Purpose: We present a new technique to improve dose uniformity and potentially reduce acute toxicity with tangential whole-breast radiotherapy (RT) using intensity-modulated radiation therapy (IMRT). ...The technique of multiple static multileaf collimator (
sMLC) segments was used to facilitate IMRT.
Methods and Materials: Ten patients with early-stage breast cancer underwent treatment planning for whole-breast RT using a new method of IMRT. The three-dimensional (3D) dose distribution was first calculated for equally weighted, open tangential fields (i.e., no blocks, no wedges). Dose calculation was corrected for density effects with the pencil-beam superposition algorithm. Separate MLC segments were constructed to conform to the beam’s-eye-view projections of the 3D isodose surfaces in 5% increments, ranging from the 120% to 100% isodose surface. Medial and lateral MLC segments that conformed to the lung tissue in the fields were added to reduce transmission. Using the beam-weight optimization utility of the 3D treatment planning system, the
sMLC segment weights were then determined to deliver the most uniform dose to 100 reference points that were uniformly distributed throughout the breast. The accuracy of the dose calculation and resultant IMRT delivery was verified with film dosimetry performed on an anthropomorphic phantom. For each patient, the dosimetric uniformity within the breast tissue was evaluated for IMRT and two other treatment techniques. The first technique modeled conventional practice where wedges were derived manually without consideration of inhomogeneity effects (or density correction). A recalculation was performed with density correction to represent the actual dose delivered. In the second technique, the wedges were optimized using the same beam-weight optimization utility as the IMRT plan and included density correction. All dose calculations were based on the pencil-beam superposition algorithm.
Results: For the
sMLC technique, treatment planning required approximately 60 min. Treatment delivery (including patient setup) required approximately 8–10 min. Film dosimetry measurements performed on an anthropomorphic phantom generally agreed with calculations to within ± 3%. Compared to the wedge techniques, IMRT with
sMLC segments resulted in smaller “hot spots” and a lower maximum dose, while maintaining similar coverage of the treatment volume. A median of only 0.1% of the treatment volume received ≥ 110% of the prescribed dose when using IMRT versus 10% with standard wedges. A total of 6–8 segments were required with the majority of the dose delivered via the open segments. The addition of the lung-block segments to IMRT was of significant benefit for patients with a greater proportion of lung parenchyma within the irradiated volume. Since August 1999, 32 patients have been treated in the clinic with the IMRT technique. No patient experienced RTOG grade III or greater acute skin toxicity.
Conclusion: The use of intensity modulation with an
sMLC technique for tangential breast RT is an efficient and effective method for achieving uniform dose throughout the breast. It is dosimetrically superior to the treatment techniques that employ only wedges. Preliminary findings reveal minimal or no acute skin reactions for patients with various breast sizes.
The active breathing control (ABC) apparatus was used to quantify the effect of breathing motion on whole breast radiotherapy (RT) with standard wedges and intensity-modulated RT (IMRT).
Ten patients ...with early-stage breast cancer underwent routine free-breathing (FB) CT simulations for whole breast RT. An ABC apparatus was used to obtain two additional CT scans with the breath held at the end of normal inhalation and normal exhalation. The FB scan was used to develop both a standard treatment plan using wedged coplanar tangents and an IMRT plan using multiple static multileaf collimator segments. To simulate breathing, each plan was copied and applied to the normal inhalation and normal exhalation CT scans.
The medial field border (defined by a radiopaque catheter) for the normal inhalation and normal exhalation scans moved an average of 0.6 cm anteriorly and 0.3 cm posteriorly compared with the FB position, respectively. The corresponding movement of the lateral field border was an average of 0.4 cm anteriorly and 0.2 cm posteriorly compared with the FB position. For both the wedged and the IMRT techniques, the dose delivered to breast tissue, biopsy cavity, and ipsilateral lung was similar for each of the three CT scan positions. However, the internal mammary node dose varied significantly with breathing.
The dose delivered to breast using standard wedges or step-and-shoot IMRT is relatively insensitive to the effects of breast motion during normal breathing. However, an appreciable portion of the internal mammary nodes are irradiated during normal inhalation, contributing to the uncertainty in the analysis of the efficacy of internal mammary nodal RT in breast treatment.
This study compares multiple planning techniques designed to improve accuracy while allowing reduced planning target volume (PTV) margins though image-guided radiotherapy (IGRT) with four-dimensional ...(4D) cone-beam computed tomography (CBCT).
Free-breathing planning and 4D-CBCT scans were obtained in 8 patients with lung tumors. Four plans were generated for each patient: 3D-conformal, 4D-union, 4D-offline adaptive with a single correction (offline ART), and 4D-online adaptive with daily correction (online ART). For the 4D-union plan, the union of gross tumor volumes from all phases of the 4D-CBCT was created with a 5-mm expansion applied for setup uncertainty. For offline and online ART, the gross tumor volume was delineated at the mean position of tumor motion from the 4D-CBCT. The PTV margins were calculated from the random components of tumor motion and setup uncertainty.
Adaptive IGRT techniques provided better PTV coverage with less irradiated normal tissues. Compared with 3D plans, mean relative decreases in PTV volumes were 15%, 39%, and 44% using 4D-union, offline ART, and online ART planning techniques, respectively. This resulted in mean lung volume receiving > or = 20Gy (V20) relative decreases of 21%, 23%, and 31% and mean lung dose relative decreases of 16%, 26%, and 31% for the 4D-union, 4D-offline ART, and 4D-online ART, respectively.
Adaptive IGRT using CBCT is feasible for the treatment of patients with lung tumors and significantly decreases PTV volume and dose to normal tissues, allowing for the possibility of dose escalation. All analyzed 4D planning strategies resulted in improvements over 3D plans, with 4D-online ART appearing optimal.
Purpose: We present the preliminary results of our in-house protocol using outpatient high-dose-rate (HDR) brachytherapy as the sole radiation modality following lumpectomy in patients with ...early-stage breast cancer.
Methods and Materials: Thirty-seven patients with 38 Stage I–II breast cancers received radiation to the lumpectomy cavity alone using an HDR interstitial implant with
192Ir. A minimum dose of 32 Gy was delivered on an outpatient basis in 8 fractions of 4 Gy to the lumpectomy cavity plus a 1- to 2-cm margin over consecutive 4 days.
Results: Median follow-up is 31 months. There has been one ipsilateral breast recurrence for a crude failure rate of 2.6% and no regional or distant failures. Wound healing was not impaired in patients undergoing an open-cavity implant. Three minor breast infections occurred, and all resolved with oral antibiotics. The cosmetic outcome was good to excellent in all patients.
Conclusion: In selected patients with early-stage breast cancer, treatment of the lumpectomy cavity alone with outpatient HDR brachytherapy is both technically feasible and well tolerated. Early results are encouraging, however, longer follow-up is necessary before equivalence to standard whole-breast irradiation can be established and to determine the most optimal radiation therapy technique to be employed.
We analyzed variables associated with long-term toxicity using three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation.
One hundred ...patients treated with 3D-CRT accelerated partial breast irradiation were evaluated using Common Terminology Criteria for Adverse Events version 4.0 scale. Cosmesis was scored using Harvard criteria. Multiple dosimetric and volumetric parameters were analyzed for their association with worst and last (W/L) toxicity outcomes.
Sixty-two patients had a minimum of 36 months of toxicity follow-up (median follow-up, 4.8 years). The W/L incidence of poor-fair cosmesis, any telangiectasia, and grade ≥2 induration, volume reduction, and pain were 16.4%/11.5%, 24.2%/14.5%, 16.1%/9.7%, 17.7%/12.9%, and 11.3%/3.2%, respectively. Only the incidence of any telangiectasia was found to be predicted by any dosimetric parameter, with the absolute breast volume receiving 5% to 50% of the prescription dose (192.5 cGy-1925 cGy) being significant. No associations with maximum dose, volumes of lumpectomy cavity, breast, modified planning target volume, and PTV, dose homogeneity index, number of fields, and photon energy used were identified with any of the aforementioned toxicities. Non-upper outer quadrant location was associated with grade ≥2 volume reduction (p = 0.02 W/p = 0.04 L). A small cavity-to-skin distance was associated with a grade ≥2 induration (p = 0.03 W/p = 0.01 L), a borderline significant association with grade ≥2 volume reduction (p = 0.06 W/p = 0.06 L) and poor-fair cosmesis (p = 0.08 W/p = 0.09 L), with threshold distances ranging from 5 to 8 mm.
No dose--volume relationships associated with long-term toxicity were identified in this large patient cohort with extended follow-up. Cosmetic results were good-to-excellent in 88% of patients at 5 years.
To determine the incidence of, and risk factors for, regional nodal failure (RNF) and to evaluate the effectiveness of, and indications for, regional nodal irradiation (RNI) in patients with Stage ...I–II breast cancer treated with breast-conserving therapy.
A total of 1500 cases of Stage I–II breast cancer were treated with breast-conserving therapy between February 1980 and December 2000. All patients underwent excisional biopsy, and 925 (62%) underwent re-excision. Level I–II axillary lymph node dissection was done in 94% of patients. The lymph nodes were pathologically involved in 335 patients (22%); 255 with 1–3 nodes and 80 with ≥4 nodes involved. All patients received whole breast irradiation to a median dose of 45 Gy, and 97% received a tumor bed boost to a median dose of 61 Gy. Treatment included the breast only in 1309 patients (87%), and the breast and regional lymphatics in 191 (13%).
With a median follow-up of 8.1 years, 35 patients had failure within the regional nodes: 12 patients (6%) who received RNI and 23 patients (2%) who did not. The 5- and 10-year rate for any RNF was 1.9% and 2.8%, respectively. The 5 and 10-year rates of axillary failure and supraclavicular failure were 0.6% and 1.0% and 0.9% and 1.6%, respectively. In patients with ≥4 positive lymph nodes, RNI reduced the 10-year rate of any RNF from 11% to 2% (
p = 0.024), the rate of axillary failure from 5% to 0% (
p = 0.019), and the rate of supraclavicular failure from 11% to 2% (
p = 0.114). RNI did not affect the rate of axillary failure or supraclavicular failure in patients with 1–3 positive nodes. In node-negative patients, the rate of RNF was significantly greater if <6 nodes were removed at the time of axillary dissection. Multiple clinical, pathologic, and treatment-related factors were analyzed for association with RNF. On univariate analysis, RNF was associated with the number of nodes excised, number of positive nodes, percentage of positive nodes, size of nodal metastasis, presence of angiolymphatic invasion, estrogen receptor status, age, systemic chemotherapy, and RNI. Three subsets of patients had unusually high rates of RNF, those with ≥67% nodes positive (16%), nodal metastasis ≥2.0 cm (44%), or age ≤35 years (14%). On multivariate analysis, the only significant predictor of RNF was the maximal size of the nodal metastasis. RNI did not improve the overall survival for any subset of patients. The number of lymph nodes excised had an impact on overall survival, with a 10-year survival rate of 33%, 65%, and 69% in patients with <6, 6–10, and >10 nodes excised, respectively (
p = 0.05)
Failure within the regional lymph nodes as an isolated site of first relapse is uncommon in patients with Stage I–II breast cancer treated with breast-conserving therapy. RNI can significantly reduce the rate of RNF (axillary failure) in patients with ≥4 positive lymph nodes. The maximal size of the lymph node metastasis was found to be the only significant independent predictor of RNF, with nodal metastases ≥2.0 cm associated with extremely high regional failure rates. Despite this, young age and the extent of axillary dissection (particularly as related to the number of positive nodes) also appear to be important and should be considered when evaluating patients for RNI. Inadequate axillary dissection was not only associated with increased regional failure, but also reduced survival.
Background
Management of mammographically detected ductal carcinoma in situ (DCIS) at a single institution was reviewed to determine long-term clinical outcomes after treatment with breast-conserving ...therapy (BCT).
Methods
Data from all patient-cases with DCIS who received BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for their effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included breast-conserving surgery followed by external-beam radiotherapy to the whole breast, with 86 % of patients receiving a lumpectomy cavity boost. The median dose to the whole breast was 50 Gy and 60.4 Gy to the lumpectomy cavity.
Results
A total of 129 cases were evaluated; the median follow-up was 19.3 years. Twenty-one patients developed an ipsilateral breast tumor recurrence (IBTR), 76.2 % of which were invasive (
n
= 16). Fourteen recurrences (66 %) were within the same breast quadrant (true recurrence), while an additional 7 cases developed an IBTR elsewhere in the breast. True recurrences were more prevalent in women <45 years of age (20 %/24 % vs. 5.1 %/8 %) at 10 and 20 years (
p
= 0.02). The 5-, 10-, 15-, and 20-year actuarial rates of IBTR for this cohort were 8.7, 10.4, 12.1, and 16.3 % (IBTR), while overall survival at 5, 10, and 20 years was 97.6, 96.8, and 96.8 %, respectively.
Conclusions
Mammographically detected DCIS remains a clinically distinct subset of noninvasive breast cancer. With 20 year follow-up, local control and overall survival are excellent after BCT.
We analyzed the risk of second malignancies developing in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) vs. surgery alone.
The S+RT cohort consisted of 256 ...women treated with breast-conserving therapy at William Beaumont Hospital. The surgery alone cohort consisted of 2,788 women with DCIS in the regional Surveillance, Epidemiology, and End Results database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 surgery alone patients (total of 2,048 patients). Matching criteria included age±2 years. The rates of second malignancies were analyzed overall and as contralateral breast vs. non-breast cancers and by organ system.
Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the surgery alone cohort. The overall 10-/15-year rates of second malignancies among the S+RT and surgery alone cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p=0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the surgery alone cohort (p=0.439). The 15-year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the surgery alone cohort (p=0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and surgery alone cohorts for pulmonary, gastrointestinal, central nervous system, gynecologic, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors.
Compared with surgery alone, S+RT is not associated with an overall increased risk of second malignancies in women with DCIS.
Purpose
: When treating high-risk prostate cancer with radiation therapy, inclusion of the seminal vesicles (SVs) within the clinical target volume (CTV) can dramatically increase the volume of ...radiated normal tissues and hinder dose escalation. Because cancer may involve only the proximal portion of the frequently lengthy SVs, we performed a complete pathology review of prostatectomy specimens to determine the appropriate length of SV to include within the CTV when SV treatment is indicated.
Methods and Materials
: A detailed pathologic analysis was performed for 344 radical prostatectomy specimens (1987–2000). All slides from each case were reviewed by a single pathologist (N.S.G.). Factors recorded for each case included length of each SV (cm), length of cancer involvement in each SV (cm) measured from the prostate-SV junction, and percentage of SV length involved.
Results
: Fifty-one patients (15%) demonstrated SV involvement in 81 SVs (21 unilateral, 30 bilateral SV involvement). The median SV length was 3.5 cm (range: 0.7–8.5 cm). Factors associated with SV involvement included the pretreatment PSA level, biopsy Gleason score, and clinical T classification. The commonly used risk group stratification was very effective at predicting SV positivity. Only 1% of low-risk patients (PSA <10 ng/mL, Gleason ≤6, and clinical stage ≤T2a) demonstrated SV involvement vs. 27% of high-risk patients. Patients with only one high-risk feature still demonstrated a 15% risk of SV involvement, whereas 58% of patients with all three high-risk features had positive SVs. The median length of SV involvement was 1.0 cm (90th percentile: 2.0 cm, range: 0.2–3.8 cm). A median of 25% of each SV was involved with adenocarcinoma (90th percentile: 54%, range: 4%–75%). For the 81 positive SVs, no factor was associated with a greater length or percentage of SV involvement. In the entire population, 7% had SV involvement beyond 1.0 cm. There was an approximate 1% risk of SV involvement beyond 2.0 cm or 60% of the SV. In addition, this risk was less than 4% for all subgroups, including high-risk patients.
Conclusions
: A portion of the SV should be included in the CTV only for higher-risk patients (PSA ≥10 ng/mL, biopsy Gleason ≥7, or clinical T stage ≥T2b). When treating the SV for prostate cancer, only the proximal 2.0–2.5 cm (approximately 60%) of the SV should be included within the CTV.
