bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of continuous dosing of sunitinib in advanced, FDG-PET avid, medullary thyroid carcinoma (MTC) and well-differentiated thyroid cancer (WDTC)
Authors: Carr L. , Goulart B. , Martins R. , Keith E. , Kell E. , Wallace S. , Capell P. , Mankoff D. 
Published: August 2020

6056 Background: Due to the low efficacy of chemotherapy in progressive, WDTC and MTC, novel treatment approaches are needed. Thyroid cancers have elevated levels of vascular endothelial growth factor and higher microvessel density than normal thyroid tissue. Sunitinib inhibits several tyrosine kinase receptors involved in angiogenesis as well as the RET kinase frequently mutated in thyroid cancer. Here we report the results of a phase II trial investigating the use of continuous dosing sunitinib in patients with metastatic WDTC and MTC. Methods: Patients were eligible for enrollment if they had metastatic, iodine-refractory WDTC or MTC. To target those patients with more aggressive thyroid cancer, enrollment was limited to FDG-PET avid disease. Sunitinib was administered at 37.5 mg po qday on a continuous basis. Planned sample size is 35 patients. The primary end-point is response rate per RECIST criteria. Secondary end-points include FDG-PET response rate (defined as 20% reduction from baseline SUV) after 7 days of treatment, toxicity, overall survival, duration of response, and time to progression. Results: To date 33 patients have been enrolled (7 MTC:26 WDTC), and 29 patients have been evaluated for disease response. Median time on study is 7.5 months. Response rates to date: CR 7% (2/29), duration of response (9m+ and 14m+), PR 25% (8/29) (median 12 months), SD 48% (14/29) (median 6 months). Rate of disease control at 3 months (SD+PR+CR) 83% (24/29). 15 patients remain on study. Among those who have progressed the median time to progression is 6.5 months. FDG-PET was performed on 22 patients following 7 days of treatment, 36% (8/22) have a PET response. Of these patients 7 have disease control per RECIST criteria. Grade 3 toxicities seen in more than one patient include: anemia (2/33), fatigue (4/33), neutropenia (12/33), hand/foot syndrome (4/33), diarrhea (5/33), and leukopenia (11/33). One patient on lovenox therapy died of gastrointestinal bleeding. Conclusions: Continuous dosing of sunitinib is active (disease control rate 83%) in patients with high risk, metatstatic WDTC and MTC, as defined by FDG-PET avid disease. [Table: see text]
Treatment (tx) with tyrosine kinase inhibitors (TKIs) for patients (pts) with differentiated thyroid cancer (DTC): The M. D. Anderson Cancer Center (MDACC) experience
Authors: Cabanillas M. E. , Waguespack S. G. , Bronstein Y. , Williams M. , Feng L. , Sherman S. I. , Busaidy N. L. 
Published: August 2020

6060 Background: DTC is a relatively common tumor and about 20% will develop distant metastases (mets) of which at least 50% will not respond to standard tx. Until recently, tx for pts with progressive, RAI negative disease was limited. However, the identification of biologic targets in DTC has led to several trials with TKIs. Objectives: We sought to describe the MDACC experience with off-label use of TKIs to determine which pts benefit the most. Methods: Adult pts with a diagnosis of DTC treated with single agent sorafenib (SOR) or sunitinib (SUN), and who had a baseline and at least 1 follow-up (f/u) scan after 3 months (mos) of therapy, were included. All imaging data, as well as the TSH-suppressed thyroglobulin (TG) levels corresponding to each scan date were collected. RECIST was used to determine response. Results: We identified 33 pts from our clinical database. 15 pts met inclusion criteria: 9 women, 6 men. No pts were excluded due to progression or death before 3 mos. Median age 61 years (range, 38–83). 7 patients had papillary, 6 follicular (including 2 insular subtypes), 2 Hurthle cell. Most patients had RAI negative disease. SOR was used in 13, SUN in 2. Both SUN pts had been on SOR; 1 failed and 1 had intolerable side effects to SOR. Median time on tx was 42 weeks. All pts had evidence of PD prior to start of tx. Best response was 3 (20%) PR, 9 (60%) SD, 3 (20%) PD. Clinical benefit (PR+SD) = 80%. The SUN pt who was refractory to SOR had a 38% reduction in tumor size. The most noticeable activity occurred in lung (median change: -16%), whereas lymph nodes had PD or SD (median change: +3%). The 2 pts with pleural mets had PD. Four pts had bone mets: 2 had XRT and had SD in bone, while the other 2 did not have XRT and had PD in bone. At 12 mos PFS was 65% and OS was 85%. Median f/u time was 16 mos. All histologic types had similar responses. Log (TG) correlated with response (p = 0.0005). Conclusions: SOR and SUN are effective in pts with widely metastatic, progressive DTC, with most pts achieving SD or PR. The most noticeable responses occurred in the lungs in contrast with minimal changes in nodal mets, suggesting a tissue-specific response to tx. Log (TG) significantly correlated with response to tx and therefore may have value as a surrogate marker of response. [Table: see text]
Differential tumor and normal mucosa biomarker modulation by epidermal growth factor receptor (EGFR) inhibition using erlotinib in oral cavity squamous cell carcinoma (OCSCC)
Authors: Tsien C. , Nyati M. , Chepeha D. , Worden F. , Helman J. , Bradford C. , Wolf G. , Lawrence T. , Eisbruch A. 
Published: August 2020

6077 Background: Targeted therapy may improve the therapeutic index in locally advanced head neck cancer if differential EGFR inhibition in tumors compared to the normal mucosa is demonstrated. Based on prior published data, EGFR degradation is an important biomarker of cytotoxicity in a preclinical model. The aim of this pilot study was to determine if there are differences in biomarker modulation between tumor and the normal mucosa and confirm our initial preclinical findings regarding EGFR degradation. Methods: Patients with primary OCSCC requiring surgical resection had normal mucosa and tumor biopsies prior to a test course of erlotinib. Patients received one week of erlotinib 150 mg qd. Repeat tumor and normal mucosal biopsies were obtained at the time of surgical resection to evaluate the effect of the EGFR inhibitor on both tumor and the normal mucosa. Changes in known preclinical markers of EGFR activity (phospho, total EGFR, AKT, STAT3) were measured by immunoblotting assays. In addition, changes in distribution of these biomarkers were analyzed by immunohistochemical analysis. Results: 12 pts were enrolled; 7 pts with paired tumor and normal mucosa biopsies. Tumor specimens showed over-expression of EGFR compared to the normal mucosa (p = 0.005). Erlotinib treatment led to marked inhibition of both pEGFR and EGFR protein (p = 0.004 and p = 0.007, respectively) in tumor biopsies. In contrast, we found heterogeneity in EGFR inhibition in the normal mucosa following erlotinib. (p = 0.1 [pEGFR], and p = 0.07 [EGFR)]) We noted dramatic reduced levels of pSrc and pSTAT3 following erlotinib in tumors compared to untreated matched tumor samples. In addition, levels of p27 were enhanced. Conclusions: Differential EGFR inhibition in tumors compared to the normal mucosa, may suggest that the addition of EGFR inhibitors to chemo-RT or accelerated RT, whose dose limiting toxicity is acute mucositis, may select patients who will benefit from targeted therapy. Our results demonstrate that EGFR inhibition by erlotinib led to marked reduction in EGFR protein levels. EGFR degradation may be an important biomarker in selecting patients predicted to have a response to TKI. These results need further validation. No significant financial relationships to disclose.
Comparison of neoadjuvant paclitaxel and carboplatin with neoadjuvant letrozole in postmenopausal patients with receptor-positive locally advanced breast cancer (LABC)
Authors: Sinha D. , Bahadur A. K. , Singh K. , Rathi A. K. 
Published: August 2020

608 Background: For the treatment of LABC using a regimen with the highest likelihood of shrinking the tumor should improve the outcome. Paclitaxel was the first taxane to show activity in breast cancer. The advent of endocrine therapy in the neoadjuvant setting allows downstaging of tumors with less morbidity. The aromatase inhibitors are now the treatment of choice in neoadjuvant setting for elderly patients with estrogen receptor-positive breast cancer. Methods: This prospective, randomized, comparative study assessed the effect of three cycles of neoadjuvant chemotherapy vs. three months of neoadjuvant hormonal therapy in terms of loss of clinical and pathological primary tumor size. Inclusion criteria required postmenopausal patients with non-metastatic, ER and/or PR positive LABC with no co-morbidity. Forty eligible patients were randomly assigned into 2 groups of 20 patients each: Group A treated with 3 cycles of 3 weekly injections of paclitaxel (175 mg/m2) and carboplatin (AUC 6) assessed after each cycle; group B received oral Letrozole 2.5mg once daily for 3 months assessed every 4 weeks. Surgery was done and primary specimen was pathologically examined. Results: Clinically mean loss in primary residual tumor compared to volume at presentation in group A vs. group B at 1st review was 45% vs. 35% (p: 0.536), 63% vs. 57% at second (p: 0.176), and 71% vs. 74% at third review (p: 0.062).Clinical complete response (WHO criteria) and stable disease each were seen in 14% in either group of patients (p: 0.632), partial response in 65% group A and in 72% group B (p: 0.117); no progressive disease was seen in either. All patients underwent surgery. The mean pathological primary cell kill in group A vs. group B was 81% vs.78 %(p:0.918). Resected nodes were pathologically positive for tumor in 47% group A and 60% group B patients (p: 0.269). Conclusions: Neoadjuvant hormonal therapy using oral Letrozole in receptor positive LABC in post menopausal women is as effective as three weekly paclitaxel and carboplatin in downstaging the tumor. No significant financial relationships to disclose.
Correlation of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) with 18f-fluoromisonidazole positron emission and computed tomography (18F-FMISO PET/CT) in assessing tumor hypoxia in a series of head and neck cancer (HNC) patients with nodal metastases
Authors: Lee N. , Jensen J. , Schoder H. , Wang Y. , Fury M. , Pfister D. G. , Stambuk H. , Humm J. , Koutcher J. , Shukla-Dave A. 
Published: August 2020

6083 Background: 18F-FMISO PET/CT is a noninvasive hypoxia imaging modality. Hypoxia can develop within the tumor which typically corresponds to regions with poor blood perfusion. DCE-MRI can yield results on tumor perfusion. The present study compares hypoxic and perfusion status of HNC with nodal metastases using DCE-MRI and 18F-FMISO PET/CT imaging. Methods: 13 HNC (7 base of tongue, 5 tonsil, 1 larynx) patients with nodal metastases underwent both DCE-MRI and 18F-FMISO PET/CT scans prior to chemoradiotherapy. MRI was performed on a 1.5 Tesla GE Excite scanner. DCE-MRI studies were acquired using a fast multi-phase spoiled gradient echo sequence. Antecubital vein catheters delivered a bolus of 0.1 mmol/kg Gd-DTPA at 2 cc/s. For 18F-FMISO PET/CT,∼10.0 mCi of 18F-FMISO was administered IV and images were acquired ∼2 hours later. PET images were reconstructed; CT data were used for attenuation correction. Region of interests (ROIs) were manually drawn by a neuroradiologist. Quantitative DCE-MRI analyses were done using the 2-compartment Tofts model. The analyses calculated the pixel Ktrans(distribution rate constant), ve(extravascular-extra-cellular volume fraction), and kep(redistribution rate constant). 18F-FMISO PET/CT images were analyzed and the uptake by the tumor was scored as: no uptake (score 0); moderate-severe uptake (score 1). Semi-quantitative analysis included standardized uptake value (SUV) measurements. Statistical significance was calculated using a 2-sided Student's t-test, with p < 0.05. Results: A total of 17 nodes were analyzed. For the nodes that showed no hypoxia on PET imaging (n = 7), the mean (±SD) values were: 18F-MISO SUV (1.1 ± 03), Ktrans(0.33 ± 0.18), ve(0.53 ± 0.23), and kep(0.66 ± 0.25). For the nodes that showed moderate to severe 18F-MISO uptake (n = 10) the values were: 18F-FMISO SUV (2.8 ± 08), Ktrans(0.24 ± 0.07), ve(0.61 ± 0.13), and kep (0.43 ± 0.17). A significant lower kep for nodes with 18F-MISO uptake (p = 0.042). Conclusions: Preliminary result supports the hypothesis that the hypoxic nodes are poorly perfused nodes (lower kep values) versus nodes with no hypoxia. No significant financial relationships to disclose.
Surgery versus primary endocrine therapy for elderly women with estrogen receptor-positive early operable primary breast cancer: Survival analysis and correlation with oestrogen receptor positivity
Authors: Syed B. M. , Johnston S. J. , Wong D. W. M. , Morgan D. A. L. , Ellis I. O. , Cheung K. L. 
Published: August 2020

612 Background: A recent Cochrane review of seven randomised trials involving 1,446 elderly women (unselected for oestrogen receptor (ER) status) has shown no significant difference in overall survival between surgery (with or without adjuvant tamoxifen) and primary endocrine therapy using tamoxifen. We now report results of a large series from a single centre with a dedicated elderly breast cancer service, with long term follow-up. Methods: During a period of > 20 years, 1,031 elderly (> 70 years) women with ER positive (H-score >50) early operable primary breast cancer received either surgery (with or without adjuvant endocrine therapy) (N = 436) or primary endocrine therapy (N = 595) (>80% using tamoxifen) as initial treatment, with complete follow-up information till deaths. The initial treatment was decided based on fitness for surgery and patient choice. Analysis was carried out on breast cancer specific survival and degree of ER positivity. Results: After a median follow up of 49 months (range 0 - 261 months), patients between 70 - 80 years, treated by surgery, had better 5-year breast cancer specific survival compared to their counterparts treated by primary endocrine therapy (95% versus 85%; p < 0.001). For patients > 80 years, there was however no statistical difference between the two groups (90% versus 90%; p = 0.813). The median survival has not reached yet in all groups. Patients in the latter group (> 80 years) were found to have a higher chance of having strongly ER positive tumours (57% versus 50% in patients between 70 - 80 years with H-score >200; p- < 0.02). Conclusions: In a selected group of elderly women (> 80 years) who tend to have strongly ER positive tumours, surgery and primary endocrine therapy did not appear to produce any difference in breast cancer specific survival. This subject is currently being investigated in a national randomised trial in the UK. No significant financial relationships to disclose.
Determinants of outcome in elderly patients with positive sentinel lymph nodes
Authors: Gemignani M. , Karam A. , Hsu M. , Patil S. , Stempel M. , Traina T. , Ho A. , Cody H. , Morrow M. 
Published: August 2020

614 Background: Older women are less likely to receive standard of care treatment for breast cancer. This undertreatment may be linked to the perception that elderly patients (pts) may not tolerate or derive benefit from treatment that is often viewed as “too toxic.” Methods: From July 1997 to July 2003, 1,470 pts with invasive cancer with positive sentinel lymph nodes (PSLN) by intraoperative frozen section or final pathologic exam by hematoxylin-eosin and/or immunohistochemistry (IHC). We examined sociodemographic, pathologic, and therapeutic variables that affected the outcome of elderly pts ≥70 years old. A comorbidity score was assigned using Adult Comorbidity Evaluation-27 system. Chi-square, Fisher's exact Wilcoxon tests, and multivariate logistic regression analysis were used. Results: The median age was 53 years (range 21–89) and median tumor size 1.6 cm (range 0.1–11). 1,265 (86.1%) pts were <70 years old and 205 (13.9%) pts were ≥70 years old. 183 (12.5%) pts had IHC only PSLN, 1,021 (69.5%) had 1–3 PSLN, and 266 (18%) ≥4 PSLN. Breast conservation therapy (BCT) was performed in 59.7% of pts. Elderly pts were more likely to have moderate to severe comorbidities (46% vs. 11%, p < 0.0001) and BCT (67% vs. 59%, p = 0.026), compared to pts <70 years old. Elderly pts were less likely to undergo completion ALND (73% vs. 89%, p < 0.0001), adjuvant chemotherapy (43% vs. 90%, p < 0.0001) and radiotherapy following BCT (82% vs. 90%) compared to pts <70 years old. The 5-year disease-free survival (DFS) was not significantly different for elderly pts compared to non-elderly pts (87.7% vs. 91.9%, p = 0.21), on the other hand the 5-year overall survival was significantly worse for elderly pts (80.4% vs. 93.2%, p < 0.0001), a difference that was mainly due to a significantly higher 5-year cumulative incidence of death due to other causes (13.2% vs. 1.9%, p < 0.0001). On multivariate analysis, ER or PR positive status, IHC only PSLN and T1 tumors were the only factors independently associated with improved odds of 5-year DFS. Conclusions: Tumor rather than patient factors were the primary determinants of breast cancer outcomes in our cohort of node positive breast cancer pts. Elderly breast cancer pts with an estimated life expectancy beyond 5 years should receive the same standard of care therapy as their younger counterparts. No significant financial relationships to disclose.
Factors influencing 3D-MRI diagnosis in preoperative breast cancer patients
Authors: Hisamatsu K. , Takiyama W. , Sakabe R. , Satou Y. , Saeki S. , Mukaida H. , Yamashita Y. , Hirabayashi N. , Kaneko M. , Ono T. 
Published: August 2020

620 Background: We presented 3D-MRI will be the useful breast imaging tool in diagnosing intraductal spread and tumor size in breast cancer patients. (ASCO 2008).To do breast conserving surgery, careful management was needed in cases with widely ductal spreading and multifocal lesion. This study was to evaluate factors influencing false negative diagnosis and multifocal types of 3D-MRI, retrospectively. Methods: From July 2000, pre-operative 3D-MRI was underwent 488 cases and images were obtained 479 cases (98%). These patients could be divided into three groups according to 3D-MRI images: pattern 1) localized type (273 cases), 2) widely enhanced type (106 cases) and 3) multi-focal type (100 cases). From April 2005, resected specimen was serially step cut and total specimens were microscopically evaluated. Tumor size in 3D-MRI was 1cm over smaller than resected specimens were defined false negative cases. Investigated factors influencing 3D-MRI were age, patterns of 3D-MRI images, presence of pre-operative chemotherapy, histological type, histological grade, microscopical invasive tumor size (mm) and presence of ductal spreading. Results: The rate of histological confirmed intraductal spread were seen in 58% (158/273cases), 89% (94/106 cases) of patients with 3D-MRI pattern 1) and 2), respectively. Tumor size was correlated between MRI and specimens, significantly (n = 162, r = 06706, p < 0.001). Factors influencing false negative diagnosis of 3D-MRI were presence of pre-operative chemotherapy (p < 0.05), presence of ductal spreading (p < 0.001) and patterns of 3D-MRI images (p < 0.05). In the cases with multi-focal 3D- images, there were only 11(11/41, 26%) cases with true multifocal lesions by total specimens examination. Selection for breast conserving surgery and margin width were based by 3D-MRI images. The proportion of breast-conserved surgery were obtained 90% (437/488 cases) and local failure seen only 6 cases (local failure rate 1.4%) in 3D-MRI guided surgery. (median follow up 52 months). Conclusions: These results suggest that MRI will be the useful breast imaging tool, but caution will be needed in cases with pre-operative systemic therapy, cases expected intraductal spread by imaging tools and cases with multi-focal 3D- images. No significant financial relationships to disclose.
Nipple areola skin-sparing mastectomy with TRAM flap reconstruction: Single-center study
Authors: Kim H. , Park E. , Lim W. , Sei J. , Koh B. , Son B. , Ahn S. 
Published: August 2020

632 Background: Cosmetic aspect of breast cancer treatment becomes important. The originally described technique of Skin sparing mastectomy (SSM) included the removal of gland, nipple areola complex (NAC), and biopsy scar. However, the risk of tumor involvement of NAC in patients with breast cancer has been overestimated. The purpose of this study is to evaluate the oncological safety and technical outcomes of nipple areola skin sparing mastectomy (NA-SSM) compared with SSM. Methods: This retrospective study includes 522 patients who underwent immediate breast reconstruction using pedicled transverse rectus abdominis musculocutaneous (TRAM) flap between July 2001 and December 2006. The indication of NA-SSM in this study was defined as being for any stage, any tumor size and any tumor areola distance. Briefly, NAC was preserved when palpation and the outlook of the nipple was normal. 364 patients underwent SSM with immediate TRAM flap reconstruction and 152 underwent NA-SSM with immediate TRAM flap reconstruction. We compared complication rate, local recurrence rate (LRR), disease-free survival (DFS), and overall survival (OS) Between NA-SSM and SSM with immediate TRAM reconstruction cases. Results: Median follow up of NA-SSM and SSM was 60 and 67 months respectively. Complete or partial nipple areola necrosis developed in 26 (17.1%; complete, partial 15). The 5 year DFS was 89% for NA SSM and 87.4% for SSM (log rank p = 0.20), The 5 year OS was 99.3% for NA SSM and 98.3 % (log rank p = 0.33) The local failure occurred in 3 (2%) of 152 underwent NA SSM, 3 (0.8%) of 364 patients underwent SSM (p = 0.27). There were 2 (1.3%) nipple areola recurrence. Cosmetic outcome of NA SSM was better than that of SSM in the majority of patients. Conclusions: Our study demonstrates that NA-SSM with immediate TRAM reconstruction is oncologically as safe as SSM with immediate TRAM reconstruction and provides a good cosmetic outcome. No significant financial relationships to disclose.