Mark Trombetta

Dosimetric and technical aspects of intraoperative I-125 brachytherapy for stage I non-small cell lung cancer

Initial treatment outcome data from our institution for stage I non-small cell lung cancer (NSCLC) patients have shown that sublobar resection in combination with iodine-125 (I-125) brachytherapy is associated with recurrence rates of 2.0%, compared to 18.6% with sublobar resection alone. In this work, the technical and dosimetric aspects required to execute this procedure from the radiation oncology perspective as well as an analysis of the dose distributions of patients treated with this technique are presented. In this treatment technique, I-125 seeds in vicryl suture are embedded into vicryl mesh and surgically inserted providing a 2.0 cm margin on each side of the resection staple line. A nomogram is developed to determine the suture spacing in the vicryl mesh, as a function of seed activity in order to deliver 120 Gy at a distance of 0.5 cm above and below the seed array. Post-operative dosimetry consists of a CT-based planning and dose volume analysis. Dose distributions, dose volume histograms and mean dose data for lung are analysed in a group of patients. Dosimetric results show significant lung sparing with only a small volume of lung irradiated for all patients with mean lung dose values ranging from 1.5 Gy to 5.4 Gy. Lung brachytherapy with I-125 at the time of sublobar resection is a highly conformal option of dose delivery for stage I NSCLC patients with compromised physiologic reserve. Patient-related toxicity clinically measured by loss of pulmonary function and radiation-induced pneumonitis have not been linked to this procedure.

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.

Tolerance of the aorta using intraoperative iodine-125 interstitial brachytherapy in cancer of the lung

PURPOSE A retrospective review to assess the efficacy and morbidity of surgical resection and (125)I interstitial lung brachytherapy placed in approximation to the aorta. METHODS AND MATERIALS The records and postoperative films of 278 patients who had undergone intrathoracic (125)I brachytherapy at our institution were reviewed. All patients had undergone a gross total resection of a non-small-cell lung cancer using segmental resection, wedge resection, or sublobar resection. Frozen section margins of resection were required to be negative before the intraoperative delivery of the implant. Of those reviewed, 29 patients were implanted with (125)I impregnated Vicryl mesh that contacted greater than 50% with the aorta. Implants consisted of (125)I seeds sewn into a nomographically guided geometric array. Only implants where 50% or greater of the implant volume directly approximated the aorta were selected for inclusion into this study. The mean aortic volume receiving the entire prescribed dose was 17.2cc (mean surface area=34.4cm(2)) and the mean prescribed dose was 114Gy (range, 85-120) over the permanent life of the implant calculated by isodose curve distribution at a depth of 0.5cm from the plane of the implant. Five patients have received postoperative mediastinal dose supplementation with external beam irradiation to further address occult mediastinal nodal disease not revealed during the intraoperative frozen section analysis. RESULTS All patients tolerated the surgery and brachytherapy well with no perioperative mortality. With a median followup of 45.3 months (range, 1-117), 1 of the 29 patients suffered a fatal hemorrhage from suspected great vessel rupture. A review of this case demonstrated that the interstitial therapy had been supplemented with 4500cGy of external irradiation, which overlapped a small portion of the implant volume overlying the aorta. No other patients suffered even minor events referable to the implant and have continued to do well without symptomatic evidence of chronic sequelae as of the publication of this article or the time of their death. Local control has been achieved in all patients still living and had been achieved in all patients who died from subsequent progression of metastatic disease or other cause. CONCLUSIONS Interstitial (125)I intrathoracic brachytherapy is a safe and effective method when used with sublobar resection in high-risk stage I non-small-cell lung cancer patients and may be used even in situations that require placement of the sources in close approximation to the aorta. The tolerance of the aorta seems to be greater than previously thought, and may well exceed 12,000cGy over the permanent life of the interstitial implant. Interstitial (125)I brachytherapy can safely be used to deliver significant radiation dose in direct contact with the aorta but supplemental, overlapping external beam irradiation should be avoided.

Long-term Cosmesis After Lumpectomy and Brachytherapy in the Management of Carcinoma of the Previously Irradiated Breast

Objective:To evaluate the cosmetic outcome of brachytherapy after lumpectomy in the management of carcinoma of the previously irradiated breast. Materials and Methods:Between January 1998 and April 2008, 26 patients with TIS or T1 breast carcinoma were offered interstitial or intracavitary brachytherapy after lumpectomy in a previously irradiated breast as an alternative to salvage mastectomy. Twenty-five of 26 patients had prior lumpectomy followed by standard postoperative external beam radiotherapy for early stage carcinoma of the breast [dose range 5000–6040 cGy]. One patient developed breast cancer after full mantle irradiation [4500 cGy to the mediastinum and axillae] for Hodgkin Lymphoma 27 years earlier. All tumors were excised with final margins of resection free of disease per National Surgical Adjuvant Breast and Bowel Project definition. After lumpectomy, tumor bed implantation was carried out utilizing a low dose rate interstitial technique in 22 patients, whereas 3 patients were treated with high dose rate brachytherapy using the MammoSite brachytherapy catheter and 1 patient was treated with high dose rate brachytherapy using the Contura catheter. The low dose rate treatment consisted of 4500 to 5000 cGy at 35 to 50 cGy per hour to the tumor bed plus a 1.0 cm margin, whereas the high dose rate treatment consisted of 3400 cGy in twice daily fractions of 340 cGy currently used in National Surgical Adjuvant Breast and Bowel Project B-39. Cosmesis was graded according to the B-39 cosmesis scale for de novo treatments: grade I as excellent, grade II as good, Grade III as fair, and Grade IV as poor. Results:Eighteen patients were scored as grade I, 6 as grade II, and 2 as grade III. No patient received a Grade IV score. All 4 balloon brachytherapy patients were scored as Grade I. Twenty-five of 26 patients remained free of local failure with a median follow-up of 38 months (range 6–75 months). The only patient to develop a second local recurrence was graded as grade I before salvage mastectomy. Two patients developed wound dehiscence after immediate postlumpectomy implantation. Two have succumbed to metastatic breast carcinoma at 17 and 24 months after salvage implant therapy. An additional patient has succumbed to chronic obstructive pulmonary disease. All patients, regardless of cosmesis grade were satisfied with their decision for repeat conservation therapy. Factors affecting cosmesis were distance from the implant to the skin, the type of device used, and the amount of residual breast tissue after repeat lumpectomy. Conclusions:The cosmetic effect of brachytherapy after lumpectomy in the management of recurrent carcinoma of the previously irradiated breast is acceptable in highly selected patients. Intracavitary technique may provide superior cosmetic results for patients retreated with brachytherapy for salvage.

MATURE FOLLOW-UP FOR HIGH-RISK STAGE I NON-SMALL-CELL LUNG CARCINOMA TREATED WITH SUBLOBAR RESECTION AND INTRAOPERATIVE IODINE-125 BRACHYTHERAPY

PURPOSE To update the Allegheny General Hospital experience of high-risk Stage I non-small-cell lung cancer patients treated with sublobar resection and intraoperative (125)I Vicryl mesh brachytherapy. METHODS AND MATERIALS Between January 5, 1996 and February 19, 2008, 145 patients with Stage I non-small-cell lung cancer who were not lobectomy candidates because of cardiopulmonary compromise underwent sublobar resection and placement of (125)I seeds along the resection line. The (125)I seeds embedded in Vicryl suture were attached with surgical clips to a sheet of Vicryl mesh, inserted over the target area, and prescribed to a 0.5-cm planar margin. RESULTS The mean target area, total activity, number of seeds implanted, and prescribed total dose was 33.3 cm(2) (range, 18.0-100.8), 20.2 mCi (range, 11.1-29.7), 46 (range, 30-100), and 117 Gy (range, 80-180), respectively. The median length of the surgical stay was 6 days (range, 1-111), with a perioperative mortality rate of 3.4%. At a median follow-up of 38.3 months (range, 1-133), 6 patients had developed local recurrence (4.1%), 9 had developed regional failure (6.2%), and 25 had distant failure (17.2%). On multivariate analysis, no patient- or tumor-specific factors or surgical or dosimetric factors were predictive of local recurrence. The overall median survival was 30.5 months with a 3- and 5-year overall survival rate of 65% and 35%, respectively. CONCLUSION (125)I brachytherapy for high-risk, Stage I non-small-cell lung cancer after sublobar resection is well tolerated and associated with a low local failure rate.

Influence of concurrent anastrozole on acute and late side effects of whole breast radiotherapy.

Objectives: To retrospectively compare radiation toxicity in patients treated with concurrent anastrozole and whole breast irradiation versus women treated sequentially with whole breast irradiation followed by hormonal suppression. Methods: The records of 249 consecutive estrogen or progesterone receptor positive breast cancer patients treated with breast-conserving surgery and postoperative whole breast irradiation were reviewed. Of total, 57 patients (the concurrent anastrozole group) received concurrent anastrozole prior to and during radiotherapy. In 126 patients (the sequential group), adjuvant hormone suppression therapy (anastrozole, other aromatase inhibitors, or tamoxifen) was administered after the completion of breast irradiation. In 66, women either concurrent tamoxifen was given with radiation or the sequence of hormonal therapy was not known. These women were excluded from the analysis. Results: The frequency of acute grade 2 radiation dermatitis (24.6% in the concurrent anastrozole group vs. 20.6% in the sequential group; P = 0.55), grade 3 radiation dermatitis (8.8% vs. 7.1%; P = 0.77) and treatment interruptions due to skin reactions (14.0% vs. 11.2%; P = 0.69) did not differ between groups. The rates of clinically detectable breast fibrosis were not different (24.2% vs. 24.7%; P = 0.97). With a median follow-up of 28 months and 30.8 months, respectively, 1 local failure occurred in the concurrent anastrozole group and 5 in the sequential group. Conclusions: Anastrozole, administered concurrently with whole breast irradiation, did not increase acute or late morbidity when compared with sequential administration of radiation and hormonal suppression therapy.

INVESTIGATION OF INTERFRACTION VARIATIONS OF MAMMOSITE BALLOON APPLICATOR IN HIGH-DOSE-RATE BRACHYTHERAPY OF PARTIAL BREAST IRRADIATION

PURPOSE To measure the interfraction changes of the MammoSite applicator and evaluate their dosimetric effect on target coverage and sparing of organs at risk. METHODS AND MATERIALS A retrospective evaluation of the data from 19 patients who received 10 fractions (34 Gy) of high-dose-rate partial breast irradiation was performed. A computed tomography-based treatment plan was generated for Fraction 1, and a computed tomography scan was acquired just before the delivery of each fraction to ensure a consistent shape of the balloon. The eccentricity, asymmetry, and planning target volume (PTV) for plan evaluation purposes (PTV_EVAL), as well as trapped air gaps, were measured for all patients. Furthermore, 169 computed tomography-based treatment plans were retrospectively generated for Fractions 2-10. Interfraction dosimetric variations were evaluated using the %PTV_EVAL coverage, target dose homogeneity index, target dose conformal index, and maximum doses to the organs at risks. RESULTS The average variation of eccentricity and asymmetry from Fraction 1 values of 3.5% and 1.1 mm was -0.4% +/- 1.6% and -0.1 +/- 0.6 mm. The average trapped air gap volume was dramatically reduced from before treatment (3.7 cm(3)) to Fraction 1 (0.8 cm(3)). The PTV_EVAL volume change was insignificant. The average variation for the %PTV_EVAL, target dose homogeneity, and target dose conformal index from Fraction 1 values of 94.7%, 0.64, and 0.85 was 0.15% +/- 2.4%, -0.35 +/- 2.4%, and -0.34 +/- 4.9%, respectively. The average Fraction 1 maximum skin and ipsilateral lung dose of 3.2 Gy and 2.0 Gy varied by 0.08 +/- 0.47 and -0.16 +/- 0.29 Gy, respectively. CONCLUSION The interfraction variations were patient specific and fraction dependent. Although the average interfraction dose variations for the target and organs at risk were not clinically significant, the maximum variations could be clinically significant.

Mammary fat necrosis following radiotherapy in the conservative management of localized breast cancer: Does it matter?

PURPOSE Fat necrosis is a well-described and relatively common complication arising from post-lumpectomy irradiation of the breast, most commonly breast brachytherapy. We wish to assess the clinical significance of fat necrosis resulting from post-lumpectomy breast irradiation. METHODS We reviewed the literature to determine the overall incidence and significance of fat necrosis to determine whether or not fat necrosis poses a significant clinical problem. RESULTS Fat necrosis occurs in up to one-quarter of patients following post-lumpectomy breast irradiation. Only rarely is invasive intervention required however, it does significantly degrade the quality of all modalities of breast imaging. CONCLUSIONS Fat necrosis is a common complication of radiotherapy which rarely requires therapeutic intervention. However, post-therapeutic clinical imaging such as mammography, ultrasound and magnetic resonance imaging are affected which may result in additional diagnostic procedures up to and including biopsy.

Dosimetric comparison of partial and whole breast external beam irradiation in the treatment of early stage breast cancer.

A dosimetric comparison was performed on external-beam three-dimensional conformal partial breast irradiation (PBI) and whole breast irradiation (WBI) plans for patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol at our institution. Twenty-four consecutive patients were treated with either PBI (12 patients) or WBI (12 patients). In the PBI arm, the lumpectomy cavity was treated to a total dose of 38.5 Gy at 3.85 Gy per fraction twice daily using a four-field noncoplanar beam setup. A minimum 6 h interval was required between fractions. In the WBI arm, the whole breast including the entirety of the lumpectomy cavity was treated to a total dose of 50.4 Gy at 1.8 Gy per fraction daily using opposed tangential beams. The lumpectomy cavity volume, planning target volume for evaluation (PTV_EVAL), and critical structure volumes were contoured for both the PBI and WBI patients. Dosimetric parameters, dose volume histograms (DVHs), and generalized equivalent uniform dose (gEUD) for target and critical structures were compared. Dosimetric results show the PBI plans, compared to the WBI plans, have smaller hot spots in the PTV_EVAL (maximum dose: 104.2% versus 110.9%) and reduced dose to the ipsilateral breast (V50: 48.6% versus 92.1% and V100: 10.2% versus 50.5%), contralateral breast (V3: 0.16% versus 2.04%), ipsilateral lung (V30: 5.8% versus 12.7%), and thyroid (maximum dose: 0.5% versus 2.0%) with p values < or = 0.01. However, similar dose coverage of the PTV_EVAL (98% for PBI and 99% for WBI, on average) was observed and the dose difference for other critical structures was clinically insignificant in both arms. The gEUD data analysis showed the reduction of dose to the ipsilateral breast and lung, contralateral breast and thyroid. In addition, preliminary dermatologic adverse event assessment data suggested reduced skin toxicity for patients treated with the PBI technique.

The use of the MammoSite balloon applicator in re-irradiation of the breast

PURPOSE To examine the feasibility of using the MammoSite brachytherapy applicator in the retreatment of the previously irradiated breast. METHODS AND MATERIALS Between March 2004 and March 2007, three patients previously treated with external beam radiotherapy were retreated using the MammoSite brachytherapy device. Two patients were treated for an ipsilateral breast tumor recurrence after breast conservation surgery and postoperative irradiation, whereas the third patient developed an in-field breast cancer likely associated with Hodgkins disease mantle irradiation 27 years before. The recurrent histology of two was ductal carcinoma in situ ([DCIS] one originally presenting as infiltrating ductal carcinoma [IDC] and the other as DCIS), whereas the Hodgkins disease patient presented with IDC. All patients received a twice-daily tumor dose of 3400 cGy at 340 cGy/fraction. The mean maximum skin dose was 53.4% (range, 49.5-60.3%) of the prescribed dose. RESULTS With a mean followup of 32 months, no patient developed a local recurrence. Cosmesis in all three cases as graded by the National Surgical Adjuvant Breast and Bowel Project, cosmesis criteria was excellent (Grade I) in all cases. Dosimetric calculations demonstrated that the device allows for appropriate local irradiation while sparing the previously irradiated skin of the involved breast as defined by the protocol standard. CONCLUSIONS Use of the MammoSite device in the treatment of the previously irradiated breast is feasible and may provide adequate local control as well as acceptable cosmesis in carefully selected patients.