Receipt Of CTx Research Articles

Abstract P4-11-08: Impact of ovarian stimulation for fertility preservation in young women with breast cancer: Updated survival and pregnancy outcomes

Abstract Background: Chemotherapy (CTx) and hormone therapy may impair fertility in women with breast cancer (BC) by direct gonadotoxicity or delayed childbearing. Inconsistent data regarding the safety and efficacy of ovarian stimulation for fertility preservation (FP) in BC may limit clinician referral and patient uptake of FP. We previously examined the effect of FP on BC recurrence and herein present updated survival and pregnancy outcomes in relation to FP from an expanded BC cohort. Methods: Women aged ≤ 40 years diagnosed with stage I-III BC between 2007-2018 referred to one of six cancer centres and to a reproductive endocrinologist in British Columbia, Canada were identified from a central database. Clinicopathologic, treatment and outcome characteristics were compared using uni/multivariate Cox and logistic regression analyses for survival and pregnancy outcomes, respectively, for patients who did and did not undergo FP prior to systemic cancer treatment. Results: 158 patients were identified. Sixty-four (41%) had lymph node involvement, 119 (75%) had ER-positive and 39 (25%) had HER2-positive BC. The 72 (46%) patients who underwent FP were more likely to be younger (mean age 33 vs 34 y, p=0.030), ECOG 0 (p=0.013), have CTx (p<0.001) and GnRH agonist during CTx (p=0.010) compared to patients with no FP. Tumor stage, ER/HER2/BRCA-positivity, BMI, radiation and number of existing children were not associated with decision to pursue FP (p>0.05). After a median follow-up of 4.7 years, BC recurrence occurred in 15 (17%) non-FP patients and 9 (13%) FP patients (Table 1). FP did not affect overall survival by univariate (HR 0.9; 95% CI 0.7-1.3) or multivariate analysis controlling for age, BMI, ECOG/ER/HER2 status, tumor stage and receipt of CTx or radiation (HR 1.0, 95% CI 0.7-1.4). Post-diagnosis, 22 (31%) FP patients and 11 (13%) non-FP patients had ≥ 1 pregnancy (Table 2). The use of assisted reproductive technology (ART) was similar in both groups. Patients who had FP were 2.8 times more likely (p=0.013) to conceive at least once. The results remained significant on multivariate analysis controlling for age, BMI, ECOG status and baseline parity (p=0.030). Non-FP patients had a 31% higher miscarriage rate than those who did (p=0.26). Conclusions: FP was not associated with an increased risk of locoregional recurrence, distant recurrence or death over a follow-up period of 3-11 years, supporting its safety in young women with BC. Despite more often receiving CTx, patients who underwent FP were significantly more likely to conceive after BC than those who did not, even when accounting for differences in patient profiles. This may relate to greater use of GnRH agonists during CTx, known to protect ovarian function, and stronger desires for future childbearing in patients who pursued FP. Although there was similar use of ART in both groups, the higher pregnancy rate and more successful reproductive outcomes in FP patients support the value and promotion of pre-oncologic treatment FP in young BC patients early in their disease trajectory, to enhance survivorship family planning. Table 1.Survival outcomes of patients.CharacteristicNo FP (n=86)FP (n=72)p-valueRecurred [n (%)]0.85Locoregional6 (7)4 (6)Distant9 (10)5 (7)Deceased [n (%)]8 (9)4 (6)0.38 Table 2.Characteristics of first pregnancies in patients conceiving after diagnosis.CharacteristicNo FP (n=11)FP (n=21)p-valuePregnancy outcome [n (%)]0.26Completed3 (27)11 (52)Miscarriage7 (64)7 (33)Ongoing1 (9)3 (14)Pregnancy interval from diagnosis [n (%)]0.29≤ 2 y04 (19)2-5 y8 (73)13 (62)> 5 y3 (27)4 (19)Type of conception [n (%)]0.52Natural9 (82)15 (71)Assisted2 (18)6 (29) Citation Format: Megan E Tesch, Ying Wang, Chloe Lim, Ying Hui Xu, Shaina Lee, Kirstin Perdrizet, Dan Yokom, Ellen Warner, Jeffrey Roberts, Caroline Lohrisch. Impact of ovarian stimulation for fertility preservation in young women with breast cancer: Updated survival and pregnancy outcomes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-08.

Does Disease Burden on PET Predict Outcomes for Advanced NSCLC Patients Treated With First-Line Immunotherapy?

First-line immunotherapy (IT), with or without chemotherapy (CTX), is now recommended for most patients with advanced non-small cell lung cancer (NSCLC) with no treatable driver mutations. Trials performed before first-line IT became standard suggested that patients with oligometastatic disease (OMD) may have a favorable prognosis and benefit from aggressive local therapy. We reviewed outcomes for NSCLC patients treated with first-line IT at our institution to test the hypothesis that measures of disease burden on staging FDG-PET would have prognostic value and examine if the presence of brain metastases (BM) affects prognosis.Advanced NSCLC patients who were staged with FDG-PET and treated with first-line IT between 2015 and 2019 were included in this analysis. Patient, disease, and treatment details were collected. A gradient-based segmentation tool was used to delineate each PET-avid extracranial lesion. Number of extrathoracic lesions, composite metabolic tumor volume (MTV), and presence of BM were tabulated. OMD was defined as having 3 or fewer extrathoracic lesions, with any number of thoracic lesions. Progression-free survival (PFS) and overall survival (OS) rates following initiation of IT were evaluated using the Kaplan-Meier method, and predictors of PFS and OS were assessed using Cox proportional hazards models and log rank tests.One hundred twenty-four patients met inclusion criteria, and 1,143 lesions were contoured. Seventy-four patients (60%) had OMD. Median MTV was 88 cc (interquartile range: 33 to 206 cc). Thirty-two patients (26%) had BM. Fifty-eight patients (47%) received IT with CTX. With a median follow-up duration of 17.3 months for surviving patients, the median PFS and OS durations were 8.5 and 36.5 months, respectively. The presence of OMD was associated with favorable PFS (median 13.1 vs. 6.9 months, P = 0.011) and OS (median not reached vs. 20.7 months, P = 0.003). In multivariable models adjusted for performance status, PD-L1 TPS, and receipt of CTX, OMD was associated with favorable PFS (HR = 0.62, P = 0.044) and OS (HR = 0.43, P = 0.018), and high MTV was associated with inferior OS (HR 1.12 per 100 cc, P = 0.048). Among patients who developed progressive disease, the brain was the first site of progression for 12 of 21 patients (57%) with BM at diagnosis and 2 of 55 patients (4%) without BM at diagnosis (P < 0.001). However, the presence of BM at diagnosis was not significantly associated with OS (HR = 0.84, P = 0.642) or PFS (HR = 1.13, P = 0.631) in multivariable models.For advanced NSCLC patients treated with first-line IT, having OMD is a favorable prognostic factor. Volume of disease on FDG-PET could provide additional prognostic information. The presence of brain metastases does not seem to affect outcomes, which may reflect the activity of IT in the central nervous system and should be considered when designing clinical trials.

Outcomes of Burkitt lymphoma (BL) managed in academic (Acad) or community (Comm) centers: real-world evidence (RWE) from 30 US sites.

8043 Background: Prior analyses have suggested better overall survival (OS) of cancer patients (pts) treated in Acad rather than Comm hospitals, but these disparities may reflect different patient characteristics. We examined outcomes of pts with BL in a large RWE cohort from 30 US healthcare systems (Evens, ASH 2019) with a mix of Acad and affiliated Comm sites. Methods: We collected clinical data on adults with BL diagnosed in 2009-2018, individually assigned to Acad or Comm principal setting of care. We compared duration of chemotherapy (CTx, incl. standard CODOX-M/IVAC, hCVAD/MA, DA-EPOCH), rates of complete response (CR), progression-free survival (PFS), and OS adjusting for age, sex, HIV, performance status (PS), stage, LDH &gt; 3x upper limit of normal (ULN), involvement of bone marrow or cerebrospinal fluid (CSF), reporting adjusted risk (RR) or hazard ratio (HR) with 95% CI. Results: Among 641 BL pts, 77 (12%) were managed in Comm setting. Comm pts had lower median age (45 vs 48 in Acad, P= .049), less frequent HIV (13% vs 23%, P= .039), less marrow (21% vs 36%, P= .009) or detected CSF involvement (8% vs 15%, P= .11), and less LDH &gt; 3xULN (21% vs 41%, P= .013), with no significant differences in sex, PS, stage, hemoglobin, or receipt of CTx (97% vs 99%). Acad sites more often applied standard intensive CTx regimens (93% vs 85%, P= .03) and rituximab (92% vs 79%, P= .001), without significant difference in median time to CTx ( P= .69) or treatment-related mortality (TRM, P= .16). Pts managed in Comm (vs Acad) sites were less likely to achieve CR (61% vs 75%, P= .03; RR = 0.79 [0.65-0.95]) and had worse 3-year PFS (46% vs 67%, log-rank P= .003; HR = 2.17 [1.51-3.14]) and OS (53% vs 72%, P= .006; HR = 2.20 [1.48-3.25]). There was no significant interaction with age, sex, HIV, PS, or CSF involvement. Excess mortality concentrated in the 1st year of follow-up. CR, PFS, and OS appeared similar between Acad and Comm settings for pts receiving hCVAD or DA-EPOCH, but outcomes were significantly worse in Comm setting for pts receiving CODOX-M/IVAC. Median number of cycles did not differ between Comm or Acad sites, but median duration of CODOX-M/IVAC delivery was significantly longer in Comm setting (113 vs 101 days, P= .023). Conclusions: In this large RWE analysis, superior outcomes of adults with BL in Acad setting were not explained by baseline patient characteristics or TRM. Differences in the use of standard CTx regimens, rituximab, duration of Ctx, and CR rates suggest need for further research on potential barriers to delivery of intensive CTx for BL in a broader Comm setting.

Baseline features predicting receipt of chemotherapy in metastatic esophageal cancer: A National Cancer Database analysis of 12,370 patients.

316 Background: We investigated predictors for chemotherapy (CTX) and prognostic variables in a large metastatic esophageal cancer (mEC) patient data set. Methods: We interrogated the National Cancer Database between 2004-2015 and included patients (pts) with M1 disease who had known CTX status (received or did not receive CTX). Univariable and multivariable analyses were performed, and a logistic regression model was used to estimate the effect of CTX with adjustment for potential confounders. Results: We included 12,370 mEC patients with available CTX status for multivariable analyses. Predictors for CTX treatment included year of diagnosis 2010-2014 (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.17-1.43), median income &gt; $46,000 (OR 1.49, 1.27-1.75), and node-positivity (OR 1.35, 1.20-1.52; all p &lt; 0.05), while female gender (OR 0.86, 0.76-0.98), black race (OR 0.76, 0.67-0.93), uninsured (OR 0.41, 0.33-0.52), and Charlson Comorbidity Index (CCI) ≥2 (OR 0.61, 0.50-0.74) predicted for lower odds of receiving CTX (all p &lt; 0.05). Median OS for pts receiving CTX was 9.53 mos (9.33-9.72) vs. 2.43 mos (2.27-2.60) with no CTX (p &lt; 0.001). Modeling the effect of CTX to OS using a time-dependent coefficient showed that CTX was associated with improved OS up to 10 months, after which there is no significant effect on OS. Independent predictors of OS included treatment at an academic center (hazard ratio (HR) 0.91, 0.87-0.94), CCI ≥2 (HR 1.16, 1.07-1.26), and uninsured status (HR 1.20, 1.09-1.31). Conclusions: We identified several predictors for receipt of CTX and OS in pts with mEC. The benefit of CTX on OS is time-dependent and favors early initiation. Focused outreach in lower income and underinsured patients is critical as receipt of CTX is associated with improved OS.

Perioperative chemotherapy is not associated with improved survival in high-grade truncal sarcoma

BackgroundThe treatment benefit of perioperative chemotherapy (CTX) for truncal soft tissue sarcoma (STS) is not well established. This study evaluates the association of CTX with survival for patients with resected primary high-grade truncal STS. Materials and methodsAdult patients with high-grade truncal STS who had curative-intent resection from 2000 to 2016 at seven U.S. institutions were evaluated retrospectively. Patients were stratified by receipt of CTX. Kaplan–Meier curves with log-rank tests were used to compare overall survival (OS) and recurrence-free survival. Logistic regression models were used to evaluate characteristics associated with OS. ResultsOf patients with primary high-grade truncal STS, 235 underwent curative-intent resections. The most common histology was undifferentiated pleomorphic sarcoma and mean tumor size was 7.8 cm. Thirty percent of the patients received CTX (n = 70). Among patients receiving CTX, 34% (n = 24) had neoadjuvant CTX, 44% (n = 31) adjuvant CTX, and 21% (n = 15) had neoadjuvant and adjuvant CTX. Patients receiving CTX were more likely to receive radiation (51% versus 34%, P = 0.01), have deep tumors (86% versus 73%, P = 0.037) and solid organ invasion (14% versus 3%, P = 0.001). On univariate analysis, patients who received CTX had worse OS (P < 0.01) and a trend toward worse recurrence-free survival (P = 0.08). Margin status was the only variable associated with improved OS on multivariate analysis (odds ratio 4.36, 95% confidence interval 1.56, 12.13, P < 0.01). ConclusionsIn this multi-institutional retrospective analysis of resected high-grade truncal STS, receipt of perioperative CTX was not associated with improved OS, which may be related to selection bias. Microscopically negative margin status was the only independent factor associated with OS.

Risk Factors Associated With Chemotherapy-Induced Nausea in the Week Before the Next Cycle and Impact of Nausea on Quality of Life Outcomes

ContextDespite current advances in antiemetic treatments, between 19% and 58% of oncology patients experience chemotherapy-induced nausea (CIN). ObjectivesAims of this post hoc exploratory analysis were to determine occurrence, severity, and distress of CIN and evaluate for differences in demographic and clinical characteristics, symptom severity, stress; and quality of life (QOL) outcomes between oncology patients who did and did not report CIN in the week before chemotherapy (CTX). Demographic, clinical, symptom, and stress characteristics associated with CIN occurrence were determined. MethodsPatients (n = 1296) completed questionnaires that provided information on demographic and clinical characteristics, symptom severity, stress, and QOL. Univariate analyses evaluated for differences in demographic and clinical characteristics, symptom severity, stress, and QOL scores between the two patient groups. Multiple logistic regression analysis was used to evaluate for factors associated with nausea group membership. ResultsOf the 1296 patients, 47.5% reported CIN. In the CIN group, 15% rated CIN as severe and 23% reported high distress. Factors associated with CIN included less education; having childcare responsibilities; poorer functional status; higher levels of depression, sleep disturbance, evening fatigue, and intrusive thoughts; as well as receipt of CTX on a 14-day CTX cycle and receipt of an antiemetic regimen that contained serotonin receptor antagonist and steroid. Patients in the CIN group experienced clinically meaningful decrements in QOL. ConclusionThis study identified new factors (e.g., poorer functional status, stress) associated with CIN occurrence. CIN negatively impacted patients' QOL. Pre-emptive and ongoing interventions may alleviate CIN occurrence in high-risk patients.

Impact of chemotherapy and external beam radiation therapy on outcomes among patients with resected gallbladder cancer: A multi-institutional analysis.

387 Background: Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) in the treatment of resectable gallbladder cancer remains varied. We sought to define the utilization and effect of adjuvant therapy on patients having undergone curative-intent resection for gallbladder cancer. Methods: Using a multi-institutional national database, 291 patients with gallbladder cancer who underwent curative-intent resection between 2000 and 2015. Patients with metastasis or an R2 margin were excluded. The impact of adjuvant therapy on survival was analyzed among patients who received surgery alone versus CTx versus cXRT. Results: Median patient age was 66 years. Most patients had a T2 (41.9%) or T3 (35.1%) lesion and 37.8% of patients had lymph node (LN) metastasis. A total of 186 (63.9%) patients underwent surgery alone, 61 (21.0%) received CTx, whereas the remaining 44 (15.1%) patients received cXRT. At a median follow-up of 16.3 months, median and 5-year overall survival (OS) was 28.3 months and 33.0%, respectively. On multivariable analysis, factors associated with worse OS included AJCC T3/T4 (hazard ratio [HR] 2.97), LN metastasis (HR 1.75) and lymphovascular invasion (HR 1.98; all P&lt;0.05). In contrast, receipt of CTx or cXRT was associated with improved long-term OS (CTx, HR 0.33; cXRT, HR 0.27; P&lt;0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS)(CTx, HR 0.53; cXRT, HR 0.45; P&lt;0.01). Of note, the OS benefit for CTx or cXRT was observed among patients with high risk features such as AJCC T3/T4 disease (HR 0.61; HR 0.31), LN-metastasis (HR 0.45; HR 0.46), and R1 disease (HR 0.33; HR 0.11) (all P&lt;0.05). In contrast, the OS benefit of CTx and cXRT was not noted among patients with T1/T2 or N0 disease, or among those with an R0 margin (all P&gt;0.05). Conclusions: Adjuvant CTx and cXRT were utilized in 36% of patients undergoing curative-intent resection for gallbladder cancer. After adjusted analysis, CTx and cXRT were independent factors associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics.

Does interval from histologic diagnosis (Dx) to start of chemotherapy (Ctx) impact survival in metastatic colorectal cancer (MCRC)?

615 Background: Optimal timing from colorectal surgery to initiation of adjuvant chemotherapy is between 4 to 6 weeks based on recent data. In MCRC, therapeutic benefits of ctx are frequently calculated from start of treatment. We investigated whether the interval between dx and commencement of ctx influences overall survival (OS) in patients (pts) with MCRC. Methods: Pts with CRC were identified from the institutional database. Inclusion criteria were MCRC and receipt of ctx. Clinicopathologic details were collected. Intervals from histologic dx to ctx were calculated. Analyses were based on receipt of ctx within 4 weeks (w), 5-8w and &gt; 8w of dx. Survival was compared between groups. OS was presented as hazard ratio (HR) with associated p value. Results: Between 2003 and 2013, 123 pts were identified, where 58 pts receive ctx within 4w, 38 within 5-8w and 27 &gt; 8w. Median OS (mOS) was 8.7, 15.7 and 13.7 months (mths) respectively. Improvement in OS was noted in pts treated 5-8w and &gt;8w compared to within 4w (HR 0.53, 0.45; p=&lt;0.01, &lt;0.01). Surgical resection of the primary was noted in 14% of pts receiving ctx in 4w, 45% between 5-8w and 70% &gt; 8w and mOS amongst these groups were 19.5, 16.3, and 22.1 mths respectively versus 6.5, 10.5 and 8.9 mths in similar groups without surgery. Improved OS in resected pts is noted in when treated 5-8w and &gt; 8w compared to 4w (HR 0.76, 0.72 p= 0.55, 0.46) with no difference in OS between groups treated at 5-8w and &gt; 8 w (HR 1.06, p= 0.85). Univariate and multivariate analyses for 5 variables are described in the Table, two of which are statistically significant on multivariate analyses. Conclusions: Our data did not suggest a detrimental effect on OS from ctx delay and the lack of survival benefit from early ctx might be due to a number of confounding variables as described above. [Table: see text]

Abstract P2-11-22: The use and influence of a 21 gene rearrangement assay in breast cancer: Clinical and pathologic predictors of recurrence score and chemotherapy receipt

Abstract Objective: Oncotype DxTM (ODx) is a gene expression profile test that is rapidly gaining popularity for its ability to stratify breast cancer patients according to risk of distant recurrence and suggest the potential benefit of adjuvant chemotherapy (CTx). Presently, National Comprehensive Cancer Network (NCCN) guidelines suggest use of ODx for all patients with node negative (or micrometastatic node positive disease), hormone receptor positive breast cancer with a primary tumor measuring over 5mm. However, if risk factors predictive of a high recurrence score (RS) were defined, clinicians would be better able to tailor use of ODx. This study was undertaken to identify standard clinicopathologic factors that correlate with a high RS by ODx, and to determine whether these factors or RS most influenced receipt of CTx. We also measured compliance with NCCN guidelines regarding ODx utilization. Methods and Materials: We performed an IRB approved retrospective review of women with invasive breast cancer treated at Yale Cancer Center from 2008-2012 to identify patients that received ODx testing, and abstracted clinical and tumor characteristics including: age, tumor size, grade, histology, lymphovascular invasion (LVI), number of involved nodes, size of nodal metastasis, presence of extracapsular extension, hormone receptor status (including percent positive), HER2 status (by FISH), RS, and receipt of CTx. The RS was categorized into low (&amp;lt;18), intermediate (18-30), and high score (&amp;gt;30). We assessed the association between these characteristics and both high RS as well as CTx receipt using Chi squared tests and Wilcoxon ranked test as appropriate. Characteristics with a p-value &amp;lt;0.1 in bivariate analysis were included in logistic models to estimate the odds of a high RS and receiving CTx. Results: We identified 432 women with a median age of 58 years. RS was low, intermediate, and high in 56%, 37%, and 7%, respectively. Median tumor size was 1.6cm (range 0.1-13.2). Differentiation was rated as well, moderate, or poor in 32%, 60%, and 8%, respectively. Tumors were hormone receptor positive in 99%. ODx was used outside of NCCN guidelines in 12%. CTx was given to 30% of patients. Younger age, HER2-positivity, LVI, poor differentiation, progesterone receptor positivity (PR+) 50% or less, and RS were associated with receipt of CTx (p&amp;lt; = 0.01) in bivariate analyses. High RS remained independently associated with CTx receipt in multivariate analysis. Poor differentiation, PR+ 50% or less, and HER2-positivity were significantly associated with a high RS (p&amp;lt;0.01), and all remained independently associated with high RS in multivariate analysis. Patients with any one of these three factors had 18% odds of a high RS, versus just 1% among those without such risk factors. Conclusions: High RS independently influences recommendations for chemotherapy. Poor differentiation, PR+ 50% or less, and HER2-positivity were associated with a high RS. In the absence of any of these three factors, the likelihood of a high RS is minimal. Noncompliance with NCCN guidelines was observed. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-22.

Prospective study of cognitive function (cog fcn) in women with early-stage breast cancer (ESBC): Predictors of cognitive decline.

104 Background: Cog complaints are common among women receiving adjuvant therapy (Rx) for ESBC. Longitudinal prospective data is needed to help identify predictors of cog decline. We conducted a prospective trial to evaluate the effects of chemo- (CTX) and hormone therapy (HRx) on brain and cog fcn in pts with ESBC using multiple objective and subjective tests as well as MRI/PET imaging. Here we report evaluation of clinical characteristics that predict decline in cog fcn. Methods: Eligibility included female patients (pts) planning to receive adjuvant Rx for ESBC. Pts were enrolled in 3 Rx groups (grps): CTX, CTX and HRx, and HRx, with a 4th no Rx age/education matched control grp. All pts underwent a battery of objective and subjective cog tests before start of Rx, 1 mo after CTX or 5 mo after start of HRx (FU1), then 9 mo (FU2) and 18 mo (FU3) after CTX. Brain MRI, PET and serum estradiol (E) were performed at baseline, FU1 and FU2. Results: 81 pts were enrolled as follows, 14 CTX, 33 CTX and HRx, 22 HRx, 12 control. 90% completed FU1, 72% FU2, and 62% FU3, with 29 pts waiting to complete testing. Demographics were similar between grps, median age 54, 78% Caucasian. At each FU, ~25% of pts showed decline in cog fcn compared to the prior time point using a reliable change index; 51% showed decline at &gt; 1 time point, primarily in tests measuring executive function and verbal memory. 62% of pts who declined from baseline to FU1 later stabilized or improved; 77% of pts who declined from FU1 to FU2 later stabilized or improved. Compared to controls, receipt of CTX and HRx (OR 3.15, p=.008), or HRx overall (OR 4.94, p=.004) but not serum E, menopausal status, or CTX, were significant predictors of decline at any time point. Rx group did not predict poorer perceived cog fcn (FACT-COG); depression and fatigue did not predict decline in objective cog fcn. Conclusions: Decline in cog fcn is common in pts receiving adjuvant Rx for ESBC. Predictors included CTX and HRx, or HRx overall but not other treatment and pt related factors. Ongoing HRx, particularly after CTX, appears to be a risk factor for worse cog fcn. Pts should be aware that HRx may be a risk factor for cog deficits, and intervention studies should be designed to focus on this group of pts. Funding: NIH R01 1AG025303-01A2. Clinical trial information: 00755313.

Prospective study of cognitive function (cog fcn) in women with early-stage breast cancer (ESBC): Predictors of cognitive decline.

6620 Background: Cog complaints are common among women receiving adjuvant therapy (Rx) for ESBC. Longitudinal prospective data is needed to help identify predictors of cog decline. We conducted a prospective trial to evaluate the effects of chemo- (CTX) &amp; hormone therapy (HRx) on brain &amp; cog fcn in pts with ESBC using multiple objective &amp; subjective tests as well as MRI/PET imaging. Here we report evaluation of clinical characteristics that predict decline in cog fcn. Methods: Eligibility included female patients (pts) planning to receive adjuvant Rx for ESBC. Pts were enrolled in 3 Rx groups (grps): CTX, CTX &amp; HRx, and HRx, with a 4thno Rx age/education matched control grp. All pts underwent a battery of objective &amp; subjective cog tests before start of Rx, 1 mo after CTX or 5 mo after start of HRx (FU1), then 9 mo (FU2) &amp; 18 mo (FU3) after CTX. Brain MRI, PET &amp; serum estradiol (E) were performed at baseline, FU1 &amp; FU2. Results: 81 pts were enrolled as follows, 14 CTX, 33 CTX &amp; HRx, 22 HRx, 12 control. 90% completed FU1, 72% FU2, &amp; 62% FU3, with 29 pts waiting to complete testing. Demographics were similar between grps, median age 54, 78% Caucasian. At each FU, ~25% of pts showed decline in cog fcn compared to the prior time point using a reliable change index; 51% showed decline at &gt; 1 time point, primarily in tests measuring executive function &amp; verbal memory. 62% of pts who declined from baseline to FU1 later stabilized or improved; 77% of pts who declined from FU1 to FU2 later stabilized or improved. Compared to controls, receipt of CTX &amp; HRx (OR 3.15, p=.008), or HRx overall (OR 4.94, p=.004) but not serum E, menopausal status, or CTX, were significant predictors of decline at any time point. Rx group did not predict poorer perceived cog fcn (FACT-COG); depression &amp; fatigue did not predict decline in objective cog fcn. Conclusions: Decline in cog fcn is common in pts receiving adjuvant Rx for ESBC. Predictors included CTX &amp; HRx, or HRx overall but not other treatment &amp; pt related factors. Ongoing HRx, particularly after CTX, appears to be a risk factor for worse cog fcn. Pts should be aware that HRx may be a risk factor for cog deficits, &amp; intervention studies should be designed to focus on this group of pts. Funding: NIH R01 1AG025303-01A2. Clinical trial information: NCT00755313.

Does interval from histologic diagnosis (Dx) to start of chemotherapy (Ctx) influence survival in advanced pancreatic adenocarcinoma (PC)?

306 Background: Pancreatic cancer is known to be aggressive and treatment-resistant. In potentially resectable PC, time from diagnostic imaging to surgery correlates with rates of metastases at laparatomy. In advanced PC, therapeutic benefits of ctx are frequently calculated from start of treatment. In view of its aggressiveness, we investigated if the interval between dx and commencement of ctx influences overall survival (OS) in patients (pts) with advanced PC. Methods: Pts with PC were identified from 4 insitutional databases. Inclusion criteria were unresectable (UPC) or metastatic disease (MPC) and receipt of ctx. Clinicopathologic details were collected. Intervals from histologic dx to ctx were calculated. Analyses were based on receipt of ctx within or after 2 weeks (w), 4w and 6w of dx. OS was presented as hazard ratio (HR) with associated p-value. Results: 212 pts were identified. Median age was 63 years (range: 33 – 83) and 58% were males. 60% of pts had MPC and 24% received doublet ctx. Median number of days from dx to ctx was 24 days (range: 2 – 202). For UPC and MPC, 20 and 31% of pts began ctx within 2w (p=0.08), 48 and 63% within 4w (p=0.03) and 73 and 82% within 6w (p=0.13), respectively. OS for the entire cohort, UPC and MPC were comparable whether ctx was commenced within pre-defined intervals or not (see table). A subgroup of pts treated with doublet ctx was examined. No OS difference was seen when treated within defined time points (HR 1.1, 1.0, 1.5; p=0.76, 0.96, 0.43). For 77% of MPC with hepatic metastases, no improvement in OS in relation to time interval was noted (HR 1.5, 1.0, 1.1; p=0.10, 0.90, 0.85). For 21% of MPC with ≥2 metastatic sites, ctx within 4w and 6w might improve OS but significance was not reached (HR 0.65, 0.61; p=0.43, 0.46). Conclusions: Commencement of ctx for PC could be delayed due pts-, disease- or infrastructural factors. Our data did not suggest a detrimental effect on OS from ctx delay. However, the lack of survival benefit from early ctx might be due to less effective ctx or inherent aggressiveness of the disease. [Table: see text]

Is survival in advanced pancreas cancer (APC) correlated to treatment-related lymphopenia (TRL)?

313 Background: Relationship between TRL and survival has been described in patients (pts) who receive adjuvant chemoradiotherapy. Evidence on TLR in APC treated with chemotherapy (ctx) is limited. We investigate the effect of ctx on TRL and its association with survival. Methods: Pts with APC were identified from two institutional databases. Inclusion criteria were: locally advanced (LA) or metastatic disease (MPC) and receipt of ctx. Baseline clinicopathologic and biochemical details including lymphocyte count at baseline and between day 21 and 28 were collected. Degree of TRL was collected prior to initiation of ctx and graded according to CTCAE v4. Descriptive statistics and survival analyses were performed. Results: Between 2001 and 2012, 97 pts were included. Median age was 64 years (range: 42 – 79), 58% were males. MPC seen in 57% of pts and 46% received doublet ctx. Ca19-9 ≥10,000 was detected in 77% pts. Uni- and multivariate analyses for six variables are described in the table. Major reduction, as defined by a 33% change in TLC, was described as a major reduction, present in 14 pts (15%). A major reduction of TLC was associated with a median overall survival (OS) of 2.5 mths (95%CI=1.2-5.3) versus 7.1 mths in those with no TLC change (95%CI=5.6-9.3) (p=0.0149). When assessed by CTCAE, difference in OS was also noted for G0 (n=47), G1 (n=39), G&gt;=2(n=10) lymphopenia: 95 pts had grade 0-2 TLC 4 weeks post chemotherapy. OS was 9.7, 5.3 and 1.9 mths for grade 0, 1, and 2 lymphopenia. (p=&lt;0.0001) respectively. Conclusions: TRL is an independent prognostic factor for APC. In comparison to existing data where chemo-radiation increases the grade and rates of TRL, APC pts treated with ctx had lower rates of TRL. This raises the question whether TRL is determined by the underlying biology of APC versus radiotherapy related effect. [Table: see text]

Influence of ABO blood group on the natural history of advanced pancreatic adenocarcinoma (PC).

307 Background: An association between blood group (ABO) and PC has been demonstrated at epidemiologic and genomic levels. Variations in ABO type may lead to higher pro-inflammatory cytokines levels with modifications in cellular adhesionand signalling promoting carcinogenesis. This study investigated the influence of ABO on the clinical behaviour of advanced PC in patients (pts) , treated with chemotherapy (ctx). Methods: Pts with confirmed PC were identified from 4 institutional databases. Inclusion criteria were unresectable (UPC) or metastatic disease (MPC), receipt of ctx and availability of ABO data. Clinicopathologic details were collected. 200 random anonymied non-cancer ABO samples were collected as control. Descriptive statistics and survival analyses were performed. Results: Between 2001 and 2012, 222 pts met inclusion criteria. Median age was 63 years (range: 33 – 83) 56% were males. 60% of pts had MPC and 27% received doublet ctx. ABO distribution was: A (40%), AB (5%), B (11%) and O (44%). The incidence of blood type A was higher in PC cohort than control (40 vs 30%, p=.03) but identical between UPC and MPC (41 vs 40%, p=.84). Overall survival between type A and non A were identical for the entire cohort (5.8 vs 6.6 mos, HR 1.04 95% CI 0.76 – 1.40, p=.82), UPC (7.6 vs 9.5 mos, HR 1.08 95% CI 0.65 – 1.76, p=.77) or MPC (5.4 vs 4.7 mos, HR 0.94 95% CI 0.66 – 1.34, p=.78). For UPC, 56 pts (64%) had radiographic documentation of the pattern of progression. Type A pts had lower propensity for developing distant metastasis (7/21) than non A (23/35), at 33 vs 66%, p=0.03. Amongst pts with MPC, the incidence of hepatic and pulmonary metastases for type A and non A were identical (77 vs 74%, p=.83; 21 vs 18%, p=.81). However, peritoneal dissemination was less common in type A pts (6 vs 23%, p=.01). Conclusions: Consistent with existing epidemiologic data, the incidence of blood type A is significantly higher in pts with PC, although this does not appear to be stage dependent. ABO did not appear to influence OS in this cohort. However, our data suggests that the pattern of disease spreadmay be related to the ABO blood type. ABO-related glycosylated products could be a target for disease modulation in further studies.

Perceptions of chemotherapy influencing treatment decisions in women with hormone-positive tumors.

e19621 Background: Women with hormone receptor positive (HR+) breast cancer can benefit from chemotherapy (CTX). Unnecessary therapy can adversely affect patient morbidity.. While tumor biology affects decision making, patient perception of cancer recurrence is also important. In this study we determine whether women with HR+ tumors (&gt;1cm) who undergo CTX, have stronger beliefs in the efficacy of CTX than women who do not get therapy. Methods: Women participating in a Breast Cancer Patient Assistance Trial in 2006-2010 were surveyed about their cancer knowledge and beliefs about its treatment; charts were abstracted 6 months later to measure treatments received. A Nottingham Prognostic indicator (NPI), which uses stage, tumor size, and lymph node involvement was calculated. Chi-square and logistic regression analyses examined associations between receipt of CTX and tumor stage, NPI, physician recommendation, patient demographics and beliefs about CTX. Results: Women with HR+ tumors 130/211(62%) received CTX and 197/211(93%) received hormonal therapy. Gene array analysis was performed in 46/211 (22%), and of these (7/46 [15%]) had high recurrence scores and received CTX. Women treated with CTX vs those without CTX were younger (mean 52.5 yrs vs 62.3 yrs, p&lt;0.0001), had higher stage cancer (stage II: 65% vs 23%, p&lt;0.0001), worse NPI (poor prognosis:15% vs 2% p&lt;0.0001), more physician recommended CTX (92% vs 34%, p&lt;0.0001) and increased concern about recurrence without CTX (very worried 70% vs 15%; p&lt;0.0001). Multivariate analysis found that physician recommendation, poor NPI and moderate NPI were most strongly associated with receiving CTX [RR= 3.2, (95% CI:1.8-5.6), 1.7, (95%CI:1.3-2.2); 1.6, (95%CI:1.2-2.0)], respectively, followed by women’s worry (RR=1.3; 95%CI: 1.0-1.6), and belief that CTX allows women to live longer (RR=1.1; 95%CI: 1.0 - 1.2). Older age was associated with less use of CTX (RR= 0.99; 95%CI: 0.978-.995). Conclusions: Physician recommendation, disease severity, concerns about recurrence and beliefs about CTX’s effectiveness influence the utilization of CTX in HR+ breast cancer. Patients may benefit from education to make informed decisions.