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Background. Nasopharyngeal carcinoma is a chemosensitive cancer characterized by prominent lymphocytic infiltration. However, recurrence remains a major challenge in treating this disease. Here, we examined the effects of idronoxil (IDX) on tumor-lymphocyte interactions. Methods The antitumor activity of cisplatin and/or IDX was tested in authentic EBV-positive NPC-derived cell lines (C666, C17 and NPC43). We analyzed 2D monolayer and 3D spheroids cocultures of NPC cell lines with immune cells to assess the infiltration, activation, phenotype and function of T cells toward human nasopharyngeal tumors in vitro. Flow cytometric and immunohistochemical analyses were carried out to evaluate infiltrating T cells in subcutaneous mice models. Results. Administration of low-dose of IDX (1-2 µM) not only sensitizes cancer cells to chemotherapy via apoptosis, but also promotes T cell proliferation and cytotoxicity. More importantly, combination treatment of IDX and cisplatin in cancer cells can enhance the expansion, trafficking and priming of CD4+, CD8+ and double-positive (DP) T cells. Mechanistically, we showed that the increase in migratory DP T cells was largely mediated by the CXCL10/type I interferon (IFN) axis, where IDX precipitates an elevation in IFNα levels and leads to CXCL10 induction. Additionally, IDX enhanced T-cell infiltration towards tumor spheroids with acquisition of increased tissue homing and functional abilities (attenuated CD62L and PD1 expression). Conclusions. Our findings underscore the potential of IDX to induce immunomodulatory responses, and in combination with conventional chemotherapies, enhance antitumor immunity. more...

Purpose: To facilitate the initiation of observational studies on late effects of proton therapy in pediatric patients, we report on current patterns of proton therapy use worldwide in patients aged less than 22 years. Materials & methods: Fifty-four proton centers treating pediatric patients in 2016 in 11 countries were invited to respond to a survey about the number of patients treated during that year by age group, intent of treatment, delivery technique and tumor types. Results: Among the 40 participating centers (participation rate: 74%), a total of 1,860 patients were treated in 2016 (North America: 1205, Europe: 432, Asia: 223). The numbers of patients per center ranged from 1 to 206 (median: 29). Twenty-four percent of the patients were more...

e15186 Background: Nasopharyngeal carcinoma (NPC) is endemic in Southern China. Although it is both radio-and chemo-sensitive, resistance to these treatments remains a major problem for successful management of NPC. The main characteristic of a cancer cell is its resistance to undergo apoptosis; therefore, reversing this resistance may represent the best approach for the treatment of cancer. Additionally, NPC is well-known to be heavily infiltrated by lymphocytes and constitute a unique but poorly defined tumor microenvironment (TME). We aimed at delineating and defining the contribution of idronoxil (IDX) in restoring sensitivity to apoptosis and potentially modulating the immune microenvironment of NPC. Methods: The IC50 of cisplatin (Cis) and IDX from 2D and 3D spheroid cultures of four NPC cancer cell lines (C666, C17, and the paired NPC43 EBV-positive and EBV-negative cell lines) were evaluated. The migration and proliferation of cells treated with IDX and/or Cis were investigated by Transwell and XTT, respectively. Cell phenotype and migratory analyses were measured by flow cytometry on Cis/IDX-pretreated NPC cell lines cocultured with HLA-matched PBMC. Results: IDX and Cis inhibited NPC migration and cell proliferation (IC50 for IDX in 2D and 3D was 2µM; IC50 for Cis in 2D and 3D: was 0.6µM and 1.4µM, respectively). A dose-dependent induction of apoptosis in NPC cell lines by IDX was observed [early apoptotic cells (Annexin V+/PI- at 1µM); late apoptotic cells (Annexin V+/PI+ at 2µM), and necrotic cells (Annexin V-/PI+, at 4µM) were distinguished]. Intriguingly, IDX increased the migratory potential of PBMC towards tumor cells in both 2D and 3D spheroid cultures. Finally, IDX, but not Cis, facilitated the migration of CD8+ T cells toward tumor cells by 3.5-fold (p < 0.05) as well as promoted the expansion of proliferative CD8+ T cells (increased by ~2.8-fold) with degranulation activities (~1.3-fold and 3-fold increase in surface CD107a and intracellular granzyme B expression, respectively) in the cocultures. Conclusions: IDX was shown to induce apoptosis in NPC cells while inhibiting their migration and proliferation. Moreover, the ability of IDX to modulate T cell populations indicates the drug’s potential to enhance the efficacy of current chemotherapy treatments in NPC by upregulating cellular trafficking to the cancer cell. more...

Ductal carcinoma in-situ (DCIS) of the breast has rapidly increased in incidence over the past several decades secondary to an increased use of screening mammography. Local treatment options for women diagnosed with DCIS include mastectomy or breast-conserving therapy (BCT). While several randomized trials have confirmed a greater than 50% reduction in the risk of local recurrence with the administration of radiation therapy (RT) compared to breast-conserving surgery (BCS) alone, controversy persists regarding whether or not RT is needed in selected ‘low-risk’ patients. Over the past two decades, two prospective single-arm studies and one randomized trial have been performed and confirm that the omission of RT after surgery alone is associated with higher rates of local recurrence even after selecting patients with the most optimal clinical and pathologic features. Importantly, these trials have failed to consistently and reproducibly identify a low-risk cohort of patients (based on clinical and pathologic features) that does not benefit from RT. As a result, adjuvant RT is still advocated in the majority of patients, even in these low-risk cases. Future research is moving beyond traditional clinical and pathologic risk factors and instead employing more modern approaches such as multi-gene assays and biomarkers with the hopes of identifying truly low-risk patients who may not require RT. However, recent studies confirm that even low-risk patients identified from multi-gene assays have higher rates of local recurrence with local excision alone than would be expected with the addition of radiation therapy. more...

To report 6-year outcomes from a phase I/II trial using balloon-based brachytherapy to deliver APBI in 2 days.A total of 45 patients with early-stage breast cancer received adjuvant APBI in 2 days with high-dose rate (HDR) brachytherapy totaling 2800 cGy in 4 fractions (700 cGy BID) using a balloon-based applicator as part of a prospective phase I/II clinical trial. All patients had negative margins and skin spacing ≥8 mm. We evaluated toxicities (CTCAE v3) as well as ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis, disease-free survival, cause-specific survival, and overall survival.Median age and tumor size were 66 years old (48 to 83) and 0.8 cm (0.2 to 2.3 cm), respectively. Four percent of patients were N1 (n=2) and 73% were estrogen receptor (ER) positive (n=32). Median follow-up was 6.2 years (2.4 to 8.0 y). Nearly all toxicities at 6 years were grade 1 to 2 except 1 instance of grade 3 telangiectasia (2%). Eleven percent (n=5) of patients had chronic asymptomatic fat necrosis whereas asymptomatic seromas were noted on mammogram in 13% of cases (n=6). Cosmesis at last follow-up was good or excellent in 91% of cases (n=40) and fair in 9% (n=4). Two of the previously reported rib fractures healed with conservative measures. There were no IBTR or RNF (6 y IBTR/RNF rate 0%); however, 2 patients experienced distant metastasis (4% at 6 y). The 6-year actuarial disease-free survival, cause-specific survival, and overall survival were 96%, 100%, and 93%, respectively.Hypofractionated 2-day APBI using brachytherapy resulted in excellent clinical outcomes with acceptable chronic toxicities. more...

We reviewed our institution's long-term experience treating patients diagnosed with ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine the impact of patient age on outcome over time. All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics (including age more...

Background: To determine six-year outcomes and patterns of failure following accelerated partial breast irradiation (APBI) within a pooled patient population from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite® Registry Trial. Methods: 2,127 cases of early-stage breast cancer were treated using APBI (WBH: n=678; ASBrS: n=1,449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3D-CRT, n=206) while all Registry Trial patients received balloon-based brachytherapy. Patients with complete coding necessary for ASTRO Consensus Panel (CP) group assignment (n = 1,813) were divided into suitable (n = 661, 36.5%), cautionary (n = 850, 46.9%), and unsuitable (n = 302, 16.7%) categories. Tumor characteristics, clinical outcomes, and patterns of failure were analyzed according to CP group. Results: Median age was 65 years (32–94 years), median tumor size was 10.0mm (0–45mm), and median follow up was 59.4 months. The WBH cohort had more node-positive disease (6.9% vs. 2.6%, p < 0.01) and cautionary patients (49.5% vs. 41.8%, p = 0.06). Margin and estrogen receptor (ER) status were not different between WBH and ASBrS cohorts (p = 0.46, 0.82). Six-year rates of ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 3.2%, 0.7%, and 1.1%, respectively. Elsewhere failures (EF) were the predominant mode of in-breast recurrence for each CP group (suitable: 2.3%, cautionary: 2.5%, unsuitable: 4.9%, p = 0.16) as compared to true recurrences (TR) near the lumpectomy bed (suitable 0.9%, cautionary: 1.5%, unsuitable: 0.8%). No statistical difference in combined rates of ipsilateral recurrence (TR+EF) were observed between the three consensus panel groups (suitable: 3.2%, cautionary: 4.1%, unsuitable: 5.7%, p = 0.25). The six-year rate of distant metastasis was higher for cautionary and unsuitable groups (3.5–3.6% vs. 1.1% for suitable, p = 0.01), although cause-specific survival was the same for all patient categories (98.0–98.6%, all groups, p = 0.47). On multivariate analysis, no factor was associated with increased risk of true recurrence while ER negative status (OR: 4.13, p < 0.01) and a positive/close margin (OR: 2.70, p = 0.02) were associated with increased rates of elsewhere failure. Conclusions: Excellent overall outcomes following breast conserving surgery and APBI were seen at six years in our pooled analysis. A nonsignificant elevation in the rate of IBTR for cautionary and unsuitable consensus panel groups was due to new primary cancers elsewhere in the breast and not treatment failures. Despite a trend towards increased elsewhere failures in the unsuitable group, the current ASTRO CP guidelines were not able to adequately differentiate patients at an increased risk of IBTR or tumor bed failure within a large patient cohort treated with APBI. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-03. more...

Purpose To analyze a pooled set of nearly 2,000 patients treated on the American Society of Breast Surgeons (ASBS) Mammosite Registry Trial and at William Beaumont Hospital (WBH) to identify factors associated with local recurrence following accelerated partial breast irradiation (APBI). Methods and Materials A total of 1,961 women underwent partial breast irradiation between April 1993 and November 2010 as part of the ASBS Registry Trial or at WBH. Rates of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed for each group and for the pooled cohort. Clinical, pathologic, and treatment-related variables were analyzed including age, tumor stage/size, estrogen receptor status, surgical margins, and lymph node status to determine their association with IBTR. Results The two groups weres similar, but WBH patients were more frequently node positive, had positive margins, and were less likely to be within the American Society for Radiation Oncology-unsuitable group. At 5 years, the rates of IBTR, RR, DM, DFS, CSS, and OS for the pooled group of patients were 2.9%, 0.5%, 2.4%, 89.1%, 98.5%, and 91.8%, respectively. The 5-year rate of true recurrence/marginal miss was 0.8%. Univariate analysis of IBTR found that negative estrogen receptor status (odds ratio [OR], 2.83, 95% confidence interval 1.55–5.13, p = 0.0007) was the only factor significantly associated with IBTR, while a trend was seen for age less than 50 (OR 1.80, 95% confidence interval 0.90–3.58, p = 0.10). Conclusions Excellent 5-year outcomes were seen following APBI in over 1,900 patients. Estrogen receptor negativity was the only factor associated with IBTR, while a trend for age less than 50 was noted. Significant differences in factors associated with IBTR were noted between cohorts, suggesting that factors driving IBTR may be predicated based on the risk stratification of the patients being treated. more...

Background: Limited data exists on outcomes following accelerated partial breast irradiation in node-positive breast cancer patients. The purpose of this analysis was to compare clinical outcomes following accelerated partial breast irradiation (APBI) between node-negative and node-positive early stage breast cancer patients and to identify if nodal positivity leads to increased rates of local or axillary failure. Materials and Methods: 510 patients with early stage breast cancer received accelerated partial breast irradiation (APBI) as part of their breast conservation therapy between April 1993 and November, 2010. Of these, 39 were lymph node positive with 10 patients having N1mi disease (median size of mets= 0.82 mm) and 29 patients having N1 disease (61.5% had one node positive [median size of mets= 2.5 mm], 30.8% had 2 nodes positive [median size of mets= 8.0 mm], and 7.7% had 3 nodes positive [median size of mets= 20 mm]). Patient, clinical, and pathologic factors were analyzed and compared for the node-negative and node-positive cohorts including age, tumor size, receptor status, margin status, adjuvant hormonal therapy, adjuvant chemotherapy, and length of follow-up. Clinical outcomes were analyzed including local recurrence (LR), regional recurrence (RR), axillary recurrence (AR), regional-nodal recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS). Results: Node-positive patients were younger (p=0.04), had larger tumors (p Discussion: No difference was seen in the rates of local recurrence or axillary failure between node-negative and node-positive following APBI with 5-years of follow-up. Increased rates of regional failure were noted with APBI in node-positive patients due to supraclavicular failures; however, traditional whole breast irradiation techniques would not have covered these failures. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-02. more...

Purpose: To determine the impact of estrogen receptor (ER) negativity on clinical outcomes for patients treated with Accelerated Partial Breast Irradiation (APBI). Materials/Methods(s): We evaluated 506 consecutive patients treated with interstitial brachytherapy (n= 199), balloon-based brachytherapy (n=203), and 3D-CRT (n=104). ER negative (ERN) status was assigned using the traditional definition of an ER nuclear IHC stain < 10%, which corresponds to an Allred/NSABP staining score of < 2. 63 patients (12.5%) were ER negative and 443 (87.5%) were ER positive (ERP). Patient demographics and clinical outcomes (IBTR, RNF, DM, DFS, CSS, OS) were analyzed for each group. Results: The two groups had similar patient characteristics. Tumor sizes were slightly larger for the ERN group at 11.9mm vs. 10.7mm, although this was not statistically significant (p=0.14). No differences were seen in median age (63 vs. 64 years, p=0.36), rate of HER-2/neu overexpression (83% vs. 91%, p=0.11), or lymph node positivity (6% vs. 9%, p=0.55) between the ERN vs. ERP groups, respectively. There were an equal distribution of invasive ductal carcinoma (ERN n=55, 87%; ERP n=387, 87%) and DCIS (ERN n=8, 13%; ERP n=56, 13%) patients within each group. The use of chemotherapy (55% vs. 15%, p Conclusion: The ER negative phenotype of early-stage breast cancer may have a decreased rate of locoregional control. We observed a higher rate of DM with reduced disease-free and cause-specific survival in ER negative cases, emphasizing the importance of systemic therapy and careful, long-term follow up for these patients. Prospective study of this histologic subtype with a larger cohort of patients is needed to substantiate these findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-09. more...

Purpose: To examine the rate of breast reconstruction failure and cosmetic outcomes following post-mastectomy radiation therapy (PMRT) with temporary tissue expander or implant in place. Methods and Materials: Ninety-four patients with 95 primary breast malignancies underwent mastectomy and immediate tissue expander reconstruction followed by PMRT. Ninety tissue expanders and five implants were irradiated. All patients received a dose of 5,400 cGy given in 180 cGy fractions. Twenty-one patients (22%) received tangents alone and seventy-four patients (78%) were treated with tangents and a supraclavicular field via a mono-isocentric technique. Bolus was used in 91 patients (96%). Eighty-eight patients (93%) received chemotherapy and 78 patients (82%) received endocrine therapy. Results: With a median follow up of 22.4 months, nineteen patients (20%) developed a reconstruction failure. Ten patients lost their tissue expanders with a median time to reconstruction failure of 7 months (range 3–9 months) while ten patients lost their permanent implant with a median time to loss of 19 months (range 9–31 months) following PMRT. The one and two-year actuarial rate of reconstruction failure was 11.2% and 24.9%, respectively. The most common cause of failure was infection (37%), followed by skin break down (21%), extrusion of expander or implant (16%), fibrosis/eschar (11%), trauma (11%) and pain (5%). Out of the 19 failures, eight patients were salvaged with an autologous flap reconstruction. Univariate analysis was performed to examine the association between age, chemotherapy, hormonal therapy, smoking status, hypertension, diabetes, menopause status, weight and the use of a third supraclavicular RT field on reconstruction failure. However no risk factors were found to be associated with reconstruction failure. In patients who did not have reconstruction failure, good/excellent cosmesis was observed in 79% of patients and fair/poor cosmesis was observed in 21% of patients. Conclusions: In our series of women with a high risk of recurrence, PMRT with a tissue expander in place followed by a prosthetic implant provides good cosmesis in the majority of women with an acceptable risk of expander or implant loss. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-04. more...

Breast-conserving therapy consisting of segmental mastectomy followed by whole-breast irradiation (WBI) has become widely accepted as an alternative to mastectomy as a treatment for women with early-stage breast cancer. WBI is typically delivered over the course of 5-6 weeks to the whole breast. Hypofractionated whole-breast irradiation and accelerated partial breast irradiation have developed as alternative radiation techniques for select patients with favorable early-stage breast cancer. These radiation regimens allow for greater patient convenience and the potential for decreased health care costs. We review here the scientific rationale behind delivering a shorter course of radiation therapy using these distinct treatment regimens in this setting as well as an overview of the published data and pending trials comparing these alternative treatment regimens to WBI. more...

To compare reimbursement and cost efficacy between accelerated partial breast irradiation (APBI) techniques.Four hundred fifty-three patients were treated with APBI using either 3-dimensional conformal radiotherapy (3D-CRT, n=207) or balloon-based brachytherapy (BB) [single-lumen (SL, n=161) and multilumen (ML, n=85)] between March 2000 and October 2011. To evaluate cost-effectiveness, reimbursement by treatment technique was calculated based on 2011 Medicare schedules. Facility costs were generated by technique based on ICD-9 codes. Incremental cost effectiveness ratios (ICER), which compares cost with clinical outcomes, were calculated according to the difference in reimbursement to the criteria being evaluated.With a median follow-up of 3.6 years, the 5-year rate of local recurrence was 1.9% for all patients (3D-CRT, 0%; BB, 4.1%; P=0.23). When pooled, BB patients had a significant improvement in excellent/good cosmesis (91.6% vs. 80.0%; P=0.03). Rates of combined grade 2 or higher dermatitis, hyper/hypopigmentation, pain, or fibrosis per technique were 62%, 28%, and 34% for 3D-CRT, SL, and ML patients, respectively (P=0.26). The ICER per percent improved cosmesis for SL/ML was $519/$850 based on reimbursement and $301/$643 based on cost compared with 3D-CRT.On the basis of ICER, brachytherapy for APBI is a cost-effective option with regard to cosmesis and toxicity. This economic analysis suggests the increased cost of applicator-based brachytherapy may be justified in appropriately selected patients. more...

This research applies vector autoregression to estimate a system composed of market share and relative advertising expenditures of the seven major competitors in the U. S. replacement passenger tire market between 1972 and 1983. The results of the study suggest that a company's market share in this market cannot be predicted from its relative advertising expenditures. more...

To review the initial experience of three institutions using multilumen catheters to deliver accelerated partial breast irradiation (APBI) and evaluate dosimetric improvements.Patients were eligible for this analysis if they met criteria for accelerated partial breast irradiation at their respective institution and were not enrolled on the national Phase III trial. Minimum guidelines for treatment planning from the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol were followed. Toxicities were coded using common toxicity criteria version 3.0 criteria.Sixty-two patients were analyzed as part of this study. Median skin spacing was 11mm with a median skin dose of 86.9% (% of prescription dose [PD]). Median rib dose was 76.1% of the PD (range, 4.3-155.7%). The V(90), V(95), and V(100) of the PD for the planning target volume evaluation was 95.4%, 95.2%, and 80.3%, respectively. Seven patients had both skin and rib spacing7mm, with the median skin dose and rib dose being 113.4% and 130.9% of the PD. For these cases, the median V(90), V(95), and V(100) of the PD was 99.2%, 94.3%, and 81.1%, respectively, whereas the median V(150) and V(200) were 22.5cc and 7.4cc. Overall, Grade I and II radiation dermatitis were noted in 41.9% and 6.5% of patients.The multilumen device led to improvements in target coverage and normal structure doses compared with traditionally accepted guidelines. Similar toxicities were seen compared with single-lumen devices, even in patients with skin and rib spacing7mm. more...

Purpose To determine the rates of breast cancer–related lymphedema (BCRL) in patients undergoing whole-breast irradiation as part of breast-conserving therapy (BCT) and to identify clinical, pathologic, and treatment factors associated with its development. Methods and Materials A total of 1,861 patients with breast cancer were treated at William Beaumont Hospital with whole-breast irradiation as part of their BCT from January 1980 to February 2006, with 1,497 patients available for analysis. Determination of BCRL was based on clinical assessment. Differences in clinical, pathologic, and treatment characteristics between patients with BCRL and those without BCRL were evaluated, and the actuarial rates of BCRL by regional irradiation technique were determined. Results The actuarial rate of any BCRL was 7.4% for the entire cohort and 9.9%, 14.7%, and 8.3% for patients receiving a supraclavicular field, posterior axillary boost, and internal mammary irradiation, respectively. BCRL was more likely to develop in patients with advanced nodal status (11.4% vs. 6.3%, p = 0.001), those who had a greater number of lymph nodes removed (14 nodes) (9.5% vs. 6.0%, p = 0.01), those who had extracapsular extension (13.4% vs. 6.9%, p = 0.009), those with Grade II/III disease (10.8% vs. 2.9%, p p = 0.02). Regional irradiation showed small increases in the rates of BCRL ( p = not significant). Conclusions These results suggest that clinically detectable BCRL will develop after traditional BCT in up to 10% of patients. High-risk subgroups include patients with advanced nodal status, those with more nodes removed, and those who receive chemotherapy, with patients receiving regional irradiation showing a trend toward increased rates. more...

Background and Purpose To compare 12-year outcomes of accelerated partial breast irradiation (APBI) versus whole-breast irradiation (WBI) in patients treated with breast conservation. Materials and Methods A matched-pair analysis was performed using 199 patients receiving WBI and 199 patients receiving interstitial APBI. Match criteria included tumor size, age, nodal status, ER status, and the use of adjuvant hormonal therapy. Patterns of failure and efficacy of salvage treatments were examined. Results No differences were seen in the 12-year rates of local recurrence (3.8% vs. 5.0%, p =0.40), regional recurrence (0% vs. 1.1%, p =0.15), disease free survival (DFS) (87% vs. 91%, p =0.30), cause-specific survival (CSS) (93% vs. 95%, p =0.28), or overall survival (OS) (78% vs. 71%, p =0.06) between the WBI and APBI groups, respectively. The rate of distant metastases was lower in the APBI group (10.1% vs. 4.5%, p =.05). Following LR, no difference in outcome was seen between the two groups with 5year post-LR rates of DFS (80% vs. 86%, p =0.55), CSS (88% vs. 75%, p =0.77), and OS (88% vs. 75%, p =0.77), respectively. Conclusions With 12-year follow-up, APBI produced outcomes equivalent to WBI. Following LR, patients treated with APBI also had similar failure patterns to those managed with WBI. more...

The Petroleum research forum (PERF) was established in 1986 to stimulate cooperative research and development of technology for environmental pollution control, safety, and waste management for the petroleum industry. Membership currently consists of 19 major companies (Table 1). At year-end 2000, PERF membership had completed 66 projects with a value of $58M, with an additional 12 projects valued at $8M underway and 11 projects worth over $3M under consideration. This paper focused on how PERF is organized; and how we generate, manage and fund projects. Special emphasis is placed on case study examples of several large, successful programs. Further information on PERF, including summaries of all projects, can be found at www.PERF.org. more...

Brachytherapy-Based Accelerated Partial Breast Irradiation Versus Canadian Whole Breast Hypofractionation: A Matched-Pair Analysis of Comparative Effectiveness P.Y. Chen, J. Wilkinson, C.S. Shah, J. Wobb, M. Wallace, H. Ye, P. Benitez, N. Dekhne, D. Brabbins, and F. Vicini; Beaumont Health System, Royal Oak, MI, Summa Akron City/St. Thomas Hospitals, Akron, OH, Michigan Healthcare Professionals/21st Century Oncology of Michigan, Farmington Hills, MI more...

65 Background: Given the initial report of the RAPID trial with greater morbidity for 3-D conformal external beam APBI [3D-APBI] vs. Canadian Hypofractionation [CHfx], a propensity-score matched-pair analysis of brachytherapy-based APBI [B-APBI] vs. CHfx was performed to assess efficacy, toxicities, and cosmesis. Methods: Early-stage breast cancer patients treated with B-APBI or CHfx were reviewed. With ≥ 1y follow-up [FU], B-APBI (n=108) pts were matched 1:1 to CHfx (n=108) by age, T-stage, nodal/ER status, endocrine or chemotherapy and laterality. Ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastasis (DM), contralateral breast cancer (CLBC), cause-specific survival (CSS), overall survival (OS) and disease-free survival (DFS) were compared by Kaplan-Meier (log-rank test). Toxicities were graded per CTCAE v3 and comesis per Harvard criteria. Results: Median FU was 5.7 y (1.0-17.8) for B-APBI and 2.1 y (1.0-5.7) for CHfx [p < 0.001]. Patients did not differ by match criteria. In comparing B-APBI to CHfx, median age was 69.0 vs. 70.0 [p = 0.72]; for laterality, T-stage, nodal/ER status, endocrine or chemotherapy, no significance [NS] was noted between the 2 groups [p = 0.79, 1.0, 0.60, 0.09, 0.15, and 0.16 respectively]. Comparing B-APBI to CHfx, NS was seen in 5-y actuarial rates of IBTR [1% vs. 0% p = 0.35], RR [0% both], DM [3.4% vs. 0% p = 0.25], CLBC [2.3% vs. 2% p = 0.63], CSS [94.3% vs. 100% p = 0.47], OS [87.7% vs. 88.3% p = 0.71] & DFS [97.5% vs. 100% p = 0.52]. The majority of maximal late toxicities were Gr 1-2. Of toxicities analyzed, including pigmentary changes, edema, pain, induration, volume reduction, telangiectasia, fat necrosis and seroma, only Gr 2-3 hyperpigmentation was significantly higher in the CHfx [8% B-APBI vs. 22% CHfx p = 0.017]. Good/excellent cosmesis was seen in > 93% in both groups. Conclusions: With FU of >5 yrs, B-APBI has similar efficacy and cosmesis but less morbidity vs. CHfx; the lesser toxicity of B-APBI vs. CHfx is in contradistinction to the RAPID results comparing 3D-APBI vs. CHfx. Further FU and more patients are needed to substantiate these findings. more...

1123 Background: DCIS remains a cautionary criterion for APBI by the ASTRO APBI consensus statement. We performed a matched analysis to compare the efficacy of WBI and APBI for patients with DCIS. Methods: Women with DCIS treated with APBI or WBI were reviewed. APBI (n=102) patients with ≥2 y follow-up were matched 1:3 to WBI (n=546) patients with ≥5 y follow-up by age, tumor size, nuclear grade, ER status, margin status, and laterality. Ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), contralateral breast cancer (CLBC) and cause-specific survival (CSS) were compared by cumulative incidence (Gray’s) and competing risks regression (Fine and Gray’s), and overall survival (OS) and disease-free survival (DFS) by Kaplan-Meier (log-rank test). Results: Median follow-up was 4.6 y (2.0-14.7) for APBI and 9.0 y (5.4-27.0) for WBI. Median (range) or percentages are shown (Table). Patients did not differ by match criteria. There were 17 LR, 1 DM, 19 CLBC, 2 CSS, 22 OS, and 19 DFS events during follow-up. The patient groups had similar rates of cancer-related events including ipsilateral and contralateral breast recurrences at both five and eight years. Treatment type, age, tumor size, nuclear grade, ER status, and hormone therapy (HT) were not prognostic of LR or CLBC on uni- and multi-variate analyses. Conclusions: APBI provides equivalent and exemplary outcomes compared to WBI following breast-conserving surgery for DCIS. These findings support previous reports on the efficacy of APBI in the treatment of noninvasive breast carcinoma. Prospective randomized comparison of APBI to WBI for DCIS is needed. [Table: see text] more...

146 Background: Current guidelines for APBI stratify appropriateness of treatment outside of a clinical trial. Limited data are available, however, regarding the impact of the number of risk factors (RFs) per patient on clinical outcomes. Methods: 692 patients were treated with APBI at a single institution between 10/1992 and 10/2011. Patients were stratified by the ASTRO guidelines as suitable, cautionary, and unsuitable. Outcomes including ipsilateral/contralateral breast tumor recurrence (IBTR/CBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause specific survival (CSS), and overall survival (OS) were evaluated by risk group and number of RFs. Results: Median follow-up was 5.2 years (range: 0-18.3).Distribution within CP risk-groups was suitable: 240, cautionary: 343, and unsuitable: 109 patients. Increased IBTR (2.0% v. 0.6%, p=0.03), DM (6.5% v. 1.5%, p=0.02), and decreased DFS (92% v. 98%, p=0.01) were noted for patients with 2+ cautionary RFs (n=115) vs. 1 RF (n=228). Those with 2+ unsuitable RFs had higher RR (7.7% v. 1.7%, p=0.05). Pooled analysis revealed increased IBTR/RR for patients with 3+ combined cautionary/unsuitable RFs vs. 2 or fewer combined RFs (Table). Univariate analysis showed increased DM with increasing tumor size/T-stage (p more...

148 Background: This analysis compares the efficacy of a 2-day vs. 5-day accelerated partial breast irradiation (APBI) schedule in treatment of early-stage breast cancer. Methods: Patients were treated between 6/2000 and 1/2011 with balloon-based brachytherapy using a 2-day (700 cGy x 4 BID) or a 5-day (340 cGy x 10 BID) fractionation. The CTV was a 1cm expansion from the balloon surface with a single-lumen device used in all cases. To compare efficacy between the two treatment groups, a matched-pair analysis was performed using a 1:2 ratio which paired 38 two-day with 76 five-day patients. Match criteria included minimal follow-up (FU) > 1.0 yr, clinical stage, age (+/- 3 yrs), and ER status. Clinical outcomes analyzed include local-regional recurrence [LR, RR] distant metastases (DM), disease-free, cause-specific and overall survival [DFS, CSS, and OS]. Results: No significant differences were noted for age (p=0.838), clinical stage (p=1.000), ER (p=1.000), tumor size (p=0.236), margin status (p=0.556), nodal stage (p=0.381), PR (p=0.749), use of chemotherapy (p=0.927) or endocrine therapy (p=0.129). Per the ASTRO Consensus Guidelines, no differences were noted in the clinical groups between the 2-and 5-day treatments with the majority categorized as suitable or cautionary (2-day: 92% vs. 5-day: 87% p=0.436). With a mean FU of 4.7 yrs (4.9 yrs for 2-day vs. 4.5 yrs for 5-day, p=0.279), no differences were seen in the 5-year actuarial rates of LR (0.0% vs. 2.6%, p=0.359), DFS (94.4% vs. 96.1%, p=0.618), CSS (100% vs. 94.9 %, p=0.207), or OS (97.3% vs. 92.5%, p=0.811) between the 2-and 5-day groups, respectively. There was no RR in either group. DM rates were similar for both (5.6% vs. 1.3 %, p=0.456). Conclusions: With near 5-year FU for the 2-day schedule, APBI with the 2-day regimen yielded outcomes equivalent to the 5-day schema. Reduced on-treatment days by such hypofractionation offers flexibility in clinical and patient scheduling. Further FU and more patients will be needed to substantiate equivalence of hypofractionated APBI. An HIC-approved protocol randomizing patients between the 2 vs. 5-day treatments is currently open for accrual at our institution. more...

145 Background: To determine whether the ASTRO Consensus Panel (CP) guidelines for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite Registry Trial. Methods: 2,127 cases of early-stage breast cancer were treated using APBI (WBH: n=678; ASBrS: n=1,449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3D-CRT, n=206) while all Registry Trial patients received balloon-based brachytherapy. Patients with complete coding necessary for ASTRO CP assignment (n=1,813) were divided into suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CP group. Results: Median age was 65 years (32-94 years) and median tumor size was 10.0mm (0-45mm). The WBH cohort had more node-positive disease (6.9% vs. 2.6%, p more...

111 Background: We present the results of an analysis of high-risk breast cancer patients as defined by the NSABP B-39/RTOG 0413 phase III trial, all treated with accelerated partial breast irradiation (APBI) from a single institution. Methods: Between July 1993 and August 2010, 130 patients with any combination of at least one of the high-risk features of estrogen receptor (ER) negativity, age < 50, and/or axillary nodal positivity were treated with 1 of 3 forms of APBI. Sixty-seven patients were treated with interstitial needle-catheter brachytherapy, 44 balloon-based brachytherapy and 19 with 3D conformal external beam radiation therapy. Aside from the high-risk features, general eligibility criteria included infiltrating ductal carcinoma, with inclusion of invasive lobular and DCIS since 2003, margins > 2 mm, and surgically staged axilla. One-hundred eighteen patients had one high-risk factor, 11 had two, and 1 had all three factors. The median tumor size was 12.0 mm with margins > 2 mm in 80% of patients. Greater than 75% had T1 tumors and 50% were ER negative. Thirty-one percent of patients were node positive. Based upon the ASTRO Consensus Guidelines for use of APBI (2009) none of these patients were suitable, 38% cautionary and 62% were unsuitable. Results: Median age was 56.5 yrs (range 40-90). With a median follow-up of 5.3 yrs (0.02-16.9) the 5-yr actuarial local recurrence rate (LR) was 4.2%; regional recurrence (RR) was 2.1%. Median time to LR and RR were 1.2 and 2.8 yrs, respectively. On univariate analysis, the only factor significant for LR was a close/positive margin (p=0.031), as ER/PR, age, nodal status, tumor size, histology, grade, hormonal or chemotherapy were all NS. The 5-yr actuarial cause specific, disease-free, and overall survivals as well as distant metastasis were 94%, 91%, 90%, and 6.4%, respectively. Conclusions: This cohort of NSABP B-39/RTOG 0413 identified high-risk patients who have undergone APBI has yielded local-regional control rates and survival outcomes comparable to standard risk patients undergoing partial breast irradiation. Continued follow-up will be needed to assess the long-term efficacy of such high-risk breast cancer patients treated with APBI. more...

107 Background: Currently, node-positive patients are considered unsuitable for APBI per the ASTRO guidelines with limited data on outcomes of node-positive patients following APBI. Methods: 510 patients with early-stage breast cancer received accelerated partial breast irradiation (APBI) between April 1993 and November 2010. Of these, 39 were lymph node positive with 10 patients having N1mi disease (median size of mets = 0.82 mm) and 29 patients having N1 disease (61.5% had 1 node positive [median size of mets = 2.5 mm], 30.8% had 2 nodes positive [median size of mets = 8.0 mm], and 7.7% had 3 nodes positive [median size of mets = 20 mm]). Patient, clinical, and pathologic factors were analyzed and compared for the node-negative (N0) and node-positive (N+) cohorts including age, tumor size, receptor status, margin status, adjuvant hormone therapy, adjuvant chemotherapy, and length of follow-up. Results: N+ patients were younger (p=0.04), had larger tumors (p Conclusions: No difference was seen in the rates of local recurrence or axillary failure between node-negative and node-positive following APBI with 5-years of follow-up. more...

83 Background: To determine clinical outcomes for patients treated with accelerated partial breast irradiation (APBI) based on breast cancer subtype. Methods: We evaluated 516 consecutive patients who received APBI with a minimum follow-up of 6 months. Methods of APBI delivery included interstitial brachytherapy (n=221), balloon-based brachytherapy (n=201), and 3D-CRT (n=106). Women were assigned a breast cancer subtype (BCST) based on results of testing for estrogen (ER), progesterone (PR), and human epidermal growth factor (HER2/neu) receptors. Those without test results for all three receptors were excluded. 278 patients were eligible and submitted for analysis. Receptor subtypes were approximated as follows: ER+, PR+/–, and HER-2 negative [luminal A (LA), 164 pts.]; ER+, PR+/–, and HER-2 positive [luminal B (LB), 81 pts.]; ER/PR–, HER-2+ [HER-2 (H2), 5 pts.], and ER/PR/HER-2 negative [basal (B), 28 pts.]. An analysis was then performed to estimate IBTR, RNF, DM, DFS, CSS, and OS. Results: Mean age was 66 years, median follow-up was 4.9 yrs. Basal and H2 subtype patients had higher histologic grades (Gr. 3 = 75% vs. 10% LA/LB, p Conclusions: Five-year local control rates after treatment with APBI are excellent for luminal, HER2, and triple-negative phenotypes of early-stage breast cancer. Further study of BCST is important and may be useful when counseling patients on adjuvant treatment options following breast-conserving surgery. more...