bluuebunny/crossref_metadata_2025 huggingface dataset:
Nomogram for predicting development of brain metastasis in patients with inflammatory breast cancer.
Authors: Raghav K. P. S. , Bekele B. N. , Valero V. , Matrana M. R. , Ibrahim N. K.
Published: February 2017

243

Background: Inflammatory breast cancer (IBC) is associated with poor prognosis and high rates of distant metastasis. Brain metastasis is particularly important due to its morbidity and mortality. The purpose of this study was to construct a nomogram from clinicopathological factors that could predict the risk of occurrence of brain metastasis in patients with IBC.

Methods: We performed a retrospective analysis of 406 patients with IBC, who were seen at the University of Texas M. D. Anderson Cancer Center between 1991 and 2009. Data was collected from IBC registry. Patients were divided in a randomized manner into a training cohort (n = 206) and a validation (n = 200) cohort. A multivariate cox proportional hazards regression analysis of selected prognostic features was performed on the training cohort. The model estimated in the training cohort was cross-validated with the validation cohort. Based on this model a nomogram was constructed to assess 5- and 10-year risk of developing brain metastasis.

Results: A total of 115 (28%) patients developed brain metastasis. Univariate analysis identified menopausal status, progesterone receptor expression, number of distant metastasis, adjuvant taxane-based therapy and age at diagnosis as significant factors associated with brain metastasis (p < 0.05). Subsequent multivariate analysis showed menopausal status and number of metastasis were independently associated with development of brain metastasis (p < 0.05). Nomogram constructed using above model was evaluated for its ability to discriminate among likelihood of occurrence of brain metastasis in patients, using the validation set. The validation set showed good discrimination with the area under the receiver operating characteristic curve of 0.68.

Conclusions: We have formulated a distinct predictive tool to evaluate 5 and 10-year risk for developing brain metastasis in patients with IBC. This nomogram can be potentially helpful for designing risk adapted therapeutic trials. Identifying patients at high risk for brain metastasis in IBC can help personalize therapy, surveillance, and prognostication.

[Table: see text]
The effect of aerobic exercise on the metabolic risk profile of breast cancer survivors 2-6 months post chemotherapy.
Authors: Guinan E. M. , Hussey J. M. , Walsh J. M. , Kennedy M. J. , Connolly E. M.
Published: February 2017

244

Background: Current literature suggests that weight gain during treatment for breast cancer is associated with a poorer prognosis and an increased risk of developing secondary health problems such as the metabolic syndrome (MetSyn). Physical activity (PA) can alter features of the MetSyn and improve body composition by reducing abdominal adiposity. We report metabolic results of a prospective randomized controlled trial (PEACH trial; Walsh JM, et al. [2010] BMC Cancer. 10[42]) which examines the effect of an exercise intervention on the metabolic risk profile of breast cancer survivors 2-6 months post chemotherapy.

Methods: All subjects gave written informed consent and were randomized to an 8-week, twice weekly aerobic exercise intervention programme or a usual care control group consisting of routine medical advice about PA. The five clinical features of the MetSyn were measured: waist circumference (WC), resting blood pressure (BP), triglycerides, high-density lipoprotein cholesterol (HDL-C) and fasting glucose. Insulin resistance was estimated by the homeostatic model assessment (HOMA). Statistical analysis was carried out using independent sample t-tests with significance set at p < 0.05.

Results: Twenty-six breast cancer survivors participated (mean (± SD) age 48.13 (8.75) years). At baseline, 50% (n = 13) of subjects were overweight and 23.1% (n = 6) were obese, with 73.1% (n = 19) centrally obese. 34.6% (n = 9) of subjects were classified with the MetSyn. There were no significant differences between groups at baseline. Intention-to-treat analysis showed no significant changes, however, analysis of those who adhered to > 70% of the supervised exercise intervention showed a significant improvement in WC when compared to the control group (p < 0.05).

Conclusions: Results show that an 8-week aerobic exercise intervention significantly reduced WC but did not modify other features of the MetSyn. The decrease in WC demonstrated by this short intervention may have important implications in terms of improving survival and the metabolic risk profile of breast cancer survivors. Final follow-up assessments are ongoing and will enable change in WC over time to be evaluated further.
Nitric oxide-releasing nanoparticle combination therapy to overcome drug resistance in platinum-resistant breast cancers.
Authors: Forrest M. L. , Cai S. , Duan S. , Cohen M. S. , Yang Q.
Published: February 2017

278

Background: The most successful cancer chemotherapy regimens usually involve the administration of multiple cytotoxic agents simultaneously. Because different chemotherapies may have different mechanisms of action; it is difficult for cancer cells to become resistant to combination therapy. Recent investigations have discovered that nitric oxide (NO) may be involved in the reversal of cisplatin (CDDP) resistance in chemotherapy. Therefore, we sought to develop a combination regimen involving a NO-releasing prodrug (NO1) and cisplatin for the treatment of breast cancer.

Methods: The prodrug NO1 was synthesized to be localized in tumor cells and to release nitric oxide over 10 hours. The antiproliferative activity of NO1 was determined in human breast cancer cell line, MDA-MB-468LN. To evaluate the effectiveness of the CDDP/NO combination regimen, platinum-resistant MDA-MB-468LN cells were treated with either cisplatin alone ([CDDP]=0.01, 0.02 or 0.03 mM) or the CDDP/NO combination ([CDDP]=0.01, 0.02 or 0.03 mM; [NO1]=0.02 mM). The cell viability was determined 48 hours post-treatment using a live/dead trypan blue exclusion assay.

Results: The toxicity to breast cancer cells was higher than JS-K, a systemic NO agent currently in preclinical development. (NO1: IC50=26µM; JS-K: IC50=42 µM). In addition, NO1 had a long sustained release of nitric oxide, approximately one fold longer than JS-K (NO1: t1/2=6 h; JS-K: t1/2=3 h). The combination treatments resulted in 6.6-, 6.9- and 7.5-fold increase in cell death compared to cisplatin treatment alone at cisplatin concentrations of 0.01, 0.02 and 0.03 mM, respectively. A subsequent study in a murine xenograft of head and neck cancer found NO-1 conjugated to nanoparticles increased survival a mean of 10 weeks compared to controls (p<0.0001).

Conclusions: Nitric oxide prodrug NO-1 and nanoparticles of it have high anticancer activity in vivo and they can reverse platinum resistance in vitro. Ongoing studies are examining the safety and efficacy of CDDP/NO combination therapy in mouse xenografts of human breast cancer.
Evaluation of complete pathologic response and histologic toxicity using a subcutaneous delivery system with combination nanoconjugated doxorubicin and cisplatin for locally advanced breast cancer in vivo.
Authors: Cohen S. M. , Mukerji R. , Cai S. , Damjanov I. , Forrest M. L. , Cohen M. S.
Published: February 2017

279

Background: Systemic doxorubicin (DOX) and platinum agents in breast cancer can be limited by their toxicity and have low penetration into lymphatics contributing to locoregional (LR) recurrence. Subcutaneous (s.c.) delivery of single agent nanoconjugated (HA-DOX) or cisplatin (HA-CIS) can significantly boost LR drug delivery with lower toxicity in vivo. The purpose of this study is to evaluate histologic response and toxicity of combination s.c. delivery of HA-DOX/HA-CIS as a significant improvement over IV delivery with standard drugs reduces dose levels and expands the therapeutic dosing range for these drugs.

Methods: 1.5x106 MDA-MB-468LN human breast cancer cells (metastatic line) were injected into the mammary fat pad of female Nu/Nu mice. When tumors reached 6mm, mice (n=8 per group) were then treated with standard DOX/CIS IV combination therapy or s.c. injections of HA-DOX/HA-CIS at 25%,50%,75%,100%,125%, and 150% MTD for these drugs. Drugs were dosed weekly x 3 wks and tissues were collected for histology at 4 and 12wk timepoints.

Results: Only the nanoconjugate groups demonstrated a complete clinical response (CR) to therapy and a complete pathologic response (CPR) histologically [CR =62.5% of mice and CPR=12.5% at 50% MTD;CR=87.5% and CPR=25% at 75%MTD; p<0.0001 vs. IV groups which had no CRs and some partial responses (12.5% at 50%MTD and 25% at 75%MTD)]. HA groups had no lymphatic or bony metastases while 1 animal (12.5%) in the IV 50% MTD group had spinal metastases (p<0.01). Mild cardiac and renal toxicity was noted in the 25% and 50% MTD IV groups respectively while no cardiac or renal toxicity was observed in the HA groups (p<0.01). Finally HA conjugation increased the therapeutic dose range of DOX and CIS up to 150% of standard formulation MTD.

Conclusions: Subcutaneous nanocarrier-delivery of combination DOX/CIS demonstrated significantly improved tumor response with CPR and lower toxicity on histology compared to standard drugs. This delivery platform successfully treats LR and distant metastatic disease at lower doses and improves the dosing range of these drugs compared to standard agents.
Management of early-stage breast cancer: Are we headed in the right direction?
Authors: Zurawska U. , Baribeau D. A. , Victor C. , Giilck S. , Florescu A. , Gandhi S. , Verma S.
Published: February 2017

284

Background: The understanding of breast cancer (BC) as a heterogeneous disease consisting of distinct subtypes based on variation in expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) has led to more personalized treatment. We postulated that with increased adoption of chemotherapy and targeted therapy for HER2 positive patients, the outcomes of ER/PR+, HER2- and of HER2+ subtypes of breast cancer would be similar.

Methods: A chart review was performed of female patients >18 years old seen by a medical oncologist at an academic cancer centre in Toronto, Canada, between January 1, 2005 and December 31, 2006, for stage I-III invasive breast cancer. Clinical features, 5-year overall (OS) and relapse-free survival (RFS) of three BC subtypes were compared: ER/PR+, HER2- (hormone receptor positive, HR), HER2+ (HER2), and ER/PR-, HER2- (triple negative, TN).

Results: Of 870 patient charts reviewed, 525 were analysed. There were 341 HR, 101 HER2 and 83 TN patients. TN patients were younger (p<0.001), and had higher stage (p<0.001) and higher histological grade tumors (p<0.001). The 5-year RFS and OS were: HR: 88.2% and 96.6%, HER2: 76.7% and 92%, TN: 79.8% and 83.9%. Chemotherapy was used in 41.1%, 84.2% and 83.1% of HR, HER2 and TN patients. Anthracycline plus taxane regimens were used in 48.6%, 52.9% and 68.1% of HR, HER2 and TN patients, respectively. Among HER2 patients, only 74.3% received trastuzumab. The 5-year RFS and OS for HER2 patients who received trastuzumab were 79.9% and 91.8%, and for those who did not: 69% and 91.6%.

Conclusions: HR+ patients have an excellent outcome. Despite significant improvement in outcomes of HER2+ patients with early stage breast cancer, they still remain at higher risk of recurrence along with TN patients. Trastuzumab was underutilized among HER2+ patients in this cohort, which may have contributed to decreased 5 year RFS. Ongoing prospective follow up of early BC outcomes by breast cancer subtypes is important.
Capecitabine in operable triple receptor–negative breast cancer: A subgroup analysis of a randomized phase III trial.
Authors: Kelly C. M. , Green M. C. , Broglio K. , Pusztai L. , Thomas E. , Brewster A. , Valero V. , Ibrahim N. K. , Gonzalez-Angulo A. M. , Booser D. J. , Hunt K. , Hortobagyi G. N. , Buzdar A.
Published: February 2017

292

Background: Recent data suggest that patients with operable triple negative breast cancer (TNBC) may derive greater benefit from the addition of capecitabine to anthracycline-taxane regimens.

Methods: We examined pathological complete response (pCR), relapse-free survival (RFS) and overall survival (OS) in patients with TNBC randomized to paclitaxel 80mg/m2 weekly (WP) x 12 followed by fluorouracil (500mg/m2), epirubicin (100mg/m2), cyclophosphamide (500mg/m2) every 3 weeks x 4 cycles (FEC) vs. docetaxel (75mg/m2) 3 weekly and capecitabine D1-14 (1500mg/m2 daily; DX) followed by FEC. Patients were stratified by timing of chemotherapy (preoperative vs. adjuvant).

Results: 149 patients with TNBC comprising 25% of all patients randomized (N=601). Median age; 49 years (IQR; 41 to 55). The number and proportion of patients by stage were; I (n=32: 21.5%), IIA (n=72: 48.3%), IIB (n=34: 22.8%), IIIA (n=9: 6.0%) and IIIC (n=2; 1.3%). Preoperative therapy was administered to 58 patients (39%) and adjuvant to 91 (61%). There were 17 events (21%) in the DX arm and 10 events (15%) in the WP arm (P=0.36) including 11 distant recurrences in the DX arm and 9 in the WP arm (P=0.99). We observed a pCR in 11 patients (37%) and 10 (36%) in the DX and WP arms respectively (P=0.94). The odds ratio for pCR for patients with TNBC given DX vs. WP was 0.98 (95% CI; 0.33 to 2.80: P=0.94). At 50-months median follow-up the RFS and OS in patients with TNBC randomized to DX or WP was 77% (66 to 86%) and 83% (73 to 92%) (P=0.41) and 78% (67 to 87%) and 87% (77 to 95%) (P=0.16) respectively. RFS and OS for WP vs. DX for non-TNBC was 93% (87 to 95%) and 92% (88 to 96%) (p=0.91) and 96% (92 to 98%) and 97% (94 to 99%) for WP and DX respectively (P=0.39).

Conclusions: In this unplanned subgroup analysis there was no difference in pCR, RFS or OS in patients with operable TNBC randomized to WP or DX however, power is limited and should be considered when interpreting these data.
Does Oncotype DX recurrence score correlate with survival benefit in “good prognosis” patients as estimated by AdjuvantOnline!?
Authors: Connell L. C. , Teo M. , O'Reilly S. , Beamish R. , Moylan E. J.
Published: February 2017

38

Background: An important question for ER positive, node negative breast cancer is the benefit of chemotherapy over hormonal therapy. We sought to explore if a low estimate of chemotherapy benefit, based on AdjuvantOnline, correlated with low risk Oncotype DX score , identifying patients (pts) for whom the “hormone therapy alone” treatment decision would not change.

Methods: Our institutional database was reviewed to identify pts with ER positive, HER2 negative, node negative breast cancer submitted for oncotype DX testing. Clinicopathologic data and Oncotype Recurrence Score (RS) were extracted and entered into ‘Adjuvantonline’ to obtain estimated survival benefit gained at 10 years (yrs) (SBG@10). Two datasets were obtained; survival benefit gained at 10 yrs from chemotherapy only (SBG@10+C) and net survival benefit gained at 10 yrs: the absolute difference between combined therapy and hormone therapy (SBG@10 net). Pts were distributed into subgroups SBG@10 ≤3% and >3%. i.e. RS ≤18 versus >18.Correlation between SBG and RS were calculated with Spearman’s Rank method. Distribution of RS were compared with Mann-Whitney and Χ2 tests.

Results: We identified 77 pts. For SBG@10+C ≤3% (n=28) and >3% (n=49) subgroups, 16 (57.1%) and 23 (46.7%) had low RS, respectively (p=0.53). Three (10.7%) and 10 (20.4%) in each subgroup had high RS (p=0.48). Distribution of RS between both subgroups was not significantly different, p=0.38. Correlation between RS and SBG@10 in the ≤3% subgroup was weak (rs=0.37, p=0.05). For SBG@10 net ≤3% (n=45) and >3% (n=32) subgroups, 25 (55.6%) and 14 (43.8%) had low RS, respectively (p=0.43). Five (11.1%) and 8 (25%) in each subgroup had high RS (p=0.20). Distribution of RS between both subgroups was not significantly different, p=0.19. Correlation between RS and SGB@10 in the ≤3% subgroup was weak (rs=0.21, p=0.15).

Conclusions: Although the decision for additional chemotherapy changed for ≈10% with Oncotype DX, we could not identify a cohort of good prognosis pts for whom Oncotype DX would not significantly alter treatment recommendations. There are no subsets of node negative, ER positive, breast cancer for whom Oncotype DX does not provide independently significant prognostic and predictive information.
Automatic breast CAD results for seven categories of abnormalities.
Authors: Brockway J. P. , Carruthers W. B. , Zapata M. , Reiling R. B.
Published: February 2017

5

Background: This prospective study was conducted to determine efficacy of preclinical use of automatic computer-aided cancer detection (CAD) system. Patients were women of high risk referred for MRI of breast with goals of assessing sensitivity/specificity of an automatic CAD platform which used kinetic and morphological (spiculation, volume, solidity, surface area, elongation, maximum extent) tools. We assessed classification of abnormality using histopathology as our gold standard.

Methods: 1,976 patients with 2,149 abnormalities included were scanned from 2007 to 2010. Patient inclusion criteria were women: with dense breasts; BRCA1 or BRCA2 genes; family history of cancer; suspected of having recurrent cancer; anomalous mammogram/ultrasound; pain; or clinical suspicion. All patients included gave institutionally IRB approved HIPAA compliant informed consent. CAD software post-processing was automatically applied to dynamic contrast-enhanced MRI (DCE-MRI). One pre- and 4 post-scan series were used to calculate wash-in/out parameters. System's automatic detection was applied to entire breast(s) volume. No manually placed regions of interest were used.

Results: Of 1,976 women scanned, 361 had mastectomies, 17 had bilateral mastectomies, 488 had lumpectomies/excisional biopsies, 623 had core biopsies, 166 had non-surgical approaches; radiation or chemotherapy. Mean tumor resected was 2.95 cm; SD=2.88 cm, while CAD detected breast tumor calculated size was 3.20 cm; SD=2.66 cm.

Conclusions: Automatic CAD applied to breast DCE-MRI demonstrated high sensitivity, reasonable specificity, and accurate estimates for location within breast, and volume of malignancy. Automatic 3D CAD translucent display will aid oncology planners in tumor localization, volume and extent estimations.

[Table: see text]
Trastuzumab use and survival in HER2 (+) nonmetastatic breast cancer among Turkish women.
Authors: Kayahan M. , Kadioglu H. , Muslumanoglu M. , Igci A. , Ozmen V. , Idiz O. , Eralp Y. , Tuzlali S.
Published: February 2017

56

Background: HER2 overexpression observed in 10-25% of breast cancers is associated with rapid proliferation. HER2-targeted trastuzumab has been used in metastatic breast cancer, and since 2004 in early breast cancer. However, trastuzumab therapy is expensive and long lasting resulting sometimes in cardiac side effects. In this study we tried to find out whether there was a subgroup of early breast cancer patients trastuzumab could be omitted.

Methods: Records of patients treated for HER2-positive breast cancer in Istanbul Medical School between Jan 2000 and Sept 2009 were retrospectively evaluated. Disease-free survival (DFS) and overall survival (OS) were calculated either from follow-ups, or by calling. Kaplan meier and LogRank tests have been used for comparison (P<0.05, 95% CI).

Results: Follow up period was 32.2±14.9mo for trastuzumab group (TG, n:87) compared to 47.4±20.8mo for non-trastuzumab group (NTG, n:63) (P=0.0001). Groups were similar for age, menopausal status, size (T), histological grade and type, location, hormone responsiveness, presence of lymphovascular invasion, surgery, and use of local/systemic/hormonal therapy. NTG had more N0 cases (44.4% vs. 12.6%, P=0.0001), breast related deaths (15.9% vs. 5.7%, P=.042) and systemic metastases (27% vs. 13.8%, P=.043). Number of local recurrences was similar. Mean DFS and OS were significantly less in TG (P<0.0001). However differences between DFS and OS of groups were not significant despite a considerable increase for both in TG at fifth year (P=0.147, P=0.450). No difference in DFS and OS between TG and NTG was observed when patients who had chemotherapy and/or radiotherapy and/or hormonotherapy were compared to those who did not. OS was not different between TG and NTG for T1, T2, and T3 tumors and for patients ≤35y. But in N2 and N3 tumors, use of trastuzumab increased OS significantly (P=0.007).

Conclusions: Both number of events and systemic relapses were less in TG but we could not find a significant difference in DFS and OS between TG and NTG in Turkish nonmetastatic cancers. Prolonged follow up might be necessary to search for the subgroup who would not benefit, if any, as an incremental benefit in both DFS and OS was observed with trastuzumab use at fifth year.
Results of Oncotype DX in early-stage invasive lobular carcinoma.
Authors: Deneve J. L. , Joh J. E. , Acs G. , Soliman H. H. , Khakpour N. , Laronga C. , Lee M. C. , Kiluk J.
Published: February 2017

59

Background: The Oncotype DX (ODX) genomic assay has been used since 2004 to estimate prognosis and guide adjuvant treatment in patients with estrogen receptor-positive, node-negative invasive breast tumors. However, the impact of ODX assay testing in patients with invasive lobular carcinoma (ILC) has not been specifically reported. We describe our experience in patients with ILC who underwent ODX assay testing and how this affected adjuvant treatment.

Methods: An IRB approved retrospective review was performed on all patients undergoing treatment for early stage, node-negative ILC from 2006-2011. All cases were reviewed by a single pathologist (GA) for verification of histology and subtype. The impact of ODX assay testing on treatment management was evaluated.

Results: Thirty-nine patients underwent ODX genomic assay testing of early stage, node-negative ILC with a median age of 62 years. ILC tumor classification included classic (67%), pleomorphic (23%) and mixed (10%) subtypes with a median tumor size of 2.0 cm (0.6-6.0). Ninety-seven percent of tumors were estrogen receptor-positive, 74% progesterone receptor-positive. Median ODX recurrence score was 15 (0-34) with an ODX 10-yr risk of 10% (3-23). ODX risk classification was: Low (N=26), Intermediate (N=12), and High (N=1). There was no difference in ODX recurrence score or risk classification between ILC subtypes (p=0.52 and p=0.35, respectively). Adjuvant chemotherapy was used in 26% (TC N=8, AC N=1, FEC 100 N=1). Tumor size or ILC tumor subtype were not significant for adjuvant chemotherapy use while tumor grade (p=0.046), ODX recurrence score (22.8 vs 13.6, p<0.0001), ODX risk classification (p=0.009) and ODX 10 year risk (15.9 vs 9.0, p<0.0001) were significant. With a median follow up of 16.5 months, there were no recurrences or tumor-related deaths.

Conclusions: ODX testing on early stage node-negative ILC may serve as a useful adjunct when counseling patients on the decision for adjuvant therapy. The long-term impact on recurrence or survival in patients with ILC who receive adjuvant chemotherapy based on ODX recurrence score remains undetermined and warrants further testing.
Characteristics of multifocal and multicentric breast cancers detetected by preoperative MRI.
Authors: Killelea B. K. , Grube B. J. , Philpotts L. , Sowden M. , Horowitz N. , Lannin D. R.
Published: February 2017

67

Background: Many newly diagnosed breast cancer patients undergo preoperative MRI to define the extent of their disease, as well as to evaluate the contralateral breast. The purpose of this study was to determine the number of patients who were diagnosed with a second malignancy detected solely on MRI at our institution, to compare them to a control group of patients who had an MRI not leading to a diagnosis of cancer, and to compare tumor characteristics of the primary and secondary tumors.

Methods: A breast center database was searched for all newly diagnosed breast cancer patients who underwent preoperative MRI from January 2005 to March 2010. Among those who were diagnosed with a biopsy-proven second malignancy based on suspicious MRI findings, pathology and imaging reports were reviewed and data regarding patients and tumors was collected.

Results: Out of 624 patients with newly diagnosed breast cancer who had a preoperative MRI, 53 (8.5%) had a second tumor identified solely by MRI. Of these, 40 were ipsilateral, 12 were contralateral, and 1 bilateral. Thirty seven percent were multifocal and 56% were multicentric. Patients who had an MRI were younger than those who didn’t, but there was no difference by age or race for those who had a second tumor found compared to those who didn’t. Tumor size, nodal status, PR status, and Her2 status were significantly associated with the group who had a second tumor. Among the group with additional tumors found on MRI, histology, ER/PR status and grade were strongly correlated between the primary and the secondary lesion.

Conclusions: Tumors that were larger, node positive, lobular histology, hormone receptor positive, or HER2-negative had a higher chance of having a second tumor on preoperative MRI.

[Table: see text]
Use of patient navigation to improve diagnostic and treatment delays among patients with abnormal mammography results from a mobile unit.
Authors: Lee J. Y. , Henry-Tillman R. S. , Klimberg V. S. , Fincher R. , Enoch K. , Preston M. , Jackson S. , Kenney P.
Published: February 2017

73

Background: Screening mammography is frequently the initial step to breast cancer diagnosis. Upon detection of an abnormality on a mammogram, the patient must undergo follow-up procedures for diagnosis and treatment. The objective of this study was to examine the diagnostic and treatment delays after detection of an abnormality on a mammogram performed at a mobile unit.

Methods: During one-year beginning in February 2010, the mobile mammography unit of the University of Arkansas for Medical Sciences (UAMS) performed 1,547 mammograms in women who resided in counties that lacked a stationary mammography unit. Most of these counties are in rural areas with high poverty rates. The women were predominantly non-Hispanic white (62%) or African-American (36%) and 41% lacked health insurance. A patient navigator was available to assist patients through scheduling follow-up appointments, when needed. Diagnostic delay was defined as time from abnormal mammogram to biopsy that exceeded 60 days. Treatment delay was defined as time from abnormal mammogram to treatment initiation that exceeded 90 days.

Results: A total of 14 cancer cases were detected among the 1,547 women screened. The median age of these patients was 56 years of age and ranged from 46-79 years. The median time from screening mammography to biopsy was 31.5 days and ranged from 9-92 days, and diagnostic delay occurred in 2 (14%) patients. The median time from screening mammography to treatment was 78 days and ranged from 37-199 days, and treatment delay occurred in 5 (36%) patients. Three of these patients were managed outside the UAMS health care system, one patient required bilateral mastectomies and one patient refused the initial treatment recommendation.

Conclusions: Responsive health systems require vehicles to strengthen the continuum of breast care. With the use of a patient navigator, the proportion of patients with breast cancer who experienced diagnostic delays is comparable to that of other studies, but the proportion with treatment delays is higher than in other reports. Patient navigation provides a promising model to decrease diagnostic delays and improve access for the medically underserved.
Impact of internal mammary node inclusion in the radiation treatment volume on the outcomes of patients with breast cancer treated with locoregional radiation after six years of follow-up.
Authors: Olson R. A. , Woods R. , Lau J. , Speers C. , Lo A. , Tyldesley S. , Weir L.
Published: February 2017

81

Background: There is ongoing controversy about radiotherapy (RT) to internal mammary nodes (IMNs). Proponents of IMN RT cite the survival benefit seen in postmastectomy RT trials that included IMNs. However, others point out that benefit cannot be definitively attributed to IMN inclusion, as other lymph node regions were included in the RT arms. The issue is important, as IMN RT potentially increases cardiac and respiratory morbidity.

Methods: 2,413 women referred to a provincial RT program with newly diagnosed node positive, or T3/4N0 non-M1 invasive breast cancer, treated with a complete course of locoregional RT from 2001 to 2006, were retrospectively identified in a provincial database. IMN RT inclusion versus exclusion was determined through review of patient charts and RT treatment plans. Breast cancer-specific survival (BCSS), relapse-free survival (RFS), and overall survival (OS) were compared between the two groups using univariate and multivariable analyses.

Results: Analyses were performed at a median follow-up of 6.2 years. 41.4% of the subjects received IMN RT. The 5-year BCSS for the IMN inclusion and exclusion group was 84.8% versus 82.9%, respectively (HR 0.93 [95% CI 0.76, 1.14]; p=.51); the 5-year RFS was 87.4% versus 86.9% (HR 0.993 [0.83, 1.19]; p=0.94); and the 5-year OS was 84.8% versus 82.9% (HR 0.84 [0.70, 1.01]; p=0.06). After controlling for potentially confounding variables, there was no significant difference in BCSS (HR 0.96 [0.78, 1.18], p=0.88), RFS (HR 1.02 [0.84, 1.22], p=0.87), or OS (HR 0.91 [0.76, 1.10]; p=0.35).

Conclusions: After a median follow-up of 6.2 years, this population-based study shows no benefit from including IMNs in the locoregional RT volume after adjusting for other prognostic and treatment variables.
Intraoperative ultrasound for improvement of re-excision rates in breast-conserving surgery.
Authors: Knauer M. , Tschann P. , Koeberle-Wuehrer R. , Obwegeser U. , Jasarevic Z. , Stockinger R. , Hefel C. , Schuster A. , Wenzl E. , Haid A.
Published: February 2017

91

Background: Due to improved screening for early breast cancer, the percentages of small and nonpalpable breast tumors have significantly increased during the last decades. After lumpectomy, re-excision rates of 32%-63% have been reported and the routine placement of localization needles is painful, time-consuming, and costly. In this study we investigated the value of intraoperative ultrasound (IOUS) in the hand of the breast surgeon as a fast and cheap method for potentially improving unacceptable re-excision rates.

Methods: Between July 2001 and December 2010, in 773 of 1,195 breast cancer patients a breast-conserving treatment has been performed at the certified breast care center Vorarlberg (breast-conservation rate 64.7%). In 74.9% (579/773) of the tumors IOUS was performed, of which 44% were nonpalpable and 56% were insufficiently palpable, respectively. 7.5-10 MHz linear ultrasound probes were used by four breast surgeons in combination with intraoperative macroscopic resection margin assessment by the pathologist for prospective evaluation of definitive resection margin status over time. Furthermore, local recurrence rates were assessed.

Results: During the study period, 579 of the included primary tumors were detected by IOUS. The metachronous re-excision rate was halved from 22% (30/135) in the period 2001-2003 to 11% (13/121) between 2008 and 2010. Between 2001 and 2010 we achieved a total re-excision rate of 13% (74/579). In 53% of re-excision specimens, no residual tumor was present, in 23% DCIS and in 24% invasive tumor was found, respectively. At a median follow-up of 56.4 months, a local recurrence rate of 1.7% was observed using our approach of IOUS combined with intraoperative margin assessment.

Conclusions: IOUS in the hand of the breast surgeon proved to be a valuable, fast, and cheap method to improve metachronous re-excision rates in breast-conserving surgery. Patients can be spared the painful, costly, and time-consuming placement of a localization needle. Furthermore, tissue-sparing operations can be performed more easily and intraoperative specimen radiography can be avoided. The actual pathologic tumor size, however, is often being underestimated, especially regarding in situ cancers.
Nipple-sparing mastectomy: Evaluation of oncologic safety and aesthetic outcomes in 94 patients.
Authors: Millen E. C. , Pinto R. R. , Menezes L. , Almeida F. C. O. , Novita G. , Frasson A. L. , Paula B. h. , Cruz M. R. D. S.
Published: February 2017

97

Background: The surgical treatment of breast cancer has evolved from radical mastectomy to breast conservation therapy. Today we have another therapeutic dilemma: how to manage the nipple-areolar complex (NAC) in mastectomy offering patients better aesthetic results with oncologic safety.

Methods: We analyzed data on 125 consecutive nipple- or skin-sparing mastectomies (SSM) with immediate reconstruction with tissue expander, prosthesis or autologous tissue performed in 94 patients from 2003 to 2010 in a tertiary referral hospital. Nipple-sparing mastectomy (NSM) was performed for treatment disease (n= 94) and prophylaxis of contralateral breast or symmetrization in selected cases (n= 31).

Results: Mean patients age was 46.8 years (range 27 to 69 years) and mean follow-up time was 27.2 months (range 2 weeks to 81 months). Twelve patients were stage 0, 41 stage I, 35 stage II A and B and 7 stage III. There were 125 nipple- or areola-sparing mastectomies (31 bilateral and 94 unilateral), including 112 NSM and 13 SSM. On pathologic review, 12 breasts had carcinoma in situ, 83 invasive carcinoma, and 31 breasts were cancer free. Thirteen nipples (13.8%) were compromised by tumor on subareolar biopsy and were removed. The location and type of incision was variable according to the tumor site and previous patient scar. Periareolar incision with prolongation along the inferior pole of breast was the preferred method. Patients with positive axillary node (27.5%) received adjuvant radiotherapy. There was no nipple necrosis. One patient presented local relapse in the skin-sparing group within 24 months.

Conclusions: These data demonstrate that NSM is oncologically safe and can be performed with all types of breast reconstruction.
Utility of esophageal stenting for esophageal cancer patients with dysphagia undergoing neoadjuvant therapy.
Authors: Brown R. E. , St. Hill C. R. , Harkenrider M. M. , Ellis S. , Sharma V. R. , El-Ghamry M. N. , Scoggins C. R. , McMasters K. M. , Abbas A. E. , Martin R. C.
Published: February 2017

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Background: For esophageal cancer patients with dysphagia, symptom relief and maintenance of nutrition remain significant barriers to completion of neoadjuvant therapy (NAT). We hypothesized that esophageal stenting would allow for successful delivery of planned NAT, with improvement in quality of life (QOL) and maintenance of nutrition.

Methods: A multi-institution prospective phase II clinical trial examined esophageal cancer patients with dysphagia undergoing NAT. All had a self-expanding polymer esophageal stent (ES) placed at initiation of NAT. Individual chemotherapy and RT regimens were determined via multidisciplinary collaboration.

Results: 32 patients were enrolled with dysphagia and potentially resectable esophageal cancers. All had ES placement prior to NAT. Two patients had stent migrations that required replacement. There were no ulcerations or perforations. Significant QOL improvements were noted within a week after ES placement, which persisted throughout NAT. NAT with chemo + RT was planned in 17 patients, of which 12 (71%) received planned dosing. NAT with chemotherapy alone was planned in 15 patients, of which 10 (67%) received planned dosing. Chemotherapy was most commonly 5FU/cisplatin based. 3D conformal RT with high dose photons was used most frequently, with a mean of 97% of the planned RT dose delivered. Among all patients, alterations (n=5, 16%) or cessation (n=5, 16%) of planned NAT regimens were required for treatment-related toxicity or disease progression. One patient required a jejunostomy tube for nutritional maintenance.

Conclusions: Esophageal stenting is an effective method of improving QOL and relieving symptoms that allows for successful completion of NAT, with maintenance of performance and nutritional status.

[Table: see text]
Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: A meta-regression approach.
Authors: Hsu C. , Shen Y. , Cheng C. , Cheng A. , Hu F. , Yeh K.
Published: February 2017

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Background: The standard of chemotherapy regimens for patients with advanced or metastatic gastric cancer vary and the clinical outcome were heterogeneous in Asian vs. non-Asian countries.

Methods: Treatment group-based meta-analysis and meta-regression were performed to analyze results of randomized trials published since 2005 for advanced or metastatic gastric cancer patients who received systemic chemotherapy as first-line treatment. Data were extracted and synthesized according to the Cochrane guidelines.

Results: Among the 24 trials (totally 6,502 patients) eligible for meta-analysis, Asian trials reported lower percentage of gastroesophageal junctional carcinoma, higher percentage of diffuse-type histology, and more frequent use of second-line chemotherapy. Meta- regression analyses indicate that, after controlling other patient or treatment factors, Asian trials are associated with 22.7% (95% CI: 19.5-26.0%, p<0.0001) lower incidence of grade 3-4 neutropenia and 3.5% (95% CI: 2.1-4.9%, p<0.0001) lower incidence of grade 3-4 diarrhea, which were the most commonly reported toxicity. The use of high-dose infusional 5-fluorouracil, compared with other fuoropyrimidine regimens, reported 16.6% lower incidence of neutropenia (95% CI: 13.3-19.9%, p<0.0001). Higher percentage of patients with gastroesophageal junction carcinoma and patients with 2 or more organs involved predicted poor progression-free survival. The use of second-line chemotherapy predicts better 1-year overall survival, which will increase by 9% (95% CI: 8-10%) for every 10 percent increase in patients who received second-line chemotherapy.

Conclusions: Geographic region (Asian vs. non-Asian) plays an important role in the heterogeneity of gastric cancer clinical trials and is an independent predictor of safety in systemic therapy for gastric cancer.

No significant financial relationships to disclose.
Radiotherapy, including sentinel lymph node, to superficial cancer of esophagus.
Authors: Kaburagi T. , Takeuchi H. , Oyama T. , Nakamura R. , Takahashi T. , Wada N. , Saikawa Y. , Kitagawa Y. ,   Keio University School of Medicine
Published: February 2017

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Background: It is known that esophageal cancer frequently causes lymph node metastasis. Even if relatively early stage of esophageal cancer, reaching muscularis mucosae (T1a-MM: Japanese Classification of Esophageal Cancer) causes subclinical node metastasis to about 10%. So when radiation therapy (RT) is administered to these patients, field of irradiation should include the areas where subclinical node metastasis may exist. But the wider field of irradiation is, the more likely adeverse event is to occur. In this study, we examined utility of RT based on sentinel lymph node (SLN) theory.

Methods: Before irradiation, Tc-99m tin colloid solution was endoscopically injected to the submucosal layer around the primary tumor and lymphoscintigraphy was examined to detect SLNs. And the irradiation field was planned as SLN regions were included. Patients with esophageal squamous cell carcinomas (ESCC) that reach cT1a-MM or cT1b and patients with ESCC who had underwent endoscopic resection and pathologically diagnosed pT1a-MM or pT1b were eligible if they had clinically no lymph node metastasis, no distant metastasis and no advanced cancer in other site. Between April 2001 and December 2009, 17 of these patients were received RT based on SLN theory. We retrospectively examined them.

Results: Characteristics of the 17 pts were: median age; 67 (58-82), male/female; 15/2, T1a-MM/T1b-SM1/T1b-SM2; 4/2/11, definitive RT/adjuvant RT; 10/7, RT alone/concurrent chemoradiotherapy; 1/16. Average dose of irradiation was 57.0 ± 6.4Gy. Median follow-up is 81.4 months (7.9-127.2). Ten pts with definitive RT gained complete remission. Two minor local relapses of the primary tumors were observed. They underwent salvage endoscopic resection and survive without other relapse. There was no treatment related death. Grade 3 or 4 late toxicity was not observed.

No significant financial relationships to disclose.
Phase II trial of irinotecan and cisplatin combination as first-line chemotherapy in patients with advanced esophageal squamous-cell carcinoma: An interim report.
Authors: Zhang X. , Shen L. , Li J. , Li Y. , Zhou J. , Lu Z. , Lu M.
Published: February 2017

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Background: Although the irinotecan and cisplatin combination has been used in esophageal cancer treatment, we tested the combination specifically in unresectable or metastatic esophageal squamous cell carcinoma with different doses to decrease the toxicity and keep the efficacy.

Methods: Patients were eligible if they had histologic proof of unresectable or metastatic squamous cell carcinoma of the esophagus, between 18-75 years of age with a Karnofsky performance status ≥ 80. No prior chemotherapy was allowed. Patients were treated with irinotecan 130 mg/m2 and cisplatin 60 mg/m2 repeated 3 weeks. Response was evaluated every two cycles of treatment by using RECIST criteria. The sample size was calculated using Simon's 2-stage design. The primary end point of the study was objective response rate. The second end points are PFS and toxicity. Accrual was planned to a total of 46 patients with the targeted response rate of 50%. The first stage requires at least 7 or more out of 16 patients to have a confirmed partial or complete response before proceeding to the second stage.

Results: Twenty one patients have been enrolled so far, of which 16 patients were assessable for response. The overall response rate was 43.8%(7/16), including one complete response (6.3%) and six partial response (37.5%). Among 13 patients who presented with dysphagia at baseline, 10 (62.5%) had the symptom either completely resolved or significantly improved. The most common toxicities were neutropenia, diarrhea and alopecia. Seven patients (33.3%) developed grade 3 neutropenia and one had (4.8%) with febrile neutropenia. One patient (4.8%) had grade 3 diarrhea. There were no treatment-related deaths.

Conclusions: The combination of irinotecan plus cisplatin with lower doses showed equivalent efficacy and less toxicity in patients with unresectable or metastatic squamous-cell carcinoma of the esophagus. The study is ongoing.

No significant financial relationships to disclose.
Effect of neoadjuvant dose-painted IMRT to 56 Gy for locally advanced esophageal cancer on outcomes.
Authors: Shridhar R. , Chuong M. D. , Hoffe S. E. , Biagioli M. , Almhanna K. , Weber J. , Kucera S. , Vignesh S. , Barthel J. S. , Meredith K. ,   Moffitt Esophageal Research Team
Published: February 2017

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Background: Standard of care chemoradiation doses of 50.4 Gy for locally advanced (T3, T4, and/or node positive) esophageal cancer is associated with a pathologic complete response (pCR) rate of 40% at our institution. We evaluated whether pCR would be increased with 4D CT planning scans, intensity-modulated radiation therapy (IMRT) delivery with motion management, and dose painting to 56 Gy in 28 fractions.

Methods: This retrospective review of 9 patients who have undergone esophagogastrectomy (7 adenocarcinoma, 2 squamous cell) evaluates our initial experience with neoadjuvant dose painted IMRT to 56 Gy. Pre-treatment workup included PET scan, chest and abdomen CT scans, endoscopic ultrasound (EUS), and EUS-guided fiducial marker placement. Fiducial markers were placed superior and inferior to the gross endoscopic tumor volume to facilitate analysis of tumor motion with 4D CT simulation. Internal target volumes (ITVs) of gross disease were generated to account for motion. Once the GITV was generated, a clinical target volume (CTV) encompassing a 3-4 cm superior margin and 3-4 cm distal margin was contoured. Two planning target volumes (PTVs) were created for dose painting: PTV 50.4 and PTV 56 Gy in 28 fractions. IMRT was utilized for all patients with either a weight belt or with compensators. Concurrent cisplatin and continuous infusion 5-FU were delivered with radiotherapy and patients were restaged 3-6 weeks after completion for response evaluation.

Results: Treatment was well tolerated without any grade 3 acute morbidity. Surgical complications were not increased in this group overall. However, there was 1 patient with a chyle leak and radiation pneumonitis, but her case was complicated by having a remote history of radiotherapy. Six of the 9 treated patients were found to have a pCR (4 adenocarcinoma, 2 squamous cell). Two had a near CR with < 5 mm of residual disease. One additional patient with an initial bulky T4N1 tumor had 9 mm of viable tumor.

Conclusions: With motion management, dose painted IMRT to 56 Gy is feasible and may be associated with improved rates of pathologic complete or near complete response.

No significant financial relationships to disclose.
The Singapore liver cancer recurrence (SLICER) score for relapse prediction in patients with resected hepatocellular carcinoma.
Authors: Ng E. , Ang S. , Li H. , Lim K. , Choo S. , Ngeow J. Y. , Toh H. , Chow P. K. , Tan M.
Published: February 2017

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Background: Hepatocellular carcinoma (HCC) is a common worldwide cancer associated with extremely poor survival, with surgery the only option for cure in patients with localized disease. Current prognostic models for HCC are algorithms developed on datasets of mainly patients with metastatic or unresectable cancer, and may be less relevant to resectable HCC. Nomograms provide individualized outcome estimates. We constructed a postoperative nomogram, the Singapore liver cancer recurrence (SLICER) score, to predict outcomes of HCC patients who have undergone surgical resection.

Methods: Records for Singaporean patients undergoing first-line curative surgery for localized HCC in one institution between 1992 and 2007 were retrospectively reviewed (n=405). Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation, was used. Calibration was tested with bootstrapping (n=200). We compared the performance of this model with other alternative models including CLIP, CUPI, BCLC, and Okuda scores using c-indices and likelihood analysis.

Results: A nomogram (SLICER score) predicting FFR was designed, incorporating vascular invasion, tumor size, multifocality, ECOG status, pre-operative AFP, Childs-Pugh score and cirrhosis. Bootstrap estimates show good calibration at 1, 2, 3, and 5 years postsurgery Comparison of the SLICER score with alternative prognostic models shows superior performance (Table).

Conclusions: The SLICER score enables individualized relapse predictions for patients following curative resection of localized HCC. It permits optimal patient selection for adjuvant therapy trials, biomarker development, and individual counseling.

[Table: see text]

No significant financial relationships to disclose.