tbuckley/cabot-search huggingface dataset:
Circulating tumor cells as a prognostic factor independent of obesity in metastatic breast cancer patients.
Authors: M. Giuliano, A. Giordano, A. Patt, L. Hsu, R. H. Alvarez, N. T. Ueno, V. Valero, G. N. Hortobagyi, M. Cristofanilli, J. M. Reuben
Journal: Journal of Clinical Oncology (2011)

610 Background: Breast cancer is now recognized to be a heterogeneous disease with differences in outcome among various molecular subtypes. Approximately 30-40% of patients diagnosed with primary breast cancer eventually die of recurrent disease indicating the need for identification of prognostic factors. Several retrospective studies suggested that obesity adversely affects outcome particularly in hormone-receptor (HR) positive early breast cancer. Detection of circulating tumor cells (CTCs) by CellSearch before treatment is an independent predictor of survival in metastatic breast cancer (MBC). We therefore investigated the value of CTCs and body mass index (BMI) as independent prognostic factors in MBC. Methods: We retrospectively analyzed 255 consecutive MBC patients treated between 2004 and 2010 who had baseline CTC enumeration by CellSearch and BMI measurements. OS was calculated from the date of CTC measurement and analyzed with Kaplan-Meier survival plots. Patients with a BMI ≥ 30 were considered as obese. Cox multivariate proportional hazards model was also performed. Results: At a median follow-up of 24.6 months, 132 (51.7%) patients had died. Among all patients, 92 (36.1%) had CTCs ≥ 5 and 81 (31.8%) were obese. Median BMI was 26.4 kg/m2 (range 15.9 - 56.8) and all collected within 1year from CTC assay. We found a BMI ≥ 30 only in patients with age >50 years (P = .022). Patients with CTCs ≥ 5 had a higher risk of death than patients with CTCs < 5 (hr =1.78, 95% CI 1.27 – 2.51); the same difference according CTC value was observed both in normal and obese patients. In the HR+/HER2-subtype (n = 129), obese patients had the same risk of death as normal patients (obese patients hr = .77, 95% CI .44 - 1.35). In the multivariate model, considering age, HR and HER2 status, metastatic disease sites and obesity, patients with CTCs ≥ 5 had a hazard ratio of death of 2.01 (95% CI 1.41-2.87) compared with patients with CTC < 5. Conclusions: This study confirms the use of CTCs in MBC as a useful tool for the prediction of OS independent of obesity. Moreover, the data suggest a lack of prognostic value of obesity in women with metastatic disease, including endocrine-sensitive disease.
Diagnostic and therapeutic workup of patients with hematuria: Analysis of 1048 consective patients in a German outpatient service.
Authors: Andreas Eisenhardt, Daniel Heinemann, Christian Niedworok, Hebert RÃƒÂ¼bben
Journal: Journal of Clinical Oncology (2016)

399 Background: The diagnostic workup of patients with hematuria especially microhematuria is discussed controversially. For this reason the diagnostic and therapeutic procedures of 1049 patients with hematuria referred to our urological outpatient service in the years 2011-2012 were analysed. Methods: A number of 1049 consecutive patients with hematuria referred to the outpatient service Praxisklinik Urologie Rhein-Ruhr in the years 2011-2012 were retrospectively included into the analysis. The following parameters were measured: demographic data, concomittant diseases, clinical symptoms regarding the urinary tract, history of cancer or radiation of the pelvis, diagnostic and therapeutic procedures. Results: The median age was 58 years and the study group comprised 479 men and 570 women. A number of 160 patients had a urinary tract infection within 4 weeks of presentation and 89 individuals presented with macrohematuria. Symptoms of urolithiasis occured in 148 patients. All patients had ultrasound of the genitourinary tract and 731 were examined by excretion urogram, 111 patients via CT-scan of the abdomen and 888 individuals via urethrocystoscopy. Further workup revealed 77 stones via radiological examination and a total of 11 renal cell cancers, 57 papillary urothelial tumors of the bladder, 1 tumor of the ureter and 6 muscle-invasive bladder tumors were detected. Conclusions: Our data presented here reassures invasive diagnostic workup of patients with hematuria due to the fact that cancer of the genitourinary tract is detected in more than 5 percent of patients.
All patients with colorectal cancer should be tested for genetic condition, NICE advises
Authors: Anne Gulland
Journal: BMJ (2017)

Everyone who has colorectal cancer diagnosed should be tested for an inherited genetic condition called Lynch syndrome, new guidance states.1

The National Institute for Health and Care Excellence (NICE) recommends microsatellite instability testing or immunohistochemistry to detect abnormalities that may indicate the syndrome.

Lynch syndrome, the most common cause of hereditary bowel cancer, has also been linked to an increased risk of developing other cancers including womb, ovarian, and stomach. People with the condition who develop colorectal …
Fulvestrant in heavily pretreated ER-positive postmenopausal metastatic breast cancer patients: A phase II study
Authors: R. Ratti, Z. Coccorullo, D. Guarneri, G. Addamo, G. Colloca, A. Venturino, E. Campora
Journal: Journal of Clinical Oncology (2008)

1144 Background: Fulvestrant (F), an estrogen receptor down-regolator drug, has been demonstrated to be effective in ER +ve postmenopausal metastatic breast cancer (MBC) progressing on tamoxifen (Howell A., 1995) and phase III trials have shown that response rates, TTP e OS are comparable to those obtained with anastrozole (Howell A., 2000 and Mauriac L., 2003). Methods: The aim of the study was to evaluate efficacy and toxicity of F in ER+ve post-menopausal metastatic breast cancer patients (MBC pts) heavily pre-treated both with hormonal agents and chemotherapy. From 5/2006 to 10/2007 22 pts. in this setting, were treated with F 250 mg i.m. q 28 days. Results: All pts, median age 63 (range 39–81), had received prior anthracycline and taxane-based chemotherapy and had been treated with a median of 2 chemotherapy regimens (range 1–5), and a median of 3 hormonal agents (range 1–4). Sites of MBC were: 13 bone, 2 liver, 4 lung, 1 CNS, 5 nodes, 3 skin, 4 breast. The 22 pts received a total of 117 cycles of F: median 6 cycles/pt. (range 1–19+). All pts were valuable for toxicity and 19/22 for efficacy. Overall response rate (OR) was 4/19 (21%) (0CR, 4PR) and SD was observed in a further 4 pts (21%); clinical benefit (response+SD) was observed in 42,1% (8/19) of pts. Median TTP in all pts was 4+ mos (range 0,5–16+ mos.) and in pts obtaining clinical benefit was 7+ mos (range 2–16+mos). Median OS in the 22 pts was 7+ mos. (range1–16+ mos) and 12+ mos. (range 2–16+) in pts with clinical benefit. No G3–4 toxicities were observed: G1–2 cutaneous rash occurred in 3/22 (13.6%) pts. and G1–2 asthenia in 3/22 (13.6%) pts. Conclusions: F can be safely administered to heavily pre-treated ER+ve post-menopausal MBC pts. Although phase III trials are lacking, results from this phase II study are comparable with the results obtained in pivotal trials when F was used as 2nd-line treatment, suggesting that F could have comparable efficacy in heavily pretreated MBC pts. No significant financial relationships to disclose.
Prescribing patterns for bevacizumab in first-line metastatic colorectal cancer: Exploring the introduction of a new drug into routine clinical practice.
Authors: Kathryn Maree Field, Jayesh Desai, Jeanne Tie, Suzanne Kosmider, Susie Bae, Joseph James McKendrick, Michael Harold, Peter Gibbs
Journal: Journal of Clinical Oncology (2012)

665 Background: Clinical trials support the addition of bevacizumab (Bev) to first line chemotherapy for metastatic colorectal cancer (mCRC). However, given that there are alternate biological agents that can be used with chemotherapy; and rare but potentially serious toxicities with Bev, there has been variable use of the drug in routine care. The purpose of this study was to prospectively explore 1 st line use of Bev in routine clinical care. Methods: A multi-site data collection was initiated in July 2009 when Bev became publicly available in Australia. A particular focus was capturing information regarding clinician decision-making that is not routinely recorded or is often poorly documented. Comprehensive comorbidity data was collected, along with specific factors, both patient (pt) and disease-related, that may impact on treatment decisions. Major adverse events that may be related to Bev were also recorded. Results: For the 2-year period from July 2009-June 2011, a database search identified 278 pts diagnosed with mCRC at five participating hospitals. 240 pts (86%) had received 1 st line chemotherapy. 102 (43%) also received Bev, the majority in combination with oxaliplatin based chemotherapy (n = 81, 79%). Bev use increased significantly from 40.4% (34/84) of all pts receiving chemotherapy in July-December 2009, to 65.8% (25/38) in January-June 2011 (p=0.0114). Overall the most frequent reasons for clinicians advising against the use of Bev were a bleeding or asymptomatic primary in situ (n=28, 23%), known hypertension (n=14, 11%), clinical trial participation (n=14, 11%), poor performance status (n=9, 7%), and perceived risk of arterial ischemic event (n=8, 6.5%). There have been four episodes of gastro-intestinal perforation, 3 in pts receiving Bev (2.9% of Bev treated patients). Conclusions: Bev use in first line mCRC has significantly increased over time, presumably as further positive safety data emerges regarding safety in older and frailer pts, and clinician prescribing experience increases. The major grounds for not using Bev in the 1 st line mCRC setting were specific clinical contexts where the risk of adverse events may be increased.
Epidemiological features of patients with breast cancer treated in a private oncologic center from Brazil.
Authors: N. Teich, R. C. Helal, L. H. De Lima Araujo, M. R. A. Schaum, A. P. O. Victorino, J. H. Salem, B. C. V. Silva, A. N. Almeida, D. D. Corrêa, F. M. Vieira, C. G. M. Ferreira
Journal: Journal of Clinical Oncology (2011)

e12023 Background: Breast cancer is the most common female cancer in Brazil and is the first cause of death from cancer among women. Studies have shown that there are marked differences between patients treated in private and public health system in Brazil, especially on overall survival, diagnosis and staging. The objective of the present study was to determine, in a real world context, the epidemiological characteristics and outcomes from patients with breast cancer observed in a private oncologic center in Brazil. Methods: Our group report the final analysis of this retrospective registry of 1,134 breast cancer patients treated in a Brazilian private oncologic institution between 1999 and 2009. Results were analyzed with SPSS v17.0, and Kaplan-Meier method was used to estimate overall survival (OS) and progression free survival (PFS). Long-term follow-up was enabled through active surveillance, using telephone contact. Results: In our series, clinical stage I, II, III and IV were 46%, 36%, 15% and 3%, respectively. Median age was 55 years (range 26-92), 78% were hormone receptor positive, and 22% were Her2 positive. Among patients with stage I, II and III, 18% received neoadjuvant treatment, 97% received adjuvant treatment and 3% had no complimentary treatment in addition to the surgical procedure. After a median follow-up of 39.1 months, the 5-year OS was 96%, 93%, 71%, and 0% for stages I, II, III, and IV, respectively. The median OS was not reached in stages I and II, and 133 and 27 months for III and IV. The 5-year PFS was 93%, 88%, and 65%, for stages I, II, and III, respectively. Conclusions: Our findings are consistent with current worldwide literature and reveal that patients with breast cancer treated in a private oncologic center in Brazil had similar outcomes to those treated in developed countries.
Pancreas resection for unresectable locally advanced pancreatic cancer (LAPC): Resection rate in the era of FOLFIRINOX and GEM+nabPTX.
Authors: Shinichiro Takahashi, Masafumi Ikeda, Naoto Gotohda, Yuichiro Kato, Masaru Konishi
Journal: Journal of Clinical Oncology (2016)

317 Background: Resection for unresectable LAPC after down-staging by chemo(radio)therapy sometimes leads to long-term survival in highly selected pts. However, neither the pts who have best possibility for resection nor resection rate according to the specific treatment were elucidated in LAPC. Methods: A retrospective single-institutional study. From a prospective database, 130 pts received any treatment for LAPC from Jan. 2010 to Mar. 2015 were identified. Main criteria for unresectability were tumor contact with superior mesenteric artery, celiac axis or common hepatic artery &gt; 180°, aortic involvement, and unreconstructible portal vein /superior mesenteric vein due to marked invasion. All MDCT findings before and during treatment of 130 pts were reviewed to check the resectability by a surgeon. Conversion rate to resection according to treatment and situation of tumor-vessel contact before treatment were analyzed. Conversion was considered when tumor was down-staged to borderline resectability. Results: Of 130 pts, gemcitabine (GEM) was administered as initial treatment to 75; GEM and erlotinib to 18; modified FOLFIRINOX to 15; S-1 and concurrent radiotherapy (S1/RT) to 12; GEM and nab-paclitaxel (GEM+nabPTX) to 4; and other regimens to 6. Six patients underwent resection after down-staging. Of the 6 pts (4.6%), 4 received S1/RT, and 1 each received GemErlo and FOLFIRINOX. Furthermore, 7 pts (5.4%) seemed to deserve further examination to check resectability because marginal resectability was shown in follow up MDCT during treatment. Resection rates among treatments were not different significantly. On the other hand, unresectability because of single-vessel invasion and the tumor-vessel contact less than 360° at the same time before treatment showed best opportunity for conversion to resection. The 6 resected pts (MST 30m) showed marginal superiority over unresected 124 pts (MST 16m) in survival (p = 0.17). Conclusions: Resection rate of LAPC did not increase significantly even after FOLFIRINOX or GEM+nabPTX treatment. Pts with LAPC due to single tumor-vessel contact less than 360° have best chance of convert to resection after effective treatment.
Prognostic factors in advanced gastric cancer after second-line treatment.
Authors: FEDERICO LONGO, Vanessa Pachon, Carmen Guillen, Reyes Ferreiro, Mercedes Rodriguez Garrote, Pablo Reguera Puertas, Ainhoa Madariaga, Maria Gion, Pedro Lopez Hervas, Julio Galindo, Eva Gonzalez Lizarbe, Constantino Varona, Jose Montans, Julie Earl, Enrique Grande, Maria Eugenia Olmedo Garcia, Pilar Garrido, Eduardo Lobo, José Palacios, Alfredo Carrato
Journal: Journal of Clinical Oncology (2015)

201 Background: Advanced gastric cancer (AGC) is a highly lethal disease worldwide with a median overall survival (OS) of less than 12 months. Ramucirumab was the first targeted agent to show survival benefit in the second-line (2L) treatment of AGD. From the REGARD trial, women exhibited a trend towards a worse survival when compared to men. Methods: We retrospectively analyzed the outcome of a Spanish cohort of 55 AGC patients who had received at least two consecutive chemotherapy lines of treatment at our institution. We preselected some clinical parameters (age, gender, Lauren subtype, Her-2 status, grade of differentiation, primary tumor localization and resection, TNM stage, neoadjuvant/adjuvant administration, mono/polychemotherapy in 2L, irinotecan- or taxane-based 2L, Trastuzumab treatment, and administration of third-lines [3L]) to be tested as potential prognostic factors. We focused our analysis on the gender effect in OS after 2L treatment in AGC. The SPSS software package was used for all statistical analyses (Mann-Whitney U test, Chi Square, Kaplan-Meier, Cox regression). Results: Women, diffuse subtype, poorly differentiated tumors, sub-cardia location, single-agent 2L and 3L administration were the clinical characteristics with a significant shorter OS by the univariable analysis. Median OS of women (5 months, 95%CI 3.9-6.0) was significant lower than that in men (13 months, 95%CI 7.9-18.0) by both Log-Rank and Breslow tests (p 0.002). We found no significant differences in age, progression-free survival or time-on-treatment between men and women. Female gender was significantly associated with more taxane-based 2L and with less 3L treatment administration. When 3L treatment administration was excluded in the multivariable analysis, female gender was the only independent prognostic factor of all the clinical parameters included in our review (HR 0.33, 95%CI 0.15-0.75, p 0.008). Conclusions: Our retrospective study found that gender, Lauren subtype, grade of differentiation, primary tumor location, polychemotherapy and 3L administration may be potential prognostic factors in AGC after 2L treatment. Female gender was an independent prognostic factor in our Spanish cohort.
Prospective study on incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer (CSP-HOR13).
Authors: N. Katakami, A. Hata, H. Kunikane, K. Takeda, K. Eguchi, K. Takayama, T. Sawa, H. Saito, M. Harada, S. Yokota, K. Ando, Y. Ohashi
Journal: Journal of Clinical Oncology (2011)

7545 Background: Although the overall incidence of BM is not known, bone metastases are a frequent complication in pts with advanced lung cancer. Bone metastases can be associated with SREs, which include pathologic fracture, need for surgery or radiation to bone, spinal cord compression, and hypercalcemia of malignancy. The aim of our study is to investigate prospectively the incidence of BM, the incidence and types of SREs, time interval between BM and SREs, influence of SREs on QOL, and predictive factor of SREs. Methods: Eligibility criteria for enrolment were a newly diagnosed pt with stage IIIB or IV lung cancer, age over 20 years old, written informed consent. Staging of lung cancer required CT scan of the chest and upper abdomen, bone scan or PET scan, and CT or MRI scan of the brain. Pts were closely followed up every 4 weeks to see if they developed SREs. During the follow up period the pts underwent CT scan of the chest and upper abdomen every 4 weeks, CT or MRI scan of the brain and bone scan or PET scan every 6 months. A QOL questionnaire was carried out at enrollment, 3 months and 12 months. Treatment for lung cancer and use of zoledronate were at the discretion of the investigator. Results: Two hundred and seventy four pts were enrolled into the study between Apr. 2007 and Dec. 2009 from 12 institutions. Median age was 68 years, small cell/non-small cell=77/197, IIIB/IV=73/124, M/F=193/81, PS 0/1/2/3-4=76/171/23/4. Median follow up time was 10.3 months (0-27.2 months). Seventy eight of 124 pts with stage IV (62%) already had BM at the time of enrollment. Twenty four of 78 pts with known BM (31%) had some kind of SREs concomitantly. Additional 11 pts developed SREs during follow up time and the total incidence of SREs was 45%. Thirty one of 196 pts without initial BM (15%) developed bone metastases, and 14 of these 31 pts developed SREs during the follow up period. The type of SREs was pathologic fracture 4.7%, radiation to bone 15.3%, spinal cord compression 1.1% and hypercalcemia 2.2%. Conclusions: The incidence of BM at initial diagnosis was 62% and was higher than initially expected. Various SREs developed in 17 % of all the pts during the follow up period.
Phase II study of combination of the hyperCVAD regimen with dasatinib in patients (pts) with newly diagnosed Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL)
Authors: F. Ravandi, S. Faderl, D. A. Thomas, D. Brown, R. Garris, G. Borthakur, A. Ferrajoli, J. E. Cortes, H. M. Kantarjian, S. M. O'Brien
Journal: Journal of Clinical Oncology (2008)

7020 Background: Combination of cytotoxic chemotherapy with imatinib has improved the outcome for pts with Ph+ ALL. Dasatinib is a significantly more potent BCR-ABL inhibitor and is effective in pts with Ph+ ALL. Methods: Pts with newly diagnosed Ph+ ALL were treated with dasatinib 50 mg po bid for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate. Pts in CR continue to receive maintenance dasatinib 50 mg po twice daily indefinitely, and vincristine and prednisone monthly for 2 yrs. Results: To date, 20 pts have received a median of 5 cycles (range, 1–8); 8 pts are receiving maintenance in CR. Median age is 55 yrs (range, 23 - 79); 16 pts were > 50 yrs. Median WBC at diagnosis was 4.7 x 109/L (range, 0.8 - 203.4 x 109/L). Four pts had CNS involvement at diagnosis. Nineteen pts are evaluable for response assessment; one pt is too early. Seventeen pts (90%) have achieved CR after the first cycle; 2 pts died before response assessment from infections. Fourteen of 17 (82%) pts have achieved cytogenetic (CG) CR after 1 cycle; 2 had a major CG response (5% and 15% Ph+) and one is unknown (no CG exam on day 21). Five pts (29%) have achieved complete molecular remission (CMR) after the first cycle with the BCR-ABL/ABL in the other pts ranging from 0.01 to 73.71. Overall, 9 (47%) patients have achieved CMR and an additional 5 (26%) have achieved a major molecular response (MMR) with the lowest BCR-ABL/ABL ranging from 0 - 10.73. The median time to neutrophil and platelet recovery for cycle 1 is 18 and 24 days and for subsequent cycles is 15 and 21 days. Grade 3/4 toxicity included GI bleeding, infections, hypophosphatemia, hypocalcemia, elevated transaminases, and elevated creatinine. With a median follow up of 7 mths (range, 1–15), 16 pts are alive and 13 are in CR; 2 died during induction, 1 died in CR from an unrelated cardiac event, and 1 died in CR from infection. Two pts have relapsed (response durations were 54 weeks and 32 weeks); one relapsed with a T315I mutation and had previously achieved a MMR. One pt is too early for response assessment. Conclusions: The combination of the hyperCVAD regimen with dasatinib can achieve a high CR rate and molecular remissions in pts with newly diagnosed Ph+ ALL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Downregulation of GATA1 drives impaired hematopoiesis in primary myelofibrosis
Authors: Laure Gilles, Ahmet Dirim Arslan, Christian Marinaccio, Qiang Jeremy Wen, Priyanka Arya, Maureen McNulty, Qiong Yang, Jonathan C. Zhao, Katerina Konstantinoff, Terra Lasho, Animesh Pardanani, Brady Stein, Isabelle Plo, Sriram Sundaravel, Amittha Wickrema, Annarita Migliaccio, Sandeep Gurbuxani, William Vainchenker, Leonidas C. Platanias, Ayalew Tefferi, John D. Crispino
Journal: Journal of Clinical Investigation (2017)

Primary myelofibrosis (PMF) is a clonal hematologic malignancy characterized by BM fibrosis, extramedullary hematopoiesis, circulating CD34+ cells, splenomegaly, and a propensity to evolve to acute myeloid leukemia. Moreover, the spleen and BM of patients harbor atypical, clustered megakaryocytes, which contribute to the disease by secreting profibrotic cytokines. Here, we have revealed that megakaryocytes in PMF show impaired maturation that is associated with reduced GATA1 protein. In investigating the cause of GATA1 downregulation, our gene-expression study revealed the presence of the RPS14-deficient gene signature, which is associated with defective ribosomal protein function and linked to the erythroid lineage in 5q deletion myelodysplastic syndrome. Surprisingly, reduced GATA1 expression and impaired differentiation were limited to megakaryocytes, consistent with a proproliferative effect of a GATA1 deficiency on this lineage. Importantly, expression of GATA1 effectively rescued maturation of PMF megakaryocytes. Together, these results suggest that ribosomal deficiency contributes to impaired megakaryopoiesis in myeloproliferative neoplasms.