bluuebunny/crossref_metadata_2025 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.
Identification of risk factors in mammographically occult contralateral breast carcinoma detected by magnetic resonance imaging (MRI)
Authors: Bernard J. R. , Vallow L. A. , Packianathan S. , Feigel D. G. , DePeri E. R. , Buskirk S. J. , Perez E. A.
Published: March 2020

614

Background: An analysis of preoperative bilateral breast MRI at our institution suggests that approximately 1/3 of patients with newly diagnosed breast cancer may have a mammographically occult, but MRI-evident, contralateral breast abnormality. A number of these patients will have pathologic confirmation of carcinoma in the contralateral breast. Identification of risk factors to predict which patients are at high risk for having a mammographically occult contralateral carcinoma was performed. Methods: MRI results of 401 women with newly diagnosed breast carcinoma who underwent MRI were reviewed (overall group; OG). Patients with a contralateral abnormality identified only by MRI were analyzed to determine the incidence of contralateral carcinoma. In addition, the following risk factors were evaluated: Age at diagnosis, menopausal status, tumor size, nodal status, ipsilateral tumor histology, tumor grade, hormone receptor status, Her-2/neu receptor status, and whether the patient had a palpable vs. mammographically detected abnormality. Results: Pathologically confirmed contralateral carcinoma (CC) was found in 13 patients (3.2%). Similar percentages of patients in both groups (OG and CC) were noted in regard to tumor size, histology, grade, nodal status, Her-2/neu receptor status, and method of detection (palpable vs. mammographic). However, median patient age was 71 (CC) vs. 62(OG); 92% (12/13) were postmenopausal (CC) compared to 75% (OG); and 100% were ER positive (CC) vs. 81% percent (OG). Conclusions: Older, postmenopausal women who have ER + tumors may have a higher likelihood of having synchronous, contralateral, mammographically occult, MRI-detected breast carcinoma. Preoperative MRI may be beneficial in patients with similar risk factors; however, further follow up and additional experience is needed for confirmation of these findings.

No significant financial relationships to disclose.
Comparing study of positron emission tomography and ultrasonography in the detection of axillary lymph node metastasis in patients with early stage breast cancer
Authors: Song B. , Bae J. , Kim J. , Jeon H. , Jung S.
Published: March 2020

616

Background: The current status of axillary lymph node is the most important prognostic factor in breast cancer. Axillary lymph node dissection (ALND) is currently the standard option for assessment of axillary lymph nodes. Positron emission tomography - computerized tomography (PET-CT) imaging and breast sonography are a noninvasive imaging modality that can detect malignant lymph node. The purpose of this study was to evaluate the clinical usefulness of axillary lymph node staging by means of PET-CT imaging compare with breast sonography in breast cancer. Methods: This study involves 129 breast cancer patients and clinically negative axillary node. All patients had whole body PET-CT imaging and breast sonography before SLN biopsy. After SLN biopsy, all patients underwent complete ALND. Axillary lymph nodes were evaluated by standard hematoxylin and eosin staining techniques, while sentinel nodes were further examined for micrometastatic disease. The findings of PET-CT imaging and breast sonography of 129 patients were compared with pathologic findings after operation. Diagnostic accuracy was evaluated applying ROC curve areas. Results: The sensitivity of PET-CT imaging was 60.0%; specificity and accuracy were 83.6% and 73.4%, respectively. The sensitivity, specificity and accuracy of breast sonography were 61.8%, 89.0%, and 77.3% respectively. The SUVs of axillary lymph node ranged from 0.0 to 7.01. Analysis using ROC curves revealed the area under each curve which indicated a diagnostic accuracy. For involvement of axillary lymph node, PET-CT imaging had the area under the curve of 0.735, breast sonography one of 0.769. Conclusions: Axillary lymph node staging using PET-CT imaging is inferior to the breast sonography in early stage of breast cancer patients. Our study reveals the value of PET-CT imaging is not good compare to the breast sonography in the detection of axillary lymph nodes metastasis in patients with early breast cancer.

No significant financial relationships to disclose.
Improvement in oncology practice performance through voluntary participation in the Quality Oncology Practice Initiative (QOPI)
Authors: Jacobson J. O. , Neuss M. N. , McNiff K. , Kadlubek P. , Thacker L. R. , Eisenberg P. D. , Simone J. V.
Published: March 2020

6505

Background: QOPI became available to all ASCO physicians in 2006 as a voluntary office-based quality improvement project. QOPI assesses practice performance for a series of evidence- and consensus-based process measures, relying on practices to do structured chart reviews and submit data via a secure web-based portal. Methods: This analysis focused on the 71 practices that participated in both the March and September 2006 data collections. Of the 33 measures common to both collections, 14 were chosen for analysis based on adequate sample size and variation from the mean. Four additional measures relating to antineoplastic therapy administration were also analyzed. Results: : 87 practices abstracted 9,324 charts in March and 113 practices abstracted 14,292 charts in September. Among the 71 practices participating in both data collections, statistically significant improvement was seen in 9 of 18 measures (mean change 2.0%, median 1.9%, range -10.1 to 8.2%) from March to September. Improvement was most marked among practices originally performing in the bottom quartile (mean change 11.8%, median 10.2%, range -10.1 to 24.7%). Table 1 shows the magnitude of change for selected measures of the lowest performing practices compared to all others. Improvement was not assessable in 4 measures where performance was uniformly very high in the first data collection (these included all measures of appropriate antineoplastic treatment). Conclusions: Participation in QOPI is associated with improved performance in self-reported process measures, with the greatest improvement demonstrated in initially low-performing practices. (The late Dr. Christopher Desch was integral to the preparation of this report and the success of QOPI.)

No significant financial relationships to disclose.

[Table: see text]
When the goal is not cure: A randomized trial of a patient decision aid in advanced colorectal cancer
Authors: Leighl N. B. , Shepherd H. , Butow P. , Clarke S. J. , McJannett M. , Beale P. , Wilcken N. , Moore M. J. , Chen E. X. , Tattersall M. H. , Goldstein D.
Published: March 2020

6509

Background: With improvements in treatment and supportive care, decisions in advanced cancer are increasingly complex. To facilitate decision-making, we developed a decision aid (DA) for patients considering first-line chemotherapy for incurable colorectal cancer, reviewing treatment options, prognostic information and toxicities. We examined its impact on patient understanding, consultation and decision- making satisfaction, anxiety, decisional conflict, quality of life, information preferences, and treatment decisions made. Methods: 207 newly diagnosed advanced colorectal cancer patients at 5 cancer centers in Australia and Canada were randomized to receive either a standard medical oncology consultation, or the same plus the DA, (take-home booklet with audio-recording, selected review by oncologist). Results: 100 were randomized to the control arm, 107 to receive the DA. Sample characteristics: median age 62 years, 58% male, 89% PS 0/1, 36% prior adjuvant chemotherapy. Patients in the DA arm demonstrated a greater increase in understanding of prognosis, options, benefits and toxicities (+19% vs +5.6%, p 0.001), with higher overall understanding (72% vs 60%, p<0.0001). Decision and consultation satisfaction, decisional conflict and quality of life were similar between groups. Anxiety, measured serially over 4–6 weeks, was similar and decreased over time. Most arrived at a decision during the first consultation; 80% chose chemotherapy, 7.5% supportive care alone, 10.5% a wait and watch strategy, with no differences between arms. 87% wanted as much information as possible, 82% wished to share decision-making with the physician, and only 15% felt the doctor alone should make the decision. More patients who received the decision aid felt they received all possible details about therapy, (72% vs 63%). 90% felt the decision was shared in part between physician and patient. Conclusion: This first randomized trial of a decision aid in advanced cancer patients shows that its use in advanced colorectal cancer improved patient understanding of prognosis, treatment options, risks and benefits without increasing anxiety. Decision aids can improve informed consent and decision-making, and can be tested through randomized trials even in the setting of advanced cancer.

No significant financial relationships to disclose.
A tool for assessing adverse events in phase I/II oncology clinical trials
Authors: Coombes M. , Mukherjee S. , Kowaleski B. , Levine M. , Cosby J. , Arnold A.
Published: March 2020

6518

Background: RECIST and NCI's Common Terminology Criteria are accepted systems that have standardized the reporting of oncology clinical trial outcomes. A standard system for attributing causality to Serious Adverse Events (SAEs) is lacking which can impact drug development and patient safety. The objectives of this study were to: 1) understand the clinical reasoning behind causality assessment during phase I/II oncology clinical trials; and, 2) use this information to develop a causality assessment tool for oncology. Methods: In-depth interviews were conducted with oncologists and trial coordinators at 6 Canadian academic cancer centres. Five main conceptual categories were explored: clinical reasoning; information resources; tools; challenges and concerns; and education. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. A new causality assessment tool was developed based upon the qualitative findings and an analysis of existing generic tools. Results: Thirty-two interviews were conducted between May and August 2006 (65% participation). Half of participants were female, 66% were oncologists and 42% had more than 10 years of clinical trial experience. Data showed that participants use a common strategy to assess causality: they gather information, eliminate alternative explanations, and consider the study drug as the cause of the SAE. Over half cited the quality of information resources as a major factor contributing to uncertainty when assessing causality. Participants expressed the need for a standardized approach to causality assessment in oncology clinical trials. The tool developed in this study guides users to consider 5 statements related to potential alternative etiologies and 4 related to other factors that support a drug-SAE connection. The user is asked for their overall impression using a continuous probability rating scale. Conclusions: Attributing causality to SAEs is complex and uncertain. Clinicians describe using a logical system of reasoning, but have encountered barriers which must be addressed. We have developed and are validating a new tool to assist cancer clinicians in providing higher quality safety data about new cancer drugs early in development.

[Table: see text]
Bisphosphonate use and osteonecrosis of the jaw: Pharmacovigilance and reporting of this serious adverse event from the Research on Adverse Drug Events and Reports (RADAR) project
Authors: Edwards B. J. , Gounder M. , McKoy J. , Raisch D. , Farrugia M. , Cesar M. , Marx R. , Ruggiero S. , Dimopoulos M. , Bennett C.
Published: March 2020

6519

Background: Two years after zoledronate, received FDA approval, four dental professionals treated 107 cases of osteonecrosis of the jaw (ONJ). We review the timeline and source for initial recognition of ONJ and the comprehensiveness of dissemination of information on this adverse drug event. Methods: Data sources included primary case series from dental professionals; published case reports, clinical trials, and cases reported to the manufacturers or the FDA. Exposure adjusted incidence rates estimates were derived from manufacturer sponsored and investigator initiated review of claims data from large cancer centers. Safety notifications were disseminated by the manufacturers, regulatory authorities, and academic investigators. Results: Between 2001 and 2003, 107 patients with ONJ received care from dental professionals. In late 2003, and 2004 peer-reviewed case series were published. By 2006, safety databases maintained by the FDA, the manufacturer, and the RADAR project included information on 2,270, 1,178, and 368 cases of ONJ, respectively. In 2004 and 2005, incidence estimates of 0.8 and 22 ONJ cases per 1,000 person-years of intravenous bisphosphonate therapy were reported by the manufacturer and academic investigators. From 2003 to 2006, safety information from manufacturers, national regulatory authorities, case series, and clinical guidelines were disseminated. Conclusions: Recognition and reporting of ONJ occurred two years after FDA approval of zoledronate, dissemination of safety information occurred in the third year, and publications were disseminated from year three to year five. The life-cycle for identification and information dissemination for this serious adverse drug reaction was short and comprehensive.

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New IRB guidelines: Will cancer patient safety improve?
Authors: Angelotta C. , Dorr D. , West D. , Burdon R. , Lagman J. , Workman D. , Hurdle J. , Belknap S. , Bennett C. L.
Published: March 2020

6520

Background: Beginning in the 1990s, drug companies increasingly sent reports of all serious adverse events (AEs) to any Institutional Review Board (IRB) overseeing a trial using the agent involved, whether or not the same study was underway at that IRB site and regardless of the likelihood of a causal link between the event and agent. This led to a flood of AE reports and a small signal-to-noise ratio. Recent federal draft guidance emphasizes that regulations require investigators to notify IRBs only when there are “unanticipated problems involving risks to subjects or others. Consequently, many IRBs relaxed their reporting requirements, focusing only on unanticipated events. The objective of this study is to estimate how adoption of the new guidance affects IRB workload and patient safety. Methods: We reviewed AEs reported since 2004 to the IRB at Oregon Health & Science University for eight oncology drugs: bevacizumab, gefitinib, imatinib mesylate, oxaliplatin, bortezomib, sorafenib, sunitinib, and cetuximab. We defined unanticipated AE as any AE not included in the patient consent forms. Results: Forty-seven studies were reviewed with 885 unique AEs reported for the eight drugs. Of these, 494 were unanticipated, meaning the event was not described in the consent form. Thus, the IRB workload would decrease by 44% under the new guidance. Twenty-six AEs led to actual consent form changes, suggesting these signal events represented serious, related, but previously unknown toxicities of the study drug. This led to a signal-to-noise ratio improvement from 3% to 5.3%. For imatinib mesylate, the signal-to-noise ratio improved from 4.1% (14 signals out of 339 reports) to 7.8% (14 signals out of 179 reports), the largest improvement of the drugs studied. Conclusions: These results suggest that adoption of the new guidance may improve signal detection capabilities of local IRBs while decreasing workload. More empirical evidence is needed to ensure patient safety. Enhanced pharmacovigilance practices at the IRB level should lead to improved detection of serious AEs during clinical trials - before the drug is approved and widely available to veterans. In addition, improving the signal-to-noise ratio should allow IRBs to improve the welfare of cancer research subjects.

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Patient-centered validation of 11 symptom indices to evaluate response to chemotherapy for advanced cancer
Authors: Rosenbloom S. K. , Beaumont J. , Diaz P. , Yount S. E. , Abernethy A. P. , Jacobsen P. B. , Paul D. , Syrjala K. , Von Roenn J. H. , Cella D.
Published: March 2020

6524

Background: Symptom burden in advanced disease has relevance both for clinical practice and in evaluating the efficacy of new chemotherapeutic agents. This study aimed to identify patients’ highest priority symptoms for 11 advanced cancers, compare priority ratings with those obtained from clinicians, and construct brief symptom indices based on their combined input. Methods: 534 patients with advanced bladder, brain, breast, colorectal, head/neck, hepatobiliary/pancreatic, kidney, lung, lymphoma, ovarian or prostate cancer from a subset of National Comprehensive Cancer Network (NCCN) member institutions and 4 Cancer Health Alliance of Metropolitan Chicago organizations completed a survey of priority symptoms and concerns and a disease-specific FACT QOL measure. 112 physicians at NCCN institutions completed a rating of whether symptoms and concerns were considered disease- or treatment-related. Symptoms endorsed more often than chance probability were retained. Expert clinician and patient ratings were equally weighted in item selection. Responses to symptom index items drawn from the QOL questionnaires allowed for validation analyses. Results: Items comprising 2 to 3 subscales (up to 20 items in length) were retained for each of the 11 disease-specific symptom indices. Content-determined subscales consisted of symptoms and concerns that were 1) exclusively or predominantly disease-related symptoms (DRS); 2) exclusively or predominantly treatment side effects (TSE); and 3) descriptive of general function or well-being (F/WB). For example, the NCCN/FACT Breast Cancer Symptom Index (FBSI) contains 17 items: 8 DRS, 4 TSE and 5 F/WB. Data on 14 of 17 FBSI items showed good internal consistency (a=.89). Correlations between FBSI and FACT-B scores were high for physical well-being, functional well-being and breast cancer subscales (r = 0.83, 0.77, and 0.61 respectively). Correlation with emotional well-being subscale was 0.55. FBSI scores differed across PSR groups in the appropriate direction (p<0.0001). Conclusions: NCCN/FACT disease-specific questionnaires have been transformed into brief, patient-centered symptom indices that can be used as stand-alone measures in oncology research and practice.

No significant financial relationships to disclose.
A study of informed consent (IC), age, and cognitive function (CF) among advanced cancer patients (acp) in phase I trials
Authors: Hlubocky F. J. , Larson E. , Sachs G. , Daugherty C. K.
Published: March 2020

6548

Background: Ethical concerns exist about acps’ ability to provide adequate informed consent (IC) for phase I trials. While cognitive impairment (CI) among acp is well-recognized due to multiple factors, e.g., previous effects of chemotherapy, age, psychological status, the prevalence of CI among acp in phase I trials has never been described. Methods: Acp CF was assessed using a neuropsychological battery of instruments: Hopkins Verbal Learning (HVLT); Verbal Fluency; Mini-Cognitive Assessment; Trail-making (Parts A& B); Boston Naming (short); WAIS subtests (Comprehension and Digit Span). Acp underwent semi-structured interviews to evaluate elements of IC, and completed the FACT-COG and the Hospital Anxiety and Depression Scale (HADS). Results: To date, a total of 34 acp enrolling in Phase I trials have been studied. Median age: 63y (range: 38–81y); 77% male; 77% Caucasian; 67% > HS education. Regarding IC understanding: Only 20% of responding acp correctly identified the purpose of Phase I trials; all subjects could recall risks of side effects, correctly stated they could refuse trial participation, and stated they could withdraw at anytime; 53% believed the trial was their only option. Older acp (>age 55y) were less likely to correctly describe the research purpose of the trial (29% v. 71% p=0.02). Older acp had measurable deficits in CF: Boston Naming (14±0.9 v.15±0.3, p=0.09); HVLT Total Recall (14±2 v.26±6, p<0.00) and Discrimination Index (7.5±3 v.11±1, p=0.03); Digit Span-Backwards (4±2 v.7±2, p<0.00); Trail-making B (244±64 v.188±51, p=0.04). While there were no differences in perceived CI (95±18 v.101±19, p=0.5) or impact on quality of life (25±7 v. 27±5, p=0.5), both groups had scores well below prior reported means. Older acp tended to report depressive symptoms more than younger acp (8±2 v.6±1, p=0.07). Conclusions: Our data suggest that CF may play a role in acp understanding of IC for clinical trials, especially among the elderly. Further research is needed, given ethical concerns regarding elderly acp in clinical trials of experimental agents who may have CI.

No significant financial relationships to disclose.
Determining knowledge transfer gaps in the life cycle of evidence for chemotherapy in non-small cell lung cancer (NSCLC) through cumulative meta-analysis
Authors: Reaume M. N. , Nurbhai M. , McGowan J. , O'Rourke K. , Moja P. L. , Evans W. K. , Graham I. D. , Grimshaw J. M.
Published: March 2020

6555

Background: The uptake of research findings into practice is often delayed (Antman et al. JAMA 1992). We investigated the relative role of evidence in determining clinical recommendations and practice for NSCLC. Novel chemotherapy agents (NCA) approved for use in Canada between 1992 and 2002 were eligible. Methods: We conducted a systematic review of evidence for vinorelbine (V), paclitaxel (P) and gemcitabine (G) in combination with a platinum agent for the treatment of advanced NSCLC. Primary endpoint of efficacy was median survival. For each included randomized controlled trial (RCT), the publications dates of abstracts and journal articles were considered. At each time point when new data was available, a new meta-analysis using the Follman methodology was performed. Bibliometric analyses were performed to identify key milestones for each drug (e.g. Health Canada Notice of Compliance, provincial drug funding, and clinical recommendations). Results: 3,399 references were obtained for NCA in advanced NSCLC. Eligibility review identified 20 references for V representing 6 RCTs (1994–2002), 16 for P representing 4 RCTs (1997–2000), and 10 for G representing 7 RCTs (1998–2003). All drugs trended towards median survival benefit throughout the time of analysis. However, over time the estimated effect for V became weaker, remained stable for P and became stronger for G. The 1997 ASCO guideline recommended V and P as standard therapy; G was only cited as a promising investigational agent. By 2003, the ASCO guideline recommended G as a standard. Only V received Ontario provincial funding in 1997, while G and P received funding in 2002 and 2003 respectively. Conclusions: This study demonstrates the relatively small pool of RCT evidence for NCAs. These three commonly used NCAs demonstrate different patterns of evolution of evidence. For advanced NSCLC, the time gap between evidence and clinical recommendations is short. Caution should be used for generating recommendations using early results, when the evidence base is not stable, which may either over or underestimate true effectiveness.

No significant financial relationships to disclose.