bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyrosine kinase profiling guides combined therapeutic strategies in head and neck cancer
Authors: Rodríguez-Barrueco R. , Ortíz-Ruiz M. , Cruz J. J. , Ocana A. , Pandiella A. 
Published: August 2020

6078 Background: Squamous cell carcinoma of the head and neck (SCCHN) is still an incurable disease in the metastatic setting. A particular subgroup of proteins implicated in the head and neck cancer are the tyrosine kinases (TK). Therapeutic inhibition of several of them including the EGF receptor with cetuximab in combination with radiotherapy or chemotherapy has shown to be clinically useful. Beyond EGFR, oncogenic activation of other TKs may be implicated in the genesis/progression of SCCHN. In this context, the identification of the TKs activated in SCCHN is a must in order to adequately target these kinases with already available inhibitors. Methods: Here we have investigated activated tyrosine kinases in head and neck cancer tumors derived from patients using a human phospho protein array for 42 receptor tyrosine kinases (RTK). Western-blot experiments were performed to validate each phospho RTK in tumors from patients. The same approach was followed in a series of head and neck cancer cell lines. In vivo xenografted models were used to study the antiproliferative effect of the combination of specific TK inhibitors against them. Results: TK receptors of the EGF and the VEGF family were the mostly activated in tumors derived from patients. 90% of patients revealed high pEGFR content. In addition, other EGFR/HER family receptors, such as HER3, were also activated (phosphorylated) in samples from patients. These data were corroborated in the SCCHN cell lines. In these cells, other RTK signalling intermediates were also active. Particularly, the Akt and FAK kinases. Combination of the anti-EGFR-HER2 TK inhibitor lapatinib with dasatinib (that targets FAK) was synergistic in vitro. Combination of lapatinib with the anti-VEGFR TK inhibitor pazopanib was inefficient in vitro, but resulted in a better trend in response in the in vivo xenografted models, as compared to the action of the single agents. Conclusions: Rational target drug combinations should be based on the identification of activated TK receptors or downstream signalling molecules. In head and neck cancer combination strategies using anti-EGFR/HER, anti-FAK, and anti-VEGFR compounds increases the action of individual treatments. These results open the door for future clinical development of these drug combinations. No significant financial relationships to disclose.
Orotate phosphoribosyl transferase and XPA expressions as predictive biomarkers for combined chemotherapy with 5-fluorouracil and cisplatin in oro- and hypopharyngeal cancers
Authors: Hasegawa Y. , Hanai N. , Terada A. , Ozawa T. , Goto M. 
Published: August 2020

6084 Background: The main purpose of the present study was to find predictive biomarkers that can be routinely used for the response to chemotherapy in head and neck squamous cell carcinomas. From this standpoint, we have investigated the gene expression profile of individual tumors as available predictive biomarkers. Methods: Sixty-four tumor specimens from patients undergoing radical treatment for squamous cell carcinomas of the oro- and hypopharynx in stage II, III, or IV, were included in the present study. There were 30 primary tumors sites in the oropharynx and 34 in the hypopharynx, respectively. All patients were administered induction chemotherapy (FP) with a combination of 5-FU (800 (600) mg/m2 d1–5 (6)) and cisplatin (80 mg/m2 d6 (7)) before definitive therapy. This chemotherapy was used in order to select patients for organ preservation based on the response and decrease in late salvage surgery rate. Treatment was repeated every 3 to 4 weeks. Using biopsy specimens, we analyzed their gene expression profiles with the following 25 markers, which we thought were likely predictors of the response to anti-cancer agents: TS, DPD, OPRT, TP, COX2, MDR1, MRP1, VEGF, EGFR, HER2, PIK3CA, PTEN, p53, Rb1, Bcl2, BclX, BAX, GSTπ, ERCC1, XPA, E2F1, ENT1, Rev3, β-tubulin, and Survivin. These mRNA expressions were quantified by real-time reverse transcription polymerase chain reaction (real-time RT-PCR) assay. Clinical markers, such as T and N factor, gender and age were added, and logistic regression analysis and likelihood ratio test were conducted. Results: Univariately, response for chemotherapy was significantly correlated with T factor (p = 0.015), and the mRNA expression level of XPA (p = 0.018) and OPRT (p = 0.047). Meanwhile, using a multivariate logistic regression analysis with these factors (clinical markers, OPRT and XPA), T factor (p = 0.048) and the expression of XPA (p = 0.035) were demonstrated to be independent predictors for chemotherapy. Conclusions: XPA (Xeroderma Pigmentosum A) and OPRT (Orotate phosphoribosyl transferase) may be possible reliable predictive biomarkers for FP therapy, and might help the decision-making strategy for individual patients with head and neck cancers. No significant financial relationships to disclose.
Visualization of invasive breast cancer and its subclinical disease spread within the breast: Precise correlation between MR imaging findings and histopathologic findings
Authors: Schmitz A. C. , van den Bosch M. A. , Loo C. , Peterse J. L. , Gertenbach M. , Mali W. P. , Rutgers E. J. , Gilhuijs K. G. 
Published: August 2020

610 Background: Magnetic Resonance Imaging (MRI) of the breast shows superior ability to visualize the extent of invasive breast cancer compared to conventional breast imaging. Nonetheless, MRI may under- or overestimate the extent of invasive disease, and the ability of MRI to depict components of disease around the primary invasive tumor is not well established. The purpose of this study was to precisely correlate MRI findings with histopathologic findings in breast cancer patients and to establish the incidence and quantity of surrounding MRI occult disease in breast cancer patients that are scheduled for breast-conserving therapy (BCT). Methods: Patients were prospectively included if they had biopsy-proven invasive breast cancer and the choice of treatment was BCT after pre-operative MRI. Pathology findings were spatially reconstructed and correlated with preoperative MRI. Tumors were stratified by absence or presence of an extensive intraductal component (EIC- or EIC+). The largest diameter of the MRI-visible lesion was compared with the largest diameter of the primary invasive tumor at pathology. Distances (mm) between the edge of the MRI-visible lesion and surrounding subclinical tumor foci (i.e., DCIS, invasive foci) were measured. At various distances from the edge of the MRI-visible tumor, the incidence of disease was determined. Results: 53 patients with 54 breast tumors were included. 42 tumors were EIC- and 12 were EIC+. The mean size (± SD) of the primary invasive tumor was 18.1 ± 7.5 mm on MRI and 19.5 ± 8.2 mm on pathology (Pearson's correlation coefficient: 0.75). The MRI-visible lesion was larger than or equal to the primary invasive tumor on pathology in 21 (39%) cases. Underestimation of the primary invasive tumor occurred up to 7 mm from the edge of the MRI-visible lesion. Beyond 10 mm, subclinical tumor foci were found in 48% off all tumors, in 36% and 92% of EIC- and EIC+ tumors (p < 0.001). Beyond 20 mm these rates were 19%, 7% and 67%, respectively (p < 0.001). Conclusions: Disease around MRI-visible lesions may be more extensive than assumed prior to treatment, especially in EIC+ tumors. This may have consequences for treatment margins in MRI-guided therapy of localized breast cancer. No significant financial relationships to disclose.
In newly diagnosed breast cancer, is a contralateral prophylactic mastectomy necessary following a negative MRI?
Authors: Bernard J. R. , Vallow L. A. , McNeil R. B. , McLaughlin S. A. , Geiger X. J. , Perez E. A. 
Published: August 2020

627 Background: With more centers using MRI to aid in initial staging, there is apprehension that the highly sensitive MRI exam may lead to “unnecessary” mastectomies. We evaluated whether a negative contralateral MRI could be used to rule out a synchronous contralateral carcinoma and hence avoid a prophylactic contralateral mastectomy (CPM) at initial breast cancer diagnosis. Methods: Data of women with a new diagnosis of breast cancer (invasive or DCIS) from February 2003-November 2007 at our institution were reviewed. Women who had a negative MRI of the contralateral breast and who subsequently underwent CPM were included. A CPM was one in which there was no histological confirmation of cancer in the contralateral breast before surgery. All mastectomy specimens were analyzed pathologically. True negatives were mastectomy samples which contained no cancer following pathologic examination. False negatives were mastectomy samples which were found to have cancer after pathologic review. Results: 538 women were identified. 51 women met the study criteria. Median patient age was 56 years (range, 33–77). Of the 51 women who underwent a CPM, 2 were found to have pathologic confirmation of cancer. One occult cancer was a 0.3 cm grade 1, invasive lobular carcinoma; the second a 0.5 cm, low grade DCIS. The overall prevalence of synchronous occult contralateral cancer after a negative MRI was 3.9% (95% CI 0.5 - 13.5%). The negative predictive value of MRI was 96.1% (95% CI 86.5 - 99.5%). Conclusions: This study provides pathologic data regarding the utility of a negative contralateral breast MRI in women with newly diagnosed breast cancer. The prevalence of a synchronous occult contralateral cancer after a negative MRI in women with newly diagnosed breast cancer is very low. Physicians and patients can be assured that the risk of occult cancer is low in the setting of a normal contralateral MRI, an important fact when considering CPM after a diagnosis of unilateral breast cancer. No significant financial relationships to disclose.
Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer
Authors: Kiel K. D. , Refaat T. , Navanandan N. , Sathiaseelan V. 
Published: August 2020

631 Background: Hyperthermia is a known radiation sensitizer. This retrospective series evaluates a single institutional experience with hyperthermia and radiotherapy (RT) for locally advanced/recurrent breast cancer, many referred for palliation. Methods: Records of 130 pts with locally advanced/recurrent breast cancers treated with hyperthermia and RT from 1991–2007 were reviewed. 40% had distant metastases. 168 different sites were irradiated to 16–76.4 Gy (median 50 Gy) with conventional fractions and treated with 1–11 hyperthermia sessions twice/wk (median 6). 58 pts required >1 hyperthermia field to cover tumor. Intratumoral temperature goal was >42.5°C for >45 min. Thermal equivalent dose (TED) was calculated for each treatment (min above 42.5 and 43°C). Results: Median and mean FU of alive patients was 20 and 32 mos, respectively. 27 pts were treated for locally advanced and 103 for recurrent cancer on the chest wall, nearby skin, or nodes. Treated sites were: intact breast (21%), chest wall/skin (66%), nodes (12%). Disease volume was microscopic in 11%, less than 3 cm in 11%, and greater than in 78%. Various concurrent chemotherapy regimens were given in 56%. 40% of treated sites had prior RT (median 50 Gy). CR was seen in 52% and CR/PR in 79% in pts with measurable tumor. 5 mastectomies were done, with no residual cancer in 1. Local control (LC) at last FU was obtained in 58% of treated sites. Type (primary vs recurrent), location (breast/chest wall/node), extent of disease (3 cm), or prior RT were not associated with LC. Improved LC was seen with increased RT dose, 36%, 52%, and 70% for 16–39.6 Gy, 40–50 Gy, and 50+ Gy, respectively. LC also improved with more minutes of hyperthermia - median of 238 min and 147 min TED 42.5°C & 43°C, respectively in pts with LC, and median of 180 min and 105 min TED 42.5°C and 43°C, respectively in pts without LC. All pts with microscopic disease are controlled. 16 pts (12%) are NED (mean 32 mos). Conclusions: Hyperthermia and RT improves local control and can palliate locally advanced or recurrent breast cancer, even in previously irradiated pts - a quality of life issue. Although the followup of this poor prognosis group is short, local control appears to be maintained to death for many pts. Pts with microscopic residual cancer after resection may benefit from the combination. No significant financial relationships to disclose.
MR quantification of abnormal stromal enhancement in the periphery of invasive breast tumors
Authors: Nabavizadeh N. , Klifa C. , Newitt D. , Lu Y. , Hattangadi J. , Fisher C. , Hylton N. , Park C. 
Published: August 2020

636 Background: In dynamic contrast-enhanced MRI (DCEMRI), properties of tissue microvasculature and overall vascularity can be quantified using kinetics of contrast enhancement. It has been shown that areas with high signal enhancement ratio (SER) were significantly correlated with high tumor vascularity, and that mean SER in nearby non-cancerous breast stroma was significantly associated with disease free survival. No universally accepted methods exist to determine the optimal extent of histologically normal breast tissue to treat. Although a relationship between normal tissue SER and recurrence has been observed, the spatial relationship of enhancement within the non-cancerous stroma with respect to proximity of the tumor has not been shown. We hypothesized that abnormalities in vasculature exist within the histologically normal breast stroma that can be detected by measuring changes in enhancement intensity. Methods: We performed a secondary analysis of pre-treatment DCEMRI data from 27 invasive breast cancer patients. An automated, user-independent program was used to segment breast tissue from all other structures. A SER threshold was set to identify invasive tumor regions, and a tumor proximity map was generated giving the 3D distance of each normal breast tissue voxel to the nearest tumor voxel. A percent enhancement (PE) map was calculated for the normal stroma using the signal intensity change between the pre-contrast and post-contrast images. The proximity and PE maps were then combined to measure breast tissue enhancement at various distances from the tumor. Results: PE levels in normal breast tissue situated within 2 cm of the tumor region were significantly higher than at all more distant regions. Pairwise comparisons with Turkey's adjusted p-values indicated that the mean PE at 0 cm-1 cm is significantly higher than all other distant levels (p = < 0.0001) and the mean PE at 1 cm-2 cm is significantly higher than 5 cm-6 cm (p = 0.006). Conclusions: Here, we show that the normal-appearing breast stroma within 0 cm to 2 cm of a primary tumor exhibits higher enhancement levels than stroma located far from the tumor. These results suggest that tissue surrounding the tumor region may contain tumor-related angiogenesis. These findings could help personalize surgery and radiation techniques. No significant financial relationships to disclose.
Racial/ethnic differences in treatment delay in a multiethnic sample of women with breast cancer
Authors: Mujahid M. , Hawley S. , Janz N. K. , Hamilton A. , Graff J. , Katz S. J. 
Published: August 2020

6503 Background: Factors contributing to racial/ethnic variation in breast cancer treatment delay remain understudied, especially in multi-ethnic population-based samples. Methods: 3,252 women with non-metastatic breast cancer diagnosed between 6/05–2/07 and reported to the Los Angeles County and Detroit, Surveillance Epidemiologic and End Results (SEER) registries were surveyed after initial treatment (mean time from diagnosis = 8.9 months). Latina and African American (AA) women were over- sampled (n=2260, eligible response rate 72.1%). Treatment delay was defined as the patient's report of the duration between when breast cancer was first diagnosed and first surgical procedure (< 1month, 1–3months, ≥4 months) . Multinomial logistic regression models were used to estimate the relative odds of treatment delay by race/ethnicity before and after adjustment for sociodemographics (age, education, income, marital status), clinical factors (number of co-morbidities, health status at diagnosis), and access barriers (difficulty: finding doctors to treat cancer, scheduling surgical procedure, getting to doctor's office). Results: Of the 2195 women who had a surgical procedure, 6.9 % experienced treatment delay of ≥4 months (10.4% Latina, 9.3% AA, 5.5% white women). Latina and AA women were more likely to experience longer treatment delay than white women [OR for ≥4 months/1–3 months vs. < 1 month: 2.18/1.77 for Latinas; 1.78/1.50 for AA (p<.001)] (Table). Racial/ethnic differences persisted after adjustment for sociodemographic, clinical factors, and access barriers [OR for ≥4 months/1–3 months vs. < 1 month: 1.31/1.79 for Latinas; 1.64/1.55 for AA, (p<.001)] (Table), although Latina vs. white differences were no longer statistically significant. Conclusions: Our results confirm that racial/ethnic minorities are vulnerable to delay in receipt of breast cancer treatment in a large population based sample of breast cancer patients. Further work is needed to evaluate the underlying causes of this delay. [Table: see text] No significant financial relationships to disclose.
Clinical-pathologic characteristics and outcomes of true interval compared to screen-detected breast cancer among participants in a Canadian breast screening program: A nested case-control study
Authors: Rayson D. , Payne J. I. , Abdolell M. , Barnes P. J. , Burns A. , MacIntosh R. , Foley T. , Younis T. , Caines J. 
Published: August 2020

6528 Background: It has been hypothesized that, compared to screen-detected breast cancer (Scr), true interval breast cancers (Int) are associated with adverse prognostic factors and outcomes. Data has remained controversial due to failure to control for age at diagnosis and screening interval as well as lack of information regarding adjuvant therapies and inclusion of other categories of interval cancers (e.g., missed or noncompliant). Methods: A case-control study nested among participants of the population-based Nova Scotia Breast Screening Program diagnosed with invasive disease between the ages 40–69 in the period 1991–2006 was performed. Ints were validated by blinded review of the pre-diagnostic screening mammogram by 3 mammographers, 2 or 3 of whom had to agree that it was negative for inclusion as a true Int. Scrs were matched to Ints on a 2:1 basis by 5 year age group at diagnosis and screening interval (40–49 yo, annual; 50–69 yo + family history, annual; 50–69 yo - family history, biennial). Results: 243 true Ints were observed and matched to 485 Scrs. The Table presents (i) univariate analysis of selected pathology variables for the entire cohort of Ints vs Scrs (ii) multivariate analysis of these selected variables. In addition to standard adjuvant hormonal, radiation and trastuzumab therapies, 62.4% of Ints received standard adjuvant chemotherapy (adjC) vs. 30.6% of Scrs. 5 year disease-free (DFS) and overall (OS) survival rates for Int vs Scr were 82.6% vs 92.3% and 87.2% vs 93.3% respectively. Cox proportional hazards modeling for (i) DFS shows HR=1.96 (p=0.0024) for Int vs Scr, dropping to HR=1.57 (p=0.0556) after adjusting for adjC received and (ii) OS shows HR=1.99 (p=0.0028) for Int vs Scr, dropping to 1.61 (p=0.0487) after adjusting for adjC received. Conclusions: True Ints present with more adverse prognostic factors compared to Scrs. Despite more use of adjC, outcomes are significantly poorer. [Table: see text] No significant financial relationships to disclose.
Cardiovascular risk factor control among cancer survivors: A population-based survey
Authors: Enright K. , Krzyzanowska M. 
Published: August 2020

6535 Background: Cardiovascular disease is a major cause of morbidity and mortality in long-term survivors of cancer. Whereas the burden of cardiovascular disease has been described in cancer survivors, the control of modifiable cardiovascular risk factors in this population is unknown. Methods: We used the National Health and Nutrition Examination Survey (NHANES 1999–2006) data to examine the rate of control of modifiable cardiac risk factors amongst US cancer survivors compared with propensity matched adult controls with no history of cancer. The modifiable cardiac risk factors (blood pressure, cholesterol, BMI, exercise, smoking) were considered to be controlled if they met the AHA/ACC guideline recommendations. Results: A total of 1,227 cancer survivors and 3,672 age, sex, and comorbidity matched controls were identified, representing 11.9 million cancer survivors and 31.2 million controls. Compared to age, sex and comorbidity matched controls cancer survivors were more likely to be current smokers (34.5% vs. 28.8%, p = 0.021), and more likely to have their BMI at target (32.8% vs. 28.6%, p = 0.034). There was no significant difference in the rate of blood pressure control (69.4% vs. 69.2%, p = 0.88), cholesterol control (47.6% vs. 48.2%, p = 0.80) or adherence to exercise recommendations (24.4% vs. 24.6%, p = 0.89). Younger cancer survivors (age 20–40 y) were 2.8 times more likely to be smokers than controls, whereas older cancer survivors (age 60–80y) were 1.2 times more likely to be smokers than controls. Compared with recent cancer survivors (10 years from diagnosis) were more likely to have optimal blood pressure control (73.3% vs. 65.5%, p = 0.02), however there was no difference in smoking rates, cholesterol, exercise or weight control with duration of cancer survival. Conclusions: Overall the control of modifiable cardiac risk factors was similar between survivors and controls, but was suboptimal in both groups. This study identified smoking cessation, particularly amongst young cancers survivors, as an important area of focus for improvement in survivorship care. No significant financial relationships to disclose.