bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences between taxanes in time on therapy and associated discontinuation events in metastatic breast cancer: Results from a U.S. claims analysis.
Authors: Force Rex W. , Pugmire Brooke A. , Binder Gary , Duval Cindy , Corzo Deya , Gluck Stefan
Published: February 2017

158

Background: Taxanes in metastatic breast cancer (mBC) have demonstrated clinical benefits but have different toxicity profiles. This study evaluated differences in time to discontinuation (D/C) between taxanes overall and by specific events associated with D/C (i.e., death, adverse events (AE), subsequent therapy). Methods: Women receiving >1 dose of either paclitaxel (P), docetaxel (D), or nab-paclitaxel (nab-P) between 2006-2009 were identified by ICD-9 codes indicative of mBC from a commercial payer claims database. Logistic regression and Cox-proportional hazards models were used to compare rates of D/C and time to D/C, respectively. Control variables were age, use of prior or concurrent chemo, and comorbidity score. Drug D/C was defined as no taxane administration for 35 days. AE within 35-days after D/C were considered taxane-associated. Death or disenrollment from the insurance plan within 90 days and initiation of subsequent therapy within 60 days after D/C were considered temporally associated with D/C. Results: 4,503 pts with mBC were included (2,599 received D; 1,643 received P, and 261 received nab-P). The most common reason for D/C in all pts was AEs (37.8%), initiation of subsequent therapy (34.4%), and death or disenrollment (8.4%). A higher proportion of pts on D (29.4%) and P (17.5%) had D/C due to neutropenia vs nab-P (6.9%, p<0.001 for both comparisons). A higher proportion of pts on nab-P (12.3%) continued on therapy until death/disenrollment vs D (8.9%, p 0.046) or P (7.1%, p 0.023). Similarly, a higher proportion of pts on nab-P (51.2%) initiated subsequent therapy at D/C of taxane vs D (31%) or P (37.3%; p<0.01 for both comparisons). Median time to D/C was 85 days for each of D and P, and 127 days for nab-P (p<0.05). Median time to D/C associated with AEs, neutropenia, death/disenrollment or subsequent therapy were significantly longer for nab-P compared with D or P (p<0.05). Conclusions: Women treated for mBC stayed on nab-P therapy 50% longer than with other taxanes. This time on therapy advantage also indicated that pts on nab-P were less likely to D/C due to AEs, more likely to stay on therapy, and more likely to be candidates for subsequent therapies.
Incidence, management, and resolution of stomatitis and noninfectious pneumonitis in BOLERO-2.
Authors: Perez Alejandra T.
Published: February 2017

159

Background: Although the mTOR inhibitor everolimus (EVE) was generally well tolerated in combination with exemestane (EXE) in patients (pts) with HR+/HER2– advanced breast cancer, stomatitis and noninfectious pneumonitis (NIP) are the most clinically relevant and potentially dose-limiting toxicities. The incidence, grade, and clinical course of stomatitis and NIP among pts participating in the BOLERO-2 study are described. Methods: Pts were randomized 2:1 to receive EVE + EXE or placebo (PBO) + EXE. Incidence and severity of stomatitis and NIP, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: Stomatitis (any grade) occurred more frequently with EVE + EXE than with PBO + EXE (59% vs 12%, respectively). Grade 3 stomatitis occurred in 8% vs 1% of EVE + EXE vs PBO + EXE pts, respectively; no grade 4 events were reported. Onset of grade ≥ 2 stomatitis after treatment initiation was earlier for EVE + EXE arm vs PBO + EXE: median time was 15 d vs 24 d, respectively. For the EVE + EXE arm, 97% of pts with grade 3 stomatitis (n = 38) improved to ≤1 after a median of 13 d. Complete resolution was observed in 82% of pts after a median of 38 d. For the PBO + EXE arm, all pts with grade 3 stomatitis (n = 2) improved to ≤1 after a median of 18 d. Complete resolution was observed after a median of 29 d. 24% of pts on EVE + EXE required dose interruptions/adjustments vs 1% of pts on PBO + EXE, and 3% of pts (n = 13) discontinued EVE + EXE vs <1% of pts (n = 1) discontinuing PBO + EXE, all related to stomatitis. Overall, 16% in the EVE + EXE vs 0% in the PBO + EXE groups had a diagnosis consistent with NIP. For EVE + EXE, grade 1, 2, and 3 NIP occurred in 7%, 6%, and 3% of pts, respectively; no grade 4 events were reported. Complete resolution of NIP to grade ≤1 was recorded for all but 4 pts for whom NIP was still observed at last follow-up before study discontinuation. Overall, in the EVE + EXE arm, NIP was reason for dose interruption and treatment discontinuation in 7.5% and 5.6% of pts, respectively. Conclusions: In the BOLERO-2 study, stomatitis and NIP were of mild to moderate intensity and were generally reversible. Most incidents were successfully managed with palliative interventions and temporary dose modifications. Clinical trial information: NCT00863655.
Lapatinib impact on pulmonary hypertension.
Authors: Alkhatib Yaser , Albashaireh Derar , Al-Aqtash Tameem Abdul Hamid , Awdish Rana , Hanbali Amr S.
Published: February 2017

160

Background: Pulmonary Arterial Hypertension (PAH) and cancer share growth factor and protein kinase signaling pathways that result in smooth muscle cell proliferation and vasculopathy. A number of tyrosine kinase inhibitors (TKI) have been developed for the treatment of cancer, and some of these like Imatinib have been investigated in PAH. There is little known about the impact of other TKI on the pulmonary vasculature. After reporting a case of lapatinib-induced PAH that reversed after withdrawal of the drug, we investigated the association of lapatinib with the development of PAH in our institution. Methods: A retrospective chart review was conducted, in accordance with IRB protocol, of all patients treated with lapatinib over the past five years at our institution. Patients who had undergone 2-D echocardiogram both prior to and after treatment were included in the analysis. Systolic Pulmonary Artery Pressures (PASP), right-sided chamber dilation and function, TAPSE were each evaluated. Through chart review, patients were evaluated in terms of risk factors for non-Group 1 PAH. A Wilcoxon signed-rank sum test was used to compare the changes in PASP before and after the initiation of lapatinib. Results: A total of 27 patients were found to have 2-D echo done before and after starting treatment with lapatinib. All patients had normal PASP before starting treatment. Eight patients developed elevated PASP following treatment. Two patients had evidence of left-sided heart disease felt to contribute to their elevated pressures, while the remaining 6 patients had no evidence for Group 2 (associated with left heart disease), 3 (associated with lung disease or hypoxemia) or chronic thromboembolic PAH. Right heart catheterization was available in one patient, confirming the diagnosis of PAH. The median pre-treatment and post treatment PASP in those 6 patients was 29.5 mmHg and 65.5 mmHg respectively (N=6; p = 0.03). Conclusions: Lapatinib is a TKI with a selective inhibition to EGFR and HER2, approved by FDA in 2007 as a second line agent in advanced breast cancer. Given the potential of TKIs as anti-proliferative agents in PAH, a number are currently under study, but little is yet known. This is the first study in the literature to show that PAH is a potential side effect of lapatinib.
Hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer: Sequencing of chemotherapy and endocrine therapy.
Authors: Engel-Nitz Nicole M. , Hao Yanni , Rogerio Jaqueline Willemann , Turnbull James D. , Gomez Rey Gabriel , Sullivan Jane , Rossof Arthur H.
Published: February 2017

164

Background: National Comprehensive Cancer Network breast cancer guidelines suggest sequencing of systemic therapy. This study examined sequencing of endocrine and chemotherapy treatments to better understand real-world treatment patterns for HR+/HER2- advanced breast cancer. Methods: A proprietary clinical cancer database with physician-reported clinical data on patients with breast cancer was linked to medical and pharmacy claims (2008-2012) from a national US health plan. Study patients had HR+ and HER2- status. Advanced cancer cohorts were defined: stage III (SIII) or IV (SIV) at initial diagnosis, or developed metastases following initial diagnosis (MET). Index date was the first date of advanced cancer diagnosis or date of metastases following initial diagnosis. Health plan enrollment for 3 months pre- and ≥ 3-months post- index date was required; patients who died within 3 months after index date and were continuously enrolled were retained. A 3-month baseline period assessed prior treatment; a variable follow-up (until disenrollment or 31 Oct 2012) assessed patterns of endocrine and chemotherapy treatments following index date. Results: A total of 954 breast cancer patients met study inclusion criteria and were HR+/HER2- with ≥ 3 months of continuous enrollment after index date, with 369 of the 954 (38.68%) SIII, 117 (12.26%) SIV, and 469 (49.16%) MET patients. In the study population, 83.65% were treated with endocrine therapy, starting an average of 179 days after index date. A total of 80.29% were treated with chemotherapy, starting an average of 53 days following the index date; 65% of patients initiated chemotherapy after index date without prior endocrine treatment. Rates varied by cohort: 90% of SIII, 57% of SIV, and 48% of MET patients had no evidence of endocrine treatment prior to initiating chemotherapy. Conclusions: This study found large proportions of HR+/HER2- advanced breast cancer patients initiated chemotherapy without prior endocrine therapy. Further investigation of patient characteristics and outcomes by therapy sequencing patterns will help illuminate the extent to which patterns adhere to NCCN guidelines.
Longer-term cardiac safety and outcomes of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) with and without lapatinib (L) in patients (pts) with early breast cancer (BC).
Authors: Iyengar Neil M. , Morris Patrick Glyn , Patil Sujata , Chen Carol , Abbruzzi Alyson , Lehman Robert James , Steingart Richard , Oeffinger Kevin C. , Lin Nancy U. , Moy Beverly , Come Steven E. , Winer Eric P. , Norton Larry , Hudis Clifford , Dang Chau T.
Published: February 2017

167

Background: The addition of H to chemotherapy has improved outcomes in HER2-positive early BC. This approach is associated with (w/) an increased risk (<4%) of congestive heart failure (CHF). Dose-dense (every 2 weeks) anthracycline-taxane therapy (Rx) improves survival compared to the every 3 week schedule and can be combined w/ anti-HER2 Rx w/ no increased risk of cardiotoxicity up to 36 months. Here we report the incidence of NYHA Class III/IV CHF in 2 phase II studies with longer follow-up. Methods: We conducted a retrospective review of pts w/ HER2 + early stage BC treated at MSKCC and DFCI on two trials: In trial A - pts received dd AC (60/600 mg/m2) x 4 → T (175mg/m2) x 4 (w/ pegfilgrastim) w/ H x 1 year. Trial B differed w/ use of weekly T (80mg/m2) x 12 and the addition of L (1000mg orally daily) x 1 year. Left ventricular ejection fraction (LVEF) was prospectively assessed by a multi-gated acquisition scan serially throughout Rx. Results: Trial A enrolled 70 pts and Trial B enrolled 95 pts w/ the median age of 46 years (range 27-73 years). Overall, the 5-year distant disease-free survival (DDFS) for trials A and B is 92% (95%Cl; 83-97%) and 89% (95%CI; 81-94%), respectively. The baseline median LVEF was 68% (range 52-81%). In total, 28 of 165 (17%) pts had pre-existing hypertension. Now at a median follow-up of 84 and 57 months respectively, only one (1.4%, 95%CI; 1.36-7.7%) and 4 (4.2%, 95%CI; 4.2-10.4%) pts developed CHF. Since our earlier report, 1 additional CHF event occurred (Trial B) at month 44. Conclusions: Longer follow-up of these 2 studies demonstrate that dd AC → TH with or without L is associated w/ a low risk of CHF. This is consistent w/ the long-term cardiac toxicity reported from the randomized phase III studies of H w/ conventionally scheduled anthracycline-based regimens (with or without taxanes). DDFS outcomes are also encouraging. Clinical trial information: NCT00591851 and NCT00482391.
Tobacco use and race as copredictors of overall survival in patients with breast cancer.
Authors: Wells Jeremy Clady , Samuel Thomas A. , Morton Kyana , Looney Stephen W.
Published: February 2017

20

Background: Tobacco use (TOB) has been linked to the development of breast cancer (BCa), but limited data exists linking TOB with overall survival (OS) and the influence of race on this relationship. Our previous research has shown that African-American (AA) patients with BCa have worse OS compared with Caucasian (C) patients. This retrospective study examines the effect of TOB on OS in BCa patients at Georgia Regents University (GRU) and the effect of race in conjunction with TOB on OS. Methods: Data were obtained from the GRU Tumor Registry. Inclusion criteria were all female patients diagnosed with BC between 2002 and 2010. The estimated hazard ratio (HR) from Cox regression was used to measure the association between TOB and OS. Race, age at diagnosis, and stage at diagnosis were considered for inclusion as covariates. A stratified OS analysis was also performed dividing patients by race (C vs. AA). Results: Data were collected on 836 females who met inclusion criteria. TOB was categorized as "none" vs. "any" at time of BCa diagnosis The Cox regression analysis indicated a decreased OS for women with any tobacco use (unadjusted HR, 1.45; p = 0.024). Statistical significance was retained when this HR was adjusted for race (HR, 1.47; p = 0.021) and age at diagnosis (HR, 1.45; p = 0.024), but not for stage at diagnosis (HR, 1.21; p = 0.266). In the stratified analysis, the results for C patients were similar to those obtained in the complete sample (HR, 1.62; p = 0.044). Statistical significance was not retained for AA patients (HR 1.31; p = 0.244). We compared C tobacco users (n = 157) vs. AA tobacco users (n = 127) (HR, 1.10; p = 0.716) and C tobacco non-users (n = 291) vs. AA tobacco non-users (n = 261) (HR, 1.36; p= 0.156) and found no statistical significance. Conclusions: Our analysis shows that patients with history of TOB at BCa diagnosis have a 45% chance of decreased OS compared to non-TOB users. The negative impact of TOB is still noted when adjusted for race and age at diagnosis but not for stage at diagnosis. When stratifying by race, we found that any TOB is a significant risk factor among C patients but not among AA patients. We conclude that any history of TOB at BCa diagnosis is an important negative prognostic factor for OS, and this is particularly true in C patients.
Hyperactivated mTOR and JAK2/STAT3 pathways: Crucial molecular drivers and potential therapeutic targets of inflammatory breast cancer (IBC).
Authors: Teplinsky Eleonora , Valeta Amanda , Arju Rezina , Giashuddin Shah , Sarfraz Yasmeen , Alexander Melissa , Darvishian Farbod , Silvera Deborah , Levine Paul H. , Hashmi Salman , Paul Ladan , Hoffman Heather J. , Singh Baljit , Goldberg Judith D. , Hochman Tsivia , Formenti Silvia , Schneider Robert , Jhaveri Komal L.
Published: February 2017

60

Background: IBC is an aggressive form of breast cancer with poor prognosis. Combined multi-modality Rx results in a 5 year OS of 30-50%, underscoring the unmet need for targeted Rx. Our preclinical research in cell lines and xenografts identifies a role for activated PI3K/mTOR pathway in IBC. IBC cells express IL-6 and IL-8 and recruit tumor activated macrophages (TAMs) that further induce IL-6, IL-8 and activate the JAK2/STAT3 pathway. We investigated the independent and combined activity of these pathways in IBC tissues. Methods: Archived tissues of 42 IBC pts and 13 controls (nl breast) were analyzed using IHC and scored by 3 independent pathologists. Results defined as: 0, 1+ = neg; 2+ = pos for activated mTOR (P-S6) and 0 = neg; 1+, 2+ = pos for activated nuclear JAK2/STAT3 (P-JAK2; P-STAT3), cytokine (IL-6), macrophage (mØ) infiltration (CD68) and TAM (CD163). Proportions of IBC cases with pos expression were compared with controls (Fishers exact tests). Clinical and survival data were obtained. Results: Median age at diagnosis: 46 yrs (31-62) in early-stage IBC [EIBC] (n=37) and 41 yrs (29-57) in pts with de novo metastatic IBC [MIBC] (n=5). In EIBC, 19/36: HER2+ (1 unk); 8/19: ER+/HER2+; 8/36: ER-/HER2-. In MIBC, all were ER- (1 unk) and 3/4 were HER2+ (1 unk). 88% Rx with neoadjuvant and/or adjuvant anthracycline and taxane w/o adjuvant trastuzumab. 24 pts died (5/5 MIBC). Median OS: 86 mo (95% CI lower 48 mo) for EIBC & 41 mo (95% CI 8-81 mo) for MIBC. Median RFS: 18 mo (95% CI 18-79 mo) for 23 pts (13 NED; 1 unk). All controls: neg for P-S6, JAK2, STAT3 and TAMs and 92% neg for mØ and IL-6. Proportion of IBC with pos expression when compared to controls listed in table (p <0.0001). Of 31 pts with complete biomarker data who were PS6+, 97% had activated JAK2, 58% had activated STAT3, 80% had strong mØ and TAM infiltration and 97% were IL6+. Conclusions: This is the first study that validates preclinical findings and shows a strong association between mTOR, cytokines, TAMs and JAK/STAT pathways in most IBC pt tissues. Findings suggest a key role for dual blockade of mTOR and JAK/STAT pathways in phase I trials. [Table: see text]
Ductal lavage cytology in patients with ductal carcinoma in situ (DCIS).
Authors: Behr Andrea , Brogi Edi , Heerdt Alexandra S. , Van Zee Kimberly J. , Montgomery Leslie L.
Published: February 2017

89

Background: Ductal lavage (DL) is a procedure used to obtain epithelial cells from a breast duct for cytologic evaluation. Previous studies have investigated DL as a potential screening procedure for women at high-risk for cancer. The data, however, does not support a significant correlation between lavage cytology and the presence of invasive carcinoma. It is postulated that an invasive cancer causes destruction of the involved ducts which prevents direct sampling of the malignant intraductal cells. Because ductal carcinoma in-situ (DCIS) does not disrupt the breast ductal structure, DL may yield a more representative cytologic sample in patients with DCIS. Methods: Ductal lavage was performed in the affected breast of 32 women undergoing mastectomy with preoperative diagnosis of DCIS. The lavage procedure was done in the operating room after induction of general anesthesia by cannulating a duct yielding fluid on the nipple and instilling saline which was then aspirated and sent for cytologic evaluation. A cytopathologist classified each sample as insufficient cellular quantity, benign, mild atypia, marked atypia, or malignant. Results: A successful lavage was obtained from 22 (69%) of 32 women undergoing DL in the operating room. Of these 22 cytology samples; 4(18%) had an insufficient cellular quantity, 4 (18%) had mild atypia, 6 (27%) had marked atypia, and 8 (36%) had malignant cells. Twenty one of these 22 women had DCIS in the surgical mastectomy specimen. Seven (32%) patients were found to have invasive ductal cancer in addition to DCIS on final pathology. Conclusions: Our results show that DL reveals markedly atypical or malignant cytology in 64% of patients with DCIS who underwent a successful lavage procedure. As an office procedure, DL may have the ability to obtain viable ductal carcinoma cells repeatedly over time in the same patient. Thus, DL may have an important role in patients with DCIS who are involved in window trial studies investigating response to medical treatments prior to surgical intervention. Further studies to evaluate the reproducibility of the ductal lavage results in patients with DCIS are needed to confirm these findings.
Adequacy of lung cancer tissue samples for ancillary molecular testing in conventionally obtained biopsy material: A 3-year experience of the Louisiana State University (LSU) public hospital in New Orleans.
Authors: Narmala Shravan Kumar , Boulmay Brian C.
Published: February 2017

105

Background: The National Comprehensive Cancer Network recommends that all patients with lung adenocarcinoma (LA) be tested for EGFR mutation and ALK gene rearrangement (EGFR/ALK). Metastatic LA is diagnosed with biopsies often sufficient only for non-molecular based diagnostic techniques; our institutional experience suggested conventionally obtained material was inadequate for EGFR/ALK. We analyzed biopsies performed only with the intent of diagnosing malignancy for adequacy for EGFR/ALK. Methods: We identified patients from LSU diagnosed with metastatic LA whose specimens were sent for EGFR/ALK from January 1, 2009, to June 30, 2013. Data collected included number of specimens sent for EGFR/ALK, number of samples with inadequate tumor, biopsy technique utilized and number of rebiopsy attempts for EGFR/ALK. Results: 54 patients were evaluated in the study time period: 58 individual biopsy specimens were sent for EGFR/ALK. 24/58 (41%) of specimens were found to be inadequate for EGFR/ALK. 11/26 (42%) of bronchoscopically obtained biopsies were inadequate, 9/18 (50%) of computed tomography guided core needle (CTGCN) biopsies were inadequate and 4/14 (28%) samples obtained via thoracentesis, wedge resection, craniotomy, spinal tumor excision, fine needle aspiration of lymph nodes or video assisted thoracoscopic surgery were inadequate. 4/54 (7%) patients underwent rebiopsy, 3 via bronchoscopy and 1 via CTGCN; 3/4 (75%) rebiopsies were sufficient for EGFR/ALK analysis. Conclusions: A substantial proportion of initial LA diagnostic biopsies were inadequate for EGFR/ALK analysis. While EGFR/ALK analysis is now standard of care for patients with LA, only a small percentage of patients in our study underwent rebiopsy. Our institutional practice will be modified to encourage additional biopsies for the specific purpose of molecular testing at the time of initial biopsy for those with suspected LA.
Determining the need and utilization of radiotherapy in cancers of the breast, cervix, lung, prostate, and rectum in Alberta, Canada.
Authors: Shack Lorraine , Lu Shuang , Weeks Lee-Anne , Craighead Peter S. , Kerba Marc
Published: February 2017

116

Background: Determining the appropriate rate of RT is important for health care planning and resource allocation. Establishing RT shortfalls (difference between observed and estimates of RT need) could provide an estimate of the capacity expansion that would be required to address them. Our primary objective was to determine the utilization of RT for cancers of the breast, cervix, lung, prostate and rectum in Alberta (AB), Canada. To determine the burden of RT shortfalls in AB, the secondary objective was to compare the observed AB RT rates to estimates of need derived from criterion-based benchmarking (CBB) and evidence-based estimates (EBEST). Methods: All incident cases of breast (B), cervix (C), lung (L), prostate (P) and rectal (R) cancers diagnosed in 2004-8 in AB were identified from the provincial cancer registry (ACR). Ethics board approval was obtained. Patients receiving RT within one year (RT-1y) of diagnosis were identified and grouped by cancer site. The proportion of cases receiving RT-1y was then calculated. Rates were compared using a Z statistic of the normal approximation for a difference in proportions. Estimates of the appropriate RT rate were derived from CBB and EBEST methods described in the literature. Results: A total of 68,164 cancer cases of interest were identified from the ACR. RT-1y rates for AB (95%CI) were: B: 50.5%(49.5-51.4), C: 45.7%(42.2-49.3), L: 36.5%(35.5-37.3), P:26.4%(25.6-27.3) and R:38.8%(37.1-40.6). Observed rates of RT in AB were lower than estimates derived using CBB and EBEST of RT-1y for B: 60.7%(59.3-62.1) and 57.1%(52.6-62.0), C: 48.6%(39.1-58.1) and 63.4%(61.1-65.7), L: 41.3%(39.9-42.7) and 44.6%(41.0-48.2), P: 37.2%(35.8-38.7) and 32.0%(28.4-36.0), and R: 43.4%(39.1-47.6) and 69.6%(68.7-70.5). Shortfalls varied across cancer sites according to whether CBB or EBEST estimates were referenced, ranging from 4.8% in lung cancer to 30.8% in rectal cancer. Conclusions: Important shortfalls exist in the utilization of RT in Alberta, Canada despite centralized cancer care and a publically funded health care system. The magnitude of the shortfall varied according to whether a CBB or EBEST estimate of RT was applied.
30-day readmission among gastrointestinal cancer patients in Texas.
Authors: Manzano Joanna-Grace , Luo Ruili , Elting Linda S. , Suarez-Almazor Maria
Published: February 2017

121

Background: 30 day readmission has become an important metric in healthcare delivery. Policymakers have started to factor in readmission rates in their recommendations on reimbursement algorithms. It is unclear whether these methods are applicable to cancer patients. More studies are needed in order to understand readmission in the context of cancer patients. A few studies have found that the elderly and those with gastrointestinal (GI) malignancies are at risk. Methods: We conducted a retrospective cohort study using linked Texas Cancer Registry and Medicare claims data to describe the patterns of 30 day unplanned readmission among GI cancer patients in Texas. Only short stays to acute care hospitals were included in the study. Claims data were analyzed for a period of 2 years from the date of cancer diagnosis. Modified Poisson regression model was used to identify factors associated with the outcome. Results: 30,199 patients aged 66 and above were included in our study. The incidence of unplanned readmission in our cohort was 15%. The top 10 reasons for readmission were fluid and electrolyte disorders, secondary malignancies, complications of surgical procedures and medical care, congestive heart failure, intestinal obstruction, pneumonia, sepsis, GI hemorrhage, urinary tract infections, and complications of device, implant or graft. After multivariate analysis, age >80 (OR 0.79, 0.73-0.85), regional (1.19, 1.11-1.27) and distant disease (1.16, 1.07-1.25), living in less affluent neighborhoods (1.10, 1.01-1.19), and increasing comorbidity index (p<0.0001) were associated with 30 day readmission. Esophageal cancer carried the highest risk for 30 day readmission (1.53, 1.38-1.70). Conclusions: Most of the top reasons for readmission appear to be cancer-related. This means that most of these readmissions are likely not preventable. This should be taken into consideration by policymakers when making recommendations. There are, however, some that may be amenable to outpatient management. This further underlines the importance of primary care involvement in the management of cancer patients. Risk factors identified can help risk–stratify patients who may need early follow up post-discharge, in order to prevent early readmission.
Patient-oncologist cost communication, financial distress, and medication adherence.
Authors: Bestvina Christine M , Zullig Leah L. , Rushing Christel , Chino Fumiko Ladd , Samsa Greg , Altomare Ivy , Tulsky James A , Ubel Peter A , Schrag Deborah , Nicolla Jonathan , Abernethy Amy Pickar , Peppercorn Jeffrey M. , Zafar Yousuf
Published: February 2017

2

Background: Little is known about the association between patient-oncologist discussion of cancer treatment out-of-pocket (OOP) cost and medication adherence, a critical component of quality cancer care. Methods: We conducted a cross-sectional survey of insured adults receiving anti-cancer therapy. Patients were asked if they had discussed OOP cost with their oncologist. Medication non-adherence was defined as skipping doses to make prescriptions last longer, taking less medication than prescribed to make prescriptions last longer, or not filling prescriptions due to cost. Multivariable analysis assessed the association between cost discussions with an oncologist and non-adherence. Results: Among 300 respondents (84% response), 77% (n=230) were white and 53% (n=158) were men. 17% (n=52) reported “high” or “overwhelming” financial distress. 19% (n=56) had talked to their oncologist about cost. 27% (n=81) reported medication non-adherence. 14% (n=43) skipped medication doses to make the prescription last longer; 7% (n=3) of these had skipped chemotherapy. 11% (n=34) took less medication than prescribed to make the prescription last longer; 15% (n=5) of these took less chemotherapy. 22% (n=67) did not fill a prescription because of cost; 15% (n=10) of these did not fill a chemotherapy prescription. In adjusted analyses, cost discussion (OR 2.56, 95% CI 1.15-5.68; p=0.02), financial distress (OR 1.57, 95% CI 1.33-1.85, P<0.001) and female gender (OR 2.02, 95% CI 1.005-4.07, p=0.048) were associated with increased odds of non-adherence. Private insurance was associated with lower odds of non-adherence (OR 0.30, 95% CI 0.14-0.60, p<0.001). Conclusions: Patients reported non-adherence to medications and chemotherapy in order to make prescriptions last longer or due to cost. While these data cannot determine temporality or the affect of cost discussion on medication non-adherence, patient-oncologist cost communication and financial distress were associated with non-adherence. Future research should examine the timing, content, and quality of cost-related discussions.
Variation in patterns of health care and survival among patients with brain metastases in the VHA health system.
Authors: Ray Saurabh , Wang Li , Martel Marie-Josee , Baser Onur
Published: February 2017

204

Background: Brain metastases (BM) occur in approximately 15-25% of patients with advanced primary cancers and cause significant morbidity and mortality. This study examines the variation in patterns of healthcare and survival among patients with brain metastases in the US veterans’ population. Methods: A retrospective cohort design identified BM patients, divided into 5 most prevalent primary cancer cohorts using claims and enrollment data (10/1/2005 - 5/31/2012) from the Veterans Health Administration (VHA), the largest integrated health care system in US. Inclusion required ≥ 2 diagnoses of BM (ICD-9 code 198.3x) separated by ≥ 7 days with 1 primary cancer diagnosed before BM. The different BM cohorts were compared to the cohort with the highest prevalence of a primary cancer for the following outcomes: median survival (Kaplan-Meier estimates), per patient month (PPM) rate of healthcare utilization, baseline comorbidities, and use of brain-directed and supportive treatments. Results: Study sample consisted 4,393 BM patients (mean age of 65.6 years, 97% male), divided into 5 most prevalent primary cancer cohorts - 2,783 lung cancer, 574 skin, 568 prostate, 236 kidney, and 232 colorectal cancer patients. Median time to death after BM diagnosis was 103 days for lung, compared to 84 (p<0.01) for skin, and 127, 109, 99 days (all p>0.05) for kidney, prostate and colorectal cohorts respectively. Patients with ≥3 comorbidities ranged from 50% (skin) to 62% (colorectal). Compared to lung, the kidney cohort reported higher emergency room visits (21.6% vs. 16.3%, p=0.04), prostate and colorectal cohorts reported higher inpatient visits (65.3%, 69.4% vs. 59.6%, p=0.011, 0.003, respectively). Whole brain radiotherapy was the most common brain-directed treatment, ranging from 24% (kidney) to 37% (lung); brain-surgery ranged from 7% (lung) to 10% (colorectal); 89% to 94% used corticosteroid supportive therapy. Conclusions: High unmet need exists in the brain metastases population in terms of poor survival, high comorbidity burden and significant healthcare resource utilization. Patient outcomes vary significantly by primary cancer sites reflecting the heterogeneity of this disease.
Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria.
Authors: Loo Ronald , Rabrenovich Violeta , Aspera Ann Michelle , Jacobsen Steven , Landa Howard , Lieberman Stephen F. , Mariani Albert J. , Nicolaisen Gary , Slezak Jeff , StLezin Mark
Published: February 2017

223

Background: AMH in the general population is common, occurring in up to 9-18%. Even low degrees of AMH have been considered a risk factor for UTMT. Although the prevalence of UTMT is low (.01-3%), many asymptomatic patients undergo unnecessary and hazardous evaluations. In 2007, the Kaiser Permanente (KP) Urologists started a multi-year QI effort to research and develop a risk stratified evidence-based approach in the evaluation of AMH. Methods: The group first conducted a retrospective analysis to determine the incidence of urinary cancer, and stratify risk according to age, gender, smoking history, and degree of hematuria. A multi-regional prospective, observational study was then conducted over a two year period. We used a data collection tool embedded within an EMR to determine patients with AMH who are at greatest risk for UTMT, and patients who might benefit from urologic evaluation or safely avoid unnecessary workup and radiation exposure. Results: 4,414 patients had full urologic work up. Overall, 100 bladder cancers were diagnosed among 4,414 patients (2.3%), and only 11 renal cancers (0.2%) were pathologically confirmed. Multivariable logistic regression was conducted for 5 common parameters: age, gender, smoking history, degree of microscopic hematuria, and history of gross hematuria within the past 6 months. The two most important risk factors were age > 50, and prior history of gross hematuria. A hematuria risk index (HRI) was developed, which significantly improved predictability (AUC = .809-HRI vs .532-AUA guideline). Overall, 32% of the population was identified as low risk with only 0.2% cancer detected; 14% of the population was identified as high risk, of whom 11.1% had a cancer diagnosed. Conclusions: These results suggest that a considerable proportion of patients may safely avoid hazardous evaluation using multivariate risk stratification. An evidence-based algorithm was developed for the management of asymptomatic microscopic hematuria and implemented within KP. We expect to significantly improve patient safety and improve reliability of patient evaluation.
Safe administration of intracerebrospinal fluid chemotherapy (ICC).
Authors: Bidros Michel , Holle Lisa , Riemer Jessie , Tannenbaum Susan , Clement Jessica Mary
Published: February 2017

229

Background: ICC administration, which includes intrathecal and intraventricular routes, is a complex procedure that involves staff from different disciplines. ICC administration errors are rare, yet potentially fatal. Since 1968, more than 55 cases of ICC administration errors have been documented, but the incidence is suspected to be higher because of underreporting. Little unified action has occurred despite alerts issued by the Joint Commission on Accreditation of Healthcare Organizations and World Health Organization. We have taken a multidisciplinary approach to address this issue. Methods: We identified two problems that could potentially lead to ICC errors: the lack of a formal institutional training/certification program and a comprehensive institutional safe ICC administration policy. Our Hematology-Oncology Fellowship Program along with Pharmacy and Nursing at the University of Connecticut Health Center (UCHC), created a multidisciplinary work group whose purpose is to create a comprehensive institutional policy and training program for disciplines involved in the administration of ICC. Results: The safeICC administration policy has been finalized and presented for approval. Creation of the training program is in progress and will be a part of the educational Core Curriculum of the Fellowship Program. Fellows will be required to demonstrate competency in lumbar and Ommaya reservoir puncture using simulation training on mannequins. Computer-based training with classroom review and testing will be required for all disciplines involved with ICC and will include safe preparation, delivery, handling, verification, administration of ICC, and identification of potential complications. Annual certification will be required. Conclusions: The lack of a formal ICC administration policy and training can lead to catastrophic errors. Development of an institutional policy and training program has heightened awareness of potential sources of ICC administration errors at UCHC and will serve as a mechanism for assessing quality care in the future. We believe the establishment of such a policy and definition of training should be part of the general ASCO/ONS guidelines for safe administration of chemotherapy.
Standardized criteria for required palliative care consultation on the solid tumor oncology service.
Authors: Adelson Kerin , Paris Julia , Smith Cardinale B. , Horton Jay , Morrison R. Sean
Published: February 2017

37

Background: Studies have shown that routine integration of Palliative Care (PC) for patients with advanced cancer is associated with improved symptom control, clearer understanding of prognosis, lower utilization of health care resources, and increased hospice use. The 2012 ASCO guidelines call for incorporation of PC for any patient with metastatic cancer and/or high symptom burden. Despite a top-rated PC division at Mount Sinai, our Solid Tumor (ST) Division utilized PC and hospice less than other medical centers. Our inpatient ST service consistently demonstrated poor quality metrics. Our 2011-2012 UHC statistics were: mortality index, 1.35 (target <1), 30-day readmission rate, 21.7%, (target < 10.3%) and length of stay (LOS) index, 1.23 (target <1). We hypothesized that implementing standardized criteria for PC consultation would improve these metrics. Methods: During this 3-month pilot, criteria for PC consultation included patients with one or more of the following: stage IV disease, Stage III lung or pancreatic cancer, hospitalization within prior 30 days, >7 day hospitalization, uncontrolled symptoms (pain, nausea, dyspnea, delirium, distress). We looked at two baseline groups for comparison: 1) patients who met eligibility in a six week period prior to the intervention 2) For UHC index data, we used the hospital dashboard average over a 1-year period prior to the intervention. This included all ST patients who were eligible for the intervention (60%) and those who were not (40%). Primary outcomes were: hospice utilization, ST mortality index, 30-day readmission rate and LOS. Results: Comparing Group 1 to the Pilot Group, palliative care consultation doubled from 41% to 82%, 30-day readmission decreased from 36% to 17% (p= .022), and hospice utilization increased from 14% to 25% (p=.146). UHC data (Group 2 vs. Pilot) showed: mortality index improved (1.35 to .59) and 30-day readmission rates decreased (21.7% to 13.5%, p=.026). LOS was unchanged (1.23 to 1.25). Conclusions: Mandating palliative care consults for patients at the highest risk for in hospital death and readmission improved hospice utilization, 30-day readmission, oncology service mortality and adherence with ASCO guidelines.
Evaluation of quality of life from a phase II study of anamorelin HCl in NSCLC patients.
Authors: Temel Jennifer S. , Bondarde Shailesh Arjun , Jain Minish Mahendra , Yan Ying , Duus Elizabeth Manning , Allen Suzan , Mann William
Published: February 2017

42

Background: Anamorelin HCl (ANA) is an oral ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-associated anorexia/cachexia. Cancer cachexia is a multifactorial syndrome, characterized by decreased body weight and muscle, and worsened survival and quality of life (QoL). Here we present Phase II data, including an evaluation of QoL using the MD Anderson Symptom Inventory (MDASI) to assess severity of core symptoms in cancer patients and their impact on daily life. Methods: An international, randomized, double-blind, placebo-controlled, 12-week Phase II trial (NCT00622193) enrolled 226 Stage IIIB/IV NSCLC patients (N=76 for 50 mg ANA; N=73 for 100 mg ANA; N=77 for placebo [PL]). Co-primary endpoints were body weight and handgrip strength (HGS); safety was also assessed. QoL by MDASI was a secondary endpoint; a negative change in MDASI score represents improvement. Assessments were performed at baseline and approximately every 3 weeks over the 12-week treatment period. Results: MDASI total and domain scores improved with 100 mg ANA vs PL, although these changes were not statistically significant (mean±SE change from baseline at Week 12 for 100 mg ANA vs PL was -8.6±4.58 vs -1.5±3.29 for total score; -6.7±2.98 vs -2.9±2.24 for symptom domain score; and -1.9±1.99 vs 1.5±1.39 for interference domain score). Seven individual MDASI symptom/interference items most improved in the 100 mg ANA vs PL group were fatigue, nausea, work around the house, disturbed sleep, distressed, general activity, and mood. Over 12 weeks, ANA also significantly increased body weight vs PL (mean change from baseline was 0.14 kg, -0.3 kg, and -1.32 kg for 100 mg ANA, 50 mg ANA, and PL, respectively [p=0.0005]), and directional (non-significant) changes in HGS were also noted for both active arms vs PL. ANA was safe and well-tolerated, with less adverse events of fatigue, anorexia, and nausea reported in ANA vs PL patients. Conclusions: In this study, ANA significantly increased body weight, improved HGS and QoL, and had an overall favorable safety/tolerability profile. MDASI individual item changes demonstrated improvements in key cancer-related symptoms including fatigue, and were consistent with the adverse event profile. Clinical trial information: NCT00622193.
Using a statewide collaborative approach to improve primary palliative care performance.
Authors: Abstoss Katie , Mahmood Tallat , Martin Claudia Jane , Muir J. Cameron , Severson Jane Alcyne , Smerage Jeffrey B. , Blayney Douglas W.
Published: February 2017

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Background: The Michigan Oncology Quality Consortium (MOQC) is a statewide collaborative of oncology practices. Using the Quality Oncology Practice Initiative (QOPI) measurement tool, MOQC identified a gap in the provision of palliative care. We designed and tested interventions to enhance the capacity and capabilities of the oncologist to deliver primary palliative care earlier in a patient’s course. Methods: MOQC created a process to assist oncology care teams in providing primary palliative care services using the Edmonton Symptom Assessment Scale tool. 11 practices participated in two pilots over 18 months. During and after these pilots, we disseminated tools for improvement, including customized palliative care dashboards, to the entire consortium. Pilot teams also shared their successes, insights, and best practices during semiannual live consortium meetings. Results: Shown are palliative care-focused QOPI results, comparing baseline (Fall 2011, F11) and post project (Spring 2013, S13) for all MOQC practices compared with all participating QOPI practices, using a paired t-test. MOQC sites outperformed the QOPI national average on multiple palliative care measures. Furthermore, the MOQC improvement rate since the project initiation was greater than that of national. Although clinically important, the measures did not reach standard statistical significance. Conclusions: Running successive pilot projects improved primary palliative care performance of the teams involved; additionally, this momentum and gain in knowledge facilitated dissemination of innovation and measurable improvement in all members of a statewide consortium. [Table: see text]
Impact of a dedicated supportive care center telephone triaging program (SCCTP) for patients with advanced cancer.
Authors: Pimentel Lindsey E , Yennurajalingam Sriram , Chisholm Gary B. , Edwards Tonya , Guerra-Sanchez Maria , De La Cruz Maxine Grace Jaucian , Vidal Marieberta , Tanco Kimberson , Bruera Eduardo
Published: February 2017

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Background: Due to high symptom burden in advanced cancer patients, ongoing symptom management for outpatient palliative care patients is vital. More patients are receiving outpatient care; Yet, most palliative care patients receive less than 2 follow ups. Nurse telephone care can improve quality of life in these patients. Our aim was to determine frequency and care provided by Supportive Care Center Telephone Program (SCCTP) in advanced cancer patients. Methods: 400 consecutive patients who utilized palliative care service, 200 from outpatient Supportive Care Center (SCC) and 200 from inpatient Palliative Care (IPC), were followed for 6 months starting 3/2012 to examine call frequency and reason and outcomes including pain and other symptoms [Edmonton Symptom Assessment Scale (ESAS) and Memorial Delirium Assessment Scale (MDAS)] associated with utilization of SCCTP. We also examined the effect of SCCTP interventions on pain, ESAS and counseling needs. Results: 375 patients were evaluable. Median age 59 years, 53% female, 70% white. Most frequent cancer type were gastrointestinal (20%, p < 0.0001) for IPC and thoracic (23%, p <0.0001) for SCC. SCC patients had higher prevalence of CAGE positivity (28% SCC vs 11% IPC, p <0.0001), ESAS SDS(p=0.0134), depression(p=0.0009), anxiety(p=0.0097) and sleep(p=0.0015); MDAS scores were significantly higher in IPC (p<0.0001).115/400 patients (29%) utilized SCCTP. 96/115 outpatients (83%) used the SCCTP vs 19/115 IPC (17%). Common reasons for calls were pain (24%), pain medication refills (24%) and counseling (12%). Of 115 phone calls, 340 recommendations were made; 43% (145/340) were regarding care at home; 56% of these recommendations were regarding opioids. Patients who utilized SCCTP had worse pain(p=0.0059), fatigue(p=0.0448), depression(p=0.0410), FWB(p=0.0149) and better MDAS scores(p=0.0138) compared to non-utilizers. Conclusions: There was more frequent SCCTP use by outpatients than inpatients. Most common reason for utilization was pain control. Frequently, recommendations were made to continue symptom management at home. Patients who utilized SCCTP had worse pain, fatigue, depression, well-being scores and better delirium scores.
Value of thoracic multidisciplinary clinic (TMDC) in determining appropriate treatment of stage III non-small cell lung cancer (NSCLC).
Authors: Friedman Eliot L , Szwerc Michael F , Kruklitis Robert , Weiss Michael J
Published: February 2017

82

Background: Treatment of stage III NSCLC involves surgery, radiation therapy and chemotherapy. Treatment depends on the size and location of the primary tumor and lymph nodes as well as clinical status of the patient. Evaluation of these patients should take place in a multidisciplinary clinic, where treating physicians and pulmonary medicine provide a unified treatment plan. Methods: All patients with Stage III NSCLC seen at the Lehigh Valley Health Network (LVHN) between March of 2010 and March of 2012 were analyzed retrospectively. We compared initial treatment of out-patients seen in our TMDC with those out-patients seen outside the TMDC. Results: Thirty-five patients were seen in TMDC (34 treated at LVHN) and 44 patients were seen outside TMDC (34 treated at LVHN). Eleven patients were treated elsewhere or were not treatable. Of patients with stage III NSCLC, 37.5% were seen in TMDC year 1 (March 2010 – March 2011) compared to 61% of patients year 2 (March 2011 – March 2012) (p = 0.05). Patients were seen by physicians from at least two specialties 100% of the time when seen in TMDC, but only 64.7% of the time when seen outside TMDC (p < 0.001). Mediastinal staging (EBUS or mediastinoscopy) was performed more frequently in patients seen in TMDC; 58.9% compared to 23.5% outside TMDC (p = 0.009). The LVHN clinical pathway for stage III NSCLC recommends initial therapy with concomitant chemoradiation, either in the neo-adjuvant setting or as definitive treatment. Eighty-eight percent of patients seen in TMDC followed our clinical pathway while 46% of patients seen outside TMDC conformed to the clinical pathway (p < 0.001). The time from first contact with a treating physician to initiation of treatment was reduced by almost 30% (29.03 days outside TMDC; 20.62 days at TMDC). Conclusions: All patients with stage III NSCLC should be seen in a multidisciplinary setting. At LVHN we saw an increase in these patients being referred to our TMDC over time. These patients were more likely to have mediastinal staging and enjoyed quicker initiation of their therapy. They were more likely to have at least two physicians involved in their initial treatment plan and were more likely to conform to our clinical pathways.