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Douglas W Arthur

Publications and source records attributed to Douglas W Arthur.

At least 19 recordsLinked to original sources
PubMed2006

Tumor bed boost omission after negative re-excision in breast-conservation treatment.

BACKGROUND: We evaluated the necessity of a tumor bed boost after whole-breast radiotherapy for early-stage breast cancer after breast-conserving surgery and negative re-excision. METHODS: Of patients treated at the Virginia Commonwealth and Tufts Universities with breast-conservation therapy for early-stage breast cancer between 1983 and 1999, 205 required re-excision of the tumor cavity to obtain clear margins and were found to be without residual disease. Adjuvant conventionally fractionated whole-breast radiotherapy was given to a total dose of 50 Gy in 25 fractions. The tumor bed boost was omitted. RESULTS: The median follow-up was 98 months (range, 6-229 months). The tumor histological diagnosis was primarily infiltrating ductal carcinoma (183 cases; 89%). Nodal involvement was documented in 49 cases (24%). There were four documented recurrences at the tumor bed site. Five in-breast recurrences were documented to be in a location removed from the tumor bed. The overall Kaplan-Meier 15-year in-breast control rate was 92.4%, and the freedom from true recurrence rate was 97.6%. CONCLUSIONS: The findings support the concept that postlumpectomy radiotherapy can be tailored according to the degree of surgical resection. There is an easily identifiable subgroup of patients who can avoid a tumor bed boost, thus resulting in a reduced treatment time and improved cosmesis, while maintaining local control rates that approach 100%. The data suggest that in patients who undergo a negative re-excision, treatment with whole-breast radiotherapy to 50 Gy is a sufficient dose to maximally reduce the risk of local recurrence.

Adult↗
PubMed2006

Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: toxicity analysis of RTOG 95-17.

PURPOSE: Accelerated partial breast irradiation (APBI) can be delivered with brachytherapy within 4-5 days compared with 5-6 weeks for conventional whole breast external beam radiotherapy. Radiation Therapy Oncology Group 95-17 is the first prospective phase I-II cooperative group trial of APBI alone after lumpectomy in select patients with breast cancer. The toxicity rates are reported for low-dose-rate (LDR) and high-dose-rate (HDR) APBI on this trial. METHODS AND MATERIALS: The inclusion criteria for this study included invasive nonlobular tumors < or =3 cm after lumpectomy with negative surgical margins and axillary dissection with zero to three positive axillary nodes without extracapsular extension. The patients were treated with either LDR APBI (45 Gy in 3.5-5 days) or HDR APBI (34 Gy in 10 twice-daily fractions within 5 days). Chemotherapy (> or =2 weeks after APBI) and/or tamoxifen could be given at the discretion of the treating physicians. RESULTS: Between August 1997 and March 2000, 100 women were enrolled in this study, and 99 were evaluated. Of the 99 women, 33 were treated with LDR and 66 with HDR APBI. The median follow-up for all patients was 2.7 years (range, 0.6-4.4 years) and was 2.9 years for LDR and 2.7 years for HDR patients. Toxicities attributed to APBI included erythema, edema, tenderness, pain, and infection. Of the 66 patients treated with HDR APBI, 2 (3%) had Grade 3 or 4 toxicity. Of the 33 patients treated with LDR, 3 (9%) had Grade 3 or 4 toxicity during brachytherapy. Late toxicities included skin thickening, fibrosis, breast tenderness, and telangiectasias. No patient experienced late Grade 4 toxicity; the rate of Grade 3 toxicity was 18% for the LDR and 4% for the HDR groups. CONCLUSION: Acute and late toxicity for this invasive breast radiation technique was modest and acceptable. Patients receiving chemotherapy, a nonprotocol therapy, had a greater rate of Grade 3 toxicity. The study design did not allow for this to be tested statistically.

Adult↗
PubMed2006

The emergence of advanced brachytherapy techniques for common malignancies.

The recent advent and integration of sophisticated radiation planning and imaging modalities has improved the quality of brachytherapy treatments, allowing for more conformal radiation delivery. Further investigation and follow-up are necessary to demonstrate improvements in outcome and morbidity with these refined approaches.

Brachytherapy↗
PubMed2006

Three-dimensional conformal external beam radiotherapy (3D-CRT) for accelerated partial breast irradiation (APBI): what is the correct prescription dose?

OBJECTIVE: This study is an evaluation of the biologic equivalence of the dose prescriptions for brachytherapy and 3-dimensional conformal external beam radiotherapy (3D-CRT) accelerated partial breast irradiation (APBI), using actual patient dose matrix data, and is based on the concept of equivalent uniform biologically effective dose (EUBED). This formalism allows a nonuniform dose distribution to be reduced to an equivalent uniform dose, while also accounting for fraction size. MATERIALS AND METHODS: Five computed tomography scans were selected from a group of patients treated with multicatheter interstitial APBI. Dose matrices for the brachytherapy plans were computed and analyzed with in-house software. For each patient, the EUBED for the brachytherapy dose matrix was generated based on calculations performed at the voxel-level. These EUBED values were then used to calculate the biologically equivalent fraction size for 3D-CRT (eud). RESULTS: The mean equivalent fraction size (eudmean) and maximum equivalent fraction size (eudmax) were calculated for each patient using 100 different values of the alpha/beta ratio. The eudmean ranged from 3.67 to 3.69 Gy, while the eudmax ranged from 3.79 to 3.82 Gy. For all values of the alpha/beta ratio, the maximum fraction size calculated to deliver a biologically equivalent dose with 3D-CRT was 3.82 Gy, with an equivalent total prescription dose of 38.2 Gy. CONCLUSION: Utilizing a wide range of established radiobiological parameters, this study suggests that the maximum fraction size needed to deliver a biologically equivalent dose using 3D-CRT is 3.82 Gy, supporting the continued use of 3.85Gy BID in the current national cooperative trial.

Brachytherapy↗
PubMed2005

Ipsilateral breast tumor recurrence after breast conservation therapy: outcomes of salvage mastectomy vs. salvage breast-conserving surgery and prognostic factors for salvage breast preservation.

PURPOSE: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. METHODS AND MATERIALS: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size < 3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with < or = 3 positive nodes. RESULTS: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n = 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. CONCLUSIONS: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is discussed.

Adult↗
PubMed2005

Accelerated partial breast irradiation: an analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy.

PURPOSE: To perform a detailed analysis of variables associated with late tissue effects of high-dose-rate (HDR) interstitial brachytherapy accelerated partial breast irradiation (APBI) in a large cohort of patients with prolonged follow-up. METHODS AND MATERIALS: Beginning in 1995, 75 women with Stage I/II breast cancer were enrolled in identical institutional trials evaluating APBI as monotherapy after lumpectomy. Patients eligible included those with T1-2, N0-1 (<or=3 nodes positive), M0 tumors of nonlobular histology with negative surgical margins, no extracapsular nodal extension, and negative results on postexcision mammogram. All patients underwent surgical excision and postoperative irradiation with HDR interstitial brachytherapy. The planning target volume was defined as the excision cavity plus a 2-cm margin. Treatment was delivered with a high-activity Ir-192 source at 3.4 Gy per fraction twice daily for 5 days to a total dose of 34 Gy. Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions. All patients were evaluated at 3-6-month intervals and assessed with a standardized cosmetic rating scale and according to Radiation Therapy Oncology Group late normal tissue toxicity scoring criteria. Clinical and therapy-related features were analyzed for their relationship to cosmetic outcome and toxicity rating. Clinical features analyzed included age, volume of resection, history of diabetes or hypertension, extent of axillary surgery, and systemic therapies. Therapy-related features analyzed included volume of tissue encompassed by the 100%, 150%, and 200% isodose lines (V100, V150, and V200, respectively), the dose homogeneity index (DHI), number of source dwell positions, and planar separation. RESULTS: The median follow-up of all patients was 73 months (range, 43-118 months). The cosmetic outcome at last follow-up was rated as excellent, good, and fair/poor in 67%, 24%, and 9% of patients, respectively. Suboptimal cosmetic outcome was significantly associated with the number of source dwell positions, V150, and V200 and inversely associated with DHI (0.77 vs. 0.73; p=0.05). Late skin toxicity was rated as Grade 0, 1, or 2 in 77%, 19%, and 4% of patients, respectively. The risk of Grade 1/2 skin toxicity was significantly associated with V150 and V200 and inversely associated with DHI (0.77 vs. 0.71; p=0.009). Late subcutaneous toxicity was rated as Grade 0, 1, 2, 3, or 4 in 55%, 15%, 12%, 5%, and 13% of patients, respectively. The risk of Grade 0/1 vs. Grade 2-4 subcutaneous toxicity was significantly associated only with a lower value of DHI (0.77 vs. 0.73; p=0.02). To further explore factors that might contribute to the risk of fat necrosis (symptomatic or asymptomatic), a separate analysis showed that only dose hotspots as reflected in V150 and V200 were significantly associated with elevated risk. The use of adriamycin-based chemotherapy after APBI was found to be associated with a significant increase in the incidence of higher-grade skin toxicity and a higher risk of fat necrosis and suboptimal cosmetic outcome. Patient age, volume of resection, extent of axillary surgery, a history of diabetes or hypertension, and the use of tamoxifen were not found to be significantly associated with cosmetic outcome or late normal tissue complications. CONCLUSIONS: Long-term cosmetic results and the risk of late skin and subcutaneous toxicity after APBI with interstitial HDR brachytherapy can be correlated with specific treatment-related variables. These data provide dosimetric parameters that might be used to minimize the risk of normal tissue injury after APBI interstitial brachytherapy.

Adipose Tissue↗
PubMed2005

CT-guided multi-catheter insertion technique for partial breast brachytherapy: reliable target coverage and dose homogeneity.

PURPOSE: To evaluate the feasibility and dosimetric reliability of a CT-guided method of catheter insertion for accelerated partial breast brachytherapy (APBB). MATERIALS AND METHODS: From 1995 to 2002, 77 patients were treated with APBB using a multi-catheter low-dose-rate or high-dose-rate approach. Within that timeframe, 29 patients with early stage invasive breast cancer were treated with high-dose-rate partial breast brachytherapy and had CT scans of the brachytherapy implant available for analysis. Initially, catheter insertion was accomplished in the operating room at the time of lumpectomy using standard free-hand insertion techniques under fluoroscopic guidance and subsequent orthogonal film dosimetry. To improve the efficiency and quality of the technique, the procedure was moved to the departmental CT-simulation suite where the catheters were placed with CT guidance. Basic guidelines of needle insertion and implant construction were followed to assure appropriate intercatheter and interplanar spacing that allowed optimal dosimetric coverage of the target volume. Target volumes were delineated and a treatment plan generated using a 3D planning system (Varian Brachyvision). PTV 1 cm was defined as the lumpectomy cavity plus 1 cm and PTV 2 cm as the lumpectomy cavity plus 2 cm. Target coverage goals were set as delivery of 100% of the prescribed dose to >95% of PTV 1 cm and >90% of the dose to >90% of PTV 2 cm. Dose homogeneity index (DHI) was defined as (V150%-V100%/V100%) with a goal of achieving >0.75. Fifteen patients were treated using the initial method and 14 patients using the CT-guided technique. Targets were retrospectively entered in the initial group and dose volume histogram analysis completed on all patients. The ability of each technique to achieve the target coverage and homogeneity goals was compared. RESULTS: With the change from traditional techniques to a CT-guided technique, the percentage of patients satisfying all dosimetric goals increased from 42% to 93%. Mean dose coverage (defined as the percentage of PTV 2 cm receiving 90% of the prescribed dose) increased from 89% to 95% (p=0.007) and the mean DHI increased from 0.77 to 0.82 with the new technique (p < 0.005). CONCLUSIONS: Reproducible target coverage and dose homogeneity were achieved with CT-guided catheter insertion and 3D planning software. Catheters can be optimally placed with intraoperative CT evaluation and 3D planning software allows improved implant visualization resulting in optimized dosimetry. Improvements in target coverage and DHI may translate into optimized local control and improved cosmesis with a corresponding reduction in the risk of complications.

Aged↗
PubMed2005

Breast brachytherapy: North American experience.

Accelerated partial breast irradiation (APBI) has been investigated for over a decade as a potential alternative adjuvant treatment approach after lumpectomy for women with early-stage breast cancer. The rationale for APBI is based on pathologic data regarding the spread of cancer within the breast and study of the patterns of in-breast recurrence after breast-conserving therapy performed with or without whole-breast irradiation. This report reviews the North American experience using interstitial brachytherapy for APBI. Studies achieving low failure rates have universally been distinguished from those with high failure rates by requiring documented microscopically negative surgical margins, using a target definition consisting of the lumpectomy cavity plus a 1- to 2-cm margin, and having a rigorous quality assurance program to assure target coverage. We conclude that APBI brachytherapy programs that include all of these components have great potential to overcome many of the barriers that have prevented women from pursuing standard breast-conserving therapy.

Brachytherapy↗
PubMed2004

Repeat breast-conserving surgery for in-breast local breast carcinoma recurrence: the potential role of partial breast irradiation.

Mastectomy is the current standard of care for in-breast local recurrence of breast carcinoma. The objective of the current study was to critically review the rationale for and the theoretic and actual risks and benefits of repeat breast-conserving surgery followed by partial breast irradiation (PBI) for in-breast local recurrence of breast carcinoma. The main outcomes of interest were local control and survival after in-breast local recurrence and side effects, complications, and cosmesis after reirradiation of the breast. The risk of local recurrence was not found to be eliminated with mastectomy; approximately 2-32% of patients treated with mastectomy develop a chest wall recurrence. The interpretation of local control rates in evaluating repeat breast-conserving surgery studies is difficult because of the lack of information regarding preoperative diagnostic mammography to rule out concurrent multicentric disease and microscopic margin status after surgery. Rates of subsequent local recurrence in these studies appeared to be between 19-50%, similar to reported rates of in-breast local recurrence in patients with a first diagnosis of breast carcinoma who were treated with conservative surgery without irradiation. Early follow-up studies of breast reirradiation suggest that catheter-based interstitial brachytherapy and standard external beam radiation therapy can be delivered to the breast more than once without significant side effects in most patients and with acceptable cosmesis in some patients. Mastectomy may not be necessary in all patients with an in-breast local recurrence of breast carcinoma. Recent advances in conformal radiation delivery and single-center published reports concerning repeat breast-conserving therapy support well designed prospective trials to formally test this hypothesis.

Breast Neoplasms↗
PubMed2004

Breast cancer: new radiation treatment options.

Conventional radiotherapeutic treatment for early and advanced breast cancer has been based on broad-field radiation treatment principles that date back several decades. Although these strategies have been successful, newer techniques now offer the ability to incorporate improved target imaging, dosimetric planning, and treatment delivery into the treatment design. These newer techniques include accelerated partial-breast irradiation and hypofractionated whole-breast irradiation for early-stage breast cancer, and intensity-modulated radiotherapy (IMRT) for both early and advanced breast cancer. Accelerated partial-breast irradiation and hypofractionated whole-breast radiotherapy are treatment approaches that promise both reduced overall treatment times and the potential for increased use of breast-conservation therapy. IMRT offers unparalleled dose homogeneity and conformality that enables dose reduction to normal structures with the potential to reduce treatment toxicity and improve cosmesis. Based on the published literature, an increasing number of treatment facilities are offering treatment with these techniques. However, further clinical study remains important to thoroughly define the appropriate clinical setting, patient selection criteria, and limitations for each of these innovative treatment approaches.

Breast Neoplasms↗
PubMed2003

Partial breast brachytherapy after lumpectomy: low-dose-rate and high-dose-rate experience.

PURPOSE: The use of partial breast brachytherapy (PBB) after lumpectomy for selected patients with early-stage breast cancer reduces the adjuvant radiotherapy treatment time to <1 week. Despite the advantages of accelerated treatment, maintaining an acceptable cosmetic outcome is important. In a cohort of patients who received low-dose-rate (LDR) or high-dose-rate (HDR) PBB after lumpectomy, the clinical characteristics and treatment parameters were analyzed to identify predictors for an unfavorable cosmetic outcome. METHODS AND MATERIALS: Early-stage breast cancer patients with clear resection margins and 0-3 positive lymph nodes were eligible for PBB. Uniform guidelines for target definition and brachytherapy catheter placement were applied. The HDR PBB dose was 34 Gy in 10 fractions within 5 days, and the LDR dose was 45 Gy given at a rate of 50 cGy/h. The end points included incidence of radiation recall reaction, telangiectasias, and cosmetic-altering fibrosis. RESULTS: Between 1995 and 2000, 44 patients with early-stage breast cancer received PBB without adjuvant external beam radiotherapy after lumpectomy (31 HDR PBB, 13 LDR PBB). After a median follow-up of 42 months (range 18-86), all patients remained locally controlled. The overall rate of good/excellent cosmetic outcome was 79.6% overall and 90% with HDR PBB. Radiation recall reactions occurred in 43% of patients (6 of 14) who received adriamycin. LDR PBB and adriamycin were significant predictors for late unfavorable cosmetic changes in univariate analysis (p = 0.003 and p = 0.005, respectively). CONCLUSION: Although a high rate of local control and good/excellent cosmetic outcome is provided with HDR PBB, the risk of unfavorable cosmetic changes when treated with both LDR PBB and adriamycin is noteworthy. This suggests that HDR PBB is preferred in patients for whom adriamycin is indicated.

Adult↗
PubMed2003

Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society.

Logistical barriers of time and travel created by the conventional six-week course of radiotherapy prevent many women from pursuing breast conservation treatment. For the past 12 years, Accelerated Partial Breast Irradiation (APBI) has been investigated as a potential alternative treatment approach in women with early stage breast cancer. The ability to complete treatment in five days has the potential to provide additional women with the option of breast conservation. The validity of this APBI is supported in the study of in-breast recurrence patterns, pathologic data and the clinical treatment experience. The review of the recent data on contemporary APBI reveals that patient selection criteria and brachytherapy quality assurance are clearly critical components and necessary to assure a successful treatment outcome. This updated report from the American Brachytherapy Society on Accelerated Partial Breast Irradiation reviews the appropriate background data supporting this treatment approach with conclusions regarding patient selection criteria and treatment delivery.

Advisory Committees↗
PubMed2002

The effect of high-dose-rate brachytherapy dwell sequence on cell survival.

PURPOSE: During a high-dose-rate (HDR) brachytherapy treatment, as the source steps through different dwell positions, the dose rate at any fixed point within the implant varies, because the distance between the point and the source continually changes. The instantaneous dose rate may vary by a factor of 100 or more, in a complex dwell position sequence. Two different points which receive the same total dose may have received that dose with a very different sequence of dose rates. Any effects due to the complex changes in dose rate, including the sequence of dose delivery, are ignored. We investigated the possible effects of the sequence in which dose is delivered at two different dose rates, representative of dose rates that occur during an HDR treatment. METHODS AND MATERIALS: The target consisted of a tube containing a 1.0 cm(3) suspension of V-79 Chinese hamster cells. Two fixed source dwell positions near and far from the target, representing high and intermediate dose rates, were considered. The experiments compared the survival of V-79 cells exposed to an irradiation sequence consisting of either an HDR component followed by an intermediate-dose-rate component (H-I arm), or the reverse (I-H arm). In either case, the total dose and the dose ratio were the same, only the order in which the high- or intermediate-dose-rate components of the dose were delivered was changed. RESULTS: When the intermediate-dose-rate component was given before the HDR component, there was increased survival. All data pairs from three experiments showed greater survival for the I-H arm than the H-I arm by amounts ranging from 4% to 24%. Simple linear-quadratic models such as the Lea-Catchside model, which is invariant to time reversal of irradiation sequence, do not predict these results. CONCLUSIONS: These results suggest that targets receiving the same total dose of radiation during an HDR implant may not experience the same biological effect. This may be related to induced radioresistance or sublethal damage repair.

Animals↗
PubMed2002

Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society.

Logistical barriers of time and travel created by the conventional six week course of radiotherapy prevent many women from pursuing breast conservation treatment. For the past 12 years, Accelerated Partial Breast Irradiation (APBI) has been investigated as a potential alternative treatment approach in women with early stage breast cancer. The ability to complete treatment in five days has the potential to provide additional women with the option of breast conservation. The validity of this APBI is supported in the study of in-breast recurrence patterns, pathologic data and the clinical treatment experience. The review of the recent data on contemporary APBI reveals that patient selection criteria and brachytherapy quality assurance are clearly critical components and necessary to assure a successful treatment outcome. This updated report from the American Brachytherapy Society on Accelerated Partial Breast Irradiation reviews the appropriate background data supporting this treatment approach with conclusions regarding patient selection criteria and treatment delivery.

Advisory Committees↗