balloon-based APBI that utilizes an electronic source of kilovoltage irradiation delivery with minimal shielding requirements. As such, EBX becomes a logical and convenient modality for delivery of intraoperative radiation therapy (IORT). We report 1-year results and clinical outcomes of a trial that utilizes EBX to deliver IORT for patients with early-stage breast cancer. METHODS: Eleven patients were enrolled on an institutional review board (IRB)-approved protocol. Inclusion criteria were patient age >45 years, unifocal tumors with infiltrating ductal or ductal carcinoma in situ (DCIS) histology, tumors ≤3 cm, and uninvolved lymph nodes. Preloaded radiation plans were used to deliver radiation prescription dose of 20 Gy to the balloon surface. RESULTS: The mean time for radiation delivery was 22 min; the total mean procedure time was 1 h 39 min. All margins of excision were negative on final pathology. At mean follow-up of 12 months, overall cosmesis was excellent in 10 of 11 patients. No infection, fat necrosis, desquamation, rib fracture or cancer recurrence has been observed. There was no evidence of fibrosis at last follow-up. CONCLUSION: IORT utilizing EBX is emerging as a feasible, well-tolerated alternative to postsurgical APBI. Further research and longer follow-up data on EBX and other IORT methods are needed to establish the clinical efficacy and safety of this treatment.

Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer.

BACKGROUND: A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer. METHODS: A total of 15 patients with stage I or II endometrial cancer were enrolled at 5 sites. Patients were treated with vaginal EBT alone or in combination with external beam radiation. RESULTS: The prescribed doses of EBT were successfully delivered in all 15 patients. From the first fraction through 3 months follow-up, there were 4 CTC Grade 1 adverse events and 2 CTC Grade II adverse events reported that were EBT related. The mild events reported were dysuria, vaginal dryness, mucosal atrophy, and rectal bleeding. The moderate treatment related adverse events included dysuria, and vaginal pain. No Grade III or IV adverse events were reported. The EBT system performed well and was associated with limited acute toxicities. CONCLUSIONS: EBT shows acute results similar to HDR brachytherapy. Additional research is needed to further assess the clinical efficacy and safety of EBT in the treatment of endometrial cancer.

Experience with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation.

OBJECTIVES: Phase IV study evaluated the safety and device performance of an electronic brachytherapy system (Axxent Electronic Brachytherapy System) as adjuvant therapy for early-stage breast cancer. METHODS: Patients were > or =50 years of age and had completely resected invasive ductal carcinoma or ductal carcinoma in situ (<2.0 cm), with N0 M0 and negative microscopic margins of > or =1 mm. The balloon applicator was placed in a closed cavity with a balloon surface to skin distance of > or =7 mm. The prescribed dose was 3.4 Gy/fraction prescribed to 1 cm beyond the balloon surface twice daily (BID) for 10 fractions. RESULTS: Of 65 patients consented, 21 (32%) were not eligible for treatment, and 44 (68%) were treated, with 6-months follow-up in 43 and 1-year follow-up in 36. The prescribed radiation treatment was successfully delivered in 42/44 (95.4%) patients; one was unsuccessful due to a controller issue and the other declined the final fraction following a balloon deflation. Side effects were as anticipated and generally manageable. Four CTCAE v3 grade 3 toxicities were reported: blistering (1), breast tenderness (1), and moist desquamation (2); all have resolved. The most common grade 2 toxicity was erythema. There were no device-related serious adverse events. CONCLUSIONS: Early experience demonstrates that the electronic brachytherapy system performed as expected. Electronic brachytherapy has similar acute toxicity profiles to other high dose rate approaches for accelerated partial breast irradiation and offers the convenience of having the treatment in an unshielded room.

Tomotherapy and multifield intensity-modulated radiotherapy planning reduce cardiac doses in left-sided breast cancer patients with unfavorable cardiac anatomy.

PURPOSE: For patients with left-sided breast cancers, radiation treatment to the intact breast results in high doses to significant volumes of the heart, increasing the risk of cardiac morbidity, particularly in women with unfavorable cardiac anatomy. We compare helical tomotherapy (TOMO) and inverse planned intensity modulated radiation therapy (IMRT) with three-dimensional conformal radiotherapy using opposed tangents (3D-CRT) for reductions in cardiac volumes receiving high doses. METHODS AND MATERIALS: Fifteen patients with left-sided breast cancers and unfavorable cardiac anatomy, determined by a maximum heart depth (MHD) of >or=1.0 cm within the tangent fields, were planned for TOMO and IMRT with five to seven beam angles, in addition to 3D-CRT. The volumes of heart and left ventricle receiving >or=35 Gy (V35) were compared for the plans, as were the mean doses to the contralateral breast and the volume receiving >or=20 Gy (V20) for the ipsilateral lung. RESULTS: The mean MHD was 1.7 cm, and a significant correlation was observed between MHD and both heart and left ventricle V35. The V35s for IMRT (0.7%) and TOMO (0.5%) were significantly lower than for 3D-CRT (3.6%). The V20 for IMRT (22%) was significantly higher than for 3D-CRT (15%) or TOMO (18%), but the contralateral breast mean dose for TOMO (2.48 Gy) was significantly higher than for 3D-CRT (0.93 Gy) or IMRT (1.38 Gy). CONCLUSIONS: Both TOMO and IMRT can significantly reduce cardiac doses, with modest increases in dose to other tissues in left-sided breast cancer patients with unfavorable cardiac anatomy.

A dosimetric analysis comparing treatment of low-risk prostate cancer with TomoTherapy versus static field intensity modulated radiation therapy.

OBJECTIVES: Static field intensity modulated radiation therapy (IMRT) has demonstrated dosimetric and clinical benefits over 3-dimensional conformal radiation therapy. TomoTherapy is a unique form of IMRT that may offer further improvements. METHODS: The study population consisted of 15 patients with low-risk prostate cancer treated at Rush University with TomoTherapy (n = 7) or IMRT (n = 8). For each patient, both a TomoTherapy plan and an IMRT plan were generated using identical planning objectives. The planning target volume (PTV) was defined as the prostate and proximal seminal vesicles plus a margin. The prescription dose was 7740 cGy in 43 fractions. Radiation Therapy Oncology Group (RTOG) normal tissue guidelines were used as constraints, and the PTV coverage was made equivalent for the paired plans by equalizing the PTV V100. RTOG benchmark DVH values for the rectum and bladder and mean dose to the penile bulb were recorded. The volume of PTV receiving ≥ 105% of the prescription dose was measured. RESULTS: The mean DVH values for each of the RTOG constraints for rectum and bladder were significantly improved using TomoTherapy. The volume of the PTV that received at least 105% of the dose was higher with IMRT (11.7% vs. 0.2%, <0.001). The mean dose to the penile bulb was higher with TomoTherapy (40.4 Gy vs. 27.4 Gy, P = 0.005). CONCLUSIONS: TomoTherapy offers a more favorable dose distribution to the bladder and rectum, as well as improved target homogeneity in comparison with IMRT.

Breast brachytherapy devices.

Multiple institutions have explored accelerated partial breast irradiation (APBI). The method of APBI with the longest reported follow-up is multicatheter interstitial brachytherapy. Balloon brachytherapy was introduced to simplify the APBI procedure. The MammoSite device was the first breast brachytherapy device designed for the treatment of APBI to hit the market. The MammoSite catheter was adopted rapidly in both academic and community settings and has led to a great increase in the number of patients undergoing the APBI procedure. We introduce and describe five additional breast brachytherapy devices.

A virtual matching technique for three-field breast irradiation using 3-D planning.

Patients with breast cancer are often treated with radiation to the breast (or chest wall) and draining regional lymph nodes. This is typically performed with a three-field technique in which an anterior supraclavicular field is matched to opposed tangent fields. A single isocenter technique is not always possible. Several techniques have been described to create a perfect match using a conventional simulator. We describe and test a simple, fast and accurate technique to estimate the couch and collimator angles required for a perfect geometric match using 3-D treatment planning software. This method requires no mathematical formulae and is verifiable relative to patient anatomy. An external skin contour is created on the axial slice at the match line and displayed with a 3-D representation. Using a beam's eye view (BEV) of a tangent field, small couch and collimator rotation adjustments are made sequentially until the contour edges are superimposed. The virtual external contour technique was easy to use, gave verification of the match in the BEV and yielded estimates of couch and collimator rotations very close to those calculated using published formulae.

Intraoperative radiation therapy in the treatment of early-stage breast cancer utilizing xoft axxent electronic brachytherapy.

BACKGROUND: In an effort to overcome the barriers to BCT, alternative methods of delivering radiation therapy have been explored. APBI allows the radiation treatment to be accomplished in one week or less. XB is a form of balloon-based APBI that uses an electronic source generated by a mobile controller unit. Investigators have also explored IORT treatment that delivers a single fraction of radiation in the operating suite at the time of surgery. METHODS: We report on the first patient treated with XB to deliver IORT. RESULTS: IORT treatment utilizing XB is feasible and can be accomplished with a total procedure time of approximately 2 hours. CONCLUSION: Further research on XB and other methods of IORT is needed to establish clinical efficacy and safety for patients with early-stage breast cancer.

Accelerated partial breast irradiation utilizing balloon brachytherapy techniques.

To overcome the barriers to BCT, methods of PBI in the setting of breast conservation have been explored. The method of PBI with the longest published follow-up is multi-catheter interstitial brachytherapy. Balloon-based brachytherapy with the MammoSite brachytherapy applicator was designed to simplify the brachytherapy procedure for PBI, enhance the reproducibility of the dosimetry, and improve patient comfort. The rates of local recurrence following PBI with the MammoSite applicator have been low, but there are few published reports and follow-up has been relatively short. The cosmetic outcomes and toxicity of MammoSite PBI are comparable to those seen after multicatheter-based PBI. Additional methods of balloon brachytherapy, including Xoft and SenoRx Contura have been developed. Finally, long-term follow-up after PBI is important for the welfare of individual patients and in order to establish the efficacy, late toxicity and cosmetic outcomes of this technique.

Xoft Axxent electronic brachytherapy: a new device for delivering brachytherapy to the breast.

Balloon-based brachytherapy was developed to simplify the brachytherapy technique and make accelerated partial breast irradiation more accessible to patients with breast cancer who are suitable candidates for this technique. Xoft Axxent (Xoft, Inc., Sunnyvale, CA) electronic brachytherapy is a novel method of accelerated partial breast irradiation that uses an electronic source to produce X-rays. Xoft Axxent treatment does not require a high-dose-rate afterloader unit or a shielded vault, unlike other brachytherapy techniques that use iridium-192, such as MammoSite brachytherapy. Xoft Axxent is associated with the delivery of less radiation to normal tissues, and increased high radiation dose regions or 'hot spots' to the target volume compared with treatment with the MammoSite device. Further research will be needed to determine subgroups of patients who might benefit from treatment with Xoft Axxent electronic brachytherapy.

A dosimetric comparison of MammoSite and ClearPath high-dose-rate breast brachytherapy devices.

PURPOSE: A new form of partial breast irradiation (PBI), ClearPath (CP) breast brachytherapy, has been introduced. We present our results of a dosimetric comparison of MammoSite (MS) and CP PBI. METHODS AND MATERIALS: The dimensions of the CP device were reconstructed onto the MS planning CT scans for 15 previously treated patients. The mean %V(100), %V(150), %V(200) (percent of the PTV that received 100%, 150%, and 200% of the prescription dose, respectively), ipsilateral breast %V(50) (percent of the ipsilateral normal breast that received 50% of the prescription dose), ipsilateral lung %V(30) (percent of the ipsilateral lung that received 30% of the prescription dose), the heart %V(5) (percent of the heart that received 5% of the prescription dose), and the maximum skin point dose per fraction were then determined for each patient using the two methods of balloon-based PBI. RESULTS: The mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 42.1% vs. 42.9% (p=ns), and the mean V(200) was 11.4% vs. 15.2% (p<.05) for the MS and CP methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs.18.0% (p<.05), the mean ipsilateral lung %V(30) was 3.7% vs. 2.8% (p<.05), the mean heart %V(5) was 57.0% vs. 54.3% (p<.05), and the maximum skin point dose per fraction was 312.2 and 273.6cGy (p<.05) for the MS and CP methods, respectively. CONCLUSIONS: The MS and CP methods of PBI offer comparable target volume coverage; however, the CP device achieves increased normal tissue sparing.

Xoft Axxent electronic brachytherapy.

Balloon-based brachytherapy was developed to render accelerated partial-breast irradiation more accessible to breast cancer patients. Xoft Axxent electronic brachytherapy (eBX) is a novel method of accelerated partial-breast irradiation that utilizes an electronic source to produce x-rays. eBX does not require a high dose rate afterloader unit or a shielded vault and, thus, may appeal to a larger number of patients undergoing the accelerated partial-breast irradiation procedure. eBX is associated with a lower radiation dose to normal tissues and larger 'hot spots' than treatment with the MammoSite device. Additional applications are also being developed for eBX, including endometrial cancer treatment.

A dosimetric comparison of Xoft Axxent Electronic Brachytherapy and iridium-192 high-dose-rate brachytherapy in the treatment of endometrial cancer.

PURPOSE: This analysis was undertaken to dosimetrically compare iridium-192 high-dose-rate brachytherapy (IB) and Xoft Axxent Electronic Brachytherapy (XB; Xoft Inc., Sunnyvale, CA) in the treatment of endometrial cancer. METHODS AND MATERIALS: The planning CT scans from 11 patients previously treated with IB were used to construct hypothetical treatment plans using the source characteristics of the XB device. The mean V95, V100, and V150 (percent of the planning target volume that received 95%, 100%, and 150% of the prescription dose) were calculated. For both the bladder and rectum, the V35 (percent of the organ that received 35% of the prescription dose) and V50 (percent of the organ that received 50% of the prescription dose) were calculated for each patient using both methods of vaginal brachytherapy. RESULTS: The mean %V95 was 99.7% vs. 99.6% (p = ns) and the mean %V100 was 99.0% vs. 99.1% (p = ns) for the IB and XB methods, respectively. The mean %V150 was 35.8% vs. 58.9% (p < 0.05) for the IB and XB methods, respectively. The mean bladder %V35 was 47.7% vs. 27.4% (p < 0.05) and the mean bladder %V50 was 26.5% vs. 15.9% (p < 0.05) for the IB and XB methods, respectively. The mean rectal %V35 was 48.3% vs. 28.3% (p < 0.05) and the mean rectal %V50 was 27.8% vs. 17.0% (p < 0.05) for the IB and XB methods, respectively. CONCLUSIONS: The IB and XB methods of vaginal brachytherapy offer equivalent target volume coverage; however, the XB method allows increased sparing of the bladder and rectum.

Case report and dosimetric analysis of an axillary recurrence after partial breast irradiation with mammosite catheter.

Partial breast irradiation (PBI) was designed in part to decrease overall treatment times associated with whole breast radiation therapy (WBRT). WBRT treats the entire breast and usually portions of the axilla. The goal of PBI is to treat a smaller volume of breast tissue in less time, focusing the dose around the lumpectomy cavity. The following is a case of a 64-year-old woman with early-stage breast cancer treated with PBI who failed regionally in the ipsilateral axilla. With our dosimetric analysis, we found that the entire area of this axillary failure would have likely received at least 45 Gy if WBRT had been used, enough to sterilize microscopic disease. With PBI, this area received a mean dose of only 2.8 Gy, which raises the possibility that this regional failure may have been prevented had WBRT been used instead of PBI.

Cost of radiotherapy versus NSAID administration for prevention of heterotopic ossification after total hip arthroplasty.

PURPOSE: Heterotopic ossification (HO), or abnormal bone formation, is a common sequela of total hip arthroplasty. This abnormal bone can impair joint function and must be surgically removed to restore mobility. HO can be prevented by postoperative nonsteroidal anti-inflammatory drug (NSAID) use or radiotherapy (RT). NSAIDs are associated with multiple toxicities, including gastrointestinal bleeding. Although RT has been shown to be more efficacious than NSAIDs at preventing HO, its cost-effectiveness has been questioned. METHODS AND MATERIALS: We performed an analysis of the cost of postoperative RT to the hip compared with NSAID administration, taking into account the costs of surgery for HO formation, treatment-induced morbidity, and productivity loss from missed work. The costs of RT, surgical revision, and treatment of gastrointestinal bleeding were estimated using the 2007 Medicare Fee Schedule and inpatient diagnosis-related group codes. The cost of lost wages was estimated using the 2006 median salary data from the U.S. Census Bureau. RESULTS: The cost of administering RT was estimated at $899 vs. $20 for NSAID use. After accounting for the additional costs associated with revision total hip arthroplasty and gastrointestinal bleeding, the corresponding estimated costs were $1,208 vs. $930. CONCLUSION: If the costs associated with treatment failure and treatment-induced morbidity are considered, the cost of NSAIDs approaches that of RT. Other NSAID morbidities and quality-of-life differences that are difficult to quantify add to the cost of NSAIDs. These considerations have led us to recommend RT as the preferred modality for use in prophylaxis against HO after total hip arthroplasty, even when the cost is considered.

Patterns of failure after MammoSite brachytherapy partial breast irradiation: a detailed analysis.

PURPOSE: To report the results of a detailed analysis of treatment failures after MammoSite breast brachytherapy for partial breast irradiation from our single-institution experience. METHODS AND MATERIALS: Between October 14, 2002 and October 23, 2006, 78 patients with early-stage breast cancer were treated with breast-conserving surgery and accelerated partial breast irradiation using the MammoSite brachytherapy applicator. We identified five treatment failures in the 70 patients with >6 months' follow-up. Pathologic data, breast imaging, and radiation treatment plans were reviewed. For in-breast failures more than 2 cm away from the original surgical bed, the doses delivered to the areas of recurrence by partial breast irradiation were calculated. RESULTS: At a median follow-up time of 26.1 months, five treatment failures were identified. There were three in-breast failures more than 2 cm away from the original surgical bed, one failure directly adjacent to the original surgical bed, and one failure in the axilla with synchronous distant metastases. The crude failure rate was 7.1% (5 of 70), and the crude local failure rate was 5.7% (4 of 70). Estimated progression-free survival at 48 months was 89.8% (standard error = 4.5%). CONCLUSIONS: Our case series of 70 patients with >6 months' follow-up and a median follow-up of 26 months is the largest single-institution report to date with detailed failure analysis associated with MammoSite brachytherapy. Our failure data emphasize the importance of patient selection when offering partial breast irradiation.

A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent electronic brachytherapy.

PURPOSE: Over 20,000 patients have been treated with partial breast irradiation (PBI) using the MammoSite balloon brachytherapy applicator (IBB). Recently, a new form of balloon-based PBI, Xoft Axxent electronic brachytherapy (KVB), which uses a 50-kV x-ray source, has been introduced. This analysis was undertaken to dosimetrically compare the results of treatment using these two methods of PBI. METHODS AND MATERIALS: The study population consisted of 15 patients previously treated with IBB. The planning CT scans from these 15 patients were used to construct hypothetical treatment plans using the source characteristics of the KVB device. The plans were then compared using the dosimetric parameters discussed below. RESULTS: The mean %V(90) was 99.6% vs. 99.0% (p=nonsignificant [ns]), the mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 41.8% vs. 59.4% (p<0.05), the mean %V(200) was 11.3% vs. 32.0% (p<0.05), and the mean %V(300) was 0.4% vs. 6.7% (p<0.05) for the IBB and KVB methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs. 13.0% (p<0.05), the mean ipsilateral lung %V(30) was 3.7% vs. 1.1% (p<0.05), and the mean heart %V(5) was 59.2% vs. 9.4% (p<0.05) for the IBB and KVB methods, respectively. CONCLUSIONS: The IBB and KVB methods of PBI offer comparable target volume coverage; however, the KVB method is associated with an increased volume of breast tissue in the high-dose regions and a decreased dose to the adjacent normal tissues.

Technology insight: MammoSite--a new device for delivering brachytherapy following breast-conserving therapy.

The MammoSite (Cytyc Corporation, Marlborough, MA) breast brachytherapy applicator was designed to overcome the logistic problems created by external-beam radiation therapy (EBRT) and the technical difficulties associated with multicatheter-based interstitial brachytherapy. The MammoSite catheter has been shown to treat a volume of tissue equivalent to that treated by multicatheter-based brachytherapy. Using ultrasound guidance, the MammoSite applicator can be placed using an open technique at the time of lumpectomy or post-lumpectomy. Initial results have shown favorable cosmesis and few significant side effects. NSABP B-39/RTOG 0413 randomizes patients between EBRT and partial-breast irradiation (PBI). The PBI arm consists of interstitial brachytherapy, MammoSite brachytherapy, or 3D conformal EBRT. This trial has the potential to provide a definitive answer regarding the benefits of PBI for certain subgroups of patients, and hence lead to more women undergoing breast conservation therapy.

A dosimetric comparison of three-dimensional conformal, intensity-modulated radiation therapy, and MammoSite partial-breast irradiation.

PURPOSE: Limited information is available comparing target volume and normal tissue dosimetry with the different techniques of partial breast irradiation (PBI). We present results of a dosimetric comparison of single catheter, balloon-based brachytherapy using the MammoSite catheter (BRT), 3D conformal radiation therapy (3DCRT), and intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Fifteen patients were treated using the BRT device. With the use of CT scans with balloons in inflated and deflated states, plans were developed for each patient using each of the methods of PBI, for a total of 45 plans. The plans were then compared using the below dosimetric parameters. RESULTS: The mean V100 was 95%, 92%, and 94% for the BRT, 3DCRT, and IMRT techniques, respectively. The mean ipsilateral breast V50 was 29%, 56%, and 46% (p < 0.0001) and the mean ipsilateral lung V30 was 5%, 7%, and 2% (p < 0.001 for IMRT vs. others) for the BRT, 3DCRT, and IMRT methods, respectively. For the 10 patients with left-sided breast tumors, the mean heart V5 was 12%, 4%, and 1% for the BRT, 3DCRT, and IMRT methods, respectively (p < 0.01). CONCLUSIONS: With increasing interest in PBI, our data may help clinicians individualize patient treatment decisions.