tbuckley/cabot-search huggingface dataset:
Quality of life as a potential predictor for morbidity and mortality in patients with metastatic hormone-refractory prostate cancer
Authors: J. B. Nelson, M. A. Carducci, N. J. Vogelzang, D. J. Sleep, S. Hulting, P. Mulani
Journal: Journal of Clinical Oncology (2005)

8095 Background: The relationship between quality of life (QoL) and morbidity and mortality in metastatic hormone-refractory prostate cancer (M+HRPC) remains unclear. The role of QoL as a predictor for morbidity and mortality measures such as survival, time to disease progression (TTP), time to bone pain (TTBP), and prostate specific antigen doubling time (PSADT) of less than 4 months was assessed using data from a phase 3 trial (n=809) of atrasentan (Xinlay) 10 mg in men with M+HRPC. Methods: QoL data were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30). The relationship between the QoL change score from baseline to week 12 for survival, TTP, and TTBP was assessed using Cox proportional hazards methodology. For PSADT, the relationship was explored using a logistic regression. All models included the baseline Karnofsky score; bone alkaline phosphatase, hemoglobin, and lactose dehydrogenase levels; and treatment assignment (ie, atrasentan or placebo) as covariates. Results: The change score of the Prostate Cancer Subscale (PCS) domain of the FACT-P was significantly associated with all of the morbidity and mortality endpoints (P <0.0001 for each). Specifically, the risk ratios were 0.57, 0.57, and 0.49 for TTP, TTBP, and survival, respectively, indicating that a greater decline in PCS values at week 12 significantly increases the risk of disease progression, bone pain, and death. The odds ratio for PSADT was 1.80, which indicates that a greater decline in PCS values at week 12 significantly increases the likelihood of experiencing a PSADT of less than 4 months. Similar results were observed for other FACT-P and EORTC domains. Conclusions: QoL change scores are significantly prognostic of survival, TTP, TTBP, and PSADT. Therapies that provide QoL benefits may have beneficial effects on the morbidity and mortality of M+HRPC patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories Abbott Laboratories, Aventis, OSI Abbott Laboratories, AstraZeneca, Lilly Oncology, NCI
Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer
Authors: H. Lote, I. Spiteri, L. Ermini, A. Vatsiou, A. Roy, A. McDonald, N. Maka, M. Balsitis, N. Bose, M. Simbolo, A. Mafficini, A. Lampis, J.C. Hahne, F. Trevisani, Z. Eltahir, G. Mentrasti, C. Findlay, E.A.J. Kalkman, M. Punta, B. Werner, S. Lise, A. Aktipis, C. Maley, M. Greaves, C. Braconi, J. White, M. Fassan, A. Scarpa, A. Sottoriva, N. Valeri
Journal: Annals of Oncology (2017)

BackgroundPatients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but lack of chronological references makes dating the exact onset of tumours very challenging.Patients and methodsHere, we describe the case of a colorectal cancer (CRC) patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urinary tract metastases over the course of 5 years. The chest wall metastasis was caused by needle tract seeding, implying a known time of onset. Using whole genome sequencing data from primary and metastatic sites we inferred the complete chronology of the cancer by exploiting the time of needle tract seeding as an in vivo 'stopwatch'. This approach allowed us to follow the progression of the disease back in time, dating each ancestral node of the phylogenetic tree in the past history of the tumour. We used a Bayesian phylogenomic approach, which accounts for possible dynamic changes in mutational rate, to reconstruct the phylogenetic tree and effectively 'carbon date' the malignant progression.ResultsThe primary colon cancer emerged between 5 and 8 years before the clinical diagnosis. The primary tumour metastasized to the lung and the thyroid within a year from its onset. The thyroid lesion presented as a tumour-to-tumour deposit within a benign Hurthle adenoma. Despite rapid metastatic progression from the primary tumour, the patient showed an indolent disease course. Primary cancer and metastases were microsatellite stable and displayed low chromosomal instability. Neo-antigen analysis suggested minimal immunogenicity.ConclusionOur data provide the first in vivo experimental evidence documenting the timing of metastatic progression in CRC and suggest that genomic instability might be more important than the metastatic potential of the primary cancer in dictating CRC fate.
Patient and tumor characteristics associated with contralateral breast cancer in a nested population-based case-control study.
Authors: M. J. Junqueira, M. Morrow, A. S. Reiner, K. Malone, C. Lynch, J. L. Bernstein
Journal: Journal of Clinical Oncology (2011)

1014 Background: The identification of patient and tumor characteristics associated with an increased risk of contralateral breast cancer (CBC) would be useful for counseling women with unilateral breast cancer (UBC) regarding risks and benefits of contralateral prophylactic mastectomy (CPM), a procedure increasingly chosen by young women. Methods: The WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study is a multicenter, population-based study of 708 cases with metachronous CBC and 1,399 matched controls with UBC nested within a cohort of 52,536 women under age 55 at diagnosis of an initial breast cancer between 1985−2000. Family history was collected by phone interviews; treatment and tumor characteristics were abstracted from medical records, and germline DNA was tested for deleterious mutations of BRCA1/2. Multivariable adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: The median age of cases and controls was 46. 111 cases and 74 controls carried BRCA1/2 mutations. Results are reported for non-carriers. Race, body mass index and menopausal status did not differ between cases and controls. Risk of CBC was elevated among women with a first primary with lobular histology (RR=1.5; 95% CI=1.1−2.2). Grade 2 (RR 0.6, 95% CI 0.5−0.9) and grade 3 tumors (RR 0.6, 95% CI 0.4−0.9) were associated with a lower risk of CBC compared to grade 1 tumors. ER status was not significantly associated with CBC, but only 35% of ER positive patients received tamoxifen. These results were not modified by age at diagnosis (<45, ≥45) or family history of breast cancer. The proportion of in situ CBC increased from 18.2% between 1985−1988 to 22.0% between 1997−2000 (p=0.04). Conclusions: In this large population based study, women with an initial diagnosis of lobular cancer or low grade histology were at increased risk of CBC in the absence of widespread use of endocrine therapy. Given the known benefit of endocrine therapy in reducing CBC, our findings suggest that consideration of standard tumor characteristics alone in women without BRCA1/2 mutations do not identify a subset of women likely to benefit from CPM.
Greater Need for FVIII Replacement in Patients of Type Non-O Blood Groups with Moderate Hemophilia A
Authors: Magaly BPLV Lima, Lúcia Helena Siqueira, Ana Suely Saraiva, Silmara Aparecida Montalvão, Tânia de Fátima Gomes Siegl Machado, Thais Trento, Aldemir Branco Oliveira-Filho, Margareth C Ozelo, José Alexandre Rodrigues Lemos
Journal: Blood (2012)
Changes in circulating lymphocyte counts and tumor-infiltrating lymphocyte subpopulations among patients receiving endorectal brachytherapy for rectal adenocarcinoma.
Authors: Susannah G. Ellsworth, Sabrina C. Sopha, Charles G. Drake, Jian Li Campian, Susan Gearhart, Nilofer Saba Azad, Amy Hacker-Prietz, Stuart A. Grossman, Joseph M. Herman
Journal: Journal of Clinical Oncology (2014)

500 Background: Radiation-induced lymphopenia (RIL) is common in patients with rectal cancer and is associated with worse outcomes in rectal cancer and other solid tumors. We investigated whether endorectal brachytherapy (EB) is associated with milder RIL than external radiation treatment (XRT) in patients with rectal cancer and whether EB is associated with altered tumor-infiltrating lymphocyte (TIL) subpopulations. Methods: Records from 11 patients enrolled in a prospective study of EB for T2-3, N0-1 rectal cancer were reviewed; total lymphocyte counts (TLC) at baseline and 2 months after treatment were recorded. EB was given to tumor alone (6.5Gy x 4). XRT was given to the whole pelvis (median dose 50.4Gy). All patients underwent proctectomy after EB/XRT. TLCs from EB patients were compared to 62 rectal cancer patients receiving pelvic XRT + capecitabine. Proctectomy specimens were immunostained for TIL (CD3, CD4, CD8, FoxP3, and CD25) subtypes. Results: Median baseline TLC in EB patients was 1930 vs 1570 cells/uL in XRT patients (p&gt;0.05). Two months after treatment, median TLC was 1550 in EB patients vs 520 in XRT patients (p&lt;0.01). EB patients had higher absolute numbers of CD3, CD4, CD8, and FoxP3+ TILs (Table). Conclusions: EB spares circulating lymphocytes and is associated with increased TIL expression after therapy. Further investigation is needed to determine if there is a causal association between these phenomena and if the increased TIL expression in EB patients is associated with better outcomes in these patients. [Table: see text]
Risk assessment of early progression among 213 pts with high-risk soft tissue sarcomas (HR-STS) treated with neoadjuvant chemotherapy ± regional hyperthermia: EORTC 62961/ESHO-RHT 95 intergroup phase III study
Authors: L. H. Lindner, M. Schlemmer, P. Hohenberger, P. Wust, M. Schmidt, J. Verweij, I. Judson, K. W. Jauch, W. Hiddemann, R. D. Issels
Journal: Journal of Clinical Oncology (2005)

9020 Background: Delay of surgery due to preoperative chemotherapy ± hyperthermia (RHT) in pts with HR-STS is of major concern because of the potential risk of early progressive disease (PD). Therefore we analyzed the risk of early PD during the 3-months duration of preoperative therapy in the ongoing phase III study. Methods: From 7/97–10/04, 254 pts with HR-STS, median age 52 yrs (range 18–70 yrs), median tumor diameter 11 cm (range 3 - 40 cm), all high-grade, and extracompartmental have been randomized to receive 4 pre- and 4 post-operative cycles EIA (etoposide 125 mg/m2 IV D1 and D4, ifosfamide 1.5 g/m2 IV D1-D4, doxorubicin 50 mg/m2 IV D1, q21 days) either combined with RHT (60 min, Tmax=42.5°C) days 1 and 4 parallel to EIA (N=127) or EIA alone (N=127). According to the high-risk groups primary (S1=118) vs recurrent (S2=31) vs previously inadequate (R1/R2) resected tumors (S3=105) pts were stratified to extremity (E=112) vs non-extremity (Non-E=142) sites. Results: 213/254 pts were eligible (41 pts not eligible: too early 16, refused therapy 6, other reasons 19) for assessment of early PD. 15/213 pts (7%) progressed within the first 3 cycles of EIA±RHT. At the time of response evaluation after completion of 4 cycles of EIA±RHT additional 18/213 pts (8%) showed PD. The other 180/213 pts (85%) showed no PD (134 SD, 9 MR) or clinical objective response (4 CR, 33 PR). For this subgroup of pts with no early PD (median follow-up time 2 yrs) the 3-year local progression free rate (LPFR), local progression free survival (LPFS), and overall survival (OS) for E was 86.1% (95%CI 77.0–95.2%), 69.1% (95%CI 57.6–80.6%) and 79.7% (95%CI 69.6–89.7%) and for Non-E 48.0% (95%CI 36.3–59.6%), 38.1% (95%CI 26.9–49.4%) and 56.7% (95%CI 45.0–68.4%), respectively. Conclusions: The estimated probability for early PD after the initial 3 months of preoperative therapy is 9.35% (95%CI 3.8–14.9%) for E and 11.8% (95%CI 6.4–17.3%) for Non-E. These pts do obviously not benefit from such preoperative treatment regimen. However, the vast majority of pts continue the protocol at least with stable disease showing promising 3-year disease control rates. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott, Boehringer Ingelheim, Cytokinetics, GlaxoSmithKline, Johnson & Johnson, Novartis, OSI, Pfizer, PharmaMar
Patient-reported outcomes (PROs) from the systemic therapies for HER2-positive metastatic breast cancer (MBC) registry study (SystHERs): Eliciting the patient experience.
Authors: Sara A. Hurvitz, Mohammad Jahanzeb, Peter Kaufman, Ginny Mason, Musa Mayer, Hope S. Rugo, Debu Tripathy, Sarika Ogale, Anthony Masaquel, Bongin Yoo, Mary Beattie, Melody A. Cobleigh
Journal: Journal of Clinical Oncology (2014)

286 Background: Patients with HER2-positive MBC are, on average, living longer. Data are limited on patient-reported quality of life (QoL) and economic burden during these extended survival periods. In accordance with guidelines for comparative effectiveness research in oncology (Basch et al, 2012), SystHERs, initiated in 2012, includes PROs to capture the patient experience. Here we report baseline (at enrollment) PRO results from SystHERs. Methods: SystHERs is a US-based prospective observational cohort study that aims to enroll 1000 patients with HER2-positive MBC within 6 months of metastatic diagnosis. Patients will be followed for 5–8 years.PROs, including QoL, economic burden, and symptoms related to neuropathy, alopecia, and cognition, are collected at baseline and ~90-day intervals during clinic visits, including after disease progression. Results: As of Feb 17, 2014, 319 patients were enrolled, and baseline data from 306 eligible patients are reported. Median time to enrollment since MBC diagnosis was 2.4 months. At least 1 PRO item was completed by 90% of eligible patients. Scale reference ranges (higher scores indicate better status) and median scores at baseline were: overall HRQoL (0–100)=80.0; FACT-B Trial Outcome Index (0–96)=58.0, and the Rotterdam Activities of Daily Living Scale (0–100)=85.7. One hundred patients (40.3%) were employed. These patients reported on average 36% work time missed (absenteeism) and 30% decreased on-the-job effectiveness (presenteeism) due to MBC. Patients reported a median out-of-pocket MBC-related expenditure of $735 in the past 3 months (range $0–11,700). Of this, the median deductible and copay-related cost was $350. Conclusions: To our knowledge, this is the only HER2-positive MBC patient registry that includes comprehensive PROs to supplement clinical data. To date, participation in PROs is high at baseline (90%).QoL and economic burden were consistent with other studies (Cortés et al, 2013; Zafar et al, 2013). Baseline results for ~500 patients are expected by the time of the congress presentation and will include data on symptoms related to neuropathy, alopecia, and cognition. Clinical trial information: NCT01615068.
Major prognostic impact of proapoptotic BAX protein expression in stage III (UICC) colon cancer treated by adjuvant chemotherapy
Authors: O. Nehls, T. Okech, C.-J. Hsieh, V. Gaco, H. G. Hass, M. Sarbia, F. Borchard, H.-H. Gruenagel, H. T. Arkenau, R. Porschen, B. Klump
Journal: Journal of Clinical Oncology (2005)

9587 Background: To analyze the expression patterns of proapoptotic BAX, antiapoptotic Bcl-2 and p53, the proposed upstream effector of these molecules, as potential prognostic markers in stage III colon cancer treated by adjuvant chemotherapy. Methods: 188 patients with UICC stage III colon carcinoma who had received a median of 12 cycles of 5-fluorouracil (FU)-based adjuvant chemotherapy (5-FU/folinic acid or 5-FU/levamisole) were enrolled. Median follow-up was 84.5 months. Protein expression patterns of BAX, Bcl-2, and p53 were analyzed by immunohistochemistry on sections of resected tumor samples. Results: BAX, Bcl-2 and p53 expression were high or positive in 59%, 70% and 50% of 188 cases, respectively. BAX was correlated with a higher degree of differentiation (p=0.01), whereas Bcl-2 was associated with left-sided tumors (p=0.03). In contrast to either p53 or Bcl-2, low BAX, advanced N-category, low grade of differentiation and treatment with 5-FU/levamisole were univariately associated with poorer disease-free (DFS) (p=0.0005, p=0.001, p=0.005, and p=0.01, respectively) and disease-specific overall survival (OS) (p=0.002, p=0.0001, p=0.003, and p=0.02, respectively). Besides N category and treatment arm, BAX was an independent variable related to both OS and DFS (p=0.003 and p=0.001, respectively). The p53 -/BAX high pattern in comparison with the p53 +/BAX high subgroup confered an significantly improved DFS (p=0.03), and an marginally improved OS (p = 0.07). Conclusions: BAX may be of central significance for clinical outcome to 5-FU-based adjuvant chemotherapy in stage III colon cancer, and bivariate analysis of p53/BAX possibly may provide further prognostic evidence. No significant financial relationships to disclose.
Patterns and predictors of locoregional recurrence following neoadjuvant chemoradiation for esophageal cancer.
Authors: Aaron Udell Blackham, Will Jin, Khaldoun Almhanna, Jacques-Pierre Fontaine, Sarah E. Hoffe, Jessica M. Frakes, Puja Venkat, Jose Mario Pimiento
Journal: Journal of Clinical Oncology (2016)

173 Background: Despite neoadjuvant chemoradiation (nCRT) followed by esophagectomy for locally advanced esophageal cancer, locoregional recurrences (LRR) are common. Specific risk factors for LRR have yet to be identified. Methods: Patients with esophageal cancer who were treated with nCRT and esophagectomy were identified from a single institution, prospectively maintained database(1996-2013). Timing and locations of recurrences were described and predicting factors of LRR were analyzed. Results: Out of 456 patients treated with nCRT for esophageal cancer, 167 patients developed known recurrence. Locoregional and distant recurrences were observed in 69(15.1%) and 140(30.9%) patients, respectively. Median recurrence-free survival was 38.5 months with a median follow-up of 30.4 months. Sixty-eight patients(40.7%) developed recurrence at multiple sites. The median time to recurrence was 13.5 months and survival following recurrence was only 8.0 months in the 27 patients(16.2%) with solitary LRR. Overall survival in patients with solitary LLR was 23.6 months, compared to 20.8 months in all patients who developed distant recurrence. Univariate analysis identified lymph node ratio &gt; 0.5(OR 2.42, p = 0.030), non-complete pathologic response(OR 1.90, p = 0.022), positive margins(OR 3.58, p = 0.028) and lymphovascular invasion(OR 2.82, p = 0.001) as significant predicting factors for LRR. While perineural invasion(p = 0.055), nodal stage(0.053) and use of adjuvant therapy(p = 0.060) approached significance, other factors such as tumor stage, type of surgery (Ivor-Lewis vs transhiatal), radiation dose and use of IMRT were not significant predictors of LRR. Only lymphovascular invasion was an independent predictor of LRR. Conclusions: Prognosis following LRR in patients with esophageal cancer treated with nCRT is poor but is better than in patients who develop distant recurrence. High lymph node ratio, positive margin status, non-complete pathologic response and the presence of lymphovascular invasion are predictive of LRR following nCRT for esophageal cancer.
Hallmarks of Alzheimer’s Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain
Authors: Ira Espuny-Camacho, Amaia M. Arranz, Mark Fiers, An Snellinx, Kunie Ando, Sebastian Munck, Jerome Bonnefont, Laurie Lambot, Nikky Corthout, Lorna Omodho, Elke Vanden Eynden, Enrico Radaelli, Ina Tesseur, Selina Wray, Andreas Ebneth, John Hardy, Karelle Leroy, Jean-Pierre Brion, Pierre Vanderhaeghen, Bart De Strooper
Journal: Neuron (2017)
Phase II trial of maintenance daily oral thalidomide in patients with extensive-stage small cell lung cancer (ES-SCLC) in remission
Authors: M. M. Cooney, S. Subbiah, R. Chapman, A. Ness, K. Rutherford, G. Warren, J. Saltzman, T. Mekhail, N. Levitan, A. Dowlati
Journal: Journal of Clinical Oncology (2005)

7166 Background: The prognosis of patients with ES-SCLC remains poor despite a high initial response to chemotherapy. Cooperative group trials have shown in general a median survival of 9 months and a 1-year survival of 35% (E7593). Thalidomide has been shown to have antiangiogenic activity in preclinical models and angiogenesis is biologically important in SCLC. Methods: Patients who have achieved a partial or complete response to induction chemotherapy for ES-SCLC were enrolled on a multicenter phase 2 clinical trial. Thalidomide was given at a fixed dose of 200 mg orally daily until disease progression. Patients had to start thalidomide within 3–6 weeks of completion of initial chemotherapy. Sample size calculation was based on the ability to demonstrate a 60% survival rate at 1 year (20% more than historical controls). A total of 30 evaluable patients are needed per design. Results: As of 12/6/04 twenty-two patients have been enrolled. Median age is 63 (51–78). Initial first line chemotherapy consisted of cisplatin or carboplatin with etoposide in 20 pts and cisplatin/irinotecan in 2 patients. All patients had achieved a partial response to induction chemotherapy with no complete responses. Toxicity has been minimal. Two episodes of grade 1 neuropathy and 2 cases of grade 1 constipation were reported. One patient was removed from trial for pulmonary embolism. Eighteen patients are currently evaluable for survival analysis. Overall survival is 15.7 months with a 1-year survival of 60%. Conclusions: Our initial data using thalidoimde as maintenance therapy for ES-SCLC in remission are encouraging and accrual is continuing. Updated data will be presented at ASCO. No significant financial relationships to disclose.
Low Risk of Infectious Events in Patients (Pts) with Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) Treated with Dasatinib.
Authors: Ali M Al -Ameri, Hagop Kantarjian, Elizabeth Burton, Susan O'Brien, Farhad Ravandi, Gautam Borthakur, Brenda Walker, Mary Bath Rios, Jorge Cortes
Journal: Blood (2009)