bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of changes in blood flow PET measurements to predict post-therapy lymph node status among locally advanced breast cancer patients
Authors: Mankoff D. A. , Dunnwald L. , Gralow J. , Ellis G. , Linden H. , Specht J. , Doot R. , Barlow W. , Schubert E. , Livingston R. 
Published: March 2020

575 Background: Response to neoadjuvant therapy in the primary tumor and nodal metastasis predicts benefit to patients as shown in several large clinical trials. We have previously shown that changes in tumor blood flow (BF) measured by [15O]-water PET predict pathologic primary tumor response. We now test whether primary tumor blood flow changes also predict axillary nodal metastases response and post-therapy lymph node status among women with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy. Methds: Fifty-five women with a primary diagnosis of LABC underwent dynamic [15O]-water PET scans prior to and at midpoint of neoadjuvant chemotherapy. We evaluated associations between tumor BF changes and pathologic primary tumor response: categorized as complete (CR), partial (PR) or no response (NR). We also assessed the relationship between primary tumor BF changes and post-therapy axillary lymph node status, categorizing the high risk (HR) group as 4+ nodes with extracapsular extension (ECE, n=12) versus the lower risk (LR) group with either fewer than 4+ nodes or without ECE (n=43). Results: The median changes in BF versus tumor response were: CR = -77%, PR = -40%, and, NR = +20% (P = <0.001). For axillary node response, the median BF change among HR patients was +20% versus - 49% among LR patients (P = 0.004). Eight of 17 patients with an increase in tumor blood flow were HR whereas 4/38 patients with decreased tumor blood flow were HR (P = 0.002). Conclusions: Change in primary tumor blood flow over the course of neoadjuvant chemotherapy predicts pathologic response to treatment with a substantial decrease observed among CRs. An increase in primary tumor BF with treatment portends significant residual primary tumor and a nearly 50% chance of very high-risk nodal disease post-therapy. No significant financial relationships to disclose.
Prospective study of changes in spindle assembly checkpoint (SAC) to predict breast tumor response to taxanes
Authors: Ueno N. T. , Kim S. , Symmans W. F. , Detry M. A. , Pusztai L. , Sanchez L. F. , Ishihara H. , Hortobagyi G. N. , Noguchi S. 
Published: March 2020

586 Background: Increased cyclin-dependent kinase 1 (CDK1) and reduced CDK2 activity reflects taxane chemosensitivity via regulation of SAC. Novel C2P device (Sysmex Inc.) measures CDK1/2 activity in human tissue within a few hours. We hypothesized that SAC functionality in breast cancer predicts taxane sensitivity. Methods: Biopsy samples obtained before preoperative therapy from 69 pts with primary breast cancer (median age 52, St II, 56%, St III, 40%, HER2 36%, HR 52%) ex vivo with paclitaxel (100 nM) for 24 h, then measured for CDK1/2 activity. Tumors with CDK1/2 ratio > 0.7 were denoted “responders” (CR, PR) based on preclinical testing. Clinical responses were evaluated with sonography. Results: 24 pts could not be evaluated because of unmeasurable or invalid CDK (n=3), no receipt of taxane (n=10), incomplete treatment/lack of imaging (n=10), or receipt of taxane as adjuvant therapy (n=1). Among the 45 evaluable pts, 30 obtained reading to determine the C2P-predicted response, which was significantly associated with the clinical response to preoperative therapy with paclitaxel, docetaxel, docetaxel/doxorubicin, paclitaxel/trastuzumab or lapatinib, or docetaxel/capecitabine (P=0.002; sensitivity 0.83; specificity 0.86; positive predictive value [PPV] 0.95; and negative predictive value [NPV] 0.60). For HER2- tumors, the sensitivity was 0.94; specificity 0.83; PPV 0.94; and NPV 0.83. We fit a series of logistic regression models to assess the relationship between C2P predicted response and clinical outcome. Each model included 1 clinical prognostic factor (HR status, stage, NG, histology, HER2) as well as the C2P prediction factor. In all 5 models C2P remained a statistically significant predictor of clinical response while adjusting for the other prognostic factor. Conclusions: CDK1/2 activity is a promising novel predictive marker to predict response to taxane- containing regimens for HER2- breast cancer. We could not predict taxane sensitivity in HER2+ tumors; this finding is consistent with preclinical findings that HER2 overexpression is involved in abnormal SAC functionality. Thus, the functional SAC reflects taxane sensitivity in HER2- tumors. We are planning a large prospective study to validate these findings. No significant financial relationships to disclose.
Factors associated with concerns about recurrence in women with breast cancer
Authors: Corbin K. , Shields C. G. , Weiss M. , Griggs J. J. , Lambert D. R. 
Published: March 2020

593 Background: The purpose of this study was to examine factors associated with concerns about disease recurrence in women with ductal carcinoma in situ (DCIS) and invasive breast cancer. Methods: Participants completed an anonymous survey instrument through the website of www.breastcancer.org , a non-profit organization. Participants provided information on diagnosis and treatment characteristics, demographics, preferences for treatment, fears of recurrence as measured by the Concerns of Recurrence Scale (Vickberg, Ann Behav Med 2003), and completed the SF-36 Mental Health Subscale. Participants were also asked if they had been told they had a “good cancer,” “good kind of cancer,” or “better cancer than others.” Bivariate and multivariate analyses examined the relationships between fears of recurrence and mental health, patient, disease, and treatment factors. Results: 331 women completed the survey instrument, 125 with DCIS and 206 with invasive breast cancer. In multivariate analysis, fear of recurrence was associated with age (β= -.24, 95% CI -.44,-.06), time since diagnosis (β= -.09, 95% CI -.16,-.02), having a mastectomy (β= -45, 95% -.83,-.08), and a diagnosis of DCIS (β= -1.00, 95% CI - 1.48,-.53). Women with DCIS who were told they had a “good cancer” had greater fear of recurrence than women with DCIS who were not told they had a good cancer (β= 1.25, 95% CI .56, 1.93). No such association in women with invasive breast cancer was found. Mental health was negatively correlated with fear of recurrence in women with DCIS (β= -0.43, 95% CI -.61,-.25). Level of education and satisfaction with the relationship with physicians were not associated with fear of recurrence. Conclusions: Older age and time since diagnosis are associated with reduced fears of recurrence. Women who have had a mastectomy also have lower fears of recurrence. Interestingly, receiving a message that one has a “good cancer” appears to be associated with increased fear of recurrence although the direction of the association cannot be determined from this study. Further research into effective and appropriate methods of informing and reassuring patients with different prognostic profiles of breast cancer is warranted. No significant financial relationships to disclose.
Measuring the quality of breast cancer care: National variation in the use of radiation among women under age 70
Authors: Edge S. B. , Stewart A. , Patel-Parekh L. , Gay G. , Palis B. , Ko C. 
Published: March 2020

599 The National Quality Forum (NQF) recently adopted accountability cancer quality measures. Careful specification of target populations makes it so that omission of recommended therapy should be uncommon. One measure is use of radiation (RT) with breast conserving therapy (BCT) for women under age 70. This study examines nationwide use of RT in 2003–04 to determine the extent of variation and the need for improvement within these tight specifications. Methods: Data from 1,303 hospitals reporting to the National Cancer Data Base (NCDB) on women under age 70 treated with BCT in 2003–04 for invasive breast cancer were examined for factors associated with the use of RT in a multivariate model. The attributable provider unit was the reporting hospital. Results: Overall among 90,611 women under age 70, RT was reported with BCT in 74.5%. RT began within 6 months diagnosis in 54% and 1 yr in 74.2%. On multivariable analysis ( Table 1 ), RT was significantly less likely among African American and Hispanic vs. Caucasian women, those with less vs. more education, with no insurance or Medicaid vs. managed care, those with Charlson comorbidity > 0, women treated outside the Great Lakes/Midwest census regions, and treated at hospitals in the lower vs. higher quartiles of case volume. RT was administered to 73% of women in non-urban hospitals, and to 82% of women in urban hospitals. RT was administered to 75% and 77% of women age 50 - 59 and 60 - 69, respectively, compared to 68% and 72% of women age < 40 and 40 - 49. Conclusions: Despite limiting measurement to populations that should clearly receive RT with BCT, there are significant variations associated with patient and institutional characteristics. Reporting cancer care quality data is important, and the use of RT with BCT is a key quality measure for improvement and provider accountability. [Table: see text] No significant financial relationships to disclose.
Retrovirus-mediated delivery of short hairpin RNA targeting human papillomavirus (HPV) 16 E6 and E7 oncogenes and induction of apoptosis in oropharyngeal squamous cell cancer (OSCC) cell line
Authors: Rampias T. , Sasaki C. , DiMaio D. , Psyrri A. 
Published: March 2020

6002 Background: Human papillomavirus type 16 is identified in almost 50% of the cases of OSCC. The E6 and E7 genes of HPVs encode oncoproteins that bind and degrade the tumor suppressor proteins p53 and Rb, respectively. We are exploring the potential use of short hairpin RNA (sh RNA) for gene therapy of HPV-positive OSCC. Methods: Small hairpin RNAs targeting E6 or E7 genes were delivered by a retrovirus vector to 93VU147T (bearing integrated HPV16 DNA) and 92VU040T (HPV negative) oropharyngeal cancer cell lines. Flow cytometry analysis was used to assess apoptosis after the retrovirus infection. The E6 and E7 mRNA downregulation was assessed by reverse transcription polymerase chain reaction (RT-PCR). At protein level p53 and Rb expression were evaluated with Western blotting analysis. Results: Apoptosis was seen in over 90% of 93VU147T cells 48 hours after infection whereas 92VU040T cells were not affected. RT-PCR demonstrated that HPV16 E6/E7 mRNA levels decreased significantly in infected 93VU147T cells. 93VU147T infected cells also showed a marked increase in p53 and Rb protein levels. Conclusions: Downregulation of E6/E7 gene expression in HPV16+ OSCC cells results in apoptosis and reactivation of p53 and Rb tumor suppression pathways. These results have significant implications in treating HPV-associated OSCC with HPV-targeted gene therapy. No significant financial relationships to disclose.
Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a predictor of response in head and neck squamous cell carcinoma (HNSCC)
Authors: Dave A. , Fury M. , Lee N. , Stambuk H. , Wang Y. , Karimi S. , Pfister D. , Koutcher J. 
Published: March 2020

6007 Background: We wish to assess on a preliminary basis whether pretreatment DCE-MRI predicts response to chemoradiation in HNSCC. Methods: Tumor perfusion was assessed in 14 patients (median age, 56y; 13 M, 1 F; squamous cell cancer 13, poorly differentiated carcinoma 1; base of tongue 6; tonsil 6; larynx 1; nasopharynx 1) with nodal metastases (size >1 cc for DCE-MRI; N1, 3; N2a, 2; N2b, 4; N2c, 4; N3, 1; Stage III, 3; Stage IVa, 10; Stage IVb, 1) prior to platin-based concurrent chemoradiation therapy. Data were acquired on a 1.5 Tesla clinical scanner with a standard MRI protocol using a clinical contrast agent (Gd-DTPA). The two compartment model analysis measured the rate constants of the contrast agent transfer between the lesion and plasma compartments (kep) and elimination by the plasma (kel). Each patient was assigned a single MR imaging parameter of uptake slope and compartmental model (Akep) on the basis of the histogram analysis of all individually fit tumor voxels. Histogram analysis calculated the amplitude (a), width (s), and median (μ) of the distribution from the fitting procedure. Overall response was determined approximately 2–5 months post treatment. Results: DCE-MRI data showed a rapid rise in the time intensity curves for viable appearing tumor, whereas muscle showed minimal signal enhancement. The mean Akep value was higher for complete responders (CR/near CR, n = 7) than for incomplete responders (ICR, n = 7; 3 partial response, 4 no response) (12.29/min±4.09 vs 7.11/min±2.51 [P = 0.04]. The preliminary histogram analysis for the slope showed that the width and median were able to differentiate between CR and ICR, P=0.039 and P=0.013 respectively, while amplitude was not significant (P=0.150). Conclusions: These preliminary data suggest that DCE-MRI may prove to be a useful predictor of response in HNSCC patients, and thus may enhance prognostication, patient selection, and treatment outcomes. No significant financial relationships to disclose.
Vandetanib in metastatic hereditary medullary thyroid cancer: Follow-up results of an open-label phase II trial
Authors: Wells S. A. , Gosnell J. E. , Gagel R. F. , Moley J. F. , Pfister D. G. , Sosa J. A. , Skinner M. , Krebs A. , Hou J. , Schlumberger M. 
Published: March 2020

6018 Background: Medullary thyroid cancer (MTC) is the most common cause of death in patients with hereditary syndromes caused by activating mutations in the RET protooncogene. RET activation is the initial oncogenic event, with the activity of other receptor tyrosine kinases, including VEGFR and EGFR, likely to contribute to tumor growth and metastasis. Vandetanib (ZD6474) is a once- daily oral agent that selectively targets RET, VEGFR and EGFR tyrosine kinases. Methods: Eligible patients had unresectable, measurable, locally advanced or metastatic hereditary MTC and a RET germline mutation. Patients received vandetanib 300 mg/day until disease progression or any other withdrawal criteria. The primary objective was to assess the objective tumor response (RECIST every 3 months). Secondary assessments included disease control rate, biochemical response (determined by decrements in plasma levels of calcitonin, a tumor marker for MTC) and safety and tolerability. Results: Thirty patients (21 female; median age 50 years) received initial treatment with vandetanib 300 mg. At data cut-off (20 Nov 2006), the median duration of treatment was 172 days. Based on site investigator assessments, 20% (6/30) of patients experienced a partial response (duration of response 59–260 days) and another 30% (9/30) of patients experienced stable disease =24 weeks, yielding a disease control rate of 50% (15/30). Centralized independent confirmation of response is planned. In 19 patients, plasma calcitonin levels showed a =50% decrease from baseline that was maintained for at least 6 weeks. Adverse events (AEs) occurring in >50% of patients were rash (73%), diarrhea (67%), fatigue (57%) and nausea (53%). Most AEs were grade 1 or 2; grade 3 AEs included asymptomatic QTc prolongation (n=5), rash and diarrhea (both n=3), all of which were manageable. Conclusions: Vandetanib has demonstrated clinical activity in this phase II study in metastatic hereditary MTC, and the safety profile is generally consistent with previous vandetanib monotherapy studies. Accrual is now complete (30 patients), and an updated analysis will be performed in April 2007. An international, randomized, placebo-controlled phase II trial of vandetanib in MTC is now recruiting patients. # No significant financial relationships to disclose.
Head and neck squamous cell cancer as part of the germline p16/INK4a mutation-induced FAMMM syndrome
Authors: Vinarsky V. , Fine R. L. , Assaad A. , Qian Y. , Chabot J. A. , Su G. H. , Frucht H. 
Published: March 2020

6052 Background: p16/INK4a constitutes an important cancer susceptibility locus. Germline mutations at this locus have been implicated in several human cancer syndromes, including familial atypical multiple mole melanoma (FAMMM) syndrome, FAMMM-pancreatic cancer (FAMMM-PC) syndrome, and more recently, in familial head and neck cancer syndrome. Methods: We present an individual with a family history of both pancreatic cancer and melanoma, who developed squamous cell carcinoma of the tongue at 21 years old, multiple melanomas, a second squamous cell cancer of the tongue at 40 years old, and ultimately a pancreatic cancer. Results: We identify a germline mutation in INK4a that leads to a substitution of tryptophan for glycine in the Ankyrin III domain of the p16 protein (G101W). We demonstrate loss of heterozygosity at the INK4a locus and lack of p16 expression in the second head and neck squamous cell cancer (HNSCC) tissue. Based on these and on previously published data, we propose that HNSCC resulting from an INK4a germline mutation is a variant of the FAMMM/FAMMM-PC syndrome. Further studies will determine whether there is genotype-phenotype correlation between these syndrome variants. Conclusions: We conclude that young individuals who develop HNSCC should be considered at high-risk for other cancers, including pancreatic cancer and melanoma. They should be advised to avoid cigarette smoking and should be considered for pancreas cancer screening. No significant financial relationships to disclose.
The use of stereotactic radiotherapy boost to improve local control in patients with locally advanced nasopharyngeal carcinoma (NPC)
Authors: Le Q. , Hara W. , Chang S. D. , Pinto H. A. , Kaplan M. J. , Goffinet D. R. 
Published: March 2020

6056 Background: To determine the long term outcomes and delayed side effects in patients receiving stereotactic radiotherapy (SRT) as a boost following external beam radiotherapy (EBRT) for locally advanced NPC. Methods: 82 NPC patients received a STR boost after EBRT at our institution between 9/1992 and 5/2006. Nine patients had T1, 31 had T2, 12 had T3, and 30 had T4 tumors (1997 AJCC staging). Sixteen patients had stage II, 20 had stage III, and 46 had stage IV neoplasms. Most patients received 66 Gy of EBRT followed by a single fraction STR boost of 7–15 Gy, delivered 2–6 weeks after EBRT. 70 patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to EBRT. Results: At median follow-up of 40.7 months for living patients (range: 6.5 –144.2 months), there was only 1 local failure in a patient with a T4 tumor. At five years, the freedom from local relapse rate was 98%, freedom from nodal relapse was 83%, freedom from distant metastasis was 68%, freedom from any relapse was 67% and overall survival was 69%. Late toxicity included unresolved V2 or V3 numbness in 2, radiation-related retinopathy in 1, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 9 patients, of which 2 were symptomatic with seizures. All but one patient with temporal lobe necrosis had intracranial tumor extension at diagnosis. Conclusions: STR boost after EBRT resulted in excellent local control. However, the incidence of temporal lobe necrosis approached 11% in these patients and higher in patients with intracranial extension. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and STR is important to avoid long-term complications. No significant financial relationships to disclose.
Weekly docetaxel as second-line (palliative) chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma (SCCHN)
Authors: Koussis H. , Scola A. , Bergamo F. , Tonello S. , Jirillo A. , Basso U. , Pasetto L. M. , Sperandio P. , Donach M. E. , Monfardini S. 
Published: March 2020

6067 Background: Relapse or distant metastases of squamous cell carcinoma of the head and neck (SCCHN) is considered to have poor prognosis with survival time of less than one year. Presently, there s no standard treatment even if palliative chemotherapy is widely used. In this setting in recent years taxanes are among the most widely used agents. Methods: From December 2004 to October 2006 24 pts (20 male and 4 female, 12 over 60 yrs) with recurrent metastatic squamous cell carcinoma were consecutively accrued and treated with weekly docetaxel 35mg/m2 for 3 of 4 weeks. Median age was 59 (range 34–74). All had good performance status (ECOG 0- 1) and had received previous standard platinum-based regimen. Primary endpoints were response rate, duration of response, time to progression and toxicity evaluation. Results: A total of 83 courses of weekly docetaxel were administered (mean 3.5; range 1–10 courses). Six partial responses (25%) (RECIST criteria) with mean duration of 3.4 months, 6 stable and 12 progressive disease were observed; no complete responses were obtained. Time to progression was 3.2 months (range 1.2–9 months). Of note, response rates and toxicity were similar in patients above (12 pts) and below (12 pts) 60 yrs. Toxicity was mild: G4 mucositis in 3 pts and G3-G4 hematologic in 4 pts. Conclusions: These data suggest that a weekly schedule of docetaxel is active and tolerable as second line therapy in patients with metastatic/recurrent SCCHN. The response rate is slightly better than that described in the literature which averages 15–20%. The schedule is easy to administer to out patients and also seems possible for elderly patients. No significant financial relationships to disclose.
Predictive factors in advanced head and neck cancer treated by radio-chemotherapy and hypoxia modification
Authors: Clavo B. , Robaina F. , Ruiz A. , Lloret M. , Macias D. , Rivero J. , Pinar B. , Quintero S. , Cuyas J. M. , Hernandez M. A. 
Published: March 2020

6085 Background: Anemia and tumor hypoxia are known factors for resistance to radio-chemotherapy (RT-CT). In a previous report we have suggested that spinal cord stimulation (SCS) can modify tumor oxygenation and regional blood flow in head and neck cancer (HNC). The aim of the present prospective study was to test the predictive value of pO2 measurement in HNC treated by RT-CT and hypoxia modification using SCS. Methods: Twelve male patients with advanced HNC were analyzed. Stage IVb-IVa: 8–4; mean age 58 + 7.6 years (46–70). Scheduled therapy was hyperfractionated RT (120 cGy/fraction, two fractions/day, total dose 81.6 Gy) from a Co- 60 source, and tegafur 800 mg/day. SCS devices were placed before RT-CT under local anesthesia. During treatment, SCS was connected from 20–30 min before to 20–30 min after each radiotherapy session. Before treatment, they were assessed: Hemoglobin levels and tumor oxygenation pre-SCS and pos-SCS (measured by a polarographic probe system ‘pO2 Histograph‘), expressed as median-pO2, and the fraction of pO2 values less than 5 mmHg (HF5) and less than 2.5 mmHg (HF2.5). Correlations were assessed using Pearson and Spearman tests, and actuarial survival using Kaplan-Meier estimates and Log-rank test. Results: Hemoglobin levels were correlated with oxygenation pre-SCS and pos-SCS: median-pO2 (p=0.005 and p=0.011), HF5 (p=0.048 and p=0.005) respectively. Anemia was associated with more advanced stage (IVb vs IVa, p=0.022), higher HF5 pos-SCS (p=0.028) and lower disease-free survival (p=0.019). The HF2.5 pos-SCS was adversely correlated with the 2 years actuarial: disease-free survival (p=0.027), cause-specific survival (p=0.008) and overall survival (p=0.008). HF2.5 was also correlated with hematocrit (p=0.044). Conclusions: Low hemoglobin levels and anemia are associated with more hypoxic and more advanced tumors. Pre-treatment tumor hypoxia (assessed by the fraction of pO2 values less than 2.5 mmHg during-SCS) is a strong predictive factor for survival in advanced HNC. Patients with highly hypoxic tumors should be selected for more aggressive treatments. Partially supported by: Grant ‘FUNCIS: PI 31–98‘. Scientific supervision was carried out by GICOR. No significant financial relationships to disclose.