bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole
Authors: Safra T. , Bernstein Molho R. , Stephansky I. , Yaal-Hahoshen N. , Inbar M. , Ackerstein A. , Geffen D.
Published: August 2020

599

Background: Adjuvant treatment with aromatase inhibitors (AIs) in postmenopausal women (PMW) with early breast cancer (EBC) can be associated with decreased bone mineral density (BMD) and increased risk of osteoporosis and fractures. Tamoxifen (TAM) has bone protective effect. BIG 1–98 recent, 71 months update suggests that sequential therapy of TAM and letrozole (LET) in either order, have similar efficacy to 5 years of LET. This study is designed to evaluate the efficacy and safety of zoledronic acid (ZA) in preventing AIs bone loss after 2.5 years of TAM. Methods: This is an open-label, randomized phase II study of PMW with hormone receptor positive EBC previously treated with TAM for the last 2.5 years (with BMD T score ≥ -2.5). Patients are randomly assigned to receive LET (2.5mg/ daily) ± ZA. Patients on treatment arm receive 4 mg IV ZA every 6 months for 2 years. All patients are being evaluated every 6 (0–36) months with blood chemistry and BMD test. All patients receive vitamin D and calcium supplement. A comparison between groups and between time points is performed by one-way ANOVA with repeated measures using the Mixed model. Results: Seventy four patients were screened. Median age was 58.9 years (46.5–83.6). All patients are alive, one had an ipsilateral recurrence. Seventy two patients were evaluable (2 were screening failure), 33 randomized to receive ZA and 39 to the control group. Median follow-up (FU) was 18.2 months (1–47). At this point in time a significant interaction between groups and time trend was found, in favor of ZA treated group in lumbar T score (p = 0.0055). While in the control group a significant decline in lumbar BMD was noticed (p = 0.008), in the treatment group BMD did not change over time (p = 0.2971). Adverse events with ZA were mild with some flue like syndrome. No serious renal adverse event or ONJ (osteonecrosis of jaw) cases were reported. ZA was safe and well tolerated. Conclusions: Sequential adjuvant treatment with TAM and AIs in PMW with EBC can be associated with decreased BMD and increased risk of osteoporosis. In our study, LET-induced bone loss increases with time. A significant benefit in BMD was seen when ZA was added to LET. A longer follow up is needed to evaluate the real magnitude of ZA protective effects.

[Table: see text]
Final results of a randomized phase III trial comparing induction chemotherapy with cisplatin/5-FU or docetaxel/cisplatin/5-FU follow by chemoradiotherapy (CRT) versus CRT alone as first-line treatment of unresectable locally advanced head and neck cancer (LAHNC)
Authors: Hitt R. , Grau J. J. , Lopez-Pousa A. , Berrocal A. , Garcia Giron C. , Irigoyen A. , Sastre J. , Martinez J. , Cortes-Funes H. , Cruz-Hernandez J.
Published: August 2020

6009

Background: Induction chemotherapy (IC) with TPF isa standard regimen for patients (pts) with locally advanced head and neck squamous cell carcinoma (N Engl J Med. 2007;357:1705–1715). However, CRT alone is standard treatment for unresectable LAHNC. We designed a trial to compare two different regimens of IC followed by CRT versus CRT alone in pts with unresectable LAHNC. Methods: Pts with unresectable, measurable LAHNC, adequate organ function, and ECOG 0–1 were enrolled and stratified according to primary tumor site. (IC) regimens (3 cycles): PF (cisplatin 100 mg/m2 day [d] 1, then 5-FU 1,000 mg/m2 continuous infusion [CI], d1–5, q21d); TPF (docetaxel 75 mg/m2 d1, cisplatin 75 mg/m2 d1, 5-FU 750 mg/m2 CI, d1–5, q21d plus G-CSF and ciprofloxacin). All pts were to receive CRT, consisting of conventional radiotherapy up to 70 Gy plus cisplatin 100 mg/m2 d 1, 22, 43. The primary end point was time to treatment failure (TTF) for (IC) vs. no (IC); secondary endpoints included locoregional control (LRC) rate and safety; 438 pts were needed to demonstrate a 15% difference in treatment failure (death, progression, surgery, other treatments) with α = 0.05, β = 0.2. Results: From December 2002 to June 2007, 439 pts were enrolled: IC 311 pts (TPF 155, PF 156) and CRT 128 pts. The majority of pts were: ECOG 1 (70%); oropharynx and oral cavity (63%); T4 (75%); N2-N3 (61%). In evaluable pts (at least 1 cycle), the median TTF was 12.5 months with IC/CRT vs. 4.9 months with CRT alone (p < 0.001; HR 0.57; 95%CI 0.44–0.74); LRC rate was 60.9% IC/CRT vs. 44.5% CRT (p = 0.003; OR = 0.52; 95%CI 0.3–0.81). Grade 3–4 adverse events (IC/CRT vs. CRT) occurred in 83% vs. 69% of pts and included febrile neutropenia (10% vs 1%), and stomatitis (43.7% vs 37%). Conclusions: This is the first phase III trial to demonstrate that (IC) followed by CRT significantly increases TTF and LRC compared with CRT alone in pts with unresectable LAHNC. IC/CRT should now be considered standard treatment for these pts.

No significant financial relationships to disclose.
Phase I/II dose escalation study of OncoVexGM-CSF and chemoradiotherapy (CRT) in untreated stage III/IV squamous cell cancer of the head and neck (SCCHN)
Authors: Harrington K. , Hingorani M. , Tanay M. , Matthews J. , Newbold K. , Renouf L. , Coffin R. S. , McNeish I. , Nutting C.
Published: August 2020

6018

Background: OncoVEXGM-CSF is a gene deleted (ICP34.5-/ICP47) oncolytic HSV-1 that encodes human GM-CSF. OncoVEXGM-CSF causes direct oncolytic tumour cell destruction and immune activation by releasing tumour antigens and GM-CSF, effects that may co-operate with CRT to increase loco-regional control in SCCHN. Methods: Patients (pts): Stage III/IVA SCCHN, N1-N3, ECOG 0–1, normal haematologic, biochemical, immune function. Pts received CRT (70 Gy/35 fractions with concomitant cisplatin 100 mg/m2 (d 1, 22, 43) and dose-escalating (106, 106, 106, 106 pfu/mL [cohort 1]; 106, 107, 107, 107 [cohort 2]; 106, 108, 108, 108 [cohort 3]) OncoVEXGM-CSF by intratumoral injection (d 1, 22, 43, 64). Pts underwent neck dissection 6–10 weeks after CRT. Primary endpoints were safety and recommended dose/schedule for future study. Secondary endpoints were anti-tumor activity, viral replication and HSV antibody levels. Results: 17 pts were treated, 9 at the top dose (15 males, median 58 years). DLT and MTD were not reached. There were no delays to CRT delivery. 13 pts had PR or CR by CT, 5 pts achieving rapid CR following only 2 or 3 viral doses. Pathological CR was observed in 94% of pts at neck dissection. Transient low level injection site viral shedding was seen in 3 pts. HSV was detected in injected and adjacent uninjected tumors by qPCR and immunohistochemistry, including at levels higher than the input dose, indicating replication. All seronegative pts seroconverted. 11 of 17 (65%) pts remain in remission at median follow-up of 23 months. No pts had local relapse, 1 pt had a new primary tumor, 3 pts distant metastatic disease, 1 pt intercurrent disease, 1 pt lost to follow up. Conclusions: OncoVEXGM-CSF combined with cisplatin-based CRT is well tolerated in pts with SCCHN. Viral replication was confirmed. Long-term locoregional control was achieved in 100% of pts, 65% of pts remaining in complete remission. Further study is warranted.

[Table: see text]
Evaluation of the correlation of baseline blood pressure (BP) and plasma renin activity (PRA) with bevacizumab (B)-mediated hypertension in patients with early-stage breast cancer
Authors: Dickler M. N. , McArthur H. L. , Nulsen B. , Patil S. , Sealey J. , Laragh J. , Merali C. , Steingart R. , Hudis C. , Rugo H.
Published: August 2020

602

Background: Although hypertension (HTN) develops in 20–30% of bevacizumab (B)-treated cancer patients, no accurate clinical predictors of B-mediated HTN have been identified. We evaluated baseline blood pressure (BP) and plasma renin activity (PRA) as potential predictors of B-mediated HTN among breast cancer patients enrolled in an adjuvant chemotherapy-B study. Methods: In this phase II study, B was administered concurrently (10 mg/kg IV q2wk x 8) with pegfilgrastim-supported chemotherapy (AC at 60/600 mg/m2 q2wk x4 then nab-paclitaxel at 260 mg/m2 q2wk x4) and continued at 15 mg/kg q3wk thereafter for a total one year of B therapy. The primary endpoint was cardiac safety. A secondary endpoint was the prospective exploration of PRA as a predictor of HTN. Patients with baseline BP >150/100 mmHg were excluded from the study. Peripheral blood for PRA was collected at baseline, week 8, week 16 and every 3 months during B administration. In this preliminary analysis, baseline data was available for 65 of the 80 enrolled patients. Baseline BP and PRA values for those who did and did not develop grade 2–4 HTN were evaluated by Wilcoxon rank sum test. Results: The baseline characteristic medians are: age 45y (27–75), baseline diastolic BP 70 mmHg (52–95), baseline systolic BP 120 mmHg (90–146), and number of B cycles administered 20 (1–21). Twenty-one patients (32%) developed grade 2–4 HTN. Median diastolic and systolic BP among patients with grade 2–4 HTN was 78 and 124 mmHg, respectively, versus 70 and 115.5 mm Hg, respectively, among patients without grade 2–4 HTN (p = 0.0256 and p = 0.0228). There was no significant association between baseline PRA values and the development of grade 2–4 HTN versus not (p = 0.2917). Conclusions: At the time of this preliminary analysis, both baseline diastolic and systolic BP appear to positively predict the development of B-mediated grade 2–4 HTN while baseline PRA does not. Studies exploring the relationship between serial PRAs and the development of HTN for all study participants are ongoing.

[Table: see text]
Serum biomarkers as predictors of clinical outcome after cetuximab-based therapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Ferris R. L. , Feinstein T. , Grandis J. , Johnson R. , Branstetter B. , Gooding W. , Argiris A.
Published: August 2020

6035

Background: We correlated a panel of serum cytokines and growth factors with antitumor activity in patients (pts) with locally advanced SCCHN treated with cetuximab-based therapy. We have shown that similar biomarkers may be promising for the early detection of SCCHN (Linkov, Can Epi Biomarkers 2007). Methods: We used multi-analyte biomarker profiling for measurement of multiple serum biomarkers (Luminex Corp., Austin, TX). 39 pts with stage III-IVB SCCHN were treated with cisplatin, docetaxel, and cetuximab (TPE) for 3 cycles followed by radiotherapy, cisplatin, and cetuximab (XPE) and then maintenance cetuximab (Argiris, ASCO 2008, A6002). 31 cytokines and growth factors were measured before and after 3 cycles (9 weeks) of induction TPE. Clinical results were correlated with biomarkers, including 23 pts with PET response. Results: 31 pts had baseline biomarkers and 25 paired samples, pre- and post-TPE. Median follow-up was 22 months. Median age 54 years (21–74); male: 27; stage IV: 29; primary site: oropharynx, 16; larynx, 4; hypopharynx, 3, nasopharynx, 3; oral cavity, 3; and unknown, 2. Eight analytes changed significantly after induction. Adjusting p values for false discovery, the following analytes retain a p <0.05: MCP1c, IP-10, Leptin, IL-5, Eotaxin, IL-6, GCSF, CXCL5. In 23 pts with PET response assessment, low vascular endothelial growth factor (VEGF) levels or low IL-6 levels at baseline may be associated with complete response: 4/5 pts with low baseline VEGF (<20.9 pg/ml) had a complete response by PET vs 1/18 pts with high baseline VEGF. Of 31 pts, 9 have progressed. Among tests of association of the 31 analytes and progression-free survival (PFS), VEGF was the only one with a raw p value <.05 (p = .027), although the adjusted p value was not significant. A decrease in VEGF with treatment had a weak but not statistically significant association with longer PFS. Conclusions: Baseline serum biomarkers and in particular, VEGF and IL-6, were identified as potentially useful predictive markers of cetuximab-based therapy. Due to the small sample size and multiple testing, these biomarkers need to be validated in a larger study in SCCHN specifically powered for biomarker associations.

No significant financial relationships to disclose.
Identifying head and neck cancer patients at risk for high symptom burden during treatment
Authors: Rosenthal D. I. , Mendoza T. , Cleeland C.
Published: August 2020

6066

Background: Treatment for head and neck cancer (HNC) is well known to be associated with high levels of toxicity and symptom burden, but patients vary in the severity of treatment related symptom burden. The pre-treatment identification of patient characteristics most at risk for high treatment related symptom levels would be helpful for clinical and trial symptom intervention planning. Methods: 134 patients with HNC participated in the study. Patients completed the M. D. Anderson Symptom Assessment Inventory - Head and Neck module (MDASI-HN) prior to radiotherapy (RT) or chemoradiotherapy (CRT) and again six weeks after treatment began. Cluster analysis was used to identify those who were highly symptomatic due to their disease prior to treatment and those who became highly symptomatic due to treatment. We used validated MDASI-HN score ranges to define symptom severity with scores 5–6 defined as ‘moderate‘ and 7 or more as ‘severe.’ Logistic regression was used to determine which baseline symptoms may predict group membership of highly symptomatic patients at the end of therapy. Results: 18% (22/120) of HNC patients were symptomatic prior to therapy. This subset of patients reported moderate levels of pain, fatigue, sleep disturbance, feeling sad and emotional distress. At six weeks after beginning treatment, 59% (73/124) of patients were highly symptomatic. The cluster of symptoms at this point included moderate levels of pain, fatigue, nausea, mouth sores and excessive mucus and severe levels of poor appetite, dry mouth, difficulty chewing and loss of taste for food. Approximately 54% (50/92) of patients who were not symptomatic at the beginning of treatment became symptomatic at the end of treatment. Patients with moderate to severe pain before beginning treatment are 4 times more likely to be severely symptomatic at the end of treatment (p < 0.009). Conclusions: As expected, only a minority of patients with HNC were highly symptomatic prior to therapy, while the majority of patients had high levels of symptoms toward the end of therapy. Patients with moderate to severe pain before beginning treatment are more likely to be have greater symptom burden at the end of treatment, so may benefit from more intensive symptom interventions.

No significant financial relationships to disclose.
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.
Time interval between final protocol approval (FPA) and inclusion of the first patient into randomized clinical trials (RCTs) performed by the Central European Cooperative Oncology Group (CECOG): A 10-year experience
Authors: Brodowicz T. , Steiner I. , Beslija S. , Ciuleanu T. E. , Inbar M. , Krzakowski M. , Kahan Z. , Tzekova V. , Vrbanec D. , Zielinski C. C.
Published: August 2020

6546

Background: CECOG has been formed in 1999 to unite centers of clinical oncology from Central and Southeastern Europe and Israel in order to conduct and coordinate multicenter oncology RCTs. Based on the European legislation passed in 2001 (Directive 2001/20/EC), clinical trials must get ethical approval and approval from the competent authorities (CA). However, the duration of these regulatory procedures to initiate a clinical trial is a factor determining the competitive position in clinical research. Methods: Within the last 10 years, CECOG conducted trials in breast, colorectal, esophago-gastric, NSCLC, pancreatic, prostate cancer and GIST. We analyzed the dates of FPA, the approvals by Ethics Review Boards (ERB) and CAs, the letters of agreement between sponsor and site (LoA), the site initiation and the inclusion of the first patient in a total of 6 multicenter trials in 25 CECOG study centers in Austria, Bosnia, Bulgaria, Croatia, the Czech Republic, Hungary, Israel, Poland, Romania, Serbia, and Slovakia. Results: The average time interval from FPA to the inclusion of the first patient was 18.4 ± 9.4 months. Most of this time has been spent for regulatory procedures, i.e. the approval by ERBs (9.6 ± 7.2 months) and CAs (10.0 ± 6.6 months). The LoA were signed 11.5 ± 9.4 months after FPA. The time interval from approval by the CAs to site initiation was 3.3 ± 3.7 months and the interval between site initiation and the inclusion of the first patient was 4.2 ± 4.5 months. Conclusions: The ‘paper to patient process‘ - the time interval between the approval of the final study protocol and the inclusion of the first patient - required 18.4 months on average in 6 multicenter trials conducted by CECOG. As the regulatory procedures used up more than 50% of duration of the whole process, optimization is necessary and realistic in order to make novel therapies available to patients more quickly.

No significant financial relationships to disclose.
Factors associated with contralateral prophylactic mastectomy use among breast cancer patients in a metropolitan hospital system
Authors: Arrington A. K. , Jarosek S. L. , Virnig B. A. , Habermann E. B. , Tuttle T. M.
Published: August 2020

6558

Background: A recent population-based study reported the proportion of women with unilateral breast cancer who underwent contralateral prophylactic mastectomy (CPM) increased by 150% between 1998 and 2003. This study evaluated all patients undergoing breast cancer surgery in a metropolitan-based hospital system to identify factors not available from tumor registries that may be associated with increased CPM rates. Methods: We reviewed the records of all patients who underwent breast cancer surgery in 2006 and 2007 in a single health care system in the Twin Cities, including one university, two suburban, and three smaller rural hospitals. Exclusion criteria included bilateral breast cancer, stage IV disease, and prior breast cancer. We recorded patient and tumor characteristics, surgery and surgeon characteristics. Logistic regression models were used to determine predictors of CPM use. Results: Of 571 eligible patients, 276 (48.3%) underwent lumpectomy, 130 (22.8%) underwent unilateral mastectomy, and 165 (28.9%) underwent mastectomy and a CPM. Among mastectomy patients, 55.9% underwent CPM. Young patients (<40 v. >55), larger tumors (>5cm v. <2cm), positive family history, lobular histology, multicentric disease, and surgeon gender (female) were independent predictors of increased CPM rates. Body mass index (BMI), tumor grade, estrogen receptor status, and preoperative breast magnetic resonance imaging were not associated with increased CPM rates. Conclusions: This cohort of patients has a much higher CPM rate than reported from population-based studies. We confirmed the role of patient age, tumor size and lobular histology as factors associated with CPM. Interestingly, factors not available through cancer registries, including positive family history and surgeon gender, are also independent predictors of CPM use. Since this study includes patients from diverse surgical practices, our findings are generally reflective of CPM use in metropolitan areas.

[Table: see text]

No significant financial relationships to disclose.
Average length of stay in hospice for five cancers
Authors: Kinzbrunner B. , Tanis D.
Published: August 2020

6593

Background: Factors which influence average length of stay (ALOS) for terminally ill cancer patients who choose hospice include patient and family preferences, availability of services, demographics, specialty, and experience of referring physician, advances in treatment options, and especially type of cancer. In this paper, we examined differences in ALOS for the top five cancers in patients who utilized a large, national hospice provider between 2000 and 2007. Methods: We reviewed the records of 73,263 patients with prostate, colorectal, breast, lung, or pancreatic cancer who were admitted to one of 45 hospice programs and died on service between January 2000 and December 2007. The top five cancers accounted for 58% of all cancer deaths in the hospice programs. The effect of type of cancer and year on ALOS was evaluated using analysis of variance. Pair-wise differences were compared using the Bonferroni correction. Results: Overall ALOS was 40.0 days (yearly range 37.8–41.1). ALOS for prostate, colorectal, breast, lung, and pancreas was 46.8, 44.9, 44.2, 37.3, and 31.4 days, respectively. Prostate, colorectal, and breast ALOS were not significantly different from one other; lung ALOS was less than the top three but greater than pancreas ALOS (p < 0.001); and pancreas ALOS was significantly lower than all others (p < 0.001). The interaction between year and type of cancer was not significant (p > 0.05). Conclusions: The longer ALOS for patients with prostate, colorectal and breast cancer may be related to differences in natural history and effectiveness of anti-neoplastic therapies when compared to cancers of the lung and pancreas. Given the remarkable stability of ALOS over the last eight years and the lack of a statistical interaction between year and type of cancer, ALOS differences also suggest a steeper rate of decline for patients with cancers of the lung and pancreas following admission to hospice.

No significant financial relationships to disclose.
The role of iron chelation activity of wheat grass juice in patients with myelodysplastic syndrome
Authors: Mukhopadhyay S. , Basak J. , Kar M. , Mandal S. , Mukhopadhyay A.
Published: August 2020

7012

Background: A pilot study with wheat grass juice in major thalassaemia patients was done by a group of clinicians in IPGMR, Chandigarh, India. We performed a study of 200 patients of intermediate thalassaemia with wheat grass juice and found 80% patients becoming transfusion independent. During the study in majority of the patients, serum ferritin level was significantly less as compared to pretreatment values. The aim of our study was to see the effect of wheat grass juice in reducing Ferritin level in myelodysplastic syndrome and also do the biochemical analysis of the wheat grass juice. Methods: During period from January 2003 to December 2007 we selected 20 patients of transfusion dependent myelodysplastic syndrome in the oncology department of Netaji Subhash Chandra Bose Cancer Research Institute. The age range of the patients was 42 years to 72 years (median 55 years). The fresh leaves of 5–7-day-old wheat grasss including stems were made fresh juice and had given 30 mL of juice daily to all 20 patients for continuous 6 months. Wheat grass juice was analyzed by column chromatography and found to be rich in oxalic and malic acid which might have some role in dietary absorption of iron from intestine. Beside that the wheat grass juice was found to contain two unique active ingredients with iron chelating property which was performed by deoxyribose degradation assay. We compared aqueous soluble extract of 5–7-day-old plant and dose-dependent study showed a significant iron chelating activity of crude extract in comparison to known standard iron chelator desferroxamine (DFO). The active compounds of crude extract of wheat grass may chelate catalytic iron in iron overload disorders when taking systematic dose. Result: The mean serum Ferritin level of the patients was 2,250 (range 650–4,800) before wheat grass treatment. The mean reduced to 950 (range 68–1680) (p < 0.0001). The performance status was improved from 60% to 80% (Karnofsky) after wheat grass treatment. The mean interval between transfusions was found increased. Conclusions: Wheat grass juice is an effective iron chelator and its use in reducing serum ferritin should be encouraged in myelodysplastic syndrome and other diseases where repeated blood transfusion is required.

No significant financial relationships to disclose.