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Purpose The in vivo dosimetric monitoring in HDR brachytherapy is important for improving patient safety. However, there are very limited options available for clinical application. In this study, we present a new in vivo dose measurement system with a plastic scintillating detector (PSD) for GYN HDR brachytherapy. Methods An FDA approved PSD system, called OARtrac (AngioDynamics, Latham, NY), was used with various applicators for in vivo dose measurements for GYN patients. An institutional workflow was established for the clinical implementation of the dosimetric system. Action levels were proposed based on the measurement and system uncertainty for measurement deviations. From October 2018 to September 2019, a total of 75 measurements (48 fractions) were acquired from 14 patients who underwent HDR brachytherapy using either a multichannel cylinder, Venezia applicator, or Syed-Neblett template. The PSDs were placed in predetermined catheters/channels. A planning CT was acquired for treatment planning in Oncentra (Elekta, Version-4.5.2) TPS. The PSDs were contoured on the CT images, and the PSD D90% values were used as the expected doses for comparison with the measured doses. Results The mean difference from patient measurements was −0.22% ± 5.98%, with 26% being the largest deviation from the expected value (Syed case). Large deviations were observed when detectors were placed in the area where dose rates were less than 1 cGy/s. Conclusions The establishment of clinical workflow for the in vivo dosimetry for both the intracavitary and interstitial GYN HDR brachytherapy will potentially improve the safety of the patient treatment.

Purpose To highlight the current evidence and the limitations in data to support a personalized approach in breast oncology radiation therapy management and define steps needed for clinical implementation. Methods and Materials A critical review of the current literature on the use of genomics in breast radiation therapy was undertaken by a group of breast radiation oncologists to discuss current data, future directions, and challenges. Results A summary of the existing data, ongoing clinical trials, and future directions is provided. The authors note many groups have developed radiation-specific genomic assays, which demonstrate promise in prediction of local control and benefit from radiation therapy; however, prospective validation of their utility is needed. Limitations continue to exist in our understanding of tumor biology and how it can be integrated into clinical practice. Conclusions Given the relative ubiquity of breast radiation therapy, the variety of dose and fractionation approaches, and the current data to support a personalized approach, it is our belief that the delivery of breast radiation therapy is uniquely poised for a genomically personalized radiation therapy approach. Prospective clinical trials implementing genomic signatures are needed at this time to advance the field.

PURPOSE/OBJECTIVE(S) The administration of concurrent chemotherapy and radiotherapy (RT) is advantageous as it addresses both the local disease, potential sites of metastatic disease and delivering both together may provide a synergistic effect resulting in better tumor control. The purpose of this analysis was to report the long-term overall survival, disease free survival and local control from our institutional study of the efficacy of post-operative doxorubicin/cyclophosphamide followed by concurrent paclitaxel and reduced dose radiotherapy in patients with node-positive breast cancer. MATERIALS/METHODS 44 women with Stage II or III pathologically confirmed node-positive breast cancer were enrolled in a Phase II, prospective, single-arm trial from June 2000 through December 2004. All patients received breast-conserving surgery and 4 cycles of doxorubicin (60 mg/m2)/cyclophosphamide (600 mg/m2) followed by 4 cycles of paclitaxel (175 mg/m2) which was delivered every 3 weeks. RT was concurrent with the first 2 cycles of paclitaxel. The breast received 39.6 Gy in 22 fractions with a tumor bed boost of 14 Gy in 7 fractions. Regional lymph nodes were treated, when indicated, using a dose of 45 Gy in 25 fractions. There was no inclusion of the internal mammary nodal chain. The diffusing capacity for carbon monoxide (DLCO) was measured as a means to evaluate functional lung volume. Pulmonary function tests with DLCO were obtained before and after RT, after completion of chemotherapy, and annually for 5 years. Breast cosmesis before initiation of RT was evaluated by the treating radiation oncologist, and scored using Harvard criteria. Cosmesis was scored weekly during RT, 1 month after RT, and every 3 months thereafter for 1 year. RESULTS At a median follow-up of 205 months (17 yrs), overall survival is 75% and disease-free survival is 86.4%. There were 2 local recurrences yielding a local recurrence free survival of 95.5%. One of the patients with a local recurrence previously had a stage IIA (T1N1M0), grade 2 infiltrating ductal carcinoma, ER 90%, PR 50%, HER2 negative. The recurrence was stage IIA, (T1N1M0) grade 2, invasive lobular carcinoma, triple negative, considered a new primary. The two patients who experienced a local recurrence were successfully salvaged and are disease free. There were no cases of radiation pneumonitis. There was no significant change in the diffusing capacity for carbon monoxide either immediately after radiotherapy (P = 0.51) or with extended follow-up (P = 0.63) CONCLUSION: With long-term follow-up, the use of concurrent chemotherapy with low dose radiation as adjuvant treatment for node positive breast cancer has continued to demonstrate efficacy with excellent disease-free survival, overall survival and local control with acceptable toxicity.

e12547 Background: Clinical trials have demonstrated radiation therapy (RT) significantly reduces local recurrence following BCS, but that omission of RT does not compromise survival in the majority of women with early stage, low risk breast cancer. Criteria for omission of RT have been based on clinical factors such as age, stage, tumor size, surgical margins and estrogen receptor (ER) status. The utility of Oncotype DX RS in determining benefit of RT is not well defined. Methods: The National Cancer Database (NCDB) was queried for women ages 50-69 with T1N0M0, grade 1-2, ER+, Her2- breast cancer who underwent BCS with negative margins and had Oncotype DX RS of 0-18. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between patients who received RT and endocrine therapy (ET) versus ET alone using logrank analysis. Propensity matching was performed to reduce the impact of potential confounders and balance sample bias. Cox proportional hazards regression was used to identify predictors of OS. Results: A total of 13,648 women met inclusion criteria. The median age was 60 years. 13,389 women had adjuvant RT+ET, while 259 women had ET alone. Five year OS was 98.6% in patients who underwent RT+ET compared to 95.5% in those that had ET alone (p = 0.0012). Propensity-matching by age, Charlson Deyo Comorbid Condition score, tumor size, Oncotype RS, and race. Five year OS in the propensity matched cohort was 99.6% for women receiving RT+ET, and 98.3% for ET alone, which was not significantly different (p = 0.095). On multivariate analysis receipt of radiotherapy was not predictive of survival. Age and comorbidity score were the only significant predictors of survival. Conclusions: Patients who receive adjuvant RT with low risk, early stage ER+/Her2- breast cancer had higher OS than women who received ET alone on univariate analysis. However, results from both multivariate analysis and propensity score matching suggest no survival benefit to the addition of RT. Prospective studies are underway assessing omission of RT on the basis of multigene assays rather than clinical features alone. [Table: see text]

BACKGROUND The objective of the current study was to determine the long-term results of breast-conservation treatment in women with early-stage, invasive lobular carcinoma of the breast. METHODS Between 1977 and 1995, 1093 women with Stage I and II invasive ductal carcinoma of the breast and 55 women with invasive lobular carcinoma of the breast underwent lumpectomy, axillary lymph node dissection, and radiation treatment. Overall, 49% of the women received adjuvant systemic therapy (chemotherapy and/or hormones). RESULTS The median age was 52 years for patients in the invasive ductal group and 54 years for patients in the invasive lobular group. The median follow-up was 8.7 years and 10.2 years for patients in the invasive ductal and invasive lobular groups, respectively. A comparison of patients who had invasive lobular carcinoma with patients who had invasive ductal carcinoma showed no difference in the 10-year actuarial rates of overall survival (85% vs. 79%, respectively; P = 0.73), cause-specific survival (93% vs. 84%, respectively; P = 0.85), or freedom from distant metastases (81% vs. 80%, respectively; P = 0.76). The 10-year rates of local failure were 18% for patients with invasive lobular carcinoma and 12% for patients with invasive ductal carcinoma (P = 0.24), and the 10-year rates of contralateral breast carcinoma development for the 2 groups were 12% and 8%, respectively (P = 0.40). CONCLUSIONS Breast-conservation treatment yielded similar long-term results for women with early-stage, invasive lobular carcinoma and women with the more prevalent invasive ductal carcinoma. Cancer 2005. © 2005 American Cancer Society.

BACKGROUND Mammography and physical examination are routine methods for the detection of ipsilateral local recurrence and contralateral breast carcinoma in patients initially undergoing breast conservation treatment. The current study reports the relation between the method of detection of the initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma. METHODS A retrospective review was performed of the records of female patients with initial American Joint Committee on Cancer (AJCC) Stage I and II invasive breast carcinoma who developed ipsilateral local recurrence or contralateral breast carcinoma after breast conservation treatment. The method of detection of local recurrence in the ipsilateral breast and the method of detection of contralateral breast carcinoma were compared with the method of detection of the primary tumor. RESULTS There were 125 ipsilateral breast local recurrences and 71 contralateral breast carcinoma cases detected. Of the 125 recurrences in the ipsilateral breast, 38% (48 recurrences) were detected by mammography only, 37% (46 recurrences) were detected by physical examination only, and 25% (31 recurrences) were detected by both methods. Of the 71 contralateral breast carcinoma cases, 53% (38 cases) were detected by mammography only, 23% (16 cases) were detected by physical examination only, and 24% (17 cases) were detected by both methods. When the primary tumors were detected by mammography only, 21% of the local recurrences (3 of 14 local recurrences) and 19% of the contralateral breast carcinoma cases (4 of 21 cases) were detected by physical examination only. When the primary tumors were detected by physical examination only, 24% of the local recurrences (14 of 58 local recurrences) and 42% of the contralateral breast carcinoma cases (8 of 19 cases) were detected by mammography only. When stratified by the interval between diagnosis of the primary tumor and ipsilateral local recurrence or contralateral breast carcinoma (≤ 5 years vs. > 5 years) or age of the patient at the time of ipsilateral breast recurrence or contralateral breast carcinoma (age ≤ 49 years vs. age ≥ 50 years), both breast examination and mammography were found to be important in the detection of locally recurrent tumor and contralateral breast carcinoma in each subgroup of the patients, regardless of the method of presentation of the primary tumor. CONCLUSIONS Both mammography and physical examination were found to be significant in the detection of locally recurrent tumor in the ipsilateral breast and in the detection of contralateral breast carcinoma, regardless of the method of detection of the primary tumor. Cancer 2003. © 2003 American Cancer Society. DOI 10.1002/cncr.11685

10527 Background: Arm lymphedema (ALE) is a serious consequence of the treatment for breast carcinoma. The objective of the current retrospective study was to analyze the time-course of minimal ALE after breast conservation treatment for early stage breast cancer. Methods: The study cohort was drawn from consecutive stage I or II patients who underwent breast conservation therapy including axillary staging followed by radiation. During follow up assessments after treatment, measurements of arm circumference were frequently performed at regular intervals, for clinically evident swelling of the arm or for complaints of swelling of the arm. ALE was documented in 274 of 1861 (15%) patients. 109 patients, 6% of overall group, and 40% of the patients with lymphedema, presented with minimal ALE, defined as a difference of 2 cm or less between the affected and unaffected arms. Results: The median age of patients was 54 years. The median interval to develop ALE was 1 year. The median follow up was 11 years. Among all 109 patients with minimal grade ALE at the time of ALE diagnosis, 21%, 13% and 14% of the patients progressed to more severe grades of lymphedema after 1,3 and 5 years of follow-up, respectively (See table). 40% of the patients with minimal grade ALE received therapy for lymphedema. Despite treatment for minimal grade ALE, 37% of treated patients progressed to more severe grades of lymphedema at 1 year follow up, and 24% progressed at 3 and 5 years follow up. Conclusions: Minimal ALE after breast conservation therapy, including axillary staging, developed in 6% of stage I or II breast cancer patients. Minimal ALE has the potential to progress to more severe grade of ALE. Despite treatment for lymphedema for minimal grade ALE, some patients still progressed to more severe grades of lymphedema. [Table: see text] No significant financial relationships to disclose.

Materials/Methods: From November 1977 to December 1995, 1379 female patients with stage I and II invasive breast cancer had been treated with breast conservation treatment. The patients have been subsequently followed with regular physical examination and yearly bilateral mammography. The results of clinical examination, mammography, recurrence in the ipsilateral breast and development of contralateral breast cancer were evaluated. The methods of detection of local recurrent tumor in the ipsilateral breast and the methods of detection of contralateral breast cancer were compared to the methods of detection of the primary tumor.

Results: Seven patients were randomized to the Adriamycin first arm (AT) and 9 patients to the Taxol first arm (TA). A mean of 137 pO2 measurements was taken in each tumor (range 86 to 153) using (4 to 8 tracks). Both IFP and pO2 measurements were performed under ultrasound guidance. The mean IFP in tumors was 8.6 mmHg (range 3-17), while the mean IFP in normal tissue was 1 mmHg (range 0 – 3) (p 0.05). The median pO2 measurements varied between 1.6 and 49.4 mmHg with an overall mean of 22 mmHg. The median pO2 measured in normal tissue varied between 26 and 55 mmHg with an overall mean of 45 mmHg (range 26-55) (p 0.0002). There was no correlation between the baseline IFP and median pO2 found (p 0.29).

Pyridozine has been synthesized by the Diels-Alder reaction of 4-methyl-5-alkoxy oxazoles with maleic anhydride, diethyl maleate, diethyl fumarate and fumaronitrile, followed by reduction. At higher temperatures, 2-butene-1,4-diol, its dimethyl ether and 2,5-dihydrofuran afforded pyridoxine and its corresponding ethers directly. The reative reactivities of dienophiles and also the failure to isolate 3-alkoxy-pyridines are briefly discussed.

_ ______________________________________________________ Bl Introduction._____________________________________________________ 1 Purpose and scope.____________________________________________ 1 Acknowledgments _____________________________________________ 2 Description of basin_______________________________________________ 3 Hydrology of basin________________________________________________ 5 Precipitation._________________________________________________ 5 Ground water.________________________________________________ 6 Surface water _________________________________________________ 6 Urban growth in the project area____________________________________ 9 Effect of urban growth..___________________________________________ 12 Summary____ _____________________________________________________ 16 References cited___________________________________________________ 18