tbuckley/cabot-search huggingface dataset:
A randomized study of adjuvant chemotherapy for malignant phyllodes tumours of the breast
Authors: F. Morales-Vasquez, A. M. Gonzalez-Angulo, H. N. López-Basave, D. Córtes, K. Broglio, A. Alvarado, D. Gallardo, A. Mohar, J. Delagarza, G. N. Hortobagyi, F. Lara
Journal: Journal of Clinical Oncology (2005)

574 Background: Phyllodes tumors of the breast (PTB) are uncommon stromal-epithelial neoplasms. Surgical remove is the treatment mainstay, but despite adequate resection, the risk of recurrence in the malignant form is as high as 40%. The effectiveness of adjuvant therapy in this histological type is unclear. The purpose of this study was to evaluate the role of adjuvant chemotherapy in malignant PTB treated at the National cancer Institute of Mexico. Methods: Twenty-eight patients with malignant PTB enrolled from 02/1993 to 09/2003 were randomized to receive 4 cycles of adjuvant chemotherapy (doxorubicin 50 mg/m2 IV 48 hr infusion and dacarbazine 600 mg/m2 IV 48 hr infusion), (n=17), versus observation, (n=11). All patients had surgical resection, 38% of them, had an axillary dissection. Seven patients (25%) received adjuvant radiotherapy. Patient and tumor characteristics were similar between the 2 groups. Log-rank test was used to test for differences in recurrence-free survival (RFS). Results: Median age was 42 years, (range 26–76). Median tumor size was 13 cm, (range 3–30 cm) and 53% of the tumors were in the left breast. At a median follow-of of 44 months (range 1–139 months), there were 7 recurrences and 5 deaths. Five-year RES rate was 58% for the patients who received adjuvant therapy and 86% for the patients who did not, (p=0.17). Median survival after recurrence was 6.5 months. Conclusions: Malignant PTB is a rare entity. Failure rate for this group was lower than described in the literature. Adjuvant chemotherapy with doxorubicin and dacarbazine did not impact patient survival. Future studies to identify relevant molecular target should be implemented in order to define effective therapies for these tumors. No significant financial relationships to disclose.
Phase I/II study of weekly docetaxel in patients with previously treated non-small cell lung cancer (NSCLC)
Authors: T. Hirata, F. Kawashita, E. Ogawa, K. Masago, M. Kato, M. Takada
Journal: Journal of Clinical Oncology (2004)

7243 Objective: Docetaxel is useful in the treatment of previously treated non-small cell lung cancer (NSCLC). However adequate treatment schedule is not well established. To assess the maximum-tolerated dose (MTD), dose limiting toxicity(DLT), and tumor response, we conducted a phase I/II trial of weekly docetaxel treatment in previously treated NSCLC patients (pts). Patient and Method: Eligibility criteria of pts included were histologically confirmed, relapsed tumor (phase I) and NSCLC (phase II), ECOG PS 0–1, adequate organ functions, measurable disease (phase II). Docetaxel was administered weekly for 3 consecutive weeks every 4 weeks. Patients were treated at the following dose levels; 25, 30, 35, 40 mg/m2 /wk (phase I). DLT was defined as grade (G) 4 neutropenia > 4 days, neutropenic fever, G 4 thrombocytopenia > 4 days, any nonhematologic G 3 or 4 toxicity with the exception of alopecia, nausea and vomiting, dose held for hematologic toxicity of grade 3 or 4 on days 8 and 15. The MTD was determined when greater than one third of patients experienced DLT at a given dose. Results: Thirty-nine patients were enrolled. Patient characteristics: NSCLC/small cell lung cancer/breast cancer: 29/6/4, median age 62 range (42–72), male/female 20/19, PS 0/1: 10/29,. The DLT of this weekly schedule was leukopenia. The MTD was 40mg/m2 /wk, so that recommend dose for phase II study was 35mg/m2/wk. There were no complete responses. Two patients had a partial response (overall response rate, 10%). Frequent hematologic toxicities were neutropenia (G 3/4, 21%) and leukocytopenia (G 3/4, 21%). Frequent nonhematologic toxicities were nausea, neuropathy and hair loss, but these side effects did not exceed grade 2. These toxicities were moderate and transient without no specific supportive cares. Conclusion: Second-line weekly schedule of docetaxel has less toxic and compatible activity with the previously reported three weeks schedule. No significant financial relationships to disclose.
Complete response of bone-only metastatic breast cancer to skeletal: Targeted radiotherapy with <sup>166</sup>HOLMIUM-DOTMP
Authors: D. J. Booser, N. T. Ueno, G. Rondon, P. A. Williams, R. Wendt, G. N. Hortobagyi, D. A. Podoloff, R. E. Champlin
Journal: Journal of Clinical Oncology (2005)

569 Background: The skeleton is the most common and sometimes the only site of metastatic disease in breast cancer. We tested the feasibility of using 166Ho-DOTMP, which localizes to bone surfaces to deliver targeted high-dose radiation to bone metastases and the adjacent marrow. Patients received autologous stem cell infusions to restore hematopoiesis. Methods: Six women < 65 years old with breast cancer and bone-only disease participated in the study. They had received a median of 2.5 prior chemotherapy or hormonal treatment regimens. Five patients had stable disease and one patient had progressive disease before the high-dose radiation. A 30-mCi test dose of 166Ho-DOTMP was given to assess skeletal uptake; if uptake was adequate, a therapeutic dose estimated to deliver 22 Gy (n=3) or 28 Gy (n=3) was prescribed. Treatment was followed by autologous stem cell transplantation when the ongoing radiation dose to the marrow was < 1 cGy/hour. Results: 870–2065 mCi 166Ho-DOTMP dose was administered.? All subjects showed prompt trilineage hematologic recovery. The most common toxicity was mild nausea. None of the patients experienced grade 3–4 acute toxicity other than the expected myelosuppression. Two patients developed hemorrhagic cystitis 2 years after therapy, which resolved in both patients. One of these patients also had gastrointestinal bleeding and pseudomembranous colitis. One subject develops myelodysplastic syndrome but had trisomy 8 before treatment. Two patients remain progression-free without evidence of disease (complete response) for more than 5 years after study entry; 4 experienced disease relapse (all at extraosseous sites), and died of progressive disease. Median time to progression was 10 months. Conclusions: 166Ho-DOTMP had an acceptable toxicity profile, and two of the six heavily pretreated patients achieved sustained complete response. A phase II study is planned to evaluate the efficacy of this strategy for treatment of bone metastases. No significant financial relationships to disclose.
Clinical outcome of metastatic melanoma involving the CNS with or without (w/o) intracranial hemorrhage (IHC)
Authors: T. Cheng, J. N. Scott, B. Eigl, P. Corbett, G. McKinnon
Journal: Journal of Clinical Oncology (2007)

8577 Background: Melanoma has a high rate of ICH associated with CNS metastasis (mets). There is no data on the clinical outcome of these patients (pts) in the literature. Methods: A retrospective review of 52 pts with melanoma CNS mets diagnosed from 11/2001 to 09/2006 at our institution. Two pts were excluded due to a second malignancy. The clinical, radiological, and pathological characteristics of these pts were reviewed. Results: 39 pts were diagnosed after onset of neurological symptoms and 11 were diagnosed during staging. Of these, 14 (28%) were solitary, 23 (46%) were = 4, and 13 (26%) were multiple brain mets. Mean age at brain mets diagnosis was 55 years (range 24–88). Mean follow-up was 25 months (mos) (range 3–61) and 64% were male. ICH was found in 22 pts (44%) with 13 pts (26%) having frank hemorrhage on cranial CT and/or MRI scan. ICH was less common (9%) in pts with brain mets diagnosed on staging. 11 pts (8 with ICH, 3 w/o ICH) underwent CNS mets resection through craniotomy followed by whole brain radiation (WBRT) and/or stereotactic radiotherapy (STR). 7 pts received best supportive care. The remaining pts received WBRT and/or STR. The median survival (MS) for the entire group from CNS mets diagnosis was 7.6 mos. For pts with ICH, overall MS was 9.6 mos with MS of 21.2 mos for pts who underwent craniotomy vs 2.9 mos for pts w/o craniotomy. One pt refused therapy and later died from frank ICH. For pts w/o ICH, overall MS was 6.0 mos with MS of 21.3 mos for pts who underwent craniotomy vs 4.2 mos for pts w/o craniotomy. Pts who underwent craniotomy followed by WBRT and/or STR fared the best with MS of 21.2 mos. Of these, 2 pts with solitary brain mets (1 with ICH, 1 w/o ICH) were alive with no relapse at 58 and 53 mos respectively. The cause of death was disease progression in almost all pts and 85% of pts died from CNS disease progression. One pt died from post-operative complications of craniotomy. Conclusions: ICH by itself is not associated with a negative clinical outcome with appropriate clinical management. Aggressive surgical resection followed by radiotherapy in selected pts improves clinical outcome with prolonged survival possible in a minority of pts. No significant financial relationships to disclose.
Human Embryonic Stem Cell-Derived Mesenchymal Stroma Cells (hES-MSC) Share Basic Properties with Bone Marrow MSC, They Have Potent Stroma Support Capacities but Lack Immune-Modulatory Function. Implications for off-the Shelf ES-MSC Therapies.
Authors: Ou Li, Ariane Tormin, Jan Claas Brune, Berit Sundberg, Johan Hyllner, Katarina Le Blanc, Stefan Scheding
Journal: Blood (2010)
Relationship of YKL-40 protein expression in pulmonary adenocarcinoma and prognosis.
Authors: I. Thöm, K. Schmid, I. Burkholder, J. S. Johansen, C. Bokemeyer, U. Schumacher, E. Laack
Journal: Journal of Clinical Oncology (2010)

e18129 Background: YKL-40 (CHI3L1) is synthesized both by cancer cells and tumor-associated macrophages and plays a functional role in tumor progression. High YKL-40 serum levels have been associated with poor prognosis in patients with several cancer types including non-small cell lung cancer (NSCLC). YKL-40 protein expression has been investigated by immunhistochemistry in several cancer types but not in NSCLC. The aim of the present investigation was to analyze the expression of YKL-40 of pulmonary adenocarcinoma cells. Methods: YKL-40 protein was assessed by immunhistochemistry using a monoclonal antibody against YKL-40 in primary tumors or lymph node metastases of 83 patients with metastatic adenocarcinoma of the lung who underwent surgery between 1999 and 2002. The immunreactivity was assessed by two independent observers using the immureactive score (IRS) according to Stegner and Remmele. YKL-40 IRS was related to tumor stage, progression-free survival (PFS) and overall survival (OS). Results: In 77 cases (93%), the IRS was positive. In most tissues, the staining intensity of the tumor cells was strong (n = 47, 57%) or moderate (n = 30, 36%). The percentage of positive tumor cells was high; in 66 tissues (80%) > 80% of the tumor cells were positive and in 3 tissues only none or < 10% of the tumor cells were positive. There was no correlation between YKL-40 IRS and tumor stage. For survival analysis, 79 patients were evaluable. Median PFS was 11.7 months (range 10.6-16.7 months) and median OS was 20.3 months (range 16.8-30.8 months). There was no difference in PFS and OS depending on the YKL-40 IRS. Conclusions: In pulmonary adenocarcinomas YKL-40 protein expression was found with a strong staining intensity and a high percentage of positive tumor cells. In contrast to serum YKL-40 levels, YKL-40 expression was not correlated with PFS or OS. This is in accordance with the results of YKL-40 protein expression in breast, ovarian and head and neck cancer. No significant financial relationships to disclose.
Survival benefit for <i>BRCA</i>-associated epithelial ovarian cancer (OC) is not explained by primary platinum sensitivity alone
Authors: J. A. Konner, D. J. Gallagher, K. M. Bell-McGuinn, J. Hansen, K. Kosarin, C. A. Aghajanian, K. Offit, R. R. Barakat, D. R. Spriggs, N. D. Kauff
Journal: Journal of Clinical Oncology (2008)

22030 Background: Patients (pts) with BRCA-associated OC appear to have a survival advantage over those with sporadic OC. It is unclear if this is due to a greater platinum sensitivity or a more indolent disease. In order to examine this issue, we investigated platinum sensitivity, DFS and OS in a cohort of stage III-IV ovarian cancer patients with known BRCA mutation status. Methods: We reviewed all stage III-IV non-mucinous ovarian, fallopian tube or primary peritoneal cancer pts who received primary chemotherapy through the Gynecologic Medical Oncology Service at MSKCC between 12/1/1996 and 9/30/2006 and also underwent BRCA mutation testing on one of two prospective follow-up studies conducted by the Clinical Genetics Service. Staging, treatment and follow-up information was obtained by record review. Recurrence was diagnosed by CT scan or rise in CA125. Platinum sensitivity was defined as recurrence at ≥ 6 months after completion of treatment. Impact on time to progression/death was determined by Kaplan-Meier analysis and a Cox proportional-hazards model adjusted for age at diagnosis (< 60, ≥ 60), debulking status (optimal, suboptimal) and platinum sensitivity (sensitive, resistant). Results: BRCA mutation status was available on 111 of 808 stage III-IV pts who received primary platinum based chemotherapy following surgical staging [33 (+), 78(−)]. BRCA (+) pts were younger (56.2 vs 60. 2; p=0.10) and less likely to be optimally debulked (55% vs 64%; p=0.40). 29 of 33 (88%) BRCA (+) and 62 of 78 (82%) BRCA (−) pts had platinum sensitive disease (p=0.58). Median DFS was 27 months in the BRCA (+) patients vs 24 months in the BRCA (−) patients (p=0.49). Median OS in BRCA (−) pts was 67.8 months and was not yet reached in BRCA (+) pts. On multivariate analysis, OS independently correlated with both platinum sensitivity (HR=0.16, 95% CI: 0.07-0.38) and BRCA (+) mutation status (HR=0.30; 95% CI; 0.10-0.88). Conclusion: In this cohort, we demonstrated that both platinum sensitivity and BRCA mutation status were independently associated with OS. These results suggest that additional factors, including possible differences in tumor biology, may account for some of the differential outcome seen between hereditary and sporadic ovarian cancer. No significant financial relationships to disclose.
Effect of mobilization chemotherapy with cyclophosphamide and etoposide on stem cell collection by lenalidomide
Authors: G. Talamo, D. F. Claxton, W. C. Ehmann, J. Mierski, W. Rybka, S. Ibrahin
Journal: Journal of Clinical Oncology (2009)

7096 Background: The combination of dexamethasone and lenalidomide is currently considered one of the standards of care for induction therapy of patients with multiple myeloma (MM) before autologous stem cell transplantation (ASCT). Increasing evidence suggests that lenalidomide impairs the ability to collect peripheral blood stem cells (PBSC). Methods: We retrospectively analyzed the outcomes of PBSC collections of MM patients who received induction therapy with dexamethasone and lenalidomide, and who were collected with either granulocyte-colony stimulating factor (G-CSF) alone, 10–16 mcg/Kg/day (group A, n= 12), or G-CSF 5 mcg/kg/day + mobilization chemotherapy, consisting of cyclophosphamide 5,000 mg/m 2 and etoposide 1,000 mg/m 2 (group B, n=27). In all patients, lenalidomide was stopped 2 weeks before the predicted day of PBSC collection. Results: The median number of PBSC collected was 3.2 million CD34 + cells/Kg in group A (range, 0.3–6.3) and 28.1 million CD34 + cells/Kg in group B (range, 4.8–134) (p&lt;0.01). The median number of days to collect PBSC was 1 in group A (range, 1–4) and 2 in group B (range, 1–5) (p=0.015). Three patients in group A failed to collect an adequate number of PBSC, either for a single ASCT (n=1) or tandem ASCT (n=2). No PBSC collection failures were observed in group B. No difference in the rapidity of PBSC engraftment was seen between the two groups. Conclusions: Chemotherapy with cyclophophamide and etoposide can overcome the inhibitory effect of lenalidomide in the collection of PBSC for ASCT in MM patients. No significant financial relationships to disclose.
A phase 1 study of MORAb-009, a monoclonal antibody against mesothelin in pancreatic cancer, mesothelioma and ovarian adenocarcinoma
Authors: D. K. Armstrong, D. Laheru, W. W. Ma, S. J. Cohen, M. Phillips, J. Brahmer, S. C. Weil, R. Hassan
Journal: Journal of Clinical Oncology (2007)

14041 Background: MORAb-009 is a monoclonal antibody that targets mesothelin, a cell surface adhesive protein overexpressed in pancreatic, ovarian, non-small cell lung carcinomas and mesothelioma and has minimal expression in normal tissue. The target is over-expressed by tumor cells. It was identified as one of the most prominent, differentially expressed cell surface antigens on pancreatic adenocarcinoma using SAGE of primary tumors vs. normal pancreatic tissue. In vitro studies show MORAb-009 to be effective in mediating cell killing by ADCC and inhibiting cell adhesion.. In xenograft models, MORAb-009 has single agent anti-tumor activity enhanced by the addition of chemotherapy. Toxicology studies show no toxicity in non-human primates and no significant binding to non-tumor tissues. Methods: Sequential cohorts of 3 patients received MORAb-009 intravenously on days 1, 8, 15 and 22 at doses of 12.5, 25, 50 and 100 mg/m 2 . Major inclusion criteria are the presence of a mesothelin-positive tumor with progression on primary therapy, acceptable organ function, ECOG PS 0–2, and measurable disease by CT. Safety pharmacology studies include chemistry, hematology, urinalysis and EKG. Tumors were re-imaged at day 35. Results: 11 patients have received MORAb-009 at doses up to 100 mg/m 2 . 6 patients had mesothelioma, 3 had pancreatic cancer and 2 had mesothelin-positive ovarian cancer. 4 patients exhibited grade 1 (3) or 2 (1) infusion reactions; no dose limiting toxicity was observed. A subject in the 50 mg/m 2 cohort with pancreatic cancer who progressed on gemcitabine showed stable disease by CT and a drop in CA 19/9. Based on the response, this patient continues on extended MORAb-009 therapy. Enrollment to the final cohort of 200mgs/m 2 is ongoing, as are pharmacokinetic and anti-MORAb-009 antibody analysis. Conclusion: MORAb-009, a monoclonal antibody against mesothelin is safe and well tolerated at doses up to 100 mg/m 2 . One subject with previously progressive pancreatic cancer had disease stabilization. In light of the positive preclinical data and safe clinical profile, this study supports further evaluation of the efficacy of MORAb-009 in mesothelin-positive tumors. No significant financial relationships to disclose.
Prognostic factors for cancer patients with good performance status considered for inclusion in phase I clinical trials
Authors: M. Bonneterre, N. Penel, M. Vanseymortier, E. Dansin, S. Clisant, Y. Vendel, M. Degardin, A. Adenis, R. Beuscart, J. Bonneterre
Journal: Journal of Clinical Oncology (2007)

2568 Background: For investigators, the selection of patients to be considered for phase I clinical trials is difficult, because of the lack of objective criteria for a rational decision-making process. From October 1997 to October 2002, we retrospectively assessed prognostic factors for cancer patients considered for Phase 1 trials. Methods: 148 consecutive patients who had been screened for inclusion in 6 different phase I trials were included in the present study. 70 out of them actually received the phase I treatment. Univariate (Log-Rank test) and multivariate analysis (Cox proportional hazard ratio model) were performed to determine the prognostic factors related to overall survival (OS) after screening. Results: The study comprised 63 men and 85 women, with a median age of 54 (range 23–79). The most frequent primary cancer sites were: breast (38 cases), head and neck (28 cases), lung (18 cases) and colorectal (17 cases). 91 out of them had a performance status PS = 0. The median OS of the 148 patients was 5.7 months (173 days, range 1–2,421). Univariate analysis identified PS = 1, Body Mass Index &lt; 20, liver and visceral metastasis, serum albumin &lt; 38 g/L, lymphocytes count &lt; 0.7 x 10 9 /L and granulocytes count &gt; 7.5 x 10 9 /L as poor prognostic factors. The Cox model identified serum albumin &lt; 38 g/L (HR 2.51 [1.51–4.18], p=0.0001) and lymphocyte count &lt; 0.7 x 10 9 /L (HR 2.27 [1.13–4.62], p=0.024) as independent prognostic variables for OS. All patients presenting with both prognostic factors died within 90 days. Conclusion: We propose a simple model, easily obtained at the patient bedside, which can discriminate patients who have a life expectancy of over 3 months and thus could be enrolled in phase-I anti-cancer trials. No significant financial relationships to disclose.
Knowing in our cancer patients (pts.) delays in consulting, diagnosis and beginning of treatment
Authors: L. Carranza, E Richardet, S Bella, D Passalaqcua, M Richardet, V García, D Kaen, A Salvatierra
Journal: Journal of Clinical Oncology (2004)

6130 Background: 1- To determine the time between the beginning of symptoms and the first office consult (TFC). 2- To establish the time between TFC and histological diagnosis (THD). 3- To define the time between THD and first treatment attempt (TFT). 4- To find explanations to delays in TFC, THD and TFT. Methods: This is a prospective study including all patients with cancer diagnosis that entered to Hospital Italiano of Córdoba Oncology Unit between 12/1999 and 3/2003. The first symptom related to cancer diagnosis was identified. TFC was defined as the moment in which the patient assist by the first time to a doctor's office with any kind of specialization. THD was the time between TFC and the date of histological diagnosis of cancer and TFT was the time between the date of histological diagnosis and the date of first treatment attempt (surgery, radiotherapy or chemotherapy). Results: 382 consecutive pts. were included. Women 193 (50.52%). Age: 59.96 (r: 11–90). Diagnosis: breast 104 (27.22%), lung 54 (14.13%), colon 28 (7.32%), gynecological 21 (5.49%), prostate 15 (3.92%), lymphoma 10 (2.61%), pancreas 10 (2.61%), gastric 7 (1.83%), esophageal 5 (1.30%), renal 5 (1.30%), other 123 (32.19%). First oncological treatment was: Surgery: 200 (52.35%), Chemotherapy: 100 (26.17%), Radiotherapy 15 (3.92%) Hormonal treatment: 8 (2.09%). 59 pts. did not received any treatment. Conclusions: 1) More than a half of patients (50.79%) delayed more than a month to arrive to a doctor's office and 12.29% of consults were made after 5 months; 2) 13.59% obtain histological diagnosis after 5 months; 3) 19.87% begun treatment after 5 months. We could not establish any significant relation between patient's job, residence or insurance and THD or TFT, although we can determine that almost all patients that delayed more than 9 months in TFT were living in Córdoba and were university graduates. No significant financial relationships to disclose.