tbuckley/cabot-search huggingface dataset:
Survivorship care plans: Strategies to enhance patient utility and value.
Authors: Diana Harris, Carrie Tompkins Stricker, Deb Walker, Amanda Katzman, Nadia Still, Laura Digiovanni, David Finitsis, Andrew L. Salner, Ellen A Dornelas
Journal: Journal of Clinical Oncology (2017)

75 Background: A decade ago the Institute of Medicine (IOM) recommended that every survivor receive a survivor care plan (SCP), yet despite endorsements of clinical merit, evidence of their effectiveness is inconsistent, and patient satisfaction with, use of, and perceived utility of SCP’s remains unclear. Methods: This ongoing multicenter pilot enrolls breast cancer (BC) patients who have recently completed active treatment. Patients complete an electronic patient reported outcomes (ePRO) survey via the Carevive Care Planning System (CPS), which is combined with clinical data to electronically generate tailored care plans with survivorship and symptom-specific recommendations (i.e. follow-up care, self-management, supportive care referrals) in real-time. Patients receive their care plan at a consultative survivorship visit. Approximately 6-weeks following SCP receipt, patients complete a survey to evaluate satisfaction Results: Over 200 patients have received SCPs to date; 101 have completed follow-up surveys. Patients are on average 59 years old (Range: (33-84 yo), female (100%), and with 0-III stage BC. Study outcomes include patient-reported use and helpfulness of, as well as satisfaction (1-5 Likert scale items) with, their SCP. On average, patients were “very satisfied” with their SCP overall (M = 4.08), and 90% (n=90) would, “recommend other women receive a similar care plan after cancer treatment”. In addition to majority of patients (99%) having read or planning to read the SCP carefully, the three most frequently cited ways for use/planned use of the SCP include to: inform about symptoms (90%); speak with healthcare professionals about concerns (88%); and help identify information online (86%). Seventy-two (78%) patients and 68 (74%) reported that SCP’s were most useful to helping them make changes in what they ate and types of exercises, respectively. Conversely, 51 (58%) of patients and 47 (59%) of patients reported that the SCP was most useful to helping them find support resources and talking about personal cancer experience with family members. When asked to recall what recommendations their SCPs endorsed, patients most commonly recalled surveillance recommendations (e.g. follow up visits (83%), mammograms (80%), compared to recommendations specific to reported concerns and symptoms (e.g, management of sexual concerns (31%), evaluation and management of lymphedema (27%)). Conclusions: n/a
Predictive factors for late (&gt;5 years) distant recurrences in estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients: &gt;20-year follow-up.
Authors: Jaskirat Singh Randhawa, Sina Shafiei, Mykola Onyshchenko, Susmita Sakruti, Rohan Garje, Vyshak Alva Venur, Xuefei Jia, Timothy Peter Spiro, Abdo S. Haddad, Hamed Daw
Journal: Journal of Clinical Oncology (2014)

543 Background: ER+ breast cancer (BC) by virtue of tumor dormancy can present with delayed recurrences, frequently years after initial diagnosis. Methods: Over 2,500 charts of ER+/HER2 negative BC patients were reviewed. Patients with follow up < 5 years, recurrence within 5 years and all local recurrences < or > 5 years were excluded. 35 late distant recurrences with minimum follow up of 5 years were identified. Data was analyzed with 50 patients without recurrences during same period. Following factors were used for analysis: age at diagnosis, tumor diameter, smoking history, T- and clinical stage at diagnosis, lymph node involvement (LNI), tumor-grade, histology, progesterone receptor(PR) status, duration of adjuvant therapy and treatment modalities. Recurrence and time to recurrence were assessed. Wilcoxon rank sum, Kruskal-Wallis tests and Chi-square tests were used for univariate analyses. Multivariate analysis was conducted using logistic regression and proportional hazards models. Results: The median/mean age at diagnosis was 58/58.5 years and median/mean age at relapse was 63/65.5 years respectively. Tumor size, T-stage at diagnosis, and duration of adjuvant therapy were associated with late relapse (p≤0.025, p≤0.012, p≤0.037 respectively). T-stage at diagnosis was only independent predictor identified; with an estimated odds ratio of 2.62 (95% CI: 1.22, 5.64) and an estimated hazard ratio of 2.22 (95% CI: 1.32, 3.72). No other significant association was detected (age at diagnosis; p≥0.21, tumor-grade; p≥0.27, histology; p≥0.17, smoking history; p≥0.79, LNI; p≥0.08, PR status; p≥0.58). Of patients with recurrent disease, 40% showed identical receptor profile and 11.4% had receptors changed/different from their initial diagnosis. Conclusions: In univariate analysis, the tumor diameter, T-stage at diagnosis and duration of adjuvant therapy are associated with both recurrences and time to relapse. Patients who received adjuvant therapy ≥ 5 years had decreased rate of late recurrences. In multivariate analysis, T-stage at diagnosis is the only independent predictor.
A genome-wide query of somatic copy number alterations to predict lymph node metastases and survival in patients with muscle-invasive bladder cancer.
Authors: Karla Lindquist, Thomas Sanford, Terence W. Friedlander, Pamela Paris, Sima P. Porten
Journal: Journal of Clinical Oncology (2017)

325 Background: Patients with muscle-invasive bladder cancer (MIBC) have a poor prognosis if the cancer has metastasized to surrounding lymph nodes (LN). Adding tumor-based genomic tests that improve prediction of LN status and prognosis over clinical variables alone would be useful to clinicians in making treatment decisions, potentially improving outcomes for these patients. Methods: We performed a genome-wide query of copy number alterations (CNAs) in MIBC tumors from 237 patients in The Cancer Genome Atlas who had radical cystectomy and lymphadenectomy ( ≥ 10 nodes) without neoadjuvant treatment. We independently analyzed pathology reports and copy number data to confirm LN status and gene-level CNAs. Using elastic net and logistic regression models, we sought to identify a set of genes with CNAs that predict LN status. We also tested for association between CNAs and survival. Results: We identified 26 genes with CNAs that predicted LN status. Those located on chr3p25 and chr11p11 had gains associated with LN positivity after adjusting for age, gender, race, pathological tumor stage, histology, and number of nodes examined (p = 0.03). CNAs at these loci were also associated with one-year survival in the cohort overall (p &lt; 0.01), as well as in LN-positive patients after adjusting for node stage, LN density, and extracapsular extension (p &lt; 0.01). Conclusions: We have identified a small set of genes with CNAs in MIBC tumors that robustly predict LN status and one-year survival. A simple copy number-based test based on these genes could potentially improve preoperative LN status determination and help inform adjuvant treatment decisions to improve outcomes in MIBC patients.
A phase I study of MDM2 antagonist RG7112 in patients (pts) with relapsed/refractory solid tumors.
Authors: Razelle Kurzrock, Jean-Yves Blay, Binh Bui Nguyen, Andrew J. Wagner, Robert G. Maki, Gary K. Schwartz, Amita Patnaik, Lia Gore, Lin Wu, Lyubomir T Vassilev, Michelle Ding, David Geho, Jianguo Zhi, Steven Middleton, Gwen L. Nichols
Journal: Journal of Clinical Oncology (2012)

e13600^ Background: RG7112 is a small molecule MDM2 antagonist, designed to non-genotoxically activate p53. A phase I dose escalation (DE) was performed, followed by a sarcoma biomarker extension (EXT) in pts with wild type TP53. Methods: 106 pts (58M, 48 F), median age 57.9 yrs (range 22-84) participated; 76 in 9 cohorts (DE) from 20 to 1800 mg/m 2 , orally QD x 10 q28 days. 30 pts with sarcoma were treated at MTD (2500 mg) (EXT) with pre-and on dose (d5+/-2) biopsies. Analyses included TP53 mutation (AmpliChip), MDM2 amplification (ISH), p53 and p21 IHC, MDM2 RT-PCR, Ki-67, TUNEL and [ 18 F]-FLT-PET. Blood was obtained for PK and MIC-1, a PD marker of p53 activation. Results: DE: MTD was1440 mg/m 2 /d (2500 mg flat dose). PK was ~dose linear (t½ 1-1.5 d) with high variability (CV~70%) in AUC and Cmax . Adverse events included nausea/GI and exposure-related neutropenia/thrombocytopenia. 3 DLTs: diarrhea, pancytopenia, hyponatremia occurred (at ≥ 640 mg/m 2 ). Evidence of activity included: 1) concentration dependent increase in plasma MIC-1 (% baseline), 2) decrease in [ 18 F]-FLT PET and PR each in liposarcoma pts at 1800 mg/m 2 and 1440 mg/m 2 , respectively. EXT: Grade3/ 4 cytopenias at MTD precluded subsequent cycles in 6/8 pts (10 day schedule). Dosing was changed to 5 days, and only 3 patients had Gr3/4 cytopenias. 8/22 pts remained on study for &gt;4 cycles, including 2 pts with SD for 7 and 9 cycles respectively. 3 of 4 EXT pts had decreased [ 18 F]-FLT-PET activity. Biopsies (pre- and on treatment) demonstrated: 1) increase in p53 (median 1.5 fold change (X) by IHC, n=15); 2) increase in p21 (median 2.7X by IHC, n=14); 3) increase in MDM2 (median 2.5X by RT-PCR, n = 27); 4) decrease in % Ki-67(+) cells (median % change from baseline -65.4%, range -91% to +275%, n=17 ); 5) increase in TUNEL(+) cells of 9.0 (density of + cells/mm 2 , range -26.2 to +45.5, n=22). These results were seen both in tumors with and without MDM2 gene amplification, and in multiple sarcoma subtypes. Conclusions: RG7112 has manageable AEs (GI ) and cytopenias correlating with AUC. Single agent disease control, and biomarker activity was seen in both MDM2 amplified and non-amplified, heavily pretreated soft tissue sarcoma pts, with changes reflecting activation of p53-related pathways.
Impact of age on the quality of systemic therapy delivery in older patients with early breast cancer (EBC).
Authors: Katherine Enright, Lingsong Yun, Melanie Powis, Nathan Taback, Christopher M. Booth, Maureen E. Trudeau, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2015)

e17620 Background: Defining quality care is a particular challenge in older women with EBC given the under representation of these patients in clinical trials. In the absence of level one evidence, population studies may provide important insights for understudied populations and aid in defining quality. We examined the impact of increasing age on a comprehensive panel of systemic therapy focused quality measures (QM) in older women with EBC. Methods: Incident EBC diagnosed 01/06 to 12/10 in Ontario, Canada were identified using the Ontario Cancer Registry. Men, patients younger than 65, or with history of second malignancy were excluded. Multiple administrative databases were linked deterministically to provide comprehensive medical follow up.The outcome was the percentage of patients that met each QM stratified by decade. Results: 11,208 patients were included in analysis. Increasing age was associated with a significantly lower performance in access, effectiveness and timeliness domains (see table). The association of age and chemotherapy toxicity was variable but treatment associated mortality increased significantly with age. Conclusions: Increasing age is associated with lower performance on systemic therapy QMs in older women with EBC. High treatment associated mortality supports low targets for chemotherapy usage in women older than 70. The definition of quality in other domains (access to medical oncologist, use of hormones, timeliness of treatment) however is less clear highlighting the need for further discussion around targets for systemic therapy QM in older women with EBC. Quality of systemic therapy in older women with EBC. 65-70 y n = 3414 70-79 y n = 5030 80-89 y n = 2515 90+ y n = 249 p Value Access Seen by a Medical oncologist 82.6% 79.6% 67.2% 45.0% < .001 Received adjuvant chemo 33.3% 16.0% 2.5% 0% < .001 Received adjuvant hormone therapy 84.8% 79.1% 61.2% 42.4% < .001 Effectiveness Adherence to hormonal therapy 90.6% 88.5% 83.7% 77.9% < .001 Timeliness Chemo started < 2 months from surgery 54.0% 48.9% 42.9% N/A < .001 Toxicity on Chemo: (n = 2006) Emergency room visit or hospitalization 49.5% 53.0% 38.1% N/A < .001 Febrile Neutropenia 16.0% 21.9% 7.9% N/A < .001 Mortality (60 days) 1.2% 2.7% 4.8% N/A < .001
Myelodysplastic syndrome (MDS) and autoimmune diseases (AD): Hypomethylating agents to treat both.
Authors: Omar Al Ustwani, Laurie Ann Ford, Sheila N. J. Sait, Anne Marie W. Block, Maurice P. Barcos, Elizabeth A. Griffiths, James E. Thompson, Eunice S. Wang, Julian L. Ambrus, Meir Wetzler
Journal: Journal of Clinical Oncology (2013)

e18018 Background: AD occurring in the setting of MDS is challenging to recognize and incorporate into the treatment plan. We assessed the clinical presentations, laboratory abnormalities and outcome of patients with MDS and AD. Methods: Records of MDS patients treated at Roswell Park Cancer Institute between 2007 and 2010 were reviewed (n=123). Results: AD was identified in 10 MDS patients (8.1%): 70% were males, median age was 60.6 years (41-75). AD manifested as seronegative polyarthritis in 2, bronchiolitis obliterans in 2, Hashimoto’s thyroiditis in 2, and 1 (10%) for each of rheumatoid arthritis, systemic lupus, polymyalgia rheumatica, Sjogren syndrome and relapsing polychondritis. Laboratory autoimmune markers were: anti nuclear antibodies in 2, rheumatoid factor in 2, anti-double stranded DNA in 1 and anti phospholipid syndrome with thrombosis in 1. Corticosteroids were the most common used treatment for AD (60%). Regarding the MDS diagnosis; 50% had refractory anemia with excess of blasts-1 and -2, 20% refractory anemia with ring sideroblasts, 10% for each of chronic myelomonocytic leukemia, refractory anemia and MDS/myeloproliferative neoplasm. Normal cytogenetics were noted in 70% of patients, 20% with complex karyotype and 10% had monosomy 7. Hypomethylating agents were used to treat MDS in 80% of patients and in one case were associated with concomitant improvement of AD. Overall survival from diagnosis with MDS was 54 months (6-127). Conclusions: Our experience with one patient and review of the literature suggest that both AD and MDS could benefit from treatment with hypomethylating agents. This warrants a prospective clinical trial.
Early Detection of Bilateral Testicular Metastases From Prostatic Adenocarcinoma Using 68Ga-PSMA Ligand PET/CT
Authors: Desiree Weiberg, Herbert Radner, Thorsten Derlin, Walter F. Thon
Journal: Clinical Nuclear Medicine (2017)

We present the case of a 76-year-old man with biochemical relapse after primary therapy for prostate cancer. Ga prostate-specific membrane antigen (PSMA) ligand PET/CT performed for localization of recurrent disease revealed bilateral metastases to the testes. Histopathologic evaluation after bilateral orchiectomy revealed testicular metastases. Metastases to the testes are rare and usually seen in advanced stages. Ga-PSMA ligand PET/CT is a highly sensitive and specific imaging method for the detection of primary and metastatic prostate cancer and has refined diagnostic approaches. This case highlights the potential of PSMA-targeted PET/CT for detection of prostate cancer metastases, even in very unusual localizations.
Results of the phase IIb part of TIME study evaluating TG4010 immunotherapy in stage IV non-small cell lung cancer (NSCLC) patients receiving first line chemotherapy.
Authors: Elisabeth A. Quoix, Frederic Forget, Zsolt Papai-Szekely, Christian H.H Ottensmeier, John J. Nemunaitis, Enriqueta Felip, Lucio Crino, Aleksandra Szczesna, Annette Tavernaro, Gisele Lacoste, Berangere Bastien, Jean-Marc Limacher
Journal: Journal of Clinical Oncology (2015)

3034 Background: TG4010 is an immunotherapy using an attenuated and modified poxvirus (MVA) coding for MUC1 and interleukin-2. A previous study showed that the baseline level of Triple Positive Activated Lymphocytes (TrPAL, CD16+CD56+CD69+) might be a predictive biomarker for TG4010 efficacy in NSCLC. Methods: TIME is a double blind, placebo-controlled phase IIb/III study. The phase IIb part compared first line chemotherapy combined with TG4010 or placebo and further assessed the predictive value of baseline level of TrPAL. Eligibility criteria included stage IV NSCLC not previously treated, MUC1+ tumor by immunohistochemistry (IHC), PS ≤ 1. TG4010 108pfu or placebo was given SC weekly for 6 weeks (w), then every 3w up to progression in immediate combination with chemotherapy. Primary endpoint was progression-free survival (PFS). Results: 222 patients (pts) were randomized 1:1. In pts with normal TrPAL the study met the primary endpoint of having a Bayesian probability for HR < 1 being > 95%. PFS was significantly improved in the TG4010 arm in pts with low TrPAL (152 pts HR = 0.66 [CI95% 0.46-0.95] p = 0.013) while it was not the case in pts with high TrPAL (70 pts HR = 0.97 [CI 95% 0.55-1.73] p = 0.463). In addition, PFS was also significantly improved in pts with non-squamous tumors (196 pts HR = 0.69 [CI95% 0.51-0.94] p = 0.009) as well as in pts with non-squamous tumors and low TrPAL (131 pts HR = 0.61 [CI95% 0.42-0.89] p = 0.005). In this last group PFS at 9 months was 37% with TG4010 versus 18% with placebo. Overall survival (OS) data show an improvement in line with that observed for PFS and will be presented at the time of the meeting. Preliminary data on the effect of PDL1 expression by IHC in the tumor support the activity of TG4010 whether the tumor is positive or negative for PDL1 expression. Frequency and severity of adverse events were similar in both treatment arms. Conclusions: These results provide additional data supporting the efficacy of TG4010, particularly in patients with non-squamous tumors and/or a low level of TrPAL at baseline. The phase III part of the TIME study will continue in patients with non-squamous tumors and with OS as primary endpoint. Clinical trial information: NCT01383148.
Prognostic impact of weight change during chemotherapy.
Authors: Nikola S. Kasprowicz, Philip Gm Hepp, Ulrich Andergassen, Christoph Scholz, Katja Annecke, Arthur Wischnik, Wolfgang Simon, Helmut Forstbauer, Doris Augustin, Thomas Zwingers, Nadia Harbeck, Harald Leo Sommer, Klaus Friese, Marion Kiechle, Wolfgang Janni, Brigitte Kathrin Rack
Journal: Journal of Clinical Oncology (2012)

1072 Background: Besides established prognostic factors such as tumor size or nodal status, individual host factors of the patient such as obesity, physical activity and diet seem to modulate the course of breast cancer (BC) as well. However, the specific impact of weight change during adjuvant chemotherapy remains unclear. The aim of this analysis was to evaluate the influence of weight change during chemotherapy on BC survival in a large, multi-center prospectively randomized trial. Methods: The ADEBAR trial compares two anthracycline based adjuvant chemotherapy regimen in patients (pts) with lymph node positive ( &gt; 3 positive) early BC: 4 x epirubicin (E) 90 mg/m 2 + cyclophosphamide (C) 600 mg/m 2 q3w followed by 4 x docetaxel 100 mg/m 2 q3w versus 6 x E 60 mg/m 2 + 5-FU 500 mg/m 2 d1+d8 and C 75 mg/m 2 d1-14 q4w. Weight was measured before each cycle. The weight before the 1 st and the 6 th cycle was assessed. Significant weight change was defined as increase or decrease of &gt; 5% of the initial weight. Overall survival (OS), disease free survival (DFS), and BC specific survival (BCSS) were assessed by Kaplan-Meier analysis. Results: In total, 1502 pts were included in the study. 1177 of them completed 6 cycles of chemotherapy. Out of the 350 pts (29.7%) who changed weight 142 pts (12.1%) lost and 208 pts (17.7 %) gained weight. There was a significant correlation between weight change and menopausal status (p&lt;0.0001), indicating that more premenopausal pts gained and postmenopausal pts lost weight. All other tumor characteristics were similarly distributed across the groups. Pts with weight change &gt; 5% showed a significantly worse outcome with respect to OS (p = 0.0028) and BCSS (p = 0.0258). A difference in DFS was not observed (p = 0.1917). The difference in OS was limited to pts who lost weight (p = 0.0008), whereas pts with weight gain have no significant different OS (p = 0.1246) in comparison to pts with constant weight. Conclusions: Our results suggest that weight loss during anthracycline-based treatment of early stage BC is associated with poorer OS. While weight normalization has shown beneficial effects in lifestyle intervention trials, patients should be advised not to lose weight during chemotherapy.
Long term outcomes of hairy cell leukemia patients treated with first and subsequent line with purine analog: The Cleveland Clinic experience.
Authors: Yazan Madanat, Lisa A. Rybicki, Deepa Jagadeesh, Robert M. Dean, Brad L. Pohlman, Matt E. Kalaycio, Mitchell Reed Smith, Brian Thomas Hill
Journal: Journal of Clinical Oncology (2015)

e18034 Background: Hairy Cell Leukemia (HCL) is an indolent B-cell lymphoproliferative disorder with high initial response rates (RR) and long remissions after treatment with purine nucleoside analogs (PNAS). At the time of relapse, re-challenge with PNAS is routinely offered but there are limited data on outcomes of this approach. To provide guidance to the management of HCL, we examined outcomes after 1stand subsequent line treatment of a large cohort of HCL pts treated at our institution. Methods: We retrospectively analyzed 61 pts ≥ 18 years old diagnosed with HCL at the Cleveland Clinic Taussig Cancer Institute from 1995 to 2013. Baseline demographics, treatment history, RR, progression-free survival (PFS) and overall survival (OS) were calculated from the start of 1st line therapy. OS and PFS were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Results: Median age was 54 years (range 31-80). 50 were male (82%). Median follow up was 72 months (3-193). 59 pts (97%) received cladribine (2CDA) as 1st line therapy, 1 patient received pentostatin, 1 patient underwent a splenectomy. After 1st line therapy, 47 of 60 pts (78%) achieved CR/CRU, 12 pts (20%) achieved PR, 1 patient did not respond. 5 year OS was 97%. PFS after response was better among pts who achieved CR as compared to pts who had PR (5 year PFS 71% vs 39% respectively) (P = 0.004). 19 pts (31%) progressed after 1st line therapy and 17 of these had 2nd line therapy. Of those, 12 pts were treated with PNAS [2CDA (9), 2CDA+Rituximab (2), pentostatin (1)]. Median time from 1st to 2nd line treatment was 59 months (12-103). The overall response rate (ORR) of the 12 pts that were treated with 2 lines of therapy was comparable for 1st line treatment (92% ORR, 83% CR) and 2nd line treatment (83%, 75% CR). With median follow-up of 50 months since 2ndline treatment, OS was 100%. Conclusions: HCL pts treated with PNAS have excellent OS. Achieving CR after 1st line treatment was associated with more favorable outcomes. 2nd line treatment with PNAS produced comparable remission rates in the 2nd line setting. These data support the practice of re-challenge with PNAS at the time of relapse with very favorable ORR and OS.