tbuckley/cabot-search huggingface dataset:
Establishing a value framework for cancer-specific patient satisfaction (PS) across a large health system.
Authors: Randall F. Holcombe, Frances Cartwright
Journal: Journal of Clinical Oncology (2016)

100 Background: The Mount Sinai Health System and the Tisch Cancer Institute (TCI) includes 7 hospitals and 6 ambulatory oncology centers in New York City, with over 9,000 new cancer cases seen annually. In order to address PS across these multiple sites, we established a framework to enhance value encompassing 4 domains: Infrastructure, Responsibility, Outcomes and Monitoring. Methods: Infrastructure. A quality dashboard was developed and distributed across all system sites. Inpatient oncology Dyads (D) (inpatient medical director and nurse manager) and ambulatory oncology Triads (T) (ambulatory medical director, nurse manager and administrator) and Quadrads (Q) (including radiation therapist) were established. Responsibility. DTQs at each location were given collective responsibility for PS performance. Outcomes. The relevant HCAHPS and Press-Ganey PS scores were defined across all groups; expectations for initiatives to improve PS were delineated. Monitoring. Each DTQ reported PS performance and progress on initiatives at a quarterly system-wide meeting of the TCI QI committee. Results: The quality dashboard provided a comprehensive PS report for all system sites and the DTQs identified specific individuals responsible for PS at each site. Within 6 months, establishment of the value framework more than doubled the number of quality initiatives, including ones focused on pain management, goals of care discussions and distress screening. Required participation in the TCI QI committee resulted in 100% compliance with reporting to a high level oversight group. Conclusions: The value framework involved the complete reorganization of how PS was reviewed, which individuals were responsible, and how initiatives to improve the patient experience were developed and monitored across the health system. Standardized dashboard-based reporting of PS facilitated review of critical information and creation of the DTQ structure facilitated engagement by key stakeholders, leading to numerous quality initiatives. Regular reporting elevated the level of attention ascribed to PS and the oversight group provided ongoing guidance for the process.
Patterns of locoregional relapses for patients with esophageal cancer for whom exclusive chemoradiotherapy failed: A plea for dose escalation and elective nodal irradiation.
Authors: Cedric Chevalier, Noemie Vulquin, Mélanie Gauthier, Aurelie Petitfils, Etienne Martin, Gilles Truc, Karine Peignaux-Casasnovas, Cedric Khoury, Nadia Wiazzane, Philippe Maingon, Gilles Crehange
Journal: Journal of Clinical Oncology (2013)

99 Background: Nearly half of the patients (pts) with an esophageal cancer (EC) have a locoregional failure (LRF) after exclusive chemoradiation (eCRT). eCRT delivering 50Gy remains the standard of care for non operable pts. We aim to evaluate the patterns of LRF with respect to planned dose and/or the incidental (unplanned) dose that covered LRF. Methods: Twenty-two pts with EC who failed locally and/or regionally in their follow-up were exclusively reviewed. All the pts have been initially treated (t0) in a curative intent with eCRT. Co-image registration of CT or PET-CT at time of failure and planning CT at t0 was used for image fusion. Each nodal failure (Nf) and each local failure of the primary tumor (Lf) has been outlined, as well as each nodal station (NS) including Nf according to the RTOG classification. Dosimetric parameters in relation with Lf, Nf and involved NS were derived from the initial dosimetric plan. Results: All the patients underwent eCRT including a 5-FU based chemotherapy regimen. Eighteen patients were treated with elective nodal irradiation (ENI) whereas 4 pts did not. The median dose delivered was 50Gy [50Gy-64Gy]. In the follow-up period, 14 pts were in complete response, 3 pts in partial response, 4 pts had a progressive disease (1pt unknown). The median delay between the start of radiotherapy and LRF was 14.3 months [4.27-48.46]. 13 pts had a Lf (included in “planned-dose”), 9 pts had a Nf, 2 pts had a Lf with Nf and 7 pts had a concomittant distant failure. Among pts with Nf, 8 failures were in-field whereas 3 pts had an out-field relapse. Re-calculated doses for NS delineated on the CT performed at t0 were significantly less important than the planned dose (see Table). Conclusions: Our results suggest that an inadequate dose to both the primary tumor and NS could explain high LRF rates observed in EC. A French randomized phase III trial (NCT 01348217) is currently testing a higher dose to the primary tumor and/or ENI with IMRT in an attempt to improve locoregional control. [Table: see text]
Randomized phase II trial of capecitabine (X) versus X plus erlotinib (E) in patients (pts) with metastatic colorectal cancer (mCRC): Differential impact of KRAS.
Authors: M. D. Vincent, S. Welch, D. Soulieres, M. S. Sanatani, F. Whiston, L. Stitt, A. O'Connell, M. J. MacKenzie, W. I. Kocha, I. G. Kerr, B. H. Dingle, A. Malpage
Journal: Journal of Clinical Oncology (2011)

e14031^ Background: Palliative X monotherapy of mCRC is generally tolerated by elderly, and/or medically unfit pts. Epidermal growth factor receptor (EGFR) inhibitors improve efficacy when added to combination chemotherapy for mCRC. It is unknown whether biologic agents add benefit to alone in pts who either opt against, or are not candidate for, combination chemotherapy. We conducted a randomized phase II trial to investigate the novel “all-oral” combination of low-dose X and E in this pt population. Methods: Eligible pts with mCRC were either deemed unfit for, or chose against, 1st-line combination chemotherapy. Pts were randomized to X (1000 mg/m2 PO BID x 14 days) alone or in combination with E (150 mg PO OD) on a 3-week schedule. A 3rd arm (E alone) was ineffective, and discontinued after a preplanned interim analysis. Imaging was performed every 9 weeks until progression. Primary endpoint was time to disease progression (TTP); secondary endpoints included: objective response rate (ORR), overall survival (OS), safety and quality of life. Results: From June 2004 to June 2008, 95 pts [median age: 67; range 40-84; ECOG PS: 0 (45pts), 1 (38 pts), or 2 (22 pts)] were randomized to X alone (40 pts), XE (42 pts), or E alone (13 pts). KRAS status, where possible, was analyzed for pts in the first 2 arms only. As compared to X alone, XE was associated with significantly more Gr 3+ toxicity: (diarrhea: 29% vs 5%; fatigue: 12% vs 0%; anorexia 7% vs 0%; stomatitis 7% vs 0%). One pt discontinued treatment in the X arm vs 2 in XE. There was 1 toxic death in XE. TTP was not different for the whole trial (X=7.9 m, XE=9.2 m; p=0.8897), but exploratory subgroup differences emerged (below). Conclusions: The addition of E to X is associated with additional toxicity. E may benefit pts with KRAS-wild-type CRC and may harm those with KRAS-mutated CRC. Further study of XE in elderly/unfit pts with KRAS-wild-type CRC is warranted. Supported by grant from Roche. Median TTP (m) X XE p All pts (n = 40 / 42) 7.9 9.2 0.8897 KRAS wt (n =18 / 24) 8.4 11.7 * KRAS mut (n = 18 / 12) 7.4 1.9 * *Cox regression p=0.0236 for interaction of study arm by Kras status.
Impact of tumor aneuploidy in pseudomyxoma peritonei.
Authors: Shreya Jagadish Shetty, Bala Natarajan, Brian W. Loggie
Journal: Journal of Clinical Oncology (2012)

414 Background: DNA aneuploidy is an indicator of poor prognosis in epithelial cancers arising from the colon, rectum, kidney and breast. To our knowledge, there is no data on the occurrence of DNA aneuploidy in Pseudomyxoma peritonei (PMP). The aim of this study is to investigate the frequency of DNA aneuploidy and analyze its relation to clinicopathological characteristics of the patients. Methods: One hundred and twenty patients with PMP were analyzed. Flow cytometry was used on paraffin embedded tissue samples and multiple tissue blocks and serial sections were analyzed for each tumor. The results of DNA analysis were correlated to clinicopathologic data. Chi- square test was used to analyze categorical variables and t-test was used for continuous variables. Kaplan-Meier analysis was used to study impact of aneuploidy on survival. Results: Of 120 patients analyzed, 41.7% (70/120) patients had disseminated peritoneal adenomucinosis (DPAM), 32.5% (39/120) patients had either peritoneal mucinous carcinomatosis- intermediate type (PMCAI) or peritoneal mucinous carcinomatosis (PMCA) and 25.8% (31/120) had signet cell carcinoma (SCC). DNA aneuploidy was detected in 13% (16/120) of the PMP patients. The incidence of aneuploidy was 2% (1/50) in patients with DPAM, 25.6% (10/39) in patients with PMCAI or PMCA and 16% (5/31) in patients with SCC (p=0.004). Nearly 56% (67/120) of patients were males and 44% (53/120) were females. Gender did not impact the incidence of aneuploidy. Mean age of patients with aneuploid tumors and diploid- near diploid tumors was 56.8 (±13.5) years and 49.6 (± 11.8) years respectively (p=0.027). Median survival in patients with aneuploidy was 54 months compared to 100 months in patients with diploid/ near-diploid status (p=0.021). Conclusions: Older age and high-grade PMP are associated with higher rates of aneuploidy. Aneuploidy was associated with worse survival in patients with PMP.
Dual inhibition of DNA double strand break (DSB) repair and PI3K pathway with BEZ235 (BEZ) to sensitize refractory metastatic (met) triple negative breast cancer (TNBC) to nab paclitaxel/cisplatin (pac/cis) in a patient with an exceptional response (ExRx).
Authors: Joyce O'Shaughnessy, Virginia A. Espina, Irene Cherni, John D. Carpten, Lance A. Liotta, David W. Craig, Jeff Kiefer, Nicholas N Hoke, Maren K. Levin, Kai Wang, Corinne Ramos
Journal: Journal of Clinical Oncology (2015)

156 Background: Whether EGFR is a critical target in met TNBC is unknown. Here we report the clinical history &amp; tumor molecular alterations in a patient with refractory metTNBC who had an ExRx to pac/cis. Methods: Following IRB-approved informed consent, targeted NGS (Foundation Medicine) and WGS (TGEN) was performed on the pt’s FFPE primary TNBC and 2 recurrent lymph nodes to characterize all classes of genomic alterations in cancer-related genes. RPPA was performed at a CLIA-certified laboratory (Theranostics Health) and George Mason Univ where immunostaining was directed against HER1/2/3 pathway and other proteins. Results: At age 58 in 2006, pt had T1c 1+ node TNBC treated with FAC/T. Between 2008 and 2011 she had 4 chemotherapy-refractory recurrences in axilla, supraclavicular (SC), internal mammary (IM) LNs treated unsuccessfully with surgery, radiation and multiple cytotoxic agents including carboplatin. In 2011, following SC LN biopsy, she was treated with BEZ, a PI3K/mTOR, ATM, ATR, DNA-PKcs inhibitor, had a 3 mo response, followed by rapidly enlarging progressive disease (PD) in IM LNs pushing sternum anteriorly. She was treated with pac/cis and had an ongoing complete response (CR) of 2.5+ yrs. NGS of 2011 SC LN (pre-BEZ) &amp; 2012 IM LN (post-BEZ): TP53 &amp; BRCA2 (somatic 15% mutant allele freq) mutations, FOXM1 amplification; SMARCA4 (BRG1) deletion RPPA (GMU) 2011 SC LN (Pre-BEZ): 3+ EGFR; 2+ p-EGFR, p-AKT, p-MEK1/2, p-mTOR RPPA (Theranostics) 2012 IM LN (post-BEZ): 3+ p-MEK1/2 (EGFR &amp; p-EGFR 0) (AR-). Conclusions: Strong EGFR signaling associated with chemo-resistant metTNBC in 2011 SC LN was not present in post-BEZ rapid PD in IM LN which then had durable CR with pac/cis. BEZ inhibits DSB repair, sensitizing cancers to DNA damaging agents (Gil del Alcazar, Clin Ca Res 20:1235, 2014). Progression of p-AKT-activated TNBC following response to inhibitors of PI3K &amp; DNA repair shows DSB repair-deficiency and MAPK activation (Juvekar, Cancer Dis 2:1048, 2012). A prospective trial of BEZ followed at PD by pac/cis in metTNBC is warranted.
Comparison of hormone receptor and HER2 status in resected brain metastases and primary breast cancer.
Authors: Z. Tomasevic, Z. Milovanovic, Z. M. Tomasevic, M. Skender, G. Pupic, Z. Kovac, D. Grujicic
Journal: Journal of Clinical Oncology (2010)

1117 Background: HER2 overexpresion and negative hormone receptors are reported as factors contributing to higher incidence of brain metastases (BM) in metastatic breast carcinoma. Therefore it could be expected that biological marker characteristics (BMC) of BM is consistent with primary breast carcinoma (PBC). Because few patients are eligible for surgery, BMC of BM is usually unknown. Methods: The aim of this analysis is to compare BMC in PBC and completely resected BM. Among 97 breast carcinoma patients with BM, 21 (21.6%) had 1-3 metastases, and underwent BM surgery. Results: All patients had pathologically confirmed BC metastases. BM BMC was known in 10/21 (47.6%). BMC is defined as ER/PR receptors (HR), (Quick score 0-8) and HER2 status (IHC 0-3+/CISH±). The only one HR+ PBC changed to HR – in BM. Among 8 HER2- PBC, 2 (25%) changed to HER2+ BM. All HR-, HER2+, and triple-negative PBC retained these BMC in BM (Table). Conclusions: According to our results, it could be expected that BM BMC profile is unchanged if PBC is HR-, HER2+ or triple-negative. PBC with more favorable BMC could change to less favorable in BM. Although obtained in small, selected subgroup of patients with resectable BM, these results should be considered in systemic treatment choice. BMC PBC No. (%) BM No. (%) No. (%) of changed BMC in BM HR+ (ER or PR≥ 4) 1/10 (10) 0/10 (0) 1/1(100) changed to HR- HR- (ER and PR ≤ 3) 9/10 (90) 10/10 (100) 0/9 (0) HER2- (0, 1+, 2+) 8/10 (80) 6/10 (60) 2/8 (25) changed to HER2+ HER2+ (3+, CISH +) 2/10 (20) 4/10 (40) 0/2 (0) Triple-negative (ER, PR, HER2 0) 6/10 (60) 6/10 (60) 0/6 (0) No significant financial relationships to disclose.
A model for predicting overall survival in men with metastatic castrate-resistant prostate cancer (CRPC) for whom first-line chemotherapy failed.
Authors: Susan Halabi, Chen-Yen Lin, Eric Jay Small, Andrew J. Armstrong, Ellen B. Kaplan, Daniel Peter Petrylak, Cora N. Sternberg, Liji Shen, Stephane Oudard, Johann Sebastian De Bono, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2013)

24 Background: Several prognostic models for overall survival (OS) have been developed and validated in men with chemotherapy naïve mCRPC. The primary objective was to develop and validate a prognostic model that can be used to predict OS in men who have failed first-line chemotherapy. Methods: Data was used from a phase III trial of 755 mCRPC men who had developed progressive disease following first-line chemotherapy and were randomized to cabazitaxel plus prednisone or mitoxantrone plus prednisone (TROPIC trial). The data was randomly split into training (n=507) and testing (n=248) sets. A separate data, consisting of 488 men previously treated with docetaxel who were randomly assigned to either satraplatin and prednisone or placebo and prednisone, was used as the validation set (SPARC trial). Penalized regression method was used to identify important prognostic factors. Adaptive Lasso selected nine variables of OS. A predictive score was computed from the estimated regression coefficients and used to classify patients into low (&lt;-1.29) and high (&gt;= -1.29) risk groups in the testing datasets. The model was assessed for its predictive accuracy using time dependent area under the curve (AUC) on the testing sets (TROPIC and SPARC trials). Results: The final selected model included: ECOG performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of prior hormonal use, hemoglobin, prostate specific antigen and alkaline phosphatase. In the TROPIC testing set, the median OS in high and low risk groups were 11 and 17 months, respectively, with a hazard ratio (HR)=2.47 (p-value&lt;0.0001). Using the SPARC set, the median OS were 11 and 20 months in the high and low risk groups, respectively, with a HR=1.94 (p&lt;0.0001). The time dependent AUC were 0.73 and 0.70 on the testing sets. Conclusions: A prognostic model of OS in the post-docetaxel mCRPC setting was developed and validated and risk groups were identified. This model can be used to select patients based on their prognosis to participate in clinical trials. Prospective validation is needed.
Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies
Authors: E C Pietsch, J Dong, R Cardoso, X Zhang, D Chin, R Hawkins, T Dinh, M Zhou, B Strake, P-H Feng, M Rocca, C Dos Santos, X Shan, G Danet-Desnoyers, F Shi, E Kaiser, H J Millar, S Fenton, R Swanson, J A Nemeth, R M Attar
Journal: Blood Cancer Journal (2017)

Abstract CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by &gt;40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices.
Hematopoietic Stem Cell Transplantation (HSCT) for Benign Indications Using Umbilical Cord Blood Units (UCB) That Were Depleted of Plasma, but Not of Red Blood Cells.
Authors: Robert Chow, Tang-Her Jaing, David Gjertson, Joseph Rosenthal, Auayporn Nademanee, Chatchada Karanes, Michael Graham, Patrick Tan, Lawrence D. Petz
Journal: Blood (2005)
Phase II study alternating mFOLFOX 6 and FOLFIRI (FIREFOX) plus bevacizumab (bev) regimen in first-line treatment of advanced colorectal cancer in Japanese patients (KSCC 0801).
Authors: Yutaka Ogata, Yoshito Akagi, Yoshihiro Kakeji, Yasunori Emi, Eiji Oki, Hiroshi Saeki, Tetsuo Touyama, Hironori Samura, Hideo Baba, Shoji Natsugoe, Kazuo Shirouzu, Shoji Tokunaga, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2012)

602 Background: The Kyushu Study group of Clinical Cancer conducted a phase II study that evaluated the FIREFOX regimen. (KSCC0701, Akagi et al, J Clin Oncol 28:15s, 2010). This study demonstrated the efficacy and mild neurotoxicity of this regimen. The present study evaluated the efficacy and safety of the FIREFOX plus bevacizumab (bev). Methods: Eligibility criteria included histologically confirmed advanced colorectal cancer, ECOG PS 0-2 and adequate bone marrow, renal and hepatic function. Patients (pts) received an alternating regimen of 4 cycles of mFOLFOX-6 plus bev (oxaliplatin 85 mg/m 2 , leucovorin 200 mg/m 2 , bev 5 mg/kg d1 followed by 400 mg/m 2 bolus 5-FU and a 46-hr 2,400 mg/m 2 5-FU infusion every 2 weeks) followed by 4 cycles of FOLFIRI plus bev (oxaliplatin replaced with irinotecan 150 mg/m 2 d1). This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint is progression-free survival. (UMIN000001312) Results: Of the 52 pts enrolled from May 2008 to July 2009. Two of the patients did not fulfill the eligibility criteria. M/F, 30/20; median age, 59.5 years (range 37 - 75); ECOG PS 0/1/2, 46/4/0. The median number of administration cycles was 14 (range, 2 - 44). Response rate (RECIST criteria) for CR, PR, SD, PD and NE were 2 (4%), 28 (56%), 14 (28%), 4 (8%) and 2 (4%), respectively. An overall response rate was 60% (95% CI: 45 - 74%). Median progression-free survival was14.2 M (95% CI: 10.6 M-16.3 M) and median overall survival was 27.5 M (95% CI; 22.4 M – not determined). The 2-year survival rate was 56.8%. Of the 52 pts evaluated for toxicity. The most common grade 3-4 adverse events were leukopenia (7.7%), neutropenia (32.7%), anemia (1.9%), fatigue (9.6%), anorexia (13.5%), stomatitis (3.8%), neurotoxicity (3.8%), hypertension (1.9%), diarrhea (7.7%), febrile neutropenia (3.8%), nausea (9.6%), vomiting (5.8%), hypersensitivity (3.8%), and thromboembolism (1.9%). Conclusions: The results of this phase II study show that the FIREFOX plus bev regimen is effective and well tolerated in the first-line treatment of advanced colorectal cancer. The low rate of neurotoxicity is also promising.
Implementation of adherence to erlotinib by a treatment-monitoring program.
Authors: V. Gebbia, M. Bellavia, P. Russo, G. L. Banna, F. Ferraù, P. Tralongo, N. Borsellino
Journal: Journal of Clinical Oncology (2011)

7611 Background: To evaluate the impact of a treatment-monitoring program (TMP) on adherence to second-line erlotinib in patients with advanced non-small cell lung cancer (A-NSCLC) Methods: A retrospective non-interventional study phase was conducted in a cohort of 50 patients (first cohort) who was prescribed erlotinib without a specifically designed management strategy; in a prospective interventional study phase 150 patients were followed by an oral TMP (second cohort), that included the identification of a patient caregiver, patient and caregiver education and training about treatment and expected side effects, a precise calendar of follow-up visits and a dedicated fax phone line to receive instructions or use a fast-track visit system. The Basel Assessment of Adherence Scale (BAAS), a Visual Analogue Scale (VAS), pill counting, and missed appointment rate were used to evaluate adherence. Correlation between adherence and clinical outcome, and treatment toxicity was investigated. Results: Self-reported adherence >95% to the first 2 months by the BAAS was 72% and 84% in the first and second cohort, respectively (p=0.044). By the VAS, adherence was 94% and 85% in the first cohort by patients and physicians, respectively; no differences were seen in the second cohort among that reported by patients, caregivers and physicians. By pill counting adherence was 78% and 87% in the first and second cohort, respectively (p=0.0021). Mean adherence to planned visits was 86% and 96% in the first and second cohort, respectively (p<0.0001). Disease control rate (=CR+PR+SD) was 44% (95% CI, 30%-58%) and 63% (95% CI, 53%-72%) in the first and second cohort, respectively (p=0.0368). A significant correlation was observed between the number of adverse events and patient reported adherence (r=0.176, p=0.035). Conclusions: A TMP including the identification of a patient caregiver, and adequate patient and caregiver education and training, may increase adherence to erlotinib and likely improve its efficacy as second-line treatment for advanced A-NSCLC patients.