bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCIC-CTG MA.20: An intergroup trial of regional nodal irradiation in early breast cancer.
Authors: Whelan T. J. , Olivotto I. , Ackerman I. , Chapman J. W. , Chua B. , Nabid A. , Vallis K. A. , White J. R. , Rousseau P. , Fortin A. , Pierce L. J. , Manchul L. , Craighead P. , Nolan M. C. , Bowen J. , McCready D. R. , Pritchard K. I. , Levine M. N. , Parulekar W. 
Published: February 2017

LBA1003 Background: Randomized trials have demonstrated that locoregional radiation after mastectomy reduces locoregional recurrence and improves overall survival (OS) in women with node positive breast cancer treated with adjuvant systemic therapy. MA.20 evaluated the addition of regional nodal irradiation (RNI) to whole breast irradiation (WBI) following breast conserving surgery (BCS). Methods: Women with high risk node-negative or node-positive breast cancer treated with BCS and adjuvant chemotherapy and/or endocrine therapy were stratified by positive nodes, axillary nodes removed, chemo- and endocrine therapy and randomized to WBI (50Gy in 25 fractions +/- boost irradiation) or WBI plus RNI (45Gy in 25 fractions) to the internal mammary, supraclavicular, and high axillary lymph nodes. The primary outcome was OS. The Data Safety Monitoring Committee approved the analysis plan for the protocol specified interim analysis of relapse patterns, survival and toxicity at 5 years. Upon review of the data, they recommended release of the results. Results: Between March 2000 to March 2007, 1,832 women were randomly assigned to WBI+RNI (916) or WBI (916). Median follow-up was 62 months. Characteristics of the study population were: mean age, 53.3 years; node negative, 10%; 1-3 positive nodes, 85%; > 4 positive nodes, 5%; adjuvant chemotherapy, 91%; and adjuvant endocrine therapy, 71%. WBI+RNI in comparison to WBI alone was associated with an improvement in isolated locoregional disease free survival (DFS; HR=.59, p=.02, 5 year risk: 96.8% and 94.5% respectively), distant DFS (HR=.64, p=.002, 5 year risk: 92.4% and 87.0% respectively), DFS (HR=.68, p=.003, 5 year risk: 89.7% and 84.0% respectively) and OS (HR=.76, p=.07, 5 year risk: 92.3% and 90.7% respectively). WBI+RNI in comparison to WBI was associated with an increase in grade 2 or greater pneumonitis (1.3% and 0.2% respectively, p=.01), and lymphedema (7.3% and 4.1% respectively, p=.004). Conclusions: The majority of women with node positive breast cancer are now managed by BCS followed by WBI and adjuvant systemic therapy. Results from MA.20 demonstrate that additional RNI reduces the risk of locoregional and distant recurrence, and improves DFS with a trend in improved OS.
Phase III study of gemcitabine/oxaliplatin (GEMOX) with or without erlotinib in unresectable, metastatic biliary tract carcinoma.
Authors: Lim H. Y. , Lee J. , Chang H. , Kim J. S. , Choi H. J. , Lee M. A. , Jang J. , Jeung H. , Kang J. H. , Lee H. W. , Shin D. , Jang H. J. , Sun J. , Park S. H. , Park J. O. , Park Y. , Kang W. K. 
Published: February 2017

LBA4032 Background: Currently, there is no standard regimen for palliative chemotherapy in metastatic, unresectable biliary tract cancer (BTC). A phase II trial of erlotinib monotherapy showed a promising anti-tumor activity in BTC with tolerable toxicity. Additionally, gemcitabine + erlotinib demonstrated superior efficacy when compared to gemcitabine alone in pancreatic cancer. Hence, we conducted a phase III trial to compare between GEMOX vs GEMOX+erlotinib (Tarceva [T]) (GEMOX/T) as first-line chemotherapy in unresectable, metastatic BTC. Methods: Eligible patients were as follows: histologically confirmed adenocarcinoma of biliary tract (CCC), ampulla of vater (AOV) or gall bladder (GB); unresectable or metastatic; ECOG performance status of 0~2; adequate marrow, hepatic, renal and cardiac functions; no prior chemotherapy. The primary endpoint was progression free survival (PFS). The study regimen was gemcitabine 1,000mg/m2, oxaliplatin 100mg/m2, erlotinib 100mg qd daily q 2 weeks. Results: From February 2009 to August 2010, 268 pts were randomized, 133 patients to GEMOX arm and 135 patients to GEMOX/T arm. Patient characteristics: median age 61 yrs (range 30-82); male (63.4%); CCC (n=180, 67.2%), GB (n=82, 30.6%), and AOV (n=6, 2.2%). With a median follow-up of 13.9 months (range, 6.7 – 25.0), median PFS was 5.8 months (95% CI, 4.6 - 7.0) in GEMOX/T arm and 4.2 months (95% CI, 2.7 - 5.7) in GEMOX arm (P=0.080). In subgroup analysis (CCC, n=180), however, median PFS was significantly longer in GEMOX/T arm (5.9 months) when compared with GEMOX arm (3.0 months, P=0.049). The overall response rate was significantly higher in the GEMOX/T arm when compared with GEMOX arm. There was no significant difference in overall survival between the two arms (GEMOX/T: 9.5 months, 95% CI, 7.6 – 11.4; GEMOX: 9.5 months, 95% CI, 7.5 – 11.5; P=0.611). The EGFR mutation testing results in correlation to responsiveness to erlotinib will be presented at the meeting. Conclusions: This phase III represents the first multicenter, randomized trial to compare GEMOX vs GEMOX/T in unresectable, metastatic BTC. Although PFS was not prolonged in GEMOX/T, there was a significant benefit in terms of PFS in GEMOX/T arm for CCC patients.
Silver in situ hybridization compared with immunohistochemistry in assessing HER2/neu status in fine-needle aspiration cytology.
Authors: Nofech-Mozes S. , Saad R. S. , Noy S. , Hanna W. , Ghorab Z. 
Published: February 2017

10 Background: Fine needle aspiration (FNA) cytology is a common diagnostic tool in breast cancer used to establish diagnoses of primary, metastatic or recurrent lesions. In these settings, knowledge of the HER2/neu status is vital for optimal therapeutic decision. We examined the accuracy of HER2/neu testing in alcohol-fixed malignant aspirates. Methods: FNAs with known HER2/neu status on concurrent/subsequent surgical specimen were retrospectively identified to select a study group of malignant aspirates in cell blocks (CB) from 38 breast and 18 axillary lymph nodes. This group was enriched for HER2/neu positive cases. Sequential sections were studied by IHC using rabbit monoclonal antibody 4B5 and SISH INFORM HER2 DNA and Chromosome 17 (both by Ventana Medical Systems, Tucson AZ, USA). IHC and SISH were evaluated by two pathologists according to 2007 ASCO/CAP criteria and results were compared with HER2/neu status of paired concurrent/subsequent surgical specimen. Results: HER2/neu IHC on CB yielded 17/56 (30.6%) positive, 30/56 (53.6%) negative and 9/56 (16.1%) equivocal cases. HER2/neu SISH on CB revealed 25/56 (44.6%) amplified, 30/56 (53.6%) not amplified cases. In one case the test was uninterpretable. HER2/neu status on available on 54 surgical specimens (combined IHC and ISH results) was positive in 26 cases and negative in 28. The concordance between negative or positive IHC and SISH on cell blocks was 93.6%. SISH on cell blocks could predict the HER2/neu status in 98.2% of surgical specimens whereas after exclusion of equivocal results, IHC on cell clocks could predict it in only 91.1%. Of the 26 cases with positive HER2/neu status, IHC-CB revealed 3 cases that scored 1+ and one case that scored 0 on cell block. These cases would have been misclassified if HER2/neu was tested on CB by IHC alone. Conclusions: SISH is a reliable methodology for testing HER2/neu in alcohol fixed cytology specimens and is superior to IHC in its ability to accurately predict the final HER2/neu status. Alternatively, cases can be first tested with IHC and further tested with in situ hybridization when the score is under 3+ to avoid false negative results.
Correlation between preoperative T1 breast cancer staging and final pathologic analysis.
Authors: Gass J. S. , Wiggins D. L. , Dizon D. S. 
Published: February 2017

101 Background: Contemporary breast surgery is exploring less invasive techniques for the treatment of breast cancer and recent approaches such as ablative therapy have shown promise in early trials. Caution is required prior to adopting of these techniques, however, as ablative treatment may hinder interpretation of final pathology, which might impact adjuvant recommendations. To address this concern, we evaluated the concordance between preoperative core needle biopsy and postoperative final pathology, to determine whether the biopsy findings predicted final pathology. Methods: A retrospective chart review was performed of women diagnosed with breast cancers less than 2 cm on radiographic evaluation between 1997 and 2004. Concordance between preoperative assessment (by imaging and core needle biopsy) and final pathology results was analyzed based on tumor size, grade, lymphovascular space invasion, and in situ component. Kappa analysis was performed to characterize agreement. Results: We identified 56 women from our institution for analysis. The median age was 56 (range, 38-94) and the majority had presented with an abnormal mammogram (61%). The vast majority also underwent breast-conserving surgery (95%). Agreement was moderately accurate between preoperative and final assessment of grade (weighted κ 0.536) and size (weighted κ 0.464). It was not accurate in the assessment of lymphovascular invasion (weighted κ 0.123) and the presence of DCIS (weighted κ 0.197). Conclusions: Information from preoperative evaluation is insufficiently accurate for the evaluation of breast tumors, which may be important for adjuvant decision making. This information must be taken in to account when assessing new technologies, which may impact on the assessment of histologic criteria in excised breast cancers.
Case-cohort study to determine the value of therapeutic touch in preventing radiation dermatitis.
Authors: Younus J. , Lock M. , Malec J. , Vujovic O. , Yu E. 
Published: February 2017

103 Background: Therapeutic touch (TT) is a noninvasive healing technique. There is evidence of value in various clinical areas, but not during radiotherapy (RT) for breast cancer. The TT Cohort was designed to assess the acceptability, compliance, and side effects of TT. The Control Cohort was used compare the impact of TT in preventing radiation dermatitis. Methods: Early breast cancer patients scheduled to undergo post-conservative surgery RT were selected. TT was administered three times per week during RT. Feasibility was defined a priori as 15 of 17 patients completing all treatments. The effectiveness of TT was evaluated by the NCIC CTC V3 dermatitis scale and EORTC Cosmetic Rating. The quality of life (QOL), mood, and fatigue were assessed by EORTC QLQ C30, POMS, and BFI, respectively. These were assessed at baseline and weekly during treatment. Results: 17 stage I/II breast were prospectively identified for the TT Cohort and 31 patients were prospectively assessed in the Control Cohort. Median age was 63 years (47-79). TT was considered feasible as all 17 patients completed treatment. In the TT Cohort, the worst grade of radiation dermatitis was grade II in 9 patients. One patient did not develop any dermatitis. Median time to develop the worst grade was 20 days. QOL, mood and energy, and fatigue levels were consistent with the previous published studies. In the Control Cohort, the worst grade of radiation dermatitis was grade III in 1 patient. The most common toxicity grade was II in 15 patients. Three patients did not develop any dermatitis. Median time to develop the worst grade was 29 days. There was no statistical difference in the overall cosmetic score and grade II/III toxicity. There was a statistically significant difference in skin pigmentation and edema. Conclusions: This study represents the first evaluation of TT in patients with EBC using objective measures. TT is a feasible addition for the management of dermatitis to a tertiary clinic. TT neither improved overall cosmesis nor grade II/III toxicity.
Comparison of locoregional recurrence in triple-negative and HER2-positive breast cancer subtype after breast-conserving therapy and modern systemic therapy.
Authors: Takita C. , Reis I. M. , Miao F. , LaFave K. E. , Gunaseelan V. , Hurley J. , Silva O. E. , Avisar E. , Wright J. L. 
Published: February 2017

112 Background: Triple-negative (basal) and HER2+ subtypes have been associated with increased risk of locoregional recurrence (LRR) in earlier studies of breast-conserving therapy (BCT), in which fewer patients received systemic therapy compared with recent standards, including HER2-targeted therapy. We analyzed whether basal and HER2+ subtypes are independent prognostic factors for LRR in BCT patients treated with modern systemic therapy. Methods: We retrospectively studied 415 patients with invasive breast cancer who received BCT from 1992 to 2009. Axillary surgery was done in 404 patients (97%). Forty eight percent of patients received chemotherapy (anthracycline/taxane 34%, trastuzumab-containing 4%, other 10%). Hormone therapy was given in 67%. Progression-free survival (PFS) and OS were estimated by the Kaplan-Meier method. Rate of LRR was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Fine and Gray’s test. Results: Median follow-up was 60 months. Median age was 54 (26–86). Stage: T1 70%, T2 26.3%, T3 8%; N0 75%, N1 23.5%, N2 1.7%. Receptor status was available in 301 patients to approximate subtypes: 66% Luminal A, 9% Luminal B, and 5% HER2+, and 20% Basal. Overall, there were 11 LRR, 15 distant metastasis, and 20 deaths. The 10-year PFS and OS were 85.4% and 90.5%, respectively. The 5 and 10-year cumulative incidence of LRR were 2.8% (95%CI: 1.4–5.2) and 4.5% (95%CI: 2.2–8.2) respectively. On univariate analysis, Basal vs. Luminal A (HR: 9.12, p<0.001) and tumor size >2cm vs. ≤2cm (HR: 4.00, p=0.022) were significant prognostic factors for LRR as first failure. On multivariate analysis, only basal subtype (HR: 6.29, p=0.011) retained significance; others effects, including luminal B/HER2 combined subtypes, were not significant. Conclusions: Long-term clinical outcomes were excellent in this cohort of breast cancer patients treated with BCT and modern systemic therapy, with 10-year LRR 4.5% and OS 90.5%. Basal subtype was an independent predictor for LRR. Conversely, HER2+ subtype was not associated with increase in LRR, in this cohort treated with BCT and trastuzumab.
Evidence-based indications for post-mastectomy radiation after neoadjuvant chemotherapy for stage II-III breast cancer.
Authors: Mayadev J. , Fowble B. , Einck J. P. , Kim D. , McCloskey S. , Yashar C. M. , Chen S. L. , Hwang S. E. ,   ATHENA Breast Health Network
Published: February 2017

114 Background: There are no established guidelines to define the role of post-mastectomy radiation therapy after neoadjuvant chemotherapy. We sought to identify a cohort of women with stage II-III breast cancer in whom radiation may be omitted based on the risk of local-regional failure (LRF). Methods: Seven breast cancer physicians participating in the multi-campus University of California (UC) Athena Breast Health Network identified, reviewed and abstracted the available literature (from MEDLINE and Cochrane databases), formulated evidence tables (endpoints LRF, disease-free, and overall survival) and developed a risk assessment table of women undergoing mastectomy after neoadjuvant chemotherapy. We created 18 hypothetical clinical case scenarios, and using the American College of Radiology appropriateness criteria methodology, assigned appropriateness ratings for post-mastectomy radiation for each scenario based on our literature review. Results: 23 of 24 studies identified were retrospective from single institutions. Consensus (80% agreement in a category) in the appropriateness rating was achieved for 78% of the clinical scenarios. Distinct LRF risk categories emerged. Patients who presented with clinical stage II (T1-2N0-1) ER(+) disease with age at diagnosis ≥35-40 years who had either a pathologic complete response (pCR) or 0-3 positive nodes without LVI or ECE were identified as having ≤10% risk of LRF without radiation. Limited data support pCR stage IIIA patients as being low risk. Conclusions: In the absence of randomized trial data, we identified existing data to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using this data and the appropriateness ratings, we found a high concordance of treatment recommendations for PMRT in our clinical scenarios and were able to identify a cohort of women with a low risk of LRF without radiation. These women will form the basis for future clinical studies in the UC Athena Breast Health Network.
Risk of breast fibrosis following irradiation using a breast-specific SBRT system compared with conventional APBI.
Authors: Husain Z. A. , Feigenberg S. J. , Nichols E. , Zhang J. , Yu C. , Prado K. , Yi B. , D'Souza W. , Mutaf Y. 
Published: February 2017

116 Background: To determine the dosimetric characteristics and risk of breast fibrosis using a normal tissue complication probability (NTCP) model in conjunction with a novel preoperative stereotactic radiotherapy system called the GammaPod. Results are compared with linac based post-lumpectomy APBI plans for the same cohort. Methods: The GammaPod breast SBRT system consists of a Co-60 irradiation unit in combination with an immobilization device with embedded fiducials. Eight patients were enrolled in an IRB-approved protocol and underwent CT scans in the prone position with breast immobilization. A preoperative target (GTV) was synthesized to match the tumor location and volume reported in imaging studies obtained prior to surgery (0.3-2.4 cc). The GTV was expanded by 1.5 cm to create a CTV, and a PTV was created using an additional 0.3 cm margin. The PTV was prescribed 25.5 Gy in 3 fx, which is radiobiologically equivalent to conventional APBI doses of 38.5 Gy in 10 fx. Following the radioablative experience in NSCLC, we also planned to deliver 60.0 Gy to the GTV+0.3 cm as a simultaneous boost in conjunction with the 25.5 Gy PTV prescription dose. For comparison, linac-based treatment plans were created for the same cohort following NSABP B-39 guidelines. Whole breast dosimetry was analyzed in terms of biologically equivalent dose (BED) and Lyman NTCP analysis was performed. Results: The volume of ipsilateral breast receiving 10, 20, 50, and 100% of the prescribed dose was substantially smaller in GammaPod vs. APBI plans, with cohort averages of 19.3, 13.0, 7.1 and 4.0% vs. 75.8, 67.3, 48.1 and 27.6% respectively (p<0.001). Even though the PTV equivalent uniform BED (EUD) was substantially higher in GammaPod plans (87.9 Gy vs. 57.3 Gy), the ipsilateral breast EUD was still smaller in these plans, 18.9 ± 5.0 Gy vs. 47.2 ± 3.2 Gy (p<0.001). Corresponding NTCP predictions for breast fibrosis rates following GammaPod and APBI treatments were 0.2 ± 0.1% vs. 2.8 ± 0.8% (p<0.001), respectively. Conclusions: The GammaPod system improves upon traditional post-lumpectomy linac-based APBI by decreasing dose to the ipsilateral breast as well as the predicted rates of breast fibrosis.
Dosimetric comparison of radiotherapy plans for left-sided breast cancer patients in rolled versus supine body position.
Authors: Tao M. L. , Mikolajczyk N. , Martyn B. , Botnick L. E. 
Published: February 2017

124 Background: Left-sided breast cancer patients receiving whole breast radiation therapy (WBRT) are potentially at increased risk for cardiac morbidity. We evaluated heart sparing of left-sided breast cancer patients when placed in the rolled vs. the standard supine body position for WBRT. Methods: Ten patients with left-sided breast cancer underwent planning CT scans in 2 different positions: supine and rolled to the right to allow for the heart to drop away from the chest wall. Patients were immobilized using vacuum cradles. The left lung, opposite breast, stomach, heart, left ventricle (LV), and left anterior descending coronary artery (LAD) were defined as organs at risk (OARs). Comparison 3D conformal tangential field plans were generated for each patient. Dose-volume histograms (DVHs) of the planning target volume (PTV) and OARs were examined. Results: All plans met PTV dose coverage and homogeneity criteria of V95 > 95% and maximal dose < 108. Median V105 for PTV was 12.75% (range, 2.5-16%). None of these parameters differed either statistically or clinically between plans done with the patient supine or rolled. The maximal doses to the opposite breast and stomach were also not significantly different between the 2 positions. The right lung V20 was similar for the 2 positions, 11.1% and 12%. Although there were no significant differences in the mean and max doses to the heart or LV, the mean heart dose decreased by 18-70% in 6 patients in the rolled vs. supine position and increased by 2.7-31.5% in 4 patients. The mean dose to the LAD and the LAD V10 and V15 were significantly decreased when the patient was rolled: 17.1 vs. 29.5 Gy, 41.1% vs. 62.6% and 40% vs. 66.7% (p < .05), respectively. Six patients had superior plans when in the rolled position with substantial differences in the mean and/or max doses and/or DVHs for the heart, LV and LAD. The remaining 4 patients had no overall improvement or worsening of the plan when the patient was rolled vs. supine. Conclusions: For patients with left-sided breast cancer receiving WBRT, the rolled position potentially reduces dose to the heart and its substructures without compromising the coverage and homogeneity of the PTV, hence limiting the need for IMRT.
Planning the boost in early-stage breast carcinoma: Comparison of two methods.
Authors: Krakobsky V. , Gwirc D. 
Published: February 2017

126 Background: When it comes to breast-conserving surgery the boost volume becomes a critical target because it has the highest risk of residual cancer cells. At our institution the most common methods to contour the tumor bed are: the scar-based planning guided by fluoroscopy (2DP) and the one that relies on the visualization of the seroma under CT (3DP). We evaluated the accuracy of the breast boost volume treated with clinical mark-up compared with the volume delineated with CT planning. Additionally, we evaluated whether or not the lumpectomy scar is a suitable landmark to define the tumor bed. Methods: 20 patients diagnosed with breast cancer stage I-IIA underwent tumor bed boost planning using two techniques: 2DP and 3DP. All the information concerning to the 2DP was reproduced in a radiotherapy planning system. Statistical analysis: the match pair t-test and the coefficient of variation were used to test for an association among the two planning techniques for tumor bed coverage. The D95, D90, V15, volume, medium lung dose and geographic miss were analyzed. Pearson correlation analysis was used to assess the relationship between CVS, date of surgery, age and previous chemotherapy treatment. Other items taken into account were the match between the scar and the seroma, and how good the visualization of the seroma was by using the CVS. Results: 2DP was inaccurate: the mean D95, D90 and V15 were 3.12 Gy, 4.6 Gy and 29% respectively (variation coefficient: 135%, 107% and 65% respectively). The difference between the mean 2DP D95 and 3DP D95 was 11 Gy (95% CI, 9 Gy to 13 Gy, p< 0.001). The difference between the mean 2DP V15 and 3DP V15 was 59% (95% CI, 49% to 69%, p < 0.001).The percentage of geographic miss was: 80% (95% CI, 63% to 97%). All the seromas were finely visualized There was no correlation between CVS, age, prior chemotherapy and date of surgery. The volumes and the medium lung dose were larger for the 3D method: 373.1 cm3 vs. 248.8 cm3 and 0.27Gy vs. 0.14 Gy respectively. Only 45% of the lumpectomy scars matched the seroma. Conclusions: CT-based planning allows for optimal tumor bed coverage compared with scar-based planning which carries a significant risk of missing the target. The lumpectomy scar is often a poor indicator of the tumor bed.