tbuckley/cabot-search huggingface dataset:
Phase II trial of weekly docetaxel (D) and complete androgen blockade (CAB) prior to radical prostatectomy (RP) in high-risk localized prostate cancer (PC) patients (pts)
Authors: B. Mellado, A. Font, L. A. Aparicio, E. Gallardo, J. R. Mel, A. Alcaraz, J. Areal, F. J. Gómez Veiga, N. Hannaoui, P. Gascón
Journal: Journal of Clinical Oncology (2006)

14515 Background: Pts with high-risk localized PC have an increased risk of positive margins and recurrence after RP or radiotherapy alone. Neoadjuvant hormonotherapy (HT) has not shown a survival benefit prior to surgery, while outcomes are improved when HT is combined with radiotherapy. D-based chemotherapy improves survival in metastatic PC. These data support the investigation of multi-modality approaches to improve the aggressive behavior of high-risk localized PC. The main objective of this study was to assess the pathologic complete response (pCR) rate of the study combination. Secondary objectives were clinical activity, toxicity profile, time to progression and survival. Methods: Pts with clinical stage T1–2 (+ Gleason ≥ 7 (4+3) and/or PSA≥20 ng/mL) and T3 PC received 3 cycles of D (35 mg/m 2 i.v. days 1, 8 and 15, every 28 days) concomitant with a depot goserelin (10.8 mg sc) plus flutamide (750 mg po daily for 3 months). RP was performed 2–4 weeks after the end of neoadjuvant therapy. Results: Fifty six pts have been included into the trial. Available data from 32 pts receiving neoadjuvant therapy were analyzed for this presentation. Median age was 69 years (53–75). Median follow-up was 3.6 months. Clinical stage was T1 (20%), T2 (53%) and T3 (27%); Gleason was ≥ 7 (4+3) in 25 (78%) pts. Eight (28%) pts had a PSA ≥ 20 ng/ml. A total of 85 cycles were administered (median 3) with a 100% median relative dose intensity for D. Grade III/IV toxicities per patient were liver toxicity (15.6%) and diarrhea (9.4%). Among the 16 pts who underwent RP to date, one (6%) achieved pCR, 11 (69%) had negative surgical margins and 9 (56%) had organ-confined disease. Conclusions: Neoadjuvant weekly D plus 3-month CAB is well tolerated and induces pCR in high-risk localized PC pts. Updated results will be available for the meeting. These results are encouraging while the true impact of neoadjuvant chemo-HT in this group of pts has to be determined in randomized trials. No significant financial relationships to disclose.
γδ T cell activation may contribute to antitumor immunity stimulated by intralesional BCG immune therapy for cutaneous melanoma metastases
Authors: Romela Ramos, Agnes Lee, Alfred Chan, Keith S Bahjat, Leland Foshag, Mark Faries, Delphine Lee, Peter Sieling
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In-transit melanoma metastasis can lead to significant locoregional toxicity, due to painful, bleeding, or necrotic lesions, which may become superinfected. Intralesional immunotherapy is a rational approach to such disease as the lesions are accessible and provide a source of
Understanding thalidomide-associated deep vein thrombosis/pulmonary emboli (DVT/PE): Comparison of quality and information included in adverse event reports from clinical trials, clinical practice, STEPS, and the medical literature
Authors: V. Singh, S. A. Klinge, S. Luminari, S. M. Belknap, D. W. Raisch, P. R. Yarnold, B. Kim, R. Chacko, M. S. Tallman, C. L. Bennett
Journal: Journal of Clinical Oncology (2004)

3142 Background: The most common serious adverse event associated with thalidomide use for cancer patients has been DVT/PE. Methods: The Research on Adverse Drug Reactions and Reports (RADAR) project reviewed: 1) all DVT/PE cases reported to the FDA from 1998 to 2003 (n= 235 cases) and 2) medical literature reports for 2002–2003 (n= 22 studies) for incidence rates. Results: Case Report Information: In comparison with reports from clinical practice settings (n=166), clinical trial reports (n = 69) had higher rates of inclusion of information on: thalidomide administration dates (77% vs. 32%), DVT/PE onset date (62% vs. 23%), number of days from thalidomide administration to DVT/PE (52% vs. 17%), and DVT/PE treatment (76% vs. 42%) [p < .0001 for each comparison]. Both clinical trial and none clinical trial FDA adverse event reports were: 1) very complete for: patient age, gender, thalidomide dose, indication, and survival and 2) incomplete for information on tests used to document DVT/PE diagnoses and notation that the case had been reported to the System for Thalidomide Education and Prescribing Safety (STEPS) program. Incidence Rates varied according to cancer diagnosis, stage, and concomitant therapies: Conclusions: 1) Reporting of information on thalidomide-associated DVT/PE to the FDA or to STEPS is rarely complete, especially outside of the clinical trial setting and 2) rates of DVT/PE continue to be high, despite increased awareness of this complication. No significant financial relationships to disclose.
Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases
Authors: S. Cheon, S. Rha, H. Jeung, C. Im, S. Kim, H. Kim, J. Ahn, J. Roh, S. Noh, H. Chung
Journal: Journal of Clinical Oncology (2008)

4580 Background: The benefit of surgical resection of liver metastases from gastric cancer has not been well established. The aim of this study was to evaluate the rationale for hepatic resection in patients with hepatic metastases from gastric cancer. Methods: Among 10,259 patients diagnosed with gastric adenocarcinoma in the Yonsei University Health System between 1995 and 2005, we reviewed the records of 58 patients with liver-only metastases from gastric cancer who underwent gastric surgical resection regardless of hepatic surgery. Results: The overall 1-year, 3-year, and 5-year survival rates of 41 patients who underwent hepatic resection with curative intent were 75.3%, 31.7%, and 20.8%, respectively, and 3 patients survived more than 7 years. Of the 41 patients, 22 had complete resection and 19 had palliative resection. Between the curative and palliative resections, survival rates after curative intent were not different. The number of liver metastasis (solitary or multiple) was a marginally significant prognostic factor for survival. Conclusions: Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases. No significant financial relationships to disclose.
Preservation of ovarian function in young women treated with neoadjuvant chemotherapy for breast cancer: A randomized trial using the GnRH agonist (triptorelin) during chemotherapy
Authors: R. Ismail-Khan, S. Minton, C. Cox, I. Sims, M. Lacevic, M. Gross-King, P. Xu, B. Carter, P. N. Munster
Journal: Journal of Clinical Oncology (2008)

524 Background: There is conflicting evidence on the use of gonadotropin releasing hormone (GnRH) analogues to preserve fertility in women undergoing adjuvant chemotherapy. This is the first randomized clinical trial designed to evaluate the benefit of GnRH use during chemotherapy. Methods: This prospective, randomized clinical trial explored whether the administration of the GnRH agonist (triptorelin) versus no triptorelin (control) affected the degree of chemotherapy related amenorrhea and fertility in premenopausal (age less than 44, FSH <40) women receiving (neo) adjuvant chemotherapy for breast cancer. Patients were stratified by age (<35, 35–39, >39), ER status, and treatment type. Menstrual status, levels of FSH, Inhibin levels were monitored every 6 months. Results: Forty-nine patients (median age 39 years, range 21–43) were enrolled with 6- month follow-up data available on 44 patients, 12-month data on 42 patients, and 18 month data on 34 patients. In the triptorelin group, menses returned after a median of 6.1 (range 1–19) versus 4.70 months (range 0–22) in the control arm (p=0.79). Menstruation had resumed at 6, 12, and 18 months post chemotherapy in the respective groups as follows: triptorelin vs control: 44% vs 60%, 83% vs 79% and 88% vs 84%. FSH levels and Inhibin B levels were inversely correlated. Two spontaneous pregnancies were noted in the control group. These differences were not significant and the study was stopped at that point. Conclusions: The use of GnRH analogues does not appear to benefit patients in preserving menstrual status. FSH levels in patients in whom menstruation has returned is not significantly different in the triptorelin arm versus the control arm. FSH levels in women with menses Months Postchemotherapy Average FSH Prechemotherapy 3 6 12 18 30 Control < 35 4.5 23.0 5.4 1.7 1.2 n/a 35–39 5.6 38.1 12.4 12.7 7.6 4 > 39 5.3 40.3 5.7 18.7 23.5 14.4 Triptorelin < 35 4.7 18.1 5.5 7.0 6.7 n/a 35-39 4.3 19.6 6.3 11.6 11.3 9.8 > 39 5.9 14.4 4.7 13.5 21.44 n/a No significant financial relationships to disclose.
Rituximab in combination with CHOP regimen in T-cell angioimmunoblastic lymphoma (AILD-TL) rich in large B cells. Favourable results in four patients
Authors: B. Joly, V. Frenkel, K. Belhadj, T. El Gnaoui, A. Rahmouni, P. Gaulard, M. H. Delfau-Larue, F. Reyes, C. Haioun
Journal: Journal of Clinical Oncology (2004)

6694 Background: B-cell clonal population is detected in 20% to 40% of AILD-TL. Moreover a subgroup of AILD-TL has been shown to display substantial number of CD20+ large B cells. This subgroup shares the poor prognosis of the classical AILD-TL with a 2-year survival of 40% (Lome-Maldonado, Leukemia 2002). We had postulated that this AILD-TL subgroup might benefit from a treatment with anti-CD20 monoclonal antibody (rituximab) combined to the classical CHOP regimen. Methods: We report four cases of untreated AILD-TL rich in large B cells treated with rituximab (375mg/m2 given on day 1 of each cycle) in combination with CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone) chemotherapy (recycling at d21). Patients were planned to receive 8 cycles, if a good response (at least partial response) was observed after 4 cycles. Results: All the patients presented classical characteristics of AILD-TL with generalized lymphadenopathy, poor performance status, elevated LDH. 2 out of 4 patients had a serum M- component. Auto-immune hemolytic anemia occurred in 2 out of 4 patients. Histologic examinations revealed classical features of AILD-TL with more than 25% of large CD20+ cells with LMP-1 positivity in 2 cases. PCR analysis of tumoral lymph node showed a dominant T-cell clone in 2 cases, one of them also with a dominant B-cell clone. The two remaining cases had oligoclonal T-cell populations with polyclonal B-cell repertoire. A complete remission was achieved in 4 cases after 4 cycles and at the end of treatment for the 3 evaluable patients (treatment is still ongoing in one patient). One patient relapsed at 13 months with a low tumor burden and was treated with cyclophosphamide alone. At the present time, all the patients are alive without evolutive disease at 3, 20, 27 and 34 months. Conclusions : These results led us to consider that rituximab adjonction to CHOP could improve the prognosis of AILD-TL rich in large B cells. This combination warrants further evaluation in a larger phase II study. No significant financial relationships to disclose.
Trends in pneumonia (PNA) hospitalization among patients (pts) with chronic lymphocytic leukemia (CLL)
Authors: J. A. Jones, J. Flynn, M. Moran, T. Lin, J. Byrd
Journal: Journal of Clinical Oncology (2009)

e20500 Background: Despite recent therapeutic advances, PNA remains a significant source of morbidity and mortality among CLL pts. We determined population-level estimates for the incidence and outcome of PNA hospitalizations. We further investigated secular trends in care by comparing cohorts before (1994) and after (2004) the widespread use of multiagent chemoimmunotherapy. Methods: Using data from the U.S. Nationwide Inpatient Sample and ICD-9CM diagnosis codes, we identified all non-governmental hospitalizations of CLL pts for a primary dx of PNA in calendar years 1994 and 2004. Admissions were described by pt demographics (age, gender, race) and comorbidity (Charlson index, presence of chronic lung disease). Ten-year prevalence estimates for CLL were obtained from NCI SEER data and used as denominators in incidence calculations. Outcomes studied included need for intubation, in-hospital mortality, and length of stay (LOS). All analyses were sample weighted. Estimates and 95% confidence limits are reported. Results: PNA was the primary dx for 7316 (13.1%) and 7651 (11.2%) CLL pt admissions in 1994 and 2004, respectively. Incidence of PNA admission was similar in 1994 (140/per 1000 pts, 95%CI 130–151) and 2004 (129/per 1000 pts, 95%CI 119–138). CLL pts admitted in 2004 were older (75.7 v. 74.2 years, p&lt;0.001) and more likely to have at least one Charlson comorbidity (67.6% v. 56.2%, p&lt;0.001) or comorbid chronic lung disease (40.6% v. 28.3%, p&lt;0.001) than pts in 1994. Intubation was rare in both cohorts (&lt;1%) and did not significantly differ by year, but in-hospital mortality was significantly higher in 2004 (11.3% v. 8.2%, p=0.005). However, LOS decreased significantly between 1994 and 2004 (9.2 v. 6.4 days, p&lt;0.001). Conclusions: PNA hospitalization rates for CLL pts have not significantly increased over the last decade despite more aggressive therapies, likely secondary to improved supportive care. However, CLL pts hospitalized for PNA are now older, increasingly likely to suffer from chronic medical illness, and significantly more likely to die while in hospital. Therapuetic strategies targeting older pts with significant comorbidities are needed. No significant financial relationships to disclose.
Case report of a 27-year-old male with DCIS
Authors: C. Hamm, C. Coroneos
Journal: Journal of Clinical Oncology (2009)

e11635 DCIS in a young male is rarely reported. Our patient is a 25 year old male who presented with symptomatic unilateral gynecomastia. He presented with a strong family history of cancer on both maternal and paternal sides of his family including breast, lung (maternal) and melanoma, colon and pancreatic (paternal). His mother tested negative for BRCA1 and BRCA2. There is no information on the paternal genetic testing. He was treated with left subcutaneous mastectomy. Upon histologic review of the sample, concurrent gyecomastia and ductal carcinoma in situ was discovered. To date, only four cases of gynecomastia and DCIS have been described in younger male patients. Since only 30 - 50% of patients with DCIS eventually develop invasive cancer in the subsequent 10 - 20 years, this figure in the general population may be higher. This case underscores the importance of family history in any patient presenting with a breast mass. Patients must be made aware of the risk, however small it may be and physicians must remain cautious of malignancy in young males with gynecomastia. No significant financial relationships to disclose.
Role of antiapoptotic STAT3 and BCL-2 signaling in promoting lung tumor cells to survive against combined MET-/EGFR-targeted inhibitors.
Authors: P. C. Ma, W. Fan, Z. Tang, S. Hafez-Khayyata, C. A. Flask, H. B. Koon
Journal: Journal of Clinical Oncology (2010)

10644 Background: Epidermal growth factor receptor (EGFR) inhibitors in lung cancer are largely limited by the development of resistant disease that ultimately limits their clinical utility. Combined targeted therapy strategies using both MET and EGFR small molecular tyrosine kinase inhibitors (TKIs) are under preclinical and clinical investigation to enhance the therapeutic efficacy and to circumvent acquired EGFR TKI resistance in lung cancer. These combined therapeutic approaches are likely to have unique mechanisms of resistance. Methods: We investigated the effects of combined MET/EGFR TKI treatment on signal transducer and activator of transcription 3 (STAT3) and B-cell lymphoma protein 2 (BCL-2) family members in lung cancer cell lines and xenografts models that are resistant to EGFR inhibitors. Results: Activated STAT3 and BCL-2/BCL-XL induction were seen in lung tumor cells that survived targeted inhibition by MET kinase inhibitors (SU11274 and PHA665752), either alone or in combination with EGFR inhibitors. Using in vivo xenograft model with luciferase-expressing H1975 cells for bioluminescence imaging (BLI), we show that while the H1975 xenograft exhibited excellent imaging tumor response when treated with combined SU11274 (MET TKI) and erlotinib (EGFR TKI), activated P-STAT3[Y705] expression was evident in the residual microscopic tumor survivor cells within the treated xenograft. Interestingly, the resistant survivor tumor cells were located predominantly along the peripheral rind juxtaposing the host stroma. BCL-2 expression was also found induced in the tumor survivor cells during the course of targeted combined MET/EGFR inhibition in vivo. Conclusions: Results of our study support the role of activated STAT3, and its downstream transcriptional targets of the antiapoptotic BCL-2 family members as potential markers for tumor resistance against combined MET/EGFR targeted inhibitors in lung cancer. Further investigations to target the intrinsic apoptotic pathway with BCL-2 family inhibitors, which may overcome or prevent resistance against combined MET/EGFR TKIs, are warranted to impact on the long term outcome in lung cancer therapy. No significant financial relationships to disclose.
Fast track multidisciplinary approach for gastrointestinal tumours.
Authors: Kristien M. A. J. Tytgat, H. H. Greuter, J. Molenaar, S. Heukels, Paul Fockens, Dirk J. Gouma, Jean H.G. Klinkenbijl
Journal: Journal of Clinical Oncology (2013)

102 Background: The incidence of gastrointestinal (GI) tract tumours in the Netherlands is rising. However, GI oncological medical care is still delayed and fragmented. There is a need for better and faster diagnostic work-up, faster start of treatment, but also for expert multidisciplinary deliberation. Therefore, the GIOCA, Gastro Intestinal Oncological Centre Amsterdam, started in 2009 as a one day fast track multidisciplinary outpatient clinic for patients with GI malignancies. The goal was an admission time (AT, time from referral to consultation) of &lt; 1 week and a run through time (RTT, time from multidisciplinary meeting to start of treatment) of &lt; 3 weeks. The aim of this study was first to evaluate the AT and RTT at GIOCA and secondly to evaluate the subjective impact of this novel strategy on patients burden and satisfaction. Methods: Patients were seen at GIOCA in the morning on a colorectal (CRC ), an oesophago/gastric (OES) or a hepatopancreaticobiliary (HPB) day. That same morning (additional) diagnostics were performed. At the multidisciplinary meeting afterwards, a final diagnosis and treatment plan was made, which was later communicated to the patient. The patient then met all involved specialists. AT and RTT were prospectively recorded for all GIOCA patients. For HPB malignancies, AT and RTT could be compared to historical controls from the preceding year. Patient impact and satisfaction was evaluated using a before/after cohort study design, with a written questionnaire prospectively administered to all GIOCA patients and compared to data obtained 3 months prior to GIOCA start. Results: Analyses of 2009 and 2010 showed the following results: The average AT for CRC, OES and HPB was 7.6, 9.5 and 9 days respectively. The average RTT for CRC, OES and HPB was 20.8, 24 and 25 days respectively. For HPB malignancies, this was 10.4 days (AT) and 59.8 days (RTT) in the year preceding GIOCA. Higher levels of patient satisfaction were obtained in GIOCA patients compared to controls. More than 90% of the patients interviewed would advice the GIOCA outpatient approach to other patients. Conclusions: Progress has been made in the AT and RTT in GI malignancies in GIOCA, but the goals were still not all reached. Patients were very satisfied with this novel approach.
High pathologic complete response (pCR) in HER2-positive breast cancer to novel nonanthracycline neoadjuvant chemotherapy.
Authors: A. B. Zelnak, B. Leyland-Jones, S. Gabram-Mendola, T. M. Styblo, M. Rizzo, W. C. Wood, J. Srinivasiah, W. S. Jonas, F. M. Schnell, R. O'Regan
Journal: Journal of Clinical Oncology (2010)

625 Background: The addition of trastuzumab to preoperative chemotherapy for HER2-positive breast cancers has been shown to increase pCR rates. The purpose of this study was to evaluate the efficacy of trastuzumab in combination with dose-dense nab-paclitaxel followed by weekly vinorelbine. Methods: Patients with stage I (> 1.0 cm), II, or IIIA HER2-positive (by standard definitions) breast cancer received nab-paclitaxel 260 mg/m2 iv every 2 weeks for 4 cycles followed by vinorelbine 25 mg/m2 iv weekly with trastuzumab given weekly throughout chemotherapy (4 mg/kg loading dose then 2 mg/kg weekly) for 20 weeks. Tissue was collected at baseline, at optional midway biopsy, and post-therapy. Primary endpoint was pCR rate; secondary endpoints included response rate and toxicity. Cardiac evaluation was performed at baseline, after 4 cycles of nab-paclitaxel, after 12 weeks of vinorelbine and every 3 months thereafter. Results: To date, 21 of 50 planned patients have been accrued (3/2008 to 12/2009). 11 patients are evaluable for primary endpoint. Median age was 50.5 years (38-64). Median tumor size was 3.7 cm (1.5-7 cm). 4 of 11 (36.4%) were clinically node-positive at study entry. Patients were accrued from a university center (54.5%), county hospital (18.2%), and community sites (27.3%). 4 patients were African American (36.4%), 7 were Caucasian (63.6%). The regimen was well-tolerated: 2 patients experienced grade 3 neuropathy, 1 patient grade 3 neutropenia, 1 patient had trastuzumab held for an asymptomatic decrease in left ventricular ejection fraction. pCR were noted in 7 patients (63.6%). All patients responded clinically: clinical complete response rate was 72.7% and partial response rate was 27.3%. Conclusions: The combination of preoperative trastuzumab with dose-dense nab-paclitaxel followed by vinorelbine was well-tolerated and resulted in a high rate of pCR in HER2-positive breast cancer. Updated efficacy and toxicity results will be presented. No significant financial relationships to disclose.