tbuckley/cabot-search huggingface dataset:
A model for delivering survivorship care: Integrating the oncology and the primary care setting—An Italian experience.
Authors: Elena Lorenzi, Lucia Morello, Rita Mazza, Isabella Garassino, Raffaele Cavina, Carmelo Carlo-Stella, Armando Santoro
Journal: Journal of Clinical Oncology (2016)

e275 Background: The population of cancer-survivors faces different lifetime health risk. Thus, models for high-quality and personalized care delivery are strongly needed. ASCO provides different models for survivorship care delivery but there is not an agreement on what is the best in meeting patients’ needs and in terms of cost-effectiveness. In our institution we started a program that tries to integrate survivors’ health care provided by the oncologist and by the Primary Care Physician (PCP). Methods: We included patients (pts) aged more than 18 yrs-old at the time of diagnosis, affected by hematologic or solid tumors. Pts had no evidence of disease from at least 5 yrs from the diagnosis. They are referred to the PCP with the following documents: Survivorship Care-Plan, Survivorship Care-Program, letter to the PCP. Recurrence rate, death rate, treatment related serious clinical events will be calculated after 12 months from the start of the project. Results: We includedin our program 269 cancer-survivors (60% of pts referred to our survivorship-clinic from April to July 2015). The median age was 67 yrs, they were mainly females. The different cancer types were: breast (157), colorectal (36), hematologic (30), gynecologic (11), gastric (9), melanoma (6) lung (5), genitourinary (5), head/neck (3), sarcoma (3) and others (4). 189 of pts had an early stage disease (stage I-II) at diagnosis. 234 of pts underwent surgical treatment and 161 received chemotherapy with different schedules based on tumor types. 59% of pts received anthracycline-based-chemotherapy, 78% at a cumulative dose &gt; 240 mg/m 2 . 154 of pts underwent radiation therapy (90% in thoracic field) with a median dose of 60 Gy. We observed 11 cases of secondary cancer after a median of 2.7 yrs from the first diagnosis. The median observation time from the diagnosis to the inclusion in our program was 10 yrs (range 2-31). Conclusions: The observation period from the beginning of the program is too short to provide follow-up data. A high percentage of pts present a high risk of cardiologic late toxicities, therefore they need a more intensive cardiologic follow-up. We will present the first follow-up analysis of this cohort of pts in April 2016.
Malignant pleural mesothelioma (MPM) in elderly patients: A multicenter survey.
Authors: Federica Grosso, Mario Botta, Paolo Andrea Zucali, Giulia Pasello, Chiara Maria La Spina, Annalisa Roveta, Matteo Perrino, Giordano D. Beretta, Valentina Polo, Armando Santoro, Adolfo G. Favaretto, Giovanni Luca Ceresoli
Journal: Journal of Clinical Oncology (2012)

7082 Background: The incidence of malignant pleural mesothelioma (MPM) in elderly patients (pts) is increasing in Western countries. Elderly pts with MPM are under-represented in clinical trials, and there are no specific guidelines for their management. The aim of this study was to perform a retrospective survey on this patient population in four Oncology Departments with high MPM accrual and expertise. Methods: The clinical records of elderly pts (≥70 years old) with MPM referred to the participating centers from January 2005 to November 2011 were reviewed. For each patient, age and gender, histology, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were collected. The study endpoint was overall survival (OS). Results: Out of a total of 610 cases, 210 elderly pts were identified (34% of the whole MPM population observed in the study period). Pts characteristics were: median age 75 yrs (range 70-92), M/F 132/78, epithelial/non-epithelial histology 140/70, ECOG-PS 0/1/2/unknown 130/67/9/4. CCI was 0 in 128 pts (61%), ≥4 in 59 pts (28%). Treatment was multimodality therapy including surgery in 16, chemotherapy in 153 (73%) and best supportive care only in 41 pts (19%). Chemotherapy was mainly pemetrexed-based. Median OS was 11.3 months. Non-epithelial histology, age ≥75 yrs and the presence of comorbidities (CCI ≥1, p=.003; CCI ≥4, p<0.0001) were significantly correlated to a shorter OS. Conclusions: Pemetrexed-based chemotherapy is feasible in selected elderly pts with MPM. Comorbidity is a significant prognostic factor, and should be carefully considered in patient selection. Prospective dedicated trials in elderly pts with MPM selected according to comorbidity scales are warranted.
Effect of single-nucleotide polymorphisms in the CYP19 gene on response to Letrozole among breast cancer patients
Authors: l. Kadouri, D. Bercovich, Y. Rottenberg, S. Korem, A. Elimelech, B. Uziely, T. Safra, I. G. Ron, T. Peretz, N. Yaal-Hahoshen
Journal: Journal of Clinical Oncology (2008)

22096 Background: Letrozole's effect in metastatic breast cancer (BC) patients was shown to be associated with a single nucleotide polymorphism (SNP) in the CYP19 aromatase gene. Two CYP19 polymorphisms; the 3'UTR rs10046 and IVS4(tct)± significantly correlate with serum estrogen levels in postmenopausal women. We evaluated their impact on response among BC patients treated with Letrozole. Methods: 70 BC patients treated with Letrozole with clinically evaluable disease (local stage III in 3, and metastatic in 67) were included. 65/67 metastatic patients, were treated with Tamoxifen before Letrozol (37-adjuvant, 28-first line for metastatic disease). DNA from whole blood was genotyped using DHLPC. Presence of WT or SNP was recorded. Correlation with tumor response (progressive, stable or responsive) in all patients and time to progression (TTP) from date of Letrozole start to progression were analyzed in 67/70 patients with metastatic disease. Results: Median age at diagnosis was 52 (range: 27–86). In 66, tumor was positive for estrogen receptor, in 2 it was negative and in additional 2 unknown. 28/70 (40%) carried the 3'UTR rs10046 wild type allele (WT). In the IVS4(tct)±, 3 genotypes, homozygous IVS4(tct)+, heterozygous IVS4(tct)± and homozygous IVS(tct)− were recorded with corresponding frequencies of 22/68 (32%), 30/68 (44%) and 15/68 (22%). These genotypes were not significantly associated with tumor response. However, median TTP was not reached at 30.4 months among carriers of IVS4 (tct)−/− allele compared with 14 and 12.7 months in heterozygots and homozygous (tct)+/+ respectively (p=0.02). Conclusion: homozygous delition of the (tct) at IVS4(tct)± of CYP19 is associated with longer TTP in patients with metastatic BC treated with Letrozole. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
Development of an integrated practice unit: Utilizing a lean approach to impact value of care for brain tumor patients.
Authors: Ivy Kwon, Christine Ahn, Preston White, Linda M. Liau, Timothy Francis Cloughesy, Phioanh Leia Nghiemphu
Journal: Journal of Clinical Oncology (2016)

99 Background: Lack of care coordination across subspecialty departments involved in the treatment of brain tumor patients at our institution has negatively impacted patient outcomes, patient experience, and costs. Meanwhile, value-based health care has become increasingly relevant as a means to respond to changing payment structures and improve quality. With the aim to increase value, we restructured medical practice across the continuum of care for brain tumor patients by developing a virtual (non co-located) Integrated Practice Unit (IPU). Methods: From June 2014 to August 2015, we engaged a core team of physicians and administrators from Neurosurgery, Neuro-Oncology, Radiation Oncology, Neuroradiology and Neuropathology to re-design care pathways for the following diagnoses: glioma, metastatic cancer to the brain, and meningioma. We applied lean methodology to map out current state, identify root causes, and develop an implementation plan based on our analyses. Results: Root causes uncovered included: 1) multiple entry points into the system, 2) silo-ed intake processes, 3) varied scheduling processes across and within departments, and 4) no consensus regarding timing and ownership of follow-up care for patients for each diagnosis. Preliminary solutions generated included: 1) developing a centralized communication point and triage process, 2) standardizing requests at intake and obtaining blanket authorizations for select services, 3) standardizing scheduling workflows across departments, 4) delineating the timing and nature of necessary post-operative appointments, and 5) onboarding a nurse navigator to optimize care coordination. Shared metrics to be monitored over time were developed and include time from scheduled-to-seen for initial consults, proportion of patients with post-operative appointments scheduled prior to discharge, number of readmissions within 30 days, patient satisfaction, and costs. Conclusions: Value-based care redesign around the development of an IPU for brain tumor patients has the potential to meaningfully impact patient outcomes, patient experience, and reduce costs in the delivery of care.
Determining argininosuccinate synthetase (ASS) expression in patients with melanoma treated with arginine depleting therapy.
Authors: V. Dinh, M. You, N. Savaraj, C. Wu, M. T. Kuo, M. Wangpaichitr, L. G. Feun
Journal: Journal of Clinical Oncology (2011)

10627 Background: In our phase II trial in advanced melanoma (ASCO 2010) with arginine depleting therapy using ADI-PEG20 (Polaris Pharmaceuticals), we found that response to therapy correlated with tumor expression of enzyme, ASS. Normal cells which possess ASS can recycle citrulline to arginine and hence evade cell death, whereas melanoma tumors lacking ASS do not. Thus, 11 of 17 patients (pts) with ASS(-) tumors (by immunohistochemistry or real-time PCR) had evidence of antitumor activity versus 1 of 10 pts with ASS (+) tumors, (P value = 0.01). To study why not all ASS(-) melanoma pts respond to ADI-PEG20, we have developed a sensitive method to detect small amounts of mRNA by PCR. Methods: Total RNA was prepared from primary culture or cell lines and used for cDNA synthesis. Real-time PCR of ASS was performed using specific primers. The reaction was based on SYBR Green and performed in a Bio-Rad iCycler PCR machine equipped with a MyiQ module. ΔΔCt method was used to calculate the relative ASS mRNA level. Levels of ASS mRNA were corrected with that of GAPDH and normalized with that of BJ-1 normal skin fibroblast, the value of which was set as 1. Results: Real-time PCR was performed in a panel of 15 primary cultures derived from patients’ melanoma samples. The relative mRNA expression ranged from 0.0005 to 4.9. 5 primary cultures were treated with ADI-PEG for three days and assayed for ASS expression. In 2/5 with ASS mRNA <0.003, ASS expression was not inducible. The ASSmRNA of less than 0.001 exhibit higher sensitivity to ADI-PEG20 treatment (ID50 <0.1 ug/ml). However, in one cell line with baseline ASS mRNA of 0.003, it increased to 0.06 upon arginine deprivation. In a panel of melanoma cell lines we have also found that immunocytochemistry cannot detect ASS when their mRNA is <0.09. Thus, it is possible that the ASS(-) melanoma pts who do not respond to ADI-PEG20 have low detectable levels of mRNA which can be induced upon arginine deprivation. Conclusions: While the assay for ASS mRNA is cumbersome, it may better define melanoma pts who will respond to arginine depleting therapy with ADI-PEG20. Other factors which regulate ASS expression such as HIF-1alpha and cMyc are also being investigated. Supported by 1R01CA109578.
Lean implementation of electronic health records (EHR).
Authors: Paula Reed, Albert Chan, Natalia Colocci, Virginia Carter-West, Matthew Kunkel, Tina Pierce, Mathew Isle, Diana Nguyen, Julie Roth, Peter Paul Yu
Journal: Journal of Clinical Oncology (2013)

211 Background: The Palo Alto Medical Foundation (PAMF), an integrated multispecialty physician group and one of five regions of Sutter Health in Northern California, is converting from an electronic chemotherapy ordering and administration system, Intellidose, to Epic Beacon to achieve full EHR integration. As chemotherapy workflows are complex with multiple interactions between providers and high potential for patient harm, we adopted a novel approach of incorporating Lean process improvement principles in advance of our Beacon deployment to improve the design of our software build and increase operational safety and efficiency. Methods: Two multi-disciplinary teams including oncologists, pharmacists, nurses, administrative and technical support staff were deployed; a Sutter Beacon team responsible for technical design and build of the Sutter Beacon standard and a second PAMF team to evaluate workflow variation among PAMF chemotherapy infusion centers, identify best practices, engage the Sutter Beacon Build team around system design and institute rapid cycle process improvement in partnership with the PAMF Lean Promotion Office. Results: Visio maps of current state workflows were constructed to reflect oncologist, pharmacy and nursing workflows from medication ordering to chemotherapy administration and billing submission. Two Rapid Process Improvement Workshops designed future state workflows and identified key areas requiring re-engineering. Lean rapid cycle improvement strategies will be leveraged to improve clinical workflows prior to Beacon implementation. To support the 40% of infusion treatments that are for non-oncology patients, a second process was designed as an important patient safety initiative to avoid discordant nursing administration workflows. Conclusions: Successful design, build and implementation of EHR require achieving consensus-driven work processes that maximize patient safety, eliminate workflow redundancies and maximizes the value-added component. It requires coordination between the EHR technical build team who design the system and the implementation team who integrate it with re-engineered workflows. Lean methodology provides the conceptual framework to achieve a successful EHR deployment.
Patterns of recurrence in advanced epithelial ovarian, fallopian tube, and peritoneal cancers treated with intraperitoneal chemotherapy.
Authors: K. M. Esselen, N. Rodriguez, N. S. Horowitz, S. M. Campos
Journal: Journal of Clinical Oncology (2011)

5072 Background: GOG 1721 established the role of intraperitoneal (IP) chemotherapy in patients with optimally debulked ovarian, fallopian tube and peritoneal cancers. Despite this advance, informational gaps exist, namely the patterns of relapse. This study examines the distribution, timing, and outcomes of recurrence after optimal cytoreduction and adjuvant IP chemotherapy. Methods: All patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between 2004-09 who underwent optimal debulking surgery and received adjuvant intravenous (IV) & IP chemotherapy with paclitaxel and a platinum-based agent were eligible. Age, performance status, tumor origin, stage, and grade were recorded. First recurrences were identified using CA125 values, radiographic studies, operative notes, and pathology reports. Site of recurrence was classified as intraperitoneal, retroperitoneal, or distant. Kaplan-Meier estimates and Cox multivariate regression modeling were used to assess the associations between disease distribution and progression-free survival (PFS) and overall survival (OS). Results: 143 patients underwent optimal debulking surgery and placement of an IP catheter. The majority had Stage III (86%) and serous histology (77%). 84 (58.7%) patients were treated with IV/IP paclitaxel/cisplatin per GOG-172, 59 (41.3%) with IV/IP paclitaxel/carboplatin. 72% (104) completed 6 cycles while 11.9% (17) received ≤ 2 cycles of IV/IP chemotherapy. There were 9 IP catheter-related infections (6.3%). 90 (62.9%) patients had a recurrence. Median PFS was 21.5 months. Primary peritoneal cancers demonstrated worse PFS (p < 0.02) and OS (p < 0.03) relative to ovary and fallopian tube origins. 69 (76.7%) of recurrences were intraperitoneal. Site of recurrence did not impact OS, however, patients who recurred in multiples sites had significantly worse overall survival (p < 0.001). Conclusions: A quarter of patients treated with IP chemotherapy have a first recurrence outside the peritoneal cavity. Though site of recurrence did not affect OS those with multi-focal recurrence have a poor survival. Improved therapeutic options are needed for this population.
Overexpression of IGF1R to predict outcome in invasive urothelial carcinoma of urinary bladder.
Authors: Jenny J. Kim, Nilda Gonzalez-Roibon, Alcides Chaux, Enrico Munari, Shiela F. Faraj, Carla Ellis, Rajni Sharma, Trinity Bivalacqua, Mark Schoenberg, Michael Anthony Carducci, George J. Netto
Journal: Journal of Clinical Oncology (2013)

280 Background: Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor involved in cell proliferation and differentiation. IGF1R is overexpressed (OE) in several tumors including bladder cancer and is currently under investigation as a target of Rx. Here we explore IGF1R expression in urothelial carcinoma (UC), its association with clinicopathologic parameters and prognostic role. Methods: Fivetissue microarrays (TMA) were constructed from 100 cystectomy specimens performed for invasive UC at our institution (1994 to 2007). Formalin-fixed paraffin-embedded paired tumor and benign samples were spotted 3-4 times each. Membranous IGF1R staining was evaluated using immunohistochemistry (G11, Ventana Medical Systems). A scoring method analogous to that of Her2 expression in breast cancer was used and the highest score was assigned to each tumor. IGF1R was considered OE in cases with score 1. Endpoints of the study included overall survival and cancer-specific survival. Patients were followed-up for a median of 33.5 months (range 1, 141 months). Results: IGF1R was OE in 62% of UC. No differences were noted between normal urothelium and malignant counterparts (74% vs. 60%; P=0.14). IGFR1 was more frequently OE in tumors from African-American patients compared to Caucasians (100% vs. 59%, P=0.04). pT4 tumors OE IGF1R more frequently than pT1-pT3 tumors (71% vs. 29%, P=0.005). No association was found with other analyzed clinicopathologic parameters such as patient's age or gender, muscularis propria invasion, or lymph node metastasis). Overall survival (OS) and disease-specific survival (DSS) rates were 58% and 69%, respectively. Patients whose tumors OE IGF1R had a lower OS and DSS compared to those whose tumors did not OE IGF1R (Mantel-Cox P=0.0007 and P=0.006, respectively). Using Cox proportional hazards regression, IGF1R overexpression remained a significant predictor of OS (HR=3.49, P=0.001) and DSS (HR=3.54, P=0.007) after adjusting for pathologic stage. Conclusions: Overexpression of IGF1R was found in 62% of UC. High stage tumors OE IGF1R more frequently than low stage tumors. More importantly, IGF1R overexpression was a significant independent predictor of OS and DSS.
Measurement of interstitial fluid pressure (IFP) and circulating biomarkers in soft tissue sarcoma (STS): An exploratory phase II clinical and correlative study of sorafenib (SOR) in patients with refractory STS (NCI Protocol 6948).
Authors: C. P. Raut, J. A. Morgan, R. H. Quek, Y. Boucher, G. D. Duda, J. Lahdenranta, M. Ancukiewicz, J. P. Eder, R. K. Jain, G. D. Demetri
Journal: Journal of Clinical Oncology (2010)

10091 Background: Interstitial hypertension may contribute to chemo-resistance in STS. Sorafenib is a small molecule tyrosine kinase inhibitor with potent activity against c-RAF/B-RAF, VEGFR-2, and PDGFR-β. By affecting vascular permeability, SOR may potentially reduce IFP. We assessed anti-tumor activity and measured the IFP and circulating biomarkers in patients with superficial refractory STS treated with SOR. Methods: Eligibility criteria included advanced/metastatic STS with no known curative therapy, measurable disease with at least one superficial lesion (>1cm) amenable to biopsy, age ≥18, ECOG performance status ≤2, and no prior SOR therapy. SOR was administered at 400mg BID. IFP measurements were performed intraoperatively as described (Boucher et al 1991); plasma biomarkers were collected pre- and on Day 28 post-SOR. Results: Fifteen patients (median age 59, range 30-84) were enrolled, 14 of whom had prior chemotherapy and/or radiation. Median tumor size was 6.6cm (range 1.3-10.7cm). Common sarcoma sub-types included leiomyosarcoma (27%), myxofibrosarcoma (13%) and synovial sarcoma (13%). Of these, 11 had superficial tumor amenable to biopsy. In this group, median TTP was 28 days (range 10-81). In four pts lacking palpable superficial tumor, mean TTP was 173 days (range 28-227). Best response was stable disease in 10 of 15 pts, maintained for a median 57 days (range 20-168 days). IFP measurements were obtained in 6 pts at baseline and showed a direct correlation with tumor size (Kendall's tau=0.87, p=0.017). Two pts with SD had corresponding post-SOR IFP evaluation and demonstrated a decline in IFP. SOR significantly increased plasma VEGF, PlGF and SDF-1a and decreased sVEGFR2 (p<0.05 for all). Conclusions: SOR has modest benefits in this population, most of whom had advanced refractory disease. IFP appears to decrease when response is maintained. Biomarker changes were consistent with inhibition of angiogenesis by SOR. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, ARIAD, ArQule, AstraZeneca, Bayer, Daiichi Sankyo, Dyax, Genentech, Infinity, Johnson & Johnson, Millennium, Novartis, Pfizer, PharmaMar, Regeneron, Roche, SynDevRx, ZIOPHARM Oncology SynDevRx Novartis, Pfizer, PharmaMar Amgen, ARIAD, ArQule, Daiichi Sankyo, Genentech, Infinity, Johnson & Johnson, Novartis, Pfizer, PharmaMar, Roche, ZIOPHARM Oncology ARIAD, ArQule, Daiichi Sankyo, Infinity, Johnson & Johnson, PharmaMar
Therapeutic Management of Acute Myeloid Leukemia Patients after Stratification on Age, Prognosis and Allogeneic Hematopoietic Stem Cell Transplantation Eligibility
Authors: Mauricette Michallet, Mohamad Sobh, Mohamed Elhamri, Jeremy Monfray, Helene Labussiere-Wallet, Sandrine Hayette, Isabelle Tigaud, Lila Gilis, Laure L Lebras, Fiorenza Barraco, Sophie Ducastelle, Adriana Plesa, Valerie Dubois, Franck E. Nicolini, Xavier Thomas
Journal: Blood (2014)