Breast Neoplasms: Marks LB

Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR. · Radiation Oncology Flight, Wilford Hall Medical Center, Lackland AFB, TX, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19545784 No free full text.

Abstract: PURPOSE: To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation (APBI), based on current published evidence complemented by expert opinion. METHODS AND MATERIALS: A systematic search of the National Library of Medicine's PubMed database yielded 645 candidate original research articles potentially applicable to APBI. Of these, 4 randomized trials and 38 prospective single-arm studies were identified. A Task Force composed of all authors synthesized the published evidence and, through a series of meetings, reached consensus regarding the recommendations contained herein. RESULTS: The Task Force proposed three patient groups: (1) a "suitable" group, for whom APBI outside of a clinical trial is acceptable, (2) a "cautionary" group, for whom caution and concern should be applied when considering APBI outside of a clinical trial, and (3) an "unsuitable" group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety. CONCLUSION: Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer.

Carlson RW, Anderson BO, Burstein HJ, Cox CE, Edge SB, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis C, Jahanzeb M, Ljung BM, Marks LB, McCormick B, Nabell LM, Pierce LJ, Reed EC, Silver SM, Smith ML, Somlo G, Theriault RL, Ward JH, Winer EP, Wolff AC, Anonymous00249. · Stanford Hospital & Clinics, USA. · J Natl Compr Canc Netw. · Pubmed #16002000 No free full text.

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Marks LB, Zeng J, Prosnitz LR. · No affiliation provided · J Clin Oncol. · Pubmed #18445836 No free full text.

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Prosnitz LR, Marks LB. · No affiliation provided · Int J Radiat Oncol Biol Phys. · Pubmed #16580790 No free full text.

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Prosnitz LR, Marks LB. · No affiliation provided · J Natl Cancer Inst. · Pubmed #16391361 links to  free full text

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Prosnitz RG, Marks LB. · No affiliation provided · J Clin Oncol. · Pubmed #16186592 No free full text.

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Marks LB, Prosnitz LR. · Duke University Medical Center, Durham, NC 27710, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #11020556 No free full text.

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Demirci S, Nam J, Hubbs JL, Nguyen T, Marks LB. · Department of Radiation Oncology, Ege University School of Medicine, Izmir, Turkey. · Int J Radiat Oncol Biol Phys. · Pubmed #19251085 No free full text.

Abstract: PURPOSE: Cardiac toxicity after breast radiotherapy (RT) has been widely described in "older" RT trials (i.e., using larger fraction sizes, wide RT fields, and orthovoltage energy). The results from more "modern" RT trials have shown less cardiac toxicity. The comparisons between the "older" and "modern" trials are confounded by the longer follow-up time in the "older" trials. We systematically assessed the effect of treatment era and follow-up duration on the reported rates of cardiac toxicity associated with RT. METHODS AND MATERIALS: The published data were surveyed using PubMed to identify studies using "breast cancer," "irradiation/radiotherapy," "cardiac/heart," and "toxicity/morbidity/mortality" in a keyword search. Relevant data were extracted from the identified trials. The trials were defined as "older" (patient accrual start year before 1980) and "modern" (patient accrual start year in or after 1980) to segregate the trials and assess the treatment era effect. A 10-year follow-up duration was used as a cutoff to segregate and analyze trials with varying lengths of follow-up. RESULTS: We analyzed 19 published reports of patients treated between 1968 and 2002 (5 randomized controlled trials, 5 single- or multi-institutional studies, and 9 national cancer registry database reviews). In the reviewed trials, all the older trials reported excess cardiac toxicity, typically with a median of >10-15 years of follow-up. However, the vast majority of modern RT trials had shorter median follow-up durations, typically <or=10 years and did not report an excess toxicity risk. The modern studies lacked longer follow-up. CONCLUSION: Additional follow-up is needed to ensure that modern methods effectively reduce cardiac toxicity. Continued diligence to minimize cardiac exposure remains prudent.

Carlson RW, Moench S, Hurria A, Balducci L, Burstein HJ, Goldstein LJ, Gradishar WJ, Hughes KS, Jahanzeb M, Lichtman SM, Marks LB, McClure JS, McCormick B, Nabell LM, Pierce LJ, Smith ML, Topham NS, Traina TA, Ward JH, Winer EP. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #18597715 No free full text.

Abstract: Breast cancer is common in older women, and the segment of the U.S. population aged 65 years and older is growing rapidly. Consequently, awareness is increasing of the need to identify breast cancer treatment recommendations to assure optimal, individualized treatment of older women with breast cancer. However, the development of these recommendations is limited by the heterogeneous nature of this population with respect to functional status, social support, life expectancy, and the presence of comorbidities, and by the underrepresentation of older patients with breast cancer in randomized clinical trials. The NCCN Breast Cancer in the Older Woman Task Force was convened to provide a forum for framing relevant questions on topics that impact older women with early-stage, locally advanced, and metastatic breast cancer. The task force is a multidisciplinary panel of 18 experts in breast cancer representing medical oncology, radiation oncology, surgical oncology, geriatric oncology, geriatrics, plastic surgery, and patient advocacy. All task force members were from NCCN institutions and were identified and invited solely by NCCN. Members were charged with identifying evidence relevant to their specific expertise. During a 2-day meeting, individual members provided didactic presentations; these presentations were followed by extensive discussions during which areas of consensus and controversy were identified on topics such as defining the "older" breast cancer patient; geriatric assessment tools in the oncology setting; attitudes of older patients with breast cancer and their physicians; tumor biology in older versus younger women with breast cancer; implementation of specific interventions in older patients with breast cancer, such as curative surgery, surgical axillary staging, radiation therapy, reconstructive surgery, endocrine therapy, chemotherapy, HER2-directed therapy, and supportive therapies; and areas requiring future studies.

Jones EL, Marks LB, Prosnitz LR. · Duke University Medical Center, Durham, NC 27710, USA. · J Natl Compr Canc Netw. · Pubmed #17439762 No free full text.

Abstract: Treatment of a locoregional recurrence of breast cancer after mastectomy remains a clinically challenging problem. Often these patients have undergone prior radiotherapy and chemotherapy. Therapeutic options usually include resection or additional radiation; however, the long-term control rates are often suboptimal with these approaches. Data from several randomized trials suggest that the addition of hyperthermia to radiation can increase the response rate for such local recurrences. Therefore, in settings where the available therapies are unlikely to yield local control (e.g., local/ regional recurrence after prior radiation), a reasonable option to consider is radiation with hyperthermia as a radiation sensitizer. This article reviews the rationale and supporting literature for this recommendation.

Carlson RW, Anderson BO, Burstein HJ, Carter WB, Edge SB, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Ljung BM, Kiel K, Marks LB, McCormick B, Nabell LM, Pierce LJ, Reed EC, Silver SM, Smith ML, Somlo G, Theriault RL, Ward JH, Winer EP, Wolff AC. · National Comprehensive Cancer Network · J Natl Compr Canc Netw. · Pubmed #17439758 No free full text.

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Raj KA, Marks LB, Prosnitz RG. · Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. · Breast Dis. · Pubmed #16823167 No free full text.

Abstract: Radiotherapy (RT) to the breast or chest wall of young women is associated with long-term cardiotoxicity and an increased risk of secondary breast cancers. As many patients with early stage breast cancer and Hodgkin's disease are cured of their disease, there is significant concern regarding the long term risks of therapy. Older RT techniques for treating the breast/chest wall and draining lymph nodes for breast cancer resulted in a relatively high dose being delivered to a substantial volume of heart, and convincing evidence exists of excess cardiovascular morbidity and mortality in patients treated with these techniques. While modern RT techniques have reduced radiation exposure to the heart, they have not eliminated it. Many large studies of Hodgkin's disease survivors have demonstrated a clear risk of secondary breast cancer development after mantle RT for Hodgkin's disease. The risk of developing breast cancer after mantle RT appears to be related to age at time of irradiation, dose delivered to the breast tissue, and whether or not chemotherapy is incorporated into the overall treatment plan. In this article we review late cardiac complications associated with tangential breast RT and the risk of developing a secondary breast cancer after mantle RT for Hodgkin's disease.

Prosnitz RG, Chen YH, Marks LB. · Department of Radiation Oncology, Duke University, Box 3085 Duke University Medical Center, Durham, NC 27710, USA. · Semin Oncol. · Pubmed #16015539 No free full text.

Abstract: While the data regarding radiotherapy (RT)-induced cardiovascular disease in lung cancer patients is limited, the cardiotoxic effects of RT have been thoroughly documented in long-term survivors of breast cancer and Hodgkin's disease. Herein we review data illustrating the cardiotoxic effects of thoracic RT in lung and breast cancer patients. Older RT techniques for treating the breast/chest wall and draining lymph nodes resulted in a relatively high dose being delivered to a substantial volume of heart, and convincing evidence exists of excess cardiovascular morbidity and mortality in patients treated with these techniques. While modern RT techniques have reduced radiation exposure to the heart, they have not eliminated it. In patients treated with modern techniques, there are conflicting data regarding the impact of radiation on late cardiovascular morbidity and mortality. Thus, it is prudent to reduce cardiac exposure as much as possible. Techniques to reduce further cardiac exposure (eg, respiratory gating, intensity modulated radiation therapy) are currently under investigation. Further work is needed to quantify the frequency and severity of cardiac injury and develop preventative methods.

Lind PA, Marks LB, Jamieson TA, Carter DL, Vredenburgh JJ, Folz RJ, Prosnitz LR. · Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA. · Cancer. · Pubmed #12115368 links to  free full text

Abstract: BACKGROUND: To study the predictive value of serial pulmonary function testing (PFT) for toxicity in patients who have received high-dose chemotherapy (HDCT) and stem-cell rescue for breast carcinoma. These patients are at risk of developing therapy-related pneumonitis (TRP) during or after radiotherapy (RT). METHODS: Sixty-eight patients who received induction chemotherapy (CT) and consolidation HDCT (cyclophosphamide, cisplatin, carmustine) underwent serial PFTs before induction CT, after HDCT, and before locoregional RT. The rate of TRP, i.e., pulmonary complications of Grade 2 or higher (World Health Organization classification), was studied during and 2 months after RT. We analyzed the time-course of changes in the diffusing capacity of carbon monoxide (DLCO) and forced expiratory volume at one second (FEV(1)) and studied the differences between patients who developed TRP and those who did not. RESULTS: The incidence of TRP was 46%. There were marked reductions in DLCO and FEV(1) at the time of RT compared with baseline (Wilcoxon signed rank test: P < 0.001). However, pre-RT PFT values did not predict subsequent development of TRP. Instead, the ratio of pre-RT DLCO to the minimum post- HDCT DLCO, i.e., trend of improvement, predicted the development of TRP in patients (logistic regression analysis: P = 0.048). At a cutoff level of 1, the positive and negative predictive values for this ratio were 61% and 87%, respectively. There was an association between this ratio and a longer interval between HDCT and RT (Spearman rank correlation: P = 0.002). CONCLUSIONS: The results suggest that the directional trend of DLCO after HDCT, i.e., no recovery from nadir values, is a predictor for TRP. TRP patients have a shorter median interval between HDCT and RT than asymptomatic patients. To minimize the occurrence of TRP, one should consider either delaying RT beyond 2 months following carmustine-based HDCT to allow the PFTs to partly recover, or confirm apositive directional trend for improvement of DLCO at the start of RT compared to the post-HDCT nadir value.

Marks LB, Hardenbergh P, Prosnitz LR. · Duke University Medical Center, Department of Radiation Oncology, Durham, North Carolina, USA. · Oncology (Williston Park). · Pubmed #10499246 No free full text.

Abstract: Postmastectomy locoregional radiation therapy markedly reduces the risk of locoregional recurrence. Several randomized trials, including two recently updated studies with 10- to 15-year follow-up, demonstrate an improvement in overall survival with radiation therapy. This improvement is seen in patients with one to three positive axillary lymph nodes, as well those with four positive nodes. Therefore, postmastectomy radiation therapy should be considered in all patients with node-positive breast cancer. Computed tomography (CT)-based treatment planning is recommended to minimize the cardiopulmonary morbidity of radiation therapy.

Hardenbergh PH, Bentel GC, Prosnitz LR, Marks LB. · Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. · Semin Radiat Oncol. · Pubmed #10378965 No free full text.

Abstract: The role of locoregional radiation therapy after mastectomy is controversial. It reduces the risk of tumor relapse, improves breast cancer-specific survival and possibly overall survival, but has potential morbidity. This article reviews the technical aspects of postmastectomy radiation therapy and its associations with treatment-related morbidity. We consider common problems that arise in the technical setup of radiation fields. Adverse effects of postmastectomy radiation therapy may be reduced or prevented by careful radiation treatment planning.

Evans ES, Prosnitz RG, Yu X, Zhou SM, Hollis DR, Wong TZ, Light KL, Hardenbergh PH, Blazing MA, Marks LB. · Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17145533 No free full text.

Abstract: PURPOSE: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. METHODS AND MATERIALS: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors on the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. RESULTS: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up "too deep" (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI > or =25 kg/m2 compared with patients of normal weight (47% vs. 28%, p = 0.068). CONCLUSIONS: BMI > or =25 kg/m2 may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.

Peters WP, Rosner GL, Vredenburgh JJ, Shpall EJ, Crump M, Richardson PG, Schuster MW, Marks LB, Cirrincione C, Norton L, Henderson IC, Schilsky RL, Hurd DD. · Cancer and Leukemia Group B, 230 W Monroe St, Suite 2050, Chicago, IL 60606, USA. · J Clin Oncol. · Pubmed #15767638 No free full text.

Abstract: PURPOSE: The prognosis for women with primary breast cancer involving multiple axillary nodes remains poor. High-dose chemotherapy with stem-cell support produced promising results in initial clinical trials conducted at single institutions. PATIENTS AND METHODS: Seven hundred eighty-five women aged 22 to 66 years with stage IIA, IIB, or IIIA breast cancer involving 10 or more axillary lymph nodes were randomized after surgery and standard adjuvant chemotherapy to either high-dose cyclophosphamide, cisplatin, and carmustine (HD-CPB) with stem-cell support or intermediate-dose cyclophosphamide, cisplatin, and carmustine (ID-CPB) with G-CSF support but without stem cells. Planned treatment for all patients included locoregional radiation therapy. Hormone-receptor-positive patients were to receive 5 years of tamoxifen. Event-free survival (EFS) was the primary end point. RESULTS: Median follow-up was 7.3 years. Event-free survival was not significantly different between the two treatment groups (P = .24). The probability of being free of an event at 5 years with HD-CPB was 61% (95% CI, 56% to 65%), and was 58% (95% CI, 53% to 63%) for ID-CPB. Thirty-three patients died of causes attributed to HD-CPB, compared with no therapy-related deaths among women treated with ID-CPB. Overall survival for the two arms was identical at 71% at 5 years (P = .75). CONCLUSION: HD-CPB with stem-cell support was not superior to ID-CPB for event-free or overall survival among all randomized women with high-risk primary breast cancer.

Solin LJ, Fourquet A, Vicini FA, Taylor M, Olivotto IA, Haffty B, Strom EA, Pierce LJ, Marks LB, Bartelink H, McNeese MD, Jhingran A, Wai E, Bijker N, Campana F, Hwang WT. · Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. · Cancer. · Pubmed #15674853 links to  free full text

Abstract: BACKGROUND: Ductal carcinoma in situ (DCIS) is detected most commonly on routine screening mammography in the asymptomatic patient, and has a long natural history. The objective of the current study was to determine the long-term outcome after breast-conservation surgery followed by definitive breast irradiation for women with mammographically detected DCIS of the breast. METHODS: In total, 1003 women with unilateral, mammographically detected DCIS of the breast underwent breast-conserving surgery followed by definitive breast irradiation. These women were treated in 10 institutions in North America and Europe. The median follow-up was 8.5 years (mean, 9.0 years; range, 0.2-24.6 years). RESULTS: The 15-year overall survival rate was 89%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 97%. In total, there were 100 local failures (10%) in the treated breast. The 15-year rate of any local failure was 19%, and the 15-year rate of local only first failure was 16%. Patient age > or = 50 years at the time of treatment and negative final pathology margins from the primary tumor excision both were associated independently with a lower risk of local failure in univariate analysis (P = 0.00062 and P = 0.024, respectively) and in multivariate analysis (P = 0.00057 and P = 0.0026, respectively). For favorable subgroups of patients age > or = 50 years or with negative resection margins, the 10-year risk of local failure was < or = 8%. CONCLUSIONS: The current results support the use of breast-conserving surgery followed by definitive breast irradiation for the treatment of patients with mammographically detected DCIS of the breast. Patient age > or = 50 years at the time of treatment and negative resection margins both were associated independently with a decreased risk of local failure.

Jones EL, Prosnitz LR, Dewhirst MW, Marcom PK, Hardenbergh PH, Marks LB, Brizel DM, Vujaskovic Z. · Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA. · Clin Cancer Res. · Pubmed #15240513 links to  free full text

Abstract: PURPOSE: The purpose of this research was to evaluate toxicity, response, and changes in oxygenation (pO(2)) in patients with locally advanced breast cancer (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy (RT) followed by mastectomy. EXPERIMENTAL DESIGN: Eighteen patients with LABC were enrolled from October 1995 through February 1999. Treatment consisted of taxol (175 mg/m(2)) given every 3 weeks for three cycles. Radiation therapy included the breast and regional nodes with a dose of 50 Gy, followed by a boost to 60-65 Gy for those not undergoing surgery. Mastectomy was performed for patients deemed resectable after this neoadjuvant program. HT was administered twice per week. Oxygenation was measured before the first HT treatment and 24 h after the first HT treatment. RESULTS: Fifteen of 18 patients responded, 6 with a clinical complete response, 9 with a partial clinical response, and 3 nonresponders. Thirteen underwent mastectomy with 3 pathological complete responses. Tumor hypoxia was present in 8 of 13 patients (pO(2) = 4.7 +/- 1.2 mmHg). Five patients had well-oxygenated tumors (pO(2) = 27.6 +/- 7.8 mmHg). Patients with well-oxygenated tumors before treatment as well as those with significant reoxygenation had a favorable clinical response. Tumor reoxygenation appeared to be temperature dependent and associated with the lower thermal doses. CONCLUSIONS: This novel therapeutic program resulted in a high response rate in patients with LABC. Hyperthermia may offer a strategy for improving tumor reoxygenation with consequent treatment response. However, the effect of hyperthermia on tumor reoxygenation appears to depend on thermal dose and requires additional investigation.

Stuart MJ, Peters WP, Broadwater G, Hussein A, Ross M, Marks LB, Folz RJ, Long GD, Rizzieri D, Chao NJ, Vredenburgh JJ. · Division of Bone Marrow Transplantation, Stanford University Medical Center, Stanford, California, USA. · Biol Blood Marrow Transplant. · Pubmed #12523579 No free full text.

Abstract: Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.

Fan M, Marks LB, Lind P, Hollis D, Woel RT, Bentel GG, Anscher MS, Shafman TD, Coleman RE, Jaszczak RJ, Munley MT. · Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #11567804 No free full text.

Abstract: PURPOSE: To determine whether the sum of radiotherapy (RT)-induced reductions in regional lung perfusion is quantitatively related to changes in global lung function as assessed by reductions in pulmonary function tests (PFTs). METHODS AND MATERIALS: Two hundred seven patients (70% with lung cancer) who received incidental partial lung irradiation underwent PFTs (forced expiratory volume in 1 s and diffusion capacity for carbon monoxide) before and repeatedly after RT as part of a prospective clinical study. Regional lung function was serially assessed before and after RT by single photon emission computed tomography perfusion scans. Of these, 53 patients had 105 post-RT evaluations of changes in both regional perfusion and PFTs, were without evidence of intrathoracic disease recurrence that might influence regional perfusion and PFT findings, and were not taking steroids. The summation of the regional functional perfusion changes were compared with changes in PFTs using linear regression analysis. RESULTS: Follow-up ranged from 3 to 86 months (median 19). Overall, a significant correlation was found between the sum of changes in regional perfusion and the changes in the PFTs (p = 0.002-0.24, depending on the particular PFT index). However, the correlation coefficients were small (r = 0.16-0.41). CONCLUSIONS: A statistically significant correlation was found between RT-induced changes in regional function (i.e., perfusion) and global function (i.e., PFTs). However, the correlation coefficients are low, making it difficult to relate changes in perfusion to changes in the PFT results. Thus, with our current techniques, the prediction of changes in perfusion alone does not appear to be sufficient to predict the changes in PFTs accurately. Additional studies to clarify the relationship between regional and global lung injury are needed.

Carter DL, Marks LB, Bean JM, Broadwater G, Hussein A, Vredenburgh JJ, Peters WP, Prosnitz LR. · Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA. · J Clin Oncol. · Pubmed #10071280 No free full text.

Abstract: PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1988 and 1994,425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT was not randomized. The RT+ and RT- groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups, respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.

Li XA, Tai A, Arthur DW, Buchholz TA, Macdonald S, Marks LB, Moran JM, Pierce LJ, Rabinovitch R, Taghian A, Vicini F, Woodward W, White JR, Anonymous00081. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19215827 No free full text.

Abstract: PURPOSE: To quantify the multi-institutional and multiobserver variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT) and its dosimetric impact as the first step of a Radiation Therapy Oncology Group effort to establish a breast cancer atlas. METHODS AND MATERIALS: Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative breast cancer patients. Interobserver differences in structure delineation were quantified regarding volume, distance between centers of mass, percent overlap, and average surface distance. Mean, median, and standard deviation for these quantities were calculated for all possible combinations. To assess the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated. RESULTS: Variability in contouring the targets and OARs between the institutions and observers was substantial. Structure overlaps were as low as 10%, and volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries and approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These interobserver differences result in substantial variations in dosimetric planning for breast RT. CONCLUSIONS: Differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of intensity-modulated and image-guided RT.

Zhang J, Wu QJ, Godfrey DJ, Fatunase T, Marks LB, Yin FF. · Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19135316 No free full text.

Abstract: PURPOSE: To evaluate digital tomosynthesis (DTS) technology for daily positioning of patients receiving accelerated partial breast irradiation (APBI) and to compare the positioning accuracy of DTS to three-dimensional cone-beam computed tomography (CBCT). METHODS AND MATERIALS: Ten patients who underwent APBI were scanned daily with on-board CBCT. A subset of the CBCT projections was used to reconstruct a stack of DTS image slices. To optimize soft-tissue visibility, the DTS images were reconstructed in oblique directions so that the tumor bed, breast tissue, ribs, and lungs were well separated. Coronal and sagittal DTS images were also reconstructed. Translational shifts of DTS images were obtained on different days from the same patients and were compared with the translational shifts of corresponding CBCT images. Seventy-seven CBCT scans and 291 DTS scans were obtained from nine evaluable patients. RESULTS: Tumor beds were best visible in the oblique DTS scans. One-dimensional positioning differences between DTS and CBCT images were 0.8-1.7 mm for the six patients with clips present and 1.2-2.0 mm for the three patients without clips. Because of the limited DTS scan angle, the DTS registration accuracy along the off-plane direction is lower than the accuracy along the in-plane directions. CONCLUSIONS: For patients receiving APBI, DTS localization offers comparable accuracy to CBCT localization for daily patient positioning while reducing mechanical constraints and imaging dose.