tbuckley/cabot-search huggingface dataset:
Invasive fungal infections (IFI) in patients (pts) receiving hyper-CVAD
Authors: M. E. Cabanillas, G. Mattiuzzi, D. Thomas, K. Vu, G. Ossa, G. Garcia-Manero, J. Cortes, F. Giles, S. O'Brien, H. Kantarjian
Journal: Journal of Clinical Oncology (2004)

6727 Background: IFI are frequent and life-threatening complications in pts with hematologic malignancies. Pts at high risk for IFI are those with acute myelogenous leukemia (AML), high-risk myelodysplastic syndrome (MDS), and pts undergoing bone marrow transplant. The incidence of IFI in AML/MDS during induction at MDACC is 3%–9% with 39% mortality. Pts who receive hyper-CVAD are susceptible to IFI due to use of steroids and neutropenia. Fluconazole 200mg daily is standard anti-fungal prophylaxis for pts undergoing hyper-CVAD for acute lymphoblastic lymphoma (ALL), lymphoblastic lymphoma (LL), or Burkitts leukemia/lymphoma (BL). Objectives: 1) To determine incidence of IFI during hyper-CVAD 2) to evaluate efficacy of our standard anti-fungal prophylaxis 3) to estimate mortality due to IFI. Methods: Retrospective chart review of pts treated with hyper-CVAD from January 1998-July 2003. Review was conducted until relapse, death, transplant, or end of chemotherapy. From 1992–2003 hyper-CVAD was administered as described by Kantarjian et al (JCO 18:547, 2000). From May 2000-December 2001, the modified hyper-CVAD regimen with or without rituximab was used. This regimen incorporated a course of anthracycline intensification on course 2, and 2 courses of early and late intensification during maintenance. No maintenance was given for BL. Results: 170 pts were reviewed, 159 were evaluable. Median age was 41 (r: 15–92), 74% ALL, 20% BL and 6% LL. Overall incidence of IFI was 13% (21/159); 62% due to mold, 38% due to yeast. Overall mortality due to IFI was 24% (5/21), 3 of them occurring in pts who were HIV+/BL and 2 in ALL pts. 3/7 pts with HIV+/BL developed and died due to IFI. Conclusion: The incidence of IFI in pts with ALL, BL, LL is similar to AML/MDS pts, however, the mortality is lower. Patients with BL/HIV, have a high risk of death due to IFI. New strategies for IFI prevention such as use of protected environment and the use of broad-spectrum anti-fungal prophylaxis should be considered in pts receiving hyper-CVAD. No significant financial relationships to disclose.
Ifosfamide, carboplatin, and etoposide (ICE) in combination with regional hyperthermia (RHT) in chemotherapy-pretreated nonresponders with locally advanced high-risk soft tissue sarcoma (HR-STS)
Authors: C. Nickenig, V. Buecklein, L. H. Lindner, S. Abdel-Rahman, M. Kuhlencordt, W. Hiddemann, R. D. Issels
Journal: Journal of Clinical Oncology (2009)

10581 Background: Regional hyperthermia (RHT) improves outcome in combination with neoadjuvant chemotherapy as first-line therapy in locally advanced HR-STS (Issels et al., Abstract 10009, ASCO 2007). Efficacy of ICE combined with RHT as second-line treatment strategy in pts with locally advanced HR-STS pretreated with anthracycline-based chemotherapy ± RHT was evaluated. Methods: Between 9/97 and 6/08, 49 pts were treated with ICE + RHT (median age: 51 years, range: 21–74 years), with high-grade (G2 24 pts; G3 25 pts) STS histology (20 Lipo-Sa; 6 Leiomyo-Sa, 6 MPNST, 5 NOS, 2 DSRCT, 10 others). As first-line therapy 35 pts had received chemotherapy combined with RHT and 14 pts without RHT. Second-line ICE consisted of 1.5 g/m 2 ifosfamide, 100 mg/m 2 carboplatin, and 150 mg/m 2 etoposide on days 1–4 combined with RHT on two days and was repeated on day 28 (4–6 cycles). Besides toxicity, primary and secondary endpoints were objective response (OR) (RECIST), progression free rate (PFR) at 3 and 6 months, and overall survival (OS). Results: Pts received a median of 4 ICE cycles (range 1–8) in combination with RHT. Hematological toxicity grade III (11 pts)/ IV (23 pts) occurred in 34 pts (69 %), 3 pts (6 %) suffered from therapy-related deaths due to infection during cytopenia (2 pts) or postsurgery-related complications (1 pt). In 35 of 49 pts evaluable for OR, 26% achieved objective remission (1 CR + 8 PR), 51% showed stable disease (18 SD) and 23% progressive disease (8 PD). OR rates after initial chemotherapy with or without RHT were 17 % (4 PR of 24 pts) and 45% (1 CR + 4 PR of 11 pts), respectively (p=0.13). Irrespective of pretreatment, for all pts the PFR after 3 and 6 months was 87% (CI95=96%-77%) and 76% (CI95=88%-63%) and median OS was 22 months (CI95=29–16 months). Conclusions: Second-line ICE combined with RHT is feasible and effective in pts with locally advanced HR-STS non-responding to first-line anthracycline-based chemotherapy with or without RHT. (Supported by Deutsche Krebshilfe and HelmholtzZentrum münchen - German Research Center for Environmental Health) No significant financial relationships to disclose.
Study of three weekly nab-paclitaxel regimens in combination with carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC)
Authors: M. J. Hawkins, G. Manikhas, A. Makhson, S. Cheporov, S. Orlov, P. Yablonsky, P. Bhar, M. Socinski
Journal: Journal of Clinical Oncology (2007)

7659 Background: We previously reported that 130-nM albumin-bound form of paclitaxel (ABI-007, nab paclitaxel) 225 - 340 mg/m 2 and carboplatin AUC of 6 mg/min·ml (C6), both administered on day (d) 1 every 3 weeks (q3w), produced an objective (PR/CR) response rate (ORR) of 27% in first line patients (pts) with NSCLC with median progression-free (PFS) and overall survivals of 6.0 and &gt;10.3 months respectively [Hawkins et al., ASCO, 2006]. Grade 2 and 3 sensory neuropathy (SN) was 36–56%. The aim of the current study was to obtain clinical experience with weekly schedules of nab- paclitaxel in combination with C6 in NSCLC prior to initiating large scale clinical trials. Methods: 75 Pts with previously untreated, stage IIIB or IV NSCLC with measurable disease and a life expectancy of over 12 weeks were recruited into 3 cohorts (n = 25 each) of successive pts and received nab paclitaxel weekly using 3 different regimens (see table ). Results: Patient Characteristics: 75 pts (100% Caucasian; 84% male; median age, 60; performance status score: 0 [16%], 1 [84%]. Accrual was completed in each cohort and serious adverse events reviewed prior to accrual at the next dose level. The primary efficacy endpoints are provided in the table . Grade 3/4 hematologic toxicities were: neutropenia 32%/35%; thrombocytopenia, 19%/11%; anemia, 24%/3%. The most common non- hematologic toxicities (any grade) were fatigue, 48%; SN, 48%; nausea, 37%; alopecia, 40%; and vomiting, 26%. Grade 2 and 3 SN was 12–28%. Graded toxicity data by regimen will be presented. Conclusions: When combined with C6, the ORR was higher and there was less peripheral neuropathy for weekly nab-paclitaxel compared to our previous experience using q3w administration. [Table: see text] [Table: see text]
Effect of SNP haplotypes associated with colorectal cancer risk on outcome
Authors: A. Walther, O. Sieber, E. Domingo, E. Jaeger, E. Johnstone, T. Ørntoft, L. Aaltonen, D. J. Kerr, I. Tomlinson
Journal: Journal of Clinical Oncology (2008)

11079 Background: Familial colorectal cancer (CRC) is associated with an early age of onset, which in turn has anecdotally been associated with worse prognosis. We previously reported six SNPs (rs6983267 on 8q, rs4779584 and rs10318 on 15q, rs4939827, rs12953717 and rs4464148 on 18q) which increase the risk of CRC. In addition, we are currently evaluating a further six SNPs for their association with CRC risk. Here we present the impact of these susceptibility alleles on CRC prognosis. Methods: 931 patients enrolled in the Victor trial were typed on the Illumina Hap300 platform (rs6983267, rs4779584, rs10318, rs4939827, rs4464148) [Illumina Inc., San Diego] or using allele- specific PCR (rs12953717). All patients had stage 2 or 3 CRC treated with surgery and chemo- or radiotherapy as appropriate and randomised to rofecoxib or placebo. Survival analysis was performed using allelic odds ratios (OR), and hazard ratios (HR) from Cox-regression for time-to- event data based on a minimum of three years follow-up. Depending on the allele frequency, we had greater 90% power to detect a 1.2 to 1.6 - fold difference in survival associated with the high-risk genotype. SNPs which initially passed the significance threshold of p<0.05 will be evaluated further in additional samples sets (599 Danish non-trial patients, 1045 Finish non-trial patients). Results: After the first phase of testing, rs6983267 and a further unpublished SNP (rsX) was associated with prognosis at the 5% significance level. The HR for phase I for rs6983267 was 1.43 (95%CI 1.04–1.97, p=0.03) and for rsX 1.33 (95%CI 1.04–1.67, p=0.022). We will present data of the further genotyping in Phase 2, and the identity of rsX if found to be associated either with susceptibility or outcome. Conclusion: Germline predisposition to CRC may be associated with outcome. If proven to be true in phase 2, this will require validation in prospective clinical trials, but could represent a first step towards building a true and clinically useful molecular profile of CRC. No significant financial relationships to disclose.
NT-pro-BNP and cTnT as markers for subclinical early-onset anthracycline-induced cardiotoxicity in children: A prospective study.
Authors: A. M. Mavinkurve-Groothuis, J. Groot-Loonen, T. Feuth, P. Hoogerbrugge, L. Kapusta
Journal: Journal of Clinical Oncology (2010)

e19503 Background: Cardiac biomarkers may play an important role in the early detection of anthracycline-induced cardiotoxicity.We aimed to document cardiac troponin T (cTnT), NT-pro-brain natriuretic peptide (NT-pro-BNP) and echocardiographic parameters during and shortly after treatment with anthracyclines in children with Acute Lymphoblastic Leukemia (ALL). Methods: In a prospective study, we monitored cardiac function in 60 children treated for ALL with conventional echocardiography and levels of NT-pro-BNP and cTnT before start (t=0), after three months (t=1) and after one year of treatment (t=2). At t=1, the cumulative anthracycline dosage of all patients was 120 mg/m2. Further anthracycline dose was dependent on risk stratification. Results: Abnormal cTnT levels were documented in 11% of the patients at t=1 and normalized in all at t=2. In one patient cTnT became abnormal only at t=2. NT-pro-BNP levels increased throughout treatment in 58% and were abnormal in 18% of patients at t=1 and in 35% at t=2. Fractional shortening, posterior and septal wall thickness at end-diastole indexed by body surface area (BSA) and left ventricular mass indexed by BSA significantly decreased during treatment. No significant relation was found between biomarkers and echocardiographic parameters. Conclusions: cTnT and NT-pro-BNP were frequently abnormal in children during treatment with anthracyclines. While cTnT levels normalized after one year of treatment, NT-pro-BNP levels increased during treatment in most of the patients. Both biomarkers are important in the detection of subclincal early-onset anthracycline-induced cardiotoxicity. No significant financial relationships to disclose.
Preoperative diagnosis of sentinel lymph node (SLN) metastasis using 3D CT lymphography (CTLG): A new technology for sentinel node navigation.
Authors: M. Nakagawa, M. Morimoto, T. Nagao, Y. Nakagawa, A. Tangoku
Journal: Journal of Clinical Oncology (2010)

553 Background: CTLG with a nonionic water soluble iodinated contrast medium can allow quick visualization of the direct connection between the primary SLN and their afferent lymphatic channels in detailed anatomy at the time of preoperative CT scan. The disadvantages of the gamma probe (GP) or blue dye (BD) methods became clear by this. Lymph node (LN) metastasis cannot be diagnosed by GP and BD preoperatively and tumor occupied SLN could not be detected with those methods. There might be the false negative. LN metastasis can be diagnosed using CTLG by detecting the obstruction of the lymph vessel and tumor replacement. Methods: From Jan 2005 to Dec 2008, 373 patients with breast cancer underwent surgery in Tokushima University Hospital. CTLG was applied to all patients. 231 patients who did not receive primary chemotherapy were studied.SLN metastasis was diagnosed according to the following criteria: (A) Defect of the SLN, scissor clubbed defect sign or mottled stain of the LN, (B) Stagnation and (C) Interruption of the lymph vessels, (D) Abnormal rerouting of the lymphatic route. Preoperative diagnosis was compared to pathological report after operation. Results: 28 of 231 patients proved metastatic SLN pathologically. 25 cases of these 28 cases diagnosed as metastasis preoperatively according to the criteria. 13 cases (52%) diagnosed from criteria A, 14 cases (56%) from B, 9 (26%) from C and 7 (28%) form D. 19 cases (76%) had more than two criteria. Accuracy of preoperative diagnosis for metastasis was 88.3% and false positive rate was 10.4% (24 cases). Sensitivity was 92.5% and specificity was 87.7%. Positive predictive value was 51% and negative predictive value was 98.3%. Of false negative cases, one case showed criteria D retrospectively. Two cases showed normal pattern in which micro metastasis was found in each. By CTLG, multiple small metastases were found in two cases of ductal carcinoma in situ. Conclusions: CTLG can detect correct SLN number and position with surrounding detailed anatomy, moreover SLN metastasis can be predicted by figuring out the flow of lymph vessels and defect of LN which occupied by tumor. No significant financial relationships to disclose.
Expression of matrix metalloproteinases (MMP1, 2, 9, and 11) in metastatic lymph node tissue of breast cancer patients
Authors: A. Fink-Retter, D. Gschwantler-Kaulich, G. Hudelist, I. Walter, K. Czerwenka, C. Singer
Journal: Journal of Clinical Oncology (2007)

21138 Background: Invasive growth requires degradation of extracellular matrix. A number of Zn 2+ -dependent matrix metalloproteinases (MMPs) is associated with this process and leads to local invasion and metastasis in malignant breast tumors. Especially the expression of MMP-2 and MMP-9 has been associated with high potential of metastasis in breast cancer. Methods: We determined the expression patterns of epithelial (E) and stromal (S) MMP-1, MMP-2, MMP-9 and MMP-11 by immunohistochemistry in tissue arrays, containing 50 paraffin-embedded sets of tissues obtained from the malignant tumor of the breast, and 50 paraffin-embedded sets of tissues from metastatic lymph nodes (purchased from Biomax, Biomax Inc, Rockville, MD). Results: MMP2-S and MMP9-S protein expression was significantly higher in lymph node tumor tissue when compared to breast tumor tissue (10% vs. 2%; p=0.005; 78.3% vs. 94.8%, p=0.01 Chi Square test, respectively). MMP9-E showed a borderline significance in lymph node tumor tissue (92.6% vs. 73.5%; p=0.05 Chi Square test). While in breast tumor tissue significant correlations were observed between all MMPs except MMP2-S, these associations were less pronounced in lymph node tumor tissue. Conclusions: We suggest that the expression of MMP-2 and MMP-9 in breast cancer tissue is associated with a high invasive and metastatic potential. This might be confirmed by our finding that MMP2-S, MMP9-S and MMP9-E are increased expressed in metastatic lymph node tissue. This is in line with other studies which showed that MMP-2 and MMP-9 expression in primary breast cancer tissue samples was associated with breast cancer progression and invasion. No significant financial relationships to disclose.
Management of side effects of aromatase inhibitors (AIs) during adjuvant therapy for postmenopausal women with HR+ breast cancer: Analysis of French practices
Authors: J. P. Guastalla, Y. Belkacemi, B. Cutuli, P. Dalivoust, N. Dohollou, A. Hardy Bessard, R. Salmon, T. Delozier
Journal: Journal of Clinical Oncology (2009)

e11593 Background: Aromatase inhibitors (AIs) are widely used as adjuvant therapy for HR+ breast cancer. Most frequently reported side effects are joint pain, osteoporosis and lipid disorders. Our aim was to describe how physicians in their clinical practice manage these side effects at initiation of treatment and during follow-up. Methods: Multicentric survey conducted in October 2008 by Internet among a sample of 293 physicians specialized in breast cancer management prescribing adjuvant AIs in post-menopausal women with HR+ breast cancer Results: At initiation of AI treatment, 97 % of the physicians interviewed declared informing their patients of the possible occurrence of joint pain; corresponding figures were 81 % for the increased risk of osteoporotic fractures, 66 % for lipid disorders, 59 % for asthenia, and only 16% for cognitive disorders. At initiation, 71% of the physicians assess fracture history, 83 % prescribe BMD, and 60 % lipid tests. Co-prescription of drugs in association with AIs from the onset of treatment is uncommon (24% of physicians interviewed), vitamin D and calcium being the most frequent prescription (19%); prescription of bisphosphonates was less frequently declared (10%). During the course of treatment, 90% of physicians assess BMD at least once, 41% repeat BMD two years after and 41% adapt monitoring of BMD according to the initial result. Lipid tests are monitored every six months by 29% of physicians, and every year by 29%. In case of joint pain, the initial therapeutic management includes: prescription of an analgesic and/or an anti-inflammatory for 66% of physicians, change of AI for 28%; the switch for tamoxifene is mentioned by only 1%. As a second step in case of failure of the initial measures, adjuvant treatment is modified by 70 % of physicians: change of AI by 50 %, switch for tamoxifene by 20 %. Conclusions: The possible side effects of aromatase inhibitors are taken into account by physicians from the initiation of treatment. They perform themselves the monitoring of the patient during follow-up, including the search for side effects. Bone-joint adverse events are managed by oncologists while the care of lipid disorders is transferred to the primary care physician. No significant financial relationships to disclose.
Effectiveness of epoetin beta 30,000 UI once weekly (QW) for treatment of anemia in solid tumor patients under chemotherapy
Authors: D. Spaeth, C. Hennequin, G. Salles, T. Facon, H. Cure, J. Ferrero, D. Avenin, L. Bergougnoux, P. Bleuzen, A. Jenabian
Journal: Journal of Clinical Oncology (2007)

19588 Background: Anemia is the most frequent hematological complication of cancer. Epoetin beta (E), an effective treatment of anemia in patients with solid tumors (ST) was administered three-times weekly. However, the QW regimen used in patients with hematological malignancies would be more convenient and may improve patient compliance. The aim of our study was to evaluate efficacy and safety of E 30 000 IU QW in patients with ST. Methods: This study was an open-label, single-arm, multicenter trial carried out in 87 French centers between December 2003 and August 2005. Eligibility criteria were: informed consent, age =18 yrs, WHO performance status 0–2, malignant ST or non-myeloid hematological malignancy, on-going chemotherapy and anemia: hemoglobin (Hb) &lt;12 g/dl. E 30 000 IU QW was administered SC for up to 16 weeks. Follow-up visits were scheduled after each chemotherapy cycle. Primary endpoint was Hb response defined as an Hb increase of =2 g/dl (whatever the baseline Hb level) and/or an achievement of Hb level of =12 g/dl or 13 g/dl (patients with Hb levels &lt;11 g/dl or &gt;11 g/dl at baseline respectively). Delay of Hb response, transfusion requirement, mood and cognitive functions were also assessed. Here we focus specifically on the subgroup of patients with ST. Results: In total, 365 patients with ST were included. The most frequent cancer sites were: lung (102 pts) and breast (86 pts). Median Hb level at baseline was 10.4 g/dl [7.9–12.3]. At endpoint, median Hb level increased to 12.5 g/dl [8.4–15.0]. Hb response rate (RR) was: 61% (IC95: 55–66%), 50% (IC95: 38–55%) in patients treated with platinum based regimen and 72% (IC95 : 62–76%) in patients treated without platinum. RR was 54% in lung (IC95: 44–64%), 76% in breast (IC95: 67- 85%). E treatment was well tolerated. Thromboembolic events occurred in 7% of patients, a rate consistent with information provided in the current label for E. Conclusion: Epoetin beta 30 000 IU once weekly is effective and well tolerated in anemic patients with solid tumor treated with chemotherapy. Once weekly treatment offers a convenient therapy which will improve patient compliance. [Table: see text]
The role of extrapleural pneumonectomy in the management of pleural cancers
Authors: D. J. Sugarbaker, T. R. Tilleman, S. J. Swanson, M. T. Jaklitsch, S. J. Mentzer, A. A. Mujoomdar, R. Bueno
Journal: Journal of Clinical Oncology (2009)

7577 Background: We report our experience with EPP for non-mesothelial malignancies. Methods: A retrospective chart review, from June 1994 to October 2007. For all cases, the site of disease involved a single pleura. Results: Sixty-five patients underwent EPP for cancers other than mesothelioma over a 13-year period at our institution. Of these, 32 patients had mediastinoscopy negative T4 lung cancer, 11 had metastases to only one pleura from extrathoracic sites, 10 had unilateral lung sarcomas involving the pleural envelope, 8 had thymomas metastatic to a pleural space, 2 were preoperatively diagnosed as mesotheliomas but at final pathology were determined to be small cell lung cancer and sarcomatoid carcinoma, and 2 represented primary mucoepidermoid and neuroectodermal malignancies. Twenty-eight patients had stage IIIB (T4-N0–1) lung adenocarcinoma representing the largest homogeneous group of patients by cell type and stage. Overall perioperative mortality was 4.6% (3/65). Postoperative morbidity was 44.6% (29/65) with the most common being arrhythmia (n=15), vocal cord paralysis (n=7), and respiratory failure (n=5). Overall survival after surgery was 15.7 months for all the patients. Survival was significantly higher for NSCLC patients with N0 (n=9) on final pathology versus any other nodal status (N1/N2), 52.1 months versus 14.1 months (p=0.0003). Median survival for stage IIIB NSCLC was 16.7 months. Seven of the 8 thymoma patients were alive at last follow-up (median follow-up 22.8 months). Median survival for patients with sarcoma (n=10) or pleural metastases from extrathoracic sites (n=11) was 3.7 and 4.2 months, respectively. Recurrence at follow-up was documented in 21 patients with only 2 (9.5%) occurring in the ipsilateral hemithorax. Conclusions: EPP can be a safe treatment option for some cancers that involve a unilateral pleura. Patients with stage IIIB (T4, N0–1) NSCLC confined to a single pleural cavity or patients with thymoma involving one pleura may benefit from multimodality treatment including EPP. Absence of residual nodal disease at resection is positively correlated with survival in the stage IIIB NSCLC group. Patients undergoing surgical resection for pleural metastases of primary sarcomas or extrathoracic metastasis, however, do not appear to benefit from EPP. No significant financial relationships to disclose.