tbuckley/cabot-search huggingface dataset:
Brain metastases from breast cancer: Survival by HER2 status in the trastuzumab era
Authors: D. G. Kirsch, C. J. Ledezma, C. S. Mathews, M. Ancukiewicz, A. K. Bahn, F. H. Hochberg, J. S. Loeffler
Journal: Journal of Clinical Oncology (2004)

779 Background: Brain metastases from breast cancer develop in 15% to 30% of women with metastatic breast cancer. Survival after brain metastases from breast cancer was assessed in the era of trastuzumab. Methods: Women with brain metastases from breast cancer that were treated or evaluated at the Massachusetts General Hospital since 1998 were retrospectively identified through hospital records or databases in the Department of Radiation Oncology and Neuro-Oncology. 109 women were identified as having breast cancer that metastasized to the brain. Tumors were classified as HER2 overexpressed if HER2 immunohistochemistry (IHC) was reported as 3+ or if Her2 gene amplification was present by fluorescent in situ hybridization (FISH). Tumors were classified as HER2 non-overexpressed if HER2 IHC was 1+ or if the Her2 gene was not amplified by FISH. Age at primary breast cancer diagnosis, time to develop brain metastasis, and survival after developing brain metastasis were compared for patients stratified by HER2 status. Results: In 91 of the 109 patients, HER2 status could be evaluated. 46 patients had tumors that did not overexpress HER2, while 45 patients had tumors that did overexpress HER2. 35 of these patients were treated with trastuzumab. There was no statistically significant difference between the age of primary breast cancer diagnosis (mean 48.1 years) or time to develop brain metastases (mean 58.2 months) according to HER2 status. However, patients with HER2 overexpressing breast cancer had a significantly longer overall survival (median 23 months vs. 10 months) after the development of brain metastases (p=0.0016 by log rank test). Conclusions: In the trastuzumab era, women with brain metastases with HER2 overexpressing breast cancer have a significantly improved survival. Better systemic disease control with HER2-targeted therapy may account for the improved survival for patients with HER2 overexpressing brain metastases. Further gains would likely result from HER2-targeted therapy that can cross the blood-brain barrier. No significant financial relationships to disclose.
Evaluation of efficacy and safety of a metronomic/anti-angiogenic regimen of low-dose oral cyclophosphamide, thalidomide, and dexamethasone in pts with chemotherapy-resistant, castration-refractory prostate cancer in Iran.
Authors: M. Salimichokami, S. Aminian, M. Ayati, M. Sanadi-Zadeh
Journal: Journal of Clinical Oncology (2010)

e15091 Background: Many studies have suggested the efficacy of metronomic/anti-angiogenic regimens in metastatic epithelial human malignancies. This has special relevance to cancers in which microvessel density plays a central role like prostate or renal cancer. Methods: Accordingly we designed a phase II trial in 28 Iranian pts with castration-refractory prostate cancer (CRPC), who had failed their 1st and 2nd line cytotoxic regimens as evidenced by PSA serial measurements. All pts were heavily pretreated and their ECOG-PS was 2 or 3. Fifteen pts were randomized to arm-A and 13 pts to arm-B. Arm-A was our tratment arm in which all pts received low-dose oral cyclophosphamide at 50 mg once daily plus thalidomide 100 mg daily and oral dexamethasone at 1 mg daily. Arm-B was our best supportive care (BSC) arm in which no specific antineoplastic therapy was used. All pts in both groups were on prophylactic ASA at 80 mg daily to prevent DVT. No patient was excluded based on chronologic age or comorbidities. The only exclusion factor was very poor PS ie: ECOG-PS4. Results: Using the widely-accepted concencus criteria, 10 pts (65%) in our Rx-group showed PSA-decline of 50% or more in comparison with 2 pts (15%) in the BSC-Arm. Grade-2 or more myelotoxicity was not seen in any patient. Three pts in our treatment arm and one patient in the BSC arm devloped DVT despite being on ASA at 80 mg daily. Conclusions: Our results support the safety and efficacy of this simple and convenient oral regimen in CRPC, especially applicable and relevant to pts with multi-comorbidities and/or those who refuse parenteral or inconvenient/toxic regimens. Such conditions are not uncommon in CRPC which is primarily a disease of the elderly with multiple organ dysfunction. No significant financial relationships to disclose.
Phase III randomized trial of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (RH) versus RH for bulky stage I/II cervical cancer (JCOG 0102)
Authors: N. Katsumata, H. Yoshikawa, T. Hirakawa, T. Saito, K. Kuzuya, T. Fujii, M. Hiura, R. Tsunematsu, H. Fukuda, T. Kamura
Journal: Journal of Clinical Oncology (2006)

5013 Background: NAC may represent an alternative to conventional RH for locally advanced cervical cancer. We compared NAC followed by RH with RH for bulky stage I/II cervical cancer. Methods: Patients (pts) with stage IB2, IIA (&gt; 4 cm), or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7mg day 1–5, vincristine 0.7mg/m 2 day 5, mitomycin 7mg/m 2 day 5 and cisplatin 14 mg/m 2 day 1–5,) q21 days, 2 to 4 cycles followed by radical hysterectomy (NAC arm) or undergo RH (RH arm). Pts with positive surgical margins, metastatic nodes, infiltration to parametrium, and/or deep myometrial invasion received postoperative irradiation. Eligibility included preserved organ function, aged 20–70, and Performance Status 0 or 1. Primary endpoint was overall survival (OS) to be compared by log-rank test. Assuming 100 eligible pts in each arm, the study had 80% power to detect a 15% increase in 5-year survival at 0.05 one-sided alpha. Results: 134 pts (67 NAC, 67 RH) were randomized between 12/01 and 08/05. The first planned interim analysis was performed in July 2005 using data from 108 pts registered as of 11/04. Data and Safety Monitoring Committee recommended to terminate the study because overall survival in NAC arm was inferior to that in RH arm (HR 2.11, multiplicity adjusted 99% CI 0.34 to 13.2) and the predictive probability of significant superiority using Spiegelhalter’s method of NAC arm was extremely low (6.4%). No increase of operability and no decrease of surgery-related morbidity were observed in NAC arm. Response Rate of NAC was 61% (33 of 54) using RECIST criteria. One-year progression-free survival and overall survival, updated as of 05/05, were 69.9% and 91.8% (95% CI 84.1–99.6) in NAC arm and 78.6% and 95.4% (95% CI 89.1–100) in RH arm respectively. Conclusions: Neoadjuvant chemotherapy with BOMP regimen followed by radical hysterectomy did not demonstrate clinical benefit, and conventional radical hysterectomy still remains to be a standard treatment option for bulky stage I/II cervical cancer. [Table: see text]
Ca 19.9 as an early predictor of response to first- and second-line treatment in patients with pancreatic cancer
Authors: M. Squadroni, R. Berardi, D. Tummarello, M. Scartozzi, G. Carbonari, C. Pierantoni, E. Maccarone, S. Cascinu
Journal: Journal of Clinical Oncology (2008)

15547 Background: The aim of this study was to define the role of early Ca19.9 modification during first and second line chemotherapy for advanced pancreatic cancer, as a predictor of response, overall survival and time to progression. Methods: we reviewed Ca19.9 levels, before starting first and second line treatment and 30 days following the beginning of chemotherapy (first and second line) of 96 patients with advanced pancreatic cancer, who received chemotherapy at our Oncology Department from January 2002 to June 2007. Results: Median age: 63 years (37,5 - 77,9); M/F ratio 55/41 (57,3/42.7%); 57 (59.4%) received second line chemotherapy. At the time of analysis 86.5% of patients had died, with a median OS of 8.1 months. Ca 19.9 values before and during treatment are summarized in the table below. A high baseline Ca19.9 value (>10 times upper limit) was associated with a significantly shorter OS and TTP (OS: 11.3 vs 11.2 vs 6.3 months, p=0.014; TTP: 5.7 vs 3.9 vs 3.2 months, p=0.0034), and similar results were observed for second line treatment (OS:14.4 vs 11.3 vs 4.3 months, p=0.0281; TTP: 5.5 vs 4.2 vs 2.3 months, p=0.0034). We found that, both during first and second line treatment, an early increase of Ca19.9 level over 20% was associated with a higher rate of progressive disease (68.7% vs 40%; p=0.0157 in first line and 86.4% vs 59.4%; p=0.037 in second line) and a worst prognosis (OS: 5,3 vs 10,2 months; p=0,001; TTP: 2,6 vs 5,8 months; p<0,0001 for first line; OS: 7,9 vs 4,1 months, p=0,0007; TTP: 4 vs 1,4 months, p=0,0009 for second line). Conclusions: our results confirmed the prognostic role of Ca19.9 in pancreatic cancer, also in the second line setting. We also observed the role of serial determination of Ca19.9 during chemotherapy as an early predictor of response rate to treatment and patients outcome. Ca 19–9 values Number of Patients (%) Baseline Ca 19–9 96 patients Normal 13 (13.5%) ≤ 10 time upper limits 22 (22.9%) > 10 times upper limits 61 (63.5%) Ca 19–9 modification during 1st line chemotherapy 46 (47.9%) Decreased 32 (33.3%) Stable 18 (18.7%) Increased over 20% Unknown Before 2nd line chemotherapy 57 patients Normal 9 (15.8%) ≤ 10 time upper limits 5 (8.8%) > 10 times upper limits 36 (63.2%) Unknown 7 (7.7%) Ca 19–9 modification during 2nd line chemotherapy 32 (56.2%) Decreased 13 (22.8%) Stable 12 (21%) Increased over 20% Unknown No significant financial relationships to disclose.
Evaluation of mini nutritional assessment (MNA) in metastatic lung cancer patients: Correlation of laboratory values indicating malnutrition, inflammation, and cachexia with clinical data
Authors: I. Gioulbasanis, A. Kalykaki, L. Vamvakas, A. Pallis, N. Vardakis, E. Saloustros, A. Karampeazis, G. Sfakiotaki, K. Kalbakis, D. Mavroudis
Journal: Journal of Clinical Oncology (2008)

19062 Background: Lung cancer is frequently associated with significant morbidity and malnutrition. Early recognition of cachexia is problematic because specific symptoms and reliable objective measurements are lacking. Screening questionnaires like the Mini Nutritional Assessment (MNA) (www.mna-elderly.com) may allow early identification of cachectic patients. Methods: From 4/2006 to 11/2007 all patients with metastatic lung cancer were evaluated using the MNA. Patients were divided into 3 groups according to MNA-score (A: adequate nutrition; B: risk of malnutrition; C: malnutrition). The primary end point was the evaluation of the relation between the MNA and laboratory measurements indicative of malnutrition, inflammation and cachexia before the onset of chemotherapy. Results: 163 patients (147 males) with median age 65.4 years were evaluated. The percentages and the observed values (mean ± SD) of the studied parameters for each group as well as comparisons between groups A+B vs C and A vs B+C are tabulated in the table below. After a median follow up of 9.5 months (range, 0.03–22.9), MNA score was significantly correlated with overall survival for group A vs BC (p=0.007) whereas there was a marked difference for groups AB vs C (p=0.081). Conclusion: The MNA is an easy and reliable questionnaire that can be used to identify early cachexia in lung cancer patients. Group [N (%)] A [46 (28.2%)] B [75 (46.0%)] C [42 (25.7%)] A+B vs C A vs B+C Age 63.0±8.5 66.9±10.6 63.4±10.2 ns 0.085 Performance status 0.6±0.7 1.4±0.9 1.9±1.2 *0.001 *<0.001 Body mass index 26.3±4.8 24.2±5.3 23.9±4.1 ns *0.032 No of metastatic sites 2.2±1.2 2.7±1.0 3.0±0.9 0.059 *0.010 Hemoglobin (gr/dl) 13±2.4 12.3±1.8 11.9±2.4 ns *0.013 Lymphocytes (/dl) 1400±699 1476±739 1451±518 ns ns Albumin (gr/dl) 4.2±0.4 3.5±0.5 3.4±0.5 *0.005 *<0.001 Cr Clearance 110±35.0 92.0±39.2 85.1±31.2 0.079 *0.016 CRP (mg/dl) 3.1±4.6 8.4±10.4 7.3±5.9 *0.027 *<0.001 Ferritine (mg/dl) 236±61 295±233 284±216 ns 0.084 IL-6 7.6±8.6 52±132 22.7±20.0 0.065 *0.001 TNFa 1073±1546 1206±1619 1237±2451 ns ns IL-8 20.7±35.2 81±210 257±694 0.050 *0.001 ns = non significant; * p<0.05 No significant financial relationships to disclose.
Alleviation of radiation lung damage by administration of gene-modified mesenchymal stem cells.
Authors: J. Xue, Y. Lu, X. Li, Y. Zhang, R. Ao, Y. Wang, H. Liu, Y. Wu, X. Mo
Journal: Journal of Clinical Oncology (2010)

e13568 Background: Radiation pneumonitis (RP) and subsequent radiation pulmonary fibrosis (RPF) is a common and serious complication in the treatment with radiation therapy (RT) for lung cancer. In order to investigate the alleviation efficacy by gene-modified mesenchymal stem cells (MSCs), we assessed whether adenovirus-transduced MSCs with the soluble transforming growth factor-beta type II receptor (Ad-sTβR) could reduce RP and RFP. Methods: MSCs from male C57BL/6 mice were isolated and verified. The whole lung of each female C57BL/6 mouse was irradiated with a single dose of 14Gy. Injection of PBS, Ad-sTβR, MSCs, and Ad-sTβR-transduced MSCs (Ad-sTβR-MSCs) by tail vein were administrated immediately and 14 days after radiation, respectively. RP and RPF were assessed by H&E, Masson trichrome staining, MDA, hydroxyproline and TGF-β1 assay as well as quantitative RT-PCR and Western Blot for CTGF and α-SMA. Furthermore, the differentiation assays of male MSCs into type II pneumocytes were performed by Real-time PCR and FISH for Y chromosome. Results: The homing effect of MSCs to irradiated murine lung was detected by Real-time PCR for Y chromosome on day 30. By comparison with groups of RT+PBS, RT+MSCs and RT+Ad-sTβR, there was a significant reduction for lung injury in the group of Ad-sTβR-MSCs on day 120, which was demonstrated not only by staining of H&E and Masson trichrome, but also by assay of MDA, hydroxyproline and plasma active TGF-β1. Administration of Ad-sTβR-MSCs significantly decreased the relative mRNA and protein levels of CTGF and α-SMA. In addition, it was observed by real-time PCR for Y chromosome that about 11% type II pneumocytes were derived from donor male MSCs, which was further confirmed by FISH. Conclusions: These findings suggested that MSCs can home to injured lung, and the strategy of Ad-sTβR gene-modified MSCs could potential alleviate RP as well as RPF by differentiation of engrafted MSCs into type II pneumocytes. No significant financial relationships to disclose.
Tumor-specific response rates to erythropoietin in chemotherapy-induced anemia in a community practice setting
Authors: S. Vasu, C. Seidler, T. Field, S. Emani
Journal: Journal of Clinical Oncology (2006)

18528 Background: Erythropoietin [Epo] is widely used in the management of Chemotherapy-Induced Anemia [CIA] with reported response rates of 70% in the setting of clinical trials. To evaluate overall response rates and tumor specific response rates a retrospective study was performed. Methods: Chart reviews of 109 consecutive patients with chemotherapy-induced anemia were conducted from 2001–2004. Inclusion criteria were: age &gt; 18 yrs, solid or non-myeloid hematological malignancy, receiving concurrent chemotherapy. Patients who received at least one dose of epo were also included, under the intention-to-treat principle. Hb, HCT and MCV during the course of chemotherapy and epo treatment were also collected. Transfusion requirements were also noted. Rise of 1gm Hb after receiving at least 8 weeks of epo was considered as evidence of responsiveness. Epoetin alpha was administered as 40,000 units weekly or darbepoietin at 200mcg q2 weeks and appropriate dose adjustments were made depending on responses. A PRBC transfusion after Day 29 was considered to be evidence of non-responsiveness. Results: Of 109 patients, 108 were considered eligible to be studied. The table shows the distribution of patients according to cancer type. Among the patients who received epo for 8 weeks, the epo response rate was 46%. 21 patients required transfusions after Day 29. Conclusions: Our data suggests that the community response rates to erythropoietin are lower than that reported in the literature. Tumor specific response rates were not statistically significantly (p &gt; 0.05), although this may reflect the small number of patients in the study. A multivariate analysis is being performed to determine if there are predictive factors for response. [Table: see text] [Table: see text]
Breast cancer in woman younger than age 35 in Tunisia: Comparative analysis between inflammatory and noninflammatory breast cancer.
Authors: H. Boussen, Y. Ben Zarkouna, T. Bouzid, F. Khomsi, A. Gamoudi, M. Hechiche, F. Benna, K. Rahal
Journal: Journal of Clinical Oncology (2010)

e11107 Background: To compare the epidemiologic clinical features and therapeutic results of inflammatory (IBC) vs non inflammatory BC (non-IBC) in Tunisian patients aged younger than age 35. Methods: Our retrospective study compared two cohorts treated at our institution between 1991 and 2000. We collected the epidemiologic, clinical features as well as the therapeutic results. Comparison was done between patients with IBC vs non IBC. Results: Between 1991 and 2000, we collected 4,427 breast cancer (BC) cases treated at the Institut Salah Azaiz of Tunis. Within these cases 40 (0.9%) were IBC (group 1) and occurred in patients younger than 35 years. We compare them to a 62 patients aged also less than 35 years and affected by non-IBC (group 2) collected during the same period. There is no significant differences for origin (rural 75% vs. 63%), mean delay to consultation (5 vs. 9.5 months), date of first menarche (13.2 vs. 13.3 years), age at first pregnancy (24.4 vs. 24.3 years), histological features i.e grade (grade 3 45.8% vs. 42%), hormone receptor status (RH positive 57.5% vs. 42.6%) . We observed significant differences for mean clinical size (93.1 vs. 45.2, p < 0.0001), mean radiological and clinical tumoral size (p = 0.001, p = 0.002), axillary node involvement (97.5% vs. 76.7% p = 0.005), and presence of metastases (p = 0.005). Overall 3years and 5 years-survival was significantly better for non-IBC (p < 0.0001 and p = 0.001). Conclusions: Comparative analysis between IBC and non-IBC in Tunisian woman younger than 35 years showed a statistical difference in term of clinical (delay to consultation, mean clinical and radiologic size, presence of metastases) and therapeutic results (3 and 5 years overall survival) confirming the pejorative entity of IBC within the classical breast cancers. No significant financial relationships to disclose.
Facing sexual difficulties: A psycho-oncology study with women affected by gynecologic cancer.
Authors: C. Pallí, M. Beltran, P. Barretina, E. Alvarez, A. Florensa, E. Sala, J. Vayreda, J. Lluch
Journal: Journal of Clinical Oncology (2010)

e19563 Background: There is a paucity of studies focusing on sexual dysfunction after gynecologic cancer (GC). We have approached this topic in a consecutive cohort of female patients. Methods: We interviewed women affected by GC treated by Medical Oncology, Gynecology and Radiotherapy Departments in our center (January-November 2008). Instruments: HADS and FSM (Woman Sexual Functioning Questionnaire), yielding a global score of sexual functioning (SF). The relationship between SF and other variables was explored by nonparametric T-test, chi2 and Pearson correlations (SPSS). Any type of hetero- and homosexual activity was included—not only penetration. Results: We interviewed 202 women. 105 were sexually inactive already before cancer diagnosis (mean age = 68). Thirty-three (mean age = 60.7) stopped having sexual relations for cancer-related reasons: treatment or illness (39.1%); lack of desire (34.8%); other (26.15%). Sixty-four women were sexually active at the time of the interview (mean age = 55.1), with these symptoms: decreased lubrication (62%); low frequency of relations (58%); low sexual desire (52%); excitation, orgasm and penetration difficulties (47, 49, 33% respectively). With depression, SF diminishes significantly (r = −0.38 p = 0.002) and a trend in the same direction was observed for anxiety (r = −0.22 p = 0.087). Age does not achieve significance for the sexually active women (p = 0.176), but influences whether a woman is active or not (p = 0.017). Longer time free of treatment tends to improve SF (p = 0.045), more than time since diagnosis (p = 0.108). Conclusions: Gynecologic cancer profoundly affects sexuality. Emotional distress influences negatively the quality of SF. No significant differences of SF were observed depending on cancer site, disease stage, age and menopause status, but caution must be taken because of small sample. However, age affects whether a woman remains sexually active and treatments cancel differences in SF because of menopause status. Further research should clarify the role of specific treatments. Nonparametric mean comparison n SF mean P Site Ovary 22 40.1 0.371 Endometrium 28 40.1 Cervix 14 44.0 Menopause at diagnosis No 30 42.2 0.309 Yes 34 39.8 FIGO stage Local (I + II) 36 41.8 0.401 Advanced (III + IV) 28 39.8 Age <40 5 49.6 0.176 41-50 16 41.1 51-60 24 40.2 61-70 13 42.1 >70 6 33.7 No significant financial relationships to disclose.
Variable morphology of human immunodeficiency virus-associated lymphomas with c-myc rearrangements. The French Study Group of Pathology for Human Immunodeficiency Virus-Associated Tumors, I
Authors: HJ Delecluse, M Raphael, JP Magaud, P Felman, IA Alsamad, GW Bornkamm, GM Lenoir
Journal: Blood (1993)
Regional hyperthermia (RHT) combined with gemcitabine (GEM) + cisplatin (CIS) in patients with GEM-refractory advanced pancreatic cancer: Results of the ESHO phase II trial
Authors: K. E. Tschoep, S. Boeck, F. Berger, V. Maier, S. Abdel-Rahman, M. Kuhlencordt, C. Salat, M. Schmidt, V. Heinemann, R. D. Issels
Journal: Journal of Clinical Oncology (2008)

4635 Background: Our recent meta-analysis of 1st-line GEM when combined with CIS or analogs indicated a significant benefit compared to GEM alone in advanced pancreatic cancer (ASCO 2007: 4515). Based on chemosensitization of CIS by RHT we performed a prospective single-center phase II trial with GEM+CIS combined with RHT under the guidance of ESHO (European Society of Hyperthermic Oncology). Methods: 22 pts with metastatic (n=19) or locally advanced (n=3) pancreatic cancer and disease progression after GEM- based 1st-line chemotherapy were eligible. Primary endpoint: TTP2 (progression free survival = start of 2nd-line therapy until progression of disease or death). Secondary endpoints: best clinical response; OS. Treatment: GEM (1,000 mg/m2) day 1 and CIS (25 mg/m2) plus RHT days 2 and 4, biweekly x4. Response evaluation was performed by CT scans. A target PFS ≥ 4 mo in 30% of all pts. corresponding to a median TTP2 ≥ 2.3 mo was anticipated. For evaluation of GEM+CIS+RHT efficacy the rate [95% CI] of pts. with TTP2 ≥ 4 mo was assessed. Results: 22 pts were enrolled until 11/2007 with median follow-up of 14.2 mo. Pt characteristics: median age 59 yrs; WHO-PS: 1(55%); 2(45%). Except grade 3 anemia (3 pts) only grade 1 or 2 toxicities occurred. Grade 2 toxicities included anemia (59%), leukopenia (32%), neutropenia (18%; with fever 9%), thrombopenia (5%), metabolic toxicity (9%) and nausea/vomiting (68%), respectively. Median TTP1 was 5.6 mo (CI: 3.6–8.8) and median TTP2 was 4.2 mo (CI: 2.1–7.7). The target TTP2 of ≥ 4 mo was reached in 12/22 pts. (54.6%; CI: 32.2–75.6). For secondary endpoints: best clinical response (20/22 pts evaluable) was 45% (1 CR, 1 PR, 8 SD). Median OS was 16.9 mo (CI: 11.8–22.0). Conclusions: GEM+CIS combined with RHT as 2nd-line treatment shows significant antitumor activity even in GEM refractory pancreatic cancer with tolerable toxicity. Based upon these data a prospective randomized 1st-line phase III clinical trial has been initiated. Supported by ESHO and Helmholtz Center Munich. No significant financial relationships to disclose.