A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.

Background: Pre-operative chemoradiation for rectal cancer is often associated with severe gastrointestinal (GI) toxicity which can interrupt, delay, and/or lead to termination of treatment. In this study, we evaluated whether the addition of YIV-906, a novel herbal medicine proven to reduce GI toxicity associated with chemotherapy could also reduce GI side effects during standard pre-operative capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting for the treatment of locally advanced rectal cancer. Methods: This single arm clinical study enrolled 24 patients between Dec 23, 2014-Sep 17, 2018 at Smilow Cancer Hospital, a comprehensive cancer center at Yale New Haven Hospital. All patients were age ≥18 years, Eastern Cooperative Oncology Group 0-1 and with histologically confirmed T3-T4 and N0-N2, M0 adenocarcinoma of the rectum. Median follow-up was 61.9 months. All patients received concurrent pelvic external beam RT (50.4 Gy in 28 fractions), YIV-906 (taken orally 800 mg twice daily on days 1-4 of RT each week), and oral capecitabine delivered in a neo-adjuvant fashion, followed by definitive surgery. Toxicity was assessed weekly during radiation and until acute symptoms resolved and then at 28 days, 4 months, 7 months and 10 months. Toxicities were graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: At the time of surgery, 4 patients (16.7%) had a complete or near-complete response. At a median follow-up of 61.9 months, the mean overall survival (OS) of our patient cohort was 74.9 months [95% confidence interval (CI): 67.3-82.5]. The estimated 5-year OS was 82.0%. We observed 0% acute grade 4 toxicities, and only two cases of acute grade 3 diarrhea (8.3%). Conclusions: The addition of YIV-906 to capecitabine based chemoradiation for locally advanced rectal cancer led to reduced rates of GI toxicity compared to historical controls, in particular grade 3 or greater diarrhea. These findings suggest YIV-906 should be evaluated in a randomized clinical trial to further assess potential reductions in the toxicity profile of chemoradiation for GI cancers.

AAPM task group report 302: Surface-guided radiotherapy.

The clinical use of surface imaging has increased dramatically, with demonstrated utility for initial patient positioning, real-time motion monitoring, and beam gating in a variety of anatomical sites. The Therapy Physics Subcommittee and the Imaging for Treatment Verification Working Group of the American Association of Physicists in Medicine commissioned Task Group 302 to review the current clinical uses of surface imaging and emerging clinical applications. The specific charge of this task group was to provide technical guidelines for clinical indications of use for general positioning, breast deep-inspiration breath hold treatment, and frameless stereotactic radiosurgery. Additionally, the task group was charged with providing commissioning and on-going quality assurance (QA) requirements for surface-guided radiation therapy (SGRT) as part of a comprehensive QA program including risk assessment. Workflow considerations for other anatomic sites and for computed tomography simulation, including motion management, are also discussed. Finally, developing clinical applications, such as stereotactic body radiotherapy (SBRT) or proton radiotherapy, are presented. The recommendations made in this report, which are summarized at the end of the report, are applicable to all video-based SGRT systems available at the time of writing.

Comparing complications in irradiated and non-irradiated free-flaps in patients with bilateral immediate breast reconstruction and unilateral post-mastectomy radiotherapy.

BACKGROUND: Numerous studies have evaluated the effect of post-mastectomy radiotherapy (PMRT) on autologous breast reconstruction, but the variability of PMRT regimens and inadequate controls have made results difficult to interpret. Therefore, in this study, irradiated free-flaps are compared to non-irradiated internal controls in patients who underwent immediate bilateral reconstruction followed by unilateral PMRT to better delineate the effect of PMRT. The role of regional nodal irradiation (RNI) is also specifically assessed. METHODS: Appropriate patients were identified through retrospective review. Complications such as fat necrosis, fibrosis, infection, delayed healing, and flap loss, as well as revision surgeries, among the irradiated free-flaps were compared to those on the contralateral non-irradiated side. Additional analyses were performed to evaluate the effect of patient demographics and treatment characteristics, such as RNI, on complications involving the irradiated free-flaps. RESULTS: Seventy-three women were included. There was no significant difference between complication rates for the irradiated and non-irradiated free-flaps (39.7% vs. 38.4%, p = .78), although irradiated free-flaps were more likely to have fibrosis (17.0% vs. 0.0%; p < .0001) and multiple complications (9.6% vs. 0.0%; p = .02). Both groups underwent a similar number of revision surgeries (42.5% vs. 41.1%; p = .29). Looking at the irradiated free-flaps, internal mammary node (IMN) irradiation was the only factor predictive of complications (IRR 3.80, CI 1.32-10.97; p = .01). CONCLUSIONS: PMRT may contribute to free-flap fibrosis, but does not appear to affect the overall risk of complications or revision surgeries. However, additional counseling is warranted if IMN irradiation is likely, as it is potentially associated with increased complications.

Surgical Outcomes of Mastectomy with Immediate Autologous Reconstruction Followed by Radiation.

INTRODUCTION: Timing of autologous reconstruction relative to postmastectomy radiation therapy (PMRT) is debated. Benefits of immediate reconstruction must be weighed against a possibly heightened risk of complications from flap irradiation. We reviewed flap outcomes after single operation plus PMRT in a large institutional cohort. METHODS: Medical records were reviewed for women who underwent simultaneous mastectomy-autologous reconstruction with PMRT from 2007 to 2016. Primary endpoints were rates and types of radiation-related flap complications and reoperations, whose predictors were assessed by multivariable analysis. A p value < 0.10 was deemed significant to avoid type II error. Non-parametric logistic regression generated a model of PMRT timing associated with probabilities of complications and reoperations. RESULTS: One-hundred and thirty women underwent 208 mastectomy reconstruction operations, with a median follow up of 35.1 months (interquartile range 23.6-56.5). Forty-seven (36.2%) women experienced radiation-related complications, commonly fat necrosis (44.1%) and chest wall asymmetry (28.8%). Complications were higher among women who received PMRT < 3 months after surgery (46.8% for < 3 months vs. 29.3% for ≥ 3 months; p = 0.06), most of whom received neoadjuvant chemotherapy, and among women treated with internal mammary nodal (IMN) radiation (65.2% vs. 26.4%; p < 0.01); IMN radiation remained strongly associated in multivariable analysis (odds ratio [OR] 5.24; p < 0.01). Thirty-two (24.6%) women underwent 70 reoperations, commonly fat grafting (51.9%) and fat necrosis excision (17.1%). Reoperations were higher among women who received PMRT < 3 months after surgery (48.9 for < 3 months vs. 36.6 for ≥ 3 months; p = 0.19), which was significantly associated in multivariable analysis (OR 0.42; p = 0.08 for ≥ 3 months). The probabilities of complications and reoperations were lowest when PMRT was administered ≥ 3 months after surgery. CONCLUSIONS: Among a large institutional cohort, immediate autologous reconstruction was associated with similar rates of adverse flap outcomes as historically reported alternatively sequenced protocols. IMN radiation increased risk, while PMRT ≥ 3 months after surgery decreased risk. Additional studies are needed to elaborate the impact of IMN radiation and early PMRT in immediate versus delayed autologous reconstruction.

Standard Tangential Radiation Fields Do Not Provide Incidental Coverage to the Internal Mammary Nodes.

PURPOSE: The purpose of the study was to evaluate the incidental dose delivered to the internal mammary nodes (IMNs) in patients treated with tangential 3-dimensional conformal radiation therapy and to identify potential parameters that may affect the IMN mean dose. METHODS AND MATERIALS: The study cohort consisted of 362 consecutively treated patients with breast cancer in our center between January 2015 and July 2017 who had received adjuvant whole-breast radiation therapy or postmastectomy radiation with or without a supraclavicular ± axillary field and without intentional inclusion of the IMN chain. The clinical target volume (CTV) for the IMNs was contoured per the Radiation Therapy Oncology Group 3509/3510 protocol and was then divided into 3 subregions: upper, mid, and lower thirds. The planning target volume for the IMNs was generated by adding 5 mm to the CTV. The primary endpoint was to assess the V40 (volume receiving 40 Gy) to the IMN planning target volume and its potential influencing parameters using a linear regression model. RESULTS: The mean (±standard deviation) dose to the CTV IMN chain was 36% ± 28.7%. The Kruskal-Wallis test demonstrated significant differences in the median dose delivered to each level: upper third (7.2%), mid third (21.5%), and lower third (41.7%) (P < .001). The mean V40 IMN planning target volume was 14.2% (standard deviation, 18.7%). Presternal fat thickness (regression coefficient [RC] = -16.4; P < .001), postmastectomy radiation (RC = 24; P < .001), reconstruction after mastectomy (RC = -22.4; P < .001), and the addition of a supraclavicular field (RC = 8.8; P = .03) were all significantly associated with IMN mean dose. CONCLUSIONS: For patients receiving standard breast/chest wall tangential radiation fields, the IMN chain is not incidentally covered with therapeutic doses in the vast majority of cases. Therefore, if regional nodal radiation is intended to include the IMNs, contouring and careful plan review are necessary to ensure adequate therapeutic coverage.

Three-dimensional Analysis of How Radiation Affects Deep Inferior Epigastric Perforator (DIEP) Flap Volume, Projection, and Position in Breast Cancer Reconstruction.

BACKGROUND: The deep inferior epigastric perforator (DIEP) flap has gained popularity for autologous free flap breast reconstruction. Historically, patients receiving post mastectomy radiation therapy (PMRT) were not candidates for immediate autologous reconstruction due to concerns for flap volume depletion, fat necrosis, and flap failure. However, this literature is anecdotal and lacks case controls. We objectively analyzed the effects radiation imparts on immediate DIEP flap reconstruction using 3-dimensional software and inherent controls. METHODS: We performed a cohort study on breast cancer patients who underwent immediate bilateral DIEP flap reconstructions followed by PMRT between 2005 and 2014. Exclusion criteria included patients less than 6 months from PMRT completion and bilateral PMRT. Three-dimensional photographs were analyzed using Geomagic (Rock Hill, SC) software to compare flap position, projection, and volume between the irradiated and nonirradiated reconstructed breasts. Breast Q survey evaluated patients' satisfaction. RESULTS: Eleven patients met inclusion criteria. Average time from PMRT completion to photo acquisition was 1.93 years. There was no statistical difference in average volume or projection in the irradiated versus nonirradiated side (P = 0.087 and P = 0.176, respectively). However, position of the irradiated flaps was significantly higher on the chest wall compared to controls (mean difference, 1.325 cm; P < 0.004). CONCLUSIONS: Three-dimensional analysis exhibited no statistical differences in projection or volume between irradiated DIEP flaps and nonirradiated controls. However, irradiated DIEP flaps were positioned higher on the chest wall, similar to observations in irradiated tissue expanders/implants. Patients were satisfied as measured by Breast Q. Immediate bilateral DIEP flap reconstructions can safely be performed with PMRT with satisfactory results.

Is Proton Therapy a "Pro" for Breast Cancer? A Comparison of Proton vs. Non-proton Radiotherapy Using the National Cancer Database.

Background: Limited data exists demonstrating the clinical benefit of proton radiotherapy (PRT) in breast cancer. Using the National Cancer Database, we evaluated predictors associated with PRT use for patients with breast cancer. An exploratory analysis also investigates the impact of PRT on overall survival (OS). Methods: Patients with non-metastatic breast cancer treated with adjuvant radiotherapy from 2004 to 2014 were identified. Patients were stratified based on receipt of PRT or non-PRT (i.e., photons ± electrons). A logistic regression model was used to determine predictors for PRT utilization. For OS, Multivariable analysis (MVA) was performed using Cox proportional hazard model. Results: A total of 724,492 patients were identified: 871 received PRT and 723,621 received non-PRT. 58.3% of the PRT patients were group stage 0-1. Median follow-up time was 62.2 months. On multivariate logistic analysis, the following factors were found to be significant for receipt of PRT (all p < 0.05): academic facility (odds ratio [OR] = 2.50), South (OR = 2.01) and West location (OR = 12.43), left-sided (OR = 1.21), ER-positive (OR = 1.59), and mastectomy (OR = 1.47); pT2-T4 disease predicted for decrease use (OR = 0.79). PRT was not associated with OS on MVA for all patients: Hazard Ratio: 0.85, p = 0.168. PRT remained not significant on MVA after stratifying for subsets likely associated with higher heart radiation doses, including: left-sided (p = 0.140), inner-quadrant (p = 0.173), mastectomy (p = 0.095), node positivity (p = 0.680), N2-N3 disease (p = 0.880), and lymph node irradiation (LNI) (p = 0.767). Conclusions: Receipt of PRT was associated with left-sided, ER+ tumors, mastectomy, South and West location, and academic facilities, but not higher group stages or LNI. PRT was not associated with OS, including in subsets likely at risk for higher heart doses. Further studies are required to determine non-OS benefits of PRT. In the interim, given the high cost of protons, only well-selected patients should receive PRT unless enrolled on a clinical trial.

Chest Wall Deformity in the Radiation Oncology Clinic.

BACKGROUND/AIM: To determine the incidence of pectus excavatum (PE) and define anatomical chest wall metrics predictive of elevated mean heart dose (MHD) in patients with left-sided breast cancer receiving adjuvant radiotherapy. PATIENTS AND METHODS: We reviewed 273 consecutively simulated patients from 1/2013-12/2014. Physical examination identified patients with clinically identifiable PE. Characteristics were compared between patients with and those without PE. Predictors of MHD were evaluated using linear regression. RESULTS: The average MHD for the entire cohort was 172 cGy. Of 273 patients, 10 (3.7%) were found to have clinically significant PE. Increase in the Haller Index was correlated with higher MHD (p<0.001). Through the use of individually optimized patient positioning and respiratory gating, MHD was not statistically different in patients with PE compared to those without (p=0.093). CONCLUSION: Although PE deformity is associated with unfavorable geometry in patients undergoing left-sided breast irradiation, carefully selected treatment technique can maintain acceptable MHD.

Treatment of early stage vaginal cancer with EBRT and MRI-based intracavitary brachytherapy: A retrospective case review.

This case series describes the use of pelvic radiotherapy (RT) and MRI-based intracavitary brachytherapy (ICBT) for patients with small volume, early-stage, primary vaginal cancer. A customized pelvic MRI protocol with a vaginal cylinder in place (MRVC) was used to measure disease extent and tumor thickness (defined as distance from lateral/apical margin of tumor to cylinder surface) at time of diagnosis. Non-bulky tumors with initial (pre-RT) thickness ≤ 2 cm from the cylinder surface received pelvic RT followed by ICBT. Ten patients with FIGO stage I-II primary vaginal cancer treated with pelvic RT +/- cisplatin and ICBT at our institution between 1998 and 2008 were included. Initial tumor thickness measured on MRVC ranged from 0 to 2 cm. Initial tumor volume ranged from 0 to 9.8 cm(3). Mean pelvic RT dose was 45 Gy. At the time of ICBT, 60% of patients had a complete response (cR) and 40% had a partial response (pR). No patients with a cR had a recurrence whereas one patient with a pR had a local recurrence following ICBT. For the entire cohort, the median follow-up time was 59.9 months (range: 15-153). The estimated 5-year overall survival, disease-specific survival, and local failure-free survival were 67%, 80%, and 90%, respectively. Among survivors, there were no late grade 3-4 toxicities. In this series of patients with small primary early-stage vaginal tumors, long term clinical outcomes were acceptable following RT and MRI-based ICBT, especially among those with a cR at time of brachytherapy.

Basal Cell Skin Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.

High-dose-rate vaginal brachytherapy with chemotherapy for surgically staged localized uterine serous carcinoma.

PURPOSE: To evaluate our institutional experience combining carboplatin-paclitaxel (C/T) chemotherapy with high-dose-rate (HDR) intra-vaginal brachytherapy (IVB) following comprehensive surgical staging in localized uterine serous carcinoma (USC). MATERIAL AND METHODS: Institutional chart review identified 56 patients with FIGO 2009 stage I-II USC treated between 2000-2010. Patients underwent total hysterectomy, bilateral salpingo-oopherectomy, and comprehensive surgical staging including pelvic and para-aortic lymph node dissection, omentectomy, and peritoneal cytology. Chemotherapy was 6 cycles of C/T, and the IVB dose was 14 Gy in 2 fractions, prescribed to 0.5 cm from the cylinder surface. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: The median follow-up time was 49 months (range: 9-145). The 5-yr RFS and OS were 85% and 93%, respectively. In all cases of recurrence (n = 8), the first site of failure was extra-pelvic. There were no isolated vaginal recurrences, however, there was one vaginal apex recurrence recorded at 19 months in a patient with simultaneous lung metastases. Thus, the 2-year vaginal RFS was 98%. CONCLUSIONS: Excellent vaginal/pelvic control rates were observed. Further study of HDR brachytherapy dose and fractionation in combination with chemotherapy is worthwhile.

Predictors of vaginal stenosis after intravaginal high-dose-rate brachytherapy for endometrial carcinoma.

PURPOSE: Intravaginal high-dose-rate brachytherapy is an effective adjuvant treatment for localized endometrial carcinoma. However, relatively little is known about risk factors of post-treatment vaginal stenosis (VS). METHODS AND MATERIALS: We included patients treated with brachytherapy for endometrial carcinoma from September 2011 to January 2014 with at least 3 months of followup. Patients who received external beam radiation therapy were excluded. VS was prospectively graded at each followup visit per Common Terminology Criteria for Adverse Events, version 4.03. χ(2) and t test analyses were used to assess the association of VS with various patient, tumor, treatment, and post-treatment factors. Multivariable logistic regression analysis was used to identify independent predictors of VS Grade ≥1 and ≥2. RESULTS: All 101 patients were disease free at last followup. Mean followup was 12.9 months (range, 3-34). Highest VS grades were zero in 67%, one in 26%, two in 6%, and three in 1%. Borderline significant variables associated with Grade ≥1 VS included vagina length, proportion of vagina treated, and total dose. Dilator use was significantly associated with Grade ≥2. Multivariable analysis revealed that proportion of vagina treated >60% (odds ratio [OR], 3.48; p = 0.009) and total dose >14 Gy (OR, 4.27; p = 0.015) were independent predictors of Grade ≥1 VS, and lack of consistent dilator use was an independent predictor of Grade ≥2 VS (OR, 5.60; p = 0.047). CONCLUSIONS: Patients treated with a higher total dose to a larger proportion of the vagina were more likely to develop Grade ≥1 VS. Consistent dilator use may also be protective against Grade ≥2 VS.

Adjuvant carboplatin, paclitaxel, and vaginal cuff brachytherapy for stage III endometrial cancer: analysis of outcomes and patterns of recurrence based on pathologic characteristics.

OBJECTIVE: The aim of this study was to evaluate outcomes of patients with stage III endometrial adenocarcinoma treated with surgery followed by adjuvant chemotherapy and vaginal cuff brachytherapy. METHODS: We retrospectively identified 83 patients treated for 1988 International Federation of Gynecology and Obstetrics (FIGO) stage III endometrial adenocarcinoma at our institution between 2003 and 2010. All patients underwent comprehensive surgical staging. Adjuvant therapy was carboplatin and paclitaxel for 6 cycles and vaginal cuff brachytherapy. For analysis, patients were grouped into type I (FIGO grade 1-2 endometrioid histology, n = 41) or type II (FIGO grade 3, clear cell or papillary serous histology, n = 42) disease. Forty-three patients (52%) had node-positive disease, with similar node-positive rates for type I (n = 21, 51.2%) and type II (n = 22, 52.4%). RESULTS: The median follow-up was 38.6 months. There were no isolated vaginal failures. The estimated 3-year disease-free survival (DFS) and overall survival (OS) for type I versus type II were 92.4% versus 58.0% (P = 0.001) and 97.2% versus 65.8% (P = 0.002), respectively. The 3-year DFS and OS for node negative versus node positive were 85.0% versus 63.6% (P = 0.02) and 84.2% versus 78.0% (P = 0.02), respectively. Associations between type I histology and node-negative disease with improved DFS and OS persisted on multivariate analysis. CONCLUSIONS: Our institutional approach of adjuvant chemotherapy and vaginal cuff brachytherapy for stage III endometrial cancer seemed acceptable for patients with low-risk histology or node-negative disease. In contrast, higher rates of failure among those with high-risk histology and/or node-positive disease support intensification of therapy in these subsets.

Phase I clinical trial of the mammalian target of rapamycin inhibitor everolimus in combination with oral topotecan for recurrent and advanced endometrial cancer.

OBJECTIVES: Preclinical data suggest that mammalian target of rapamycin inhibitors may potentiate the efficacy of topotecan. We evaluated the optimal schedule of oral topotecan in combination with everolimus in patients with endometrial cancer. METHODS: Women with a history of advanced or recurrent endometrial cancer were enrolled. Escalating dose of oral topotecan (1.5 mg/m, 1.9 mg/m, and 2.3 mg/m) daily on days 1 to 5 and everolimus (5 mg every other day, 5 mg daily, and 10 mg daily) were administered in a 21-day cycle. A "run-in" treatment of topotecan daily for 5 days followed by everolimus for 7 days (4-7 doses depending on dose level) was administered for the purpose of pharmacokinetic assessments. RESULTS: Ten patients were enrolled on the study, and 9 were evaluable for safety analysis. A total of 28 cycles were administered (range, 1-10 cycles per patient). The patients had a median age of 73 years (range, 42-79 years). Previous lines of chemotherapy were 1 (n = 2), 2 (n = 5), 3 (n = 2), and 4 (n = 1). Seven patients had previous vaginal brachytherapy, and 2 had pelvic external beam radiation therapy. The median number of cycles (including cycle 1) is 2 (range, 1-10). Dose-limiting toxicity occurred in 3 patients (1 patient treated with 1.9-mg/m topotecan and 5-mg everolimus given every other day as well as 2 patients treated with 1.9-mg/m topotecan and 5-mg of everolimus daily) and included neutropenia and thrombocytopenia. Seven patients were evaluable for response. Stable disease was the best response in 3 patients who completed the 3, 4, and 10 cycles each. CONCLUSIONS: The dose-limiting toxicity for the combination of oral topotecan and everolimus was myelosuppression. The maximum tolerated dose was topotecan 1.9 mg/m on days 1 to 5 in combination with oral everolimus 5 mg every other day. Administration of higher dose of each agent in combination was limited because of overlapping myelosuppression.

Breast conservation therapy for ductal carcinoma in situ (DCIS): does presentation of disease affect long-term outcomes?

BACKGROUND: For DCIS patients eligible for breast conservation treatment (BCT), it remains unclear whether presenting with physical signs/symptoms (Phys) confers a worse long-term prognosis compared to mammographically detected DCIS (Mam). METHODS: We collected data on 669 DCIS patients treated with BCT from 1974 to 2007 of whom 80 were identified as category "Phys" and 589 were in category "Mam." RESULTS: Treatment parameters (i.e., the RT dose delivered, boost, rates of stereotactic biopsy, re-excision, node dissection) did not differ significantly between the two cohorts (p = NS). At a 60-month median follow-up, significant associations included younger age at presentation (p < 0.001), non-white race (p = 0.041), larger tumor size (p = 0.002), more 1°/2° papillary histology (1°, p = 0.001; 2°, p = 0.005) for the Phys cohort. As expected, mammograms were more likely to show mass/nodules/asymmetrical densities and less likely to show microcalcifications for the Phys versus Mam group (p < 0.0001). There were no differences in family history, multifocality, grade, necrosis, or residual disease at re-excision, nodal involvement, status of margins, or ER/PR/HER-2 between the cohorts. The local relapse-free survival was similar at 5 years (100 vs. 96.9 %, p = 0.116) and 10 years (96.2 vs. 96.2 %, p = 0.906), with no significant overall survival difference at 10 years (97.5 vs. 95.9 %, p = 0.364) between the Phys and Mam patients, respectively. On multivariate analysis, presentation was not an independent predictor of local relapse-free survival or overall survival when accounting for age, race, tumor size, mammogram appearance, and adjuvant hormone treatment. CONCLUSIONS: Our findings suggest that although some clinicopathological differences exist between DCIS patients presenting with physical signs/symptoms compared with those presenting with mammographically detected disease, long-term outcomes are similar for patients appropriately selected for BCT.

Radiation therapy and expander-implant breast reconstruction: an analysis of timing and comparison of complications.

BACKGROUND: The optimal timing of expander-implant exchange in the setting of postmastectomy radiation therapy (PMRT) remains unclear with prior reports yielding inconsistent and variable results. The purpose of this study was to characterize complications associated with the sequencing of expander-implant breast reconstruction before or after PMRT and to compare the outcomes between early (<4 months) and late (>4 months) expander-implant exchange in the subset of patients who received PMRT before exchange. MATERIALS AND METHODS: The medical records of all patients PMRT in the setting of tissue expander-implant breast reconstruction between June 2004 and June 2011 at our institution were reviewed retrospectively. Patients were first classified as having undergone expander-implant exchange before the initiation of PMRT or after the completion of PMRT. Patients who underwent expander-implant exchange after PMRT were then classified as having undergone exchange early (<4 months after PMRT) or late (>4 months after PMRT). All complications requiring additional surgery or hospitalization were recorded. RESULTS: Fifty-five eligible patients were identified as having undergone 56 two-stage tissue expander-implant breast reconstructions. Twenty-two reconstructions underwent exchange before PMRT and 34 reconstructions underwent exchange after PMRT. There was no significant difference in overall complication rate (54.55% vs 47.06%, P = 0.785) or reconstruction failure rate (13.64% vs 20.59%, P = 0.724) between the 2 cohorts. Twenty reconstructions underwent exchange less than 4 months after PMRT and 14 underwent exchange more than 4 months after PMRT. There was no significant difference in overall complication rate (40% vs 57.14%, P = 0.487) or failure rate (25% vs 14.29%, P = 0.672) between the 2 groups. Trends suggest a higher rate of infection in patients who underwent exchange earlier (30% vs 14.29%, P = 0.422) and a higher rate of capsular contracture in patients who underwent exchange later (5% vs 21.43%, P = 0.283); however, statistical significance was not reached. CONCLUSIONS: Our findings suggest that neither the sequencing nor timing of expander-implant exchange in the setting of PMRT affects overall complication or reconstruction failure rate. However, the timing of exchange may impact the type of complication encountered. Further investigation is necessary to determine an optimal time for expander-implant exchange.

Roundtable--the changing oncology landscape: evolution or revolution?

Complex challenges face all players in the oncology landscape, from health care policy leaders and third-party payers, to practicing physicians and nurses, to patients and their families. In these unsteady economic times, possible answers proposed by some may represent part of the problem to others. A distinguished panel assembled at the NCCN 18th Annual Conference: Advancing the Standard of Cancer Care to explore the changing oncology landscape. This article is the synopsis of that discussion, with panelists shedding light on such issues as the astronomic cost of medical care, the need for clinicians to think outside the formulary, and the therapeutic decision-making process in the new world of "big data."

Analysis of coronary artery dosimetry in the 3-dimensional era: Implications for organ-at-risk segmentation and dose tolerances in left-sided tangential breast radiation.

PURPOSE: To evaluate the dose to the left anterior descending artery in patients receiving left-sided tangential breast radiation. METHODS AND MATERIALS: The study cohort consisted of 50 left-sided breast cancer patients who were sequentially simulated at our institution. The heart and left anterior descending (LAD) artery were contoured from its origin on the left main coronary artery down to the last visible segment of the vessel. Detailed dosimetry of the heart and LAD artery were obtained and analyzed. RESULTS: Excellent correlation between the dose to the heart and LAD artery was discovered. The mean LAD dose was 17.98 Gy. The mean dose to the proximal LAD was 2.46 Gy. The median V25 was 2.91% and the mean heart dose 3.10 Gy. For every 100 cGy increase in mean heart dose, mean LAD dose increased by 4.82 Gy. For every percent increase in the heart V10 and V25, there was a 2.23 Gy and 2.77 Gy increase in mean LAD dose, respectively. For every percent increase of heart V25, a 5.6% increase in the LAD V20 was demonstrated. CONCLUSIONS: The LAD artery dose correlates very closely with all of the commonly measured heart dose constraints, and does not need to be contoured separately when standard tangential borders are used. Incidental LAD artery doses remain with supine breast tangential radiation therapy.