tbuckley/cabot-search huggingface dataset:
Prostate specific antigen doubling time (PSA-DT) and velocity (PSA-V) provide independent prognostic information in androgen independent prostate cancer (AIPC) patients receiving chemotherapy
Authors: T. J. Daskivich, M. M. Regan, P. W. Kantoff, W. K. Oh
Journal: Journal of Clinical Oncology (2006)

4616 Background: PSA-DT and PSA-V at AIPC have each demonstrated prognostic significance in retrospective studies. No study has compared PSA-DT and PSA-V at AIPC to determine if they are independent prognostic factors. Methods: PSA-DT and PSA-V were calculated in 91 AIPC patients treated with taxane chemotherapy. PSA-DT was calculated as log 2 divided by the slope of the linear regression of log PSA versus time, from the first rise above the PSA nadir on androgen deprivation therapy (ADT) until the start of the next treatment. PSA-V was calculated from the slope of the linear regression of the raw PSA values over time. PSA-DT and PSA-V were split into tertiles for analysis. The primary endpoint was overall survival (OS) from the date of AIPC. OS was analyzed using Cox proportional hazards regression. Results: In univariate analysis, shorter PSA-DT and higher PSA-V were associated with decreased OS. Also associated with decreased OS were: higher M stage at dx; PSA nadir on ADT &gt;0.2; &lt;12 wks to failure of ADT; presence of mets, bony mets, low Hb, high AP, and low albumin at AIPC; and type of chemotherapy. In multivariate analysis, PSA-DT ≤12 weeks (HR=3.2), PSA-V &gt;10 ng/ml/yr (HR=2.8), PSA nadir &gt;0.2 on ADT, low Hb, and type of taxane chemotherapy persisted as significant predictors of decreased OS (each p &lt; 0.01). Rapid PSA-DT (≤12 wks) and high PSA-V (&gt;10 ng/ml/yr) predicted the worst prognosis (25 mos median OS, unadjusted); slow PSA-DT (&gt;12 wks) and low PSA-V (≤10 ng/ml/yr) the best prognosis (75 mos); and other combinations had intermediate prognoses (49 and 50 mos). Modifications of PSA-DT calculation such as nadir subtraction did not alter prognostic ability of either component. Conclusions: PSA-V at the start of AIPC contributes prognostic information independent of PSA-DT. Future studies should investigate the relative contribution of each of these factors in predicting survival. No significant financial relationships to disclose.
High dose Interferon-α2b (HDI): Toxicity, response, and predictive markers in a neoadjuvant trial for regional lymph node metastatic melanoma
Authors: S. J. Moschos, H. D. Edington, U. N. Rao, D. Jukic, J. Shipe-Spotloe, S. R. Land, S. Agarwala, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2005)

7517 Background: High-dose interferon-α2b (HDI) is the only adjuvant therapy to show consistently significant clinical benefit in resected high-risk melanoma, as tested in randomized multicenter cooperative group trials. However, the mechanism of HDI action remains uncertain, and definition of its mechanism and response markers would allow improvement upon this therapy. Neoadjuvant application of interferon may improve surgical resectability, treatment responsiveness, and enable identification of surrogate endpoints for therapy. We investigated neoadjuvant HDI in patients (pts) with palpable regional lymph node positive melanoma (AJCC Stage IIIB and IIIC) to assess the feasibility, efficacy, and molecular-histological predictors of clinical outcome. Methods: Consenting pts with palpable biopsy-proven regional lymph node metastasis received one month of daily intravenous HDI followed by lymphadenectomy and standard maintenance HDI for one year. Responses were assessed clinically, pathologically, and radiographically at day 29. Proteomic and immunohistochemical (IHC) analysis of the pre- and post-treatment biopsies was performed. Results: 17 pts (age: median 57, range 41–76) were enrolled; 11 had regional lymph node recurrence and 6 initial node + presentation. 13 completed 4 weeks of intravenous HDI, and 4 required dose reduction. Response at day 29 was complete in 1, partial in 8, and pathology established complete response in 3, with microscopic residual disease in 4. At median follow up of 14 months (range 2–38 months) there were 4 deaths from metastatic disease, 4 alive with metastatic disease, and 9 have no evidence of disease. Grade 3 and 4 toxicities occurred in 4/17 pts requiring dose reduction in 3 pts and discontinuation of HDI in 1 pt. HDI significantly increased CD4+ cell infiltration of the tumor (p=0.03). Conclusions: Neoadjuvant HDI is well-tolerated and active in stage IIIB-IIIC disease, inducing clinical response in 53% of pts prior to definitive surgery in this study. In pts with clinical response to HDI an increase in CD4+ cell infiltration of tumor by IHC suggests an indirect immunomodulatory mechanism that is currently under intense study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Schering-Plough
Phase II study of short course CHOP-rituximab (R) followed by ibritumomab tiuxetan (IT) as first-line treatment for follicular lymphoma (FL)
Authors: R. C. Jankowitz, K. A. Foon, N. A. DeMonaco, J. Osborn, M. Wu, T. Evans, S. H. Swerdlow, J. Joyce, S. Land, S. A. Jacobs
Journal: Journal of Clinical Oncology (2007)

8005 Background: Therapy with CHOP-R and radioimmunotherapy (RIT) is a promising treatment for untreated FL. Press reports complete responses (CR) of 69% in FL patients (pts.) with 6 cycles of CHOP followed by I-131 tositumomab. We report efficacy and safety using 3 cycles of CHOP-R followed by IT and extended R. Methods: Eligibility criteria include symptomatic or grade 3 untreated FL. 60 pts. have been accrued and 47 evaluated. The treatment consists of two phases: CHOP-R for 3 cycles followed by IT. One week after IT, pts receive R weekly × 4. Bone marrow (BM) biopsies and fusion PET-CT scans are obtained at baseline, after CHOP-R, and 12 weeks post RIT. The primary endpoint is CR rate. CR requires a neg. PET scan and conventional Working Group criteria. Results: Toxicity data are available for 47 pts of median age 56 (range, 39–78), 44 of whom completed both phases of therapy and are evaluated for response. Characteristics and CR rates after IT are shown: 3 pts. did not receive RIT (1 second malignancy, 1 non-compliance, 1 septic death). Of the 44, CR after CHOP-R is 41%. After IT, CR improved to 89%. Of the 5 pts who did not achieve CR, 3 had neg. PET scans (2 with PR, 1 with SD by CT), and 2 had residual disease by PET with PR by CT. At a mean follow-up of 16 months (range, 6–33 months), there are 4 relapses: 3 who achieved CR by PET-CT, 1 with PR by PET-CT. Toxicity was predominantly myelosuppression. There was 1 episode of febrile neutropenia after RIT. Conclusions: 3 cycles of CHOP-R followed by IT and R achieve a high CR in previously-untreated pts. with FL. Addition of RIT increased CR from 41% to 89%. Data will be presented on the affect of bulky disease, positive BM, grade 2 or 3 histology, and high FLIPI score on CR. Further follow-up is necessary to evaluate response duration and determine whether there is a correlation with early or late CR. [Table: see text] [Table: see text]
Abstract 18853: Rivaroxaban is Associated with Higher Incidence of Major Bleeding Compared to Low Molecular Weight Heparin for Venous Thromboembolism Prophylaxis.- A Meta-analysis
Authors: Angeline Opina, Harsh Golwala, Mazen AbuFadel, Alfonso Tafur
Journal: Circulation (2012)

Introduction: The American College of Physicians guidelines for venous thromboembolism (VTE) prophylaxis stresses bleeding risk assessment before VTE prophylaxis. Rivaroxaban has recently been accepted for VTE prevention. However most of the publications heavily focus on the thrombosis rate. Hypothesis: The rate of major bleeding in patients receiving Rivaroxaban is higher than those receiving LMWH for VTE prophylaxis. Methods: MEDLINE, EMBASE, Cochrane Register of Randomized Controlled Trials as well as abstracts presented at national meetings [AHA, ACC, ASH]. We included all prospective experimental trials which declared and counted major bleeding criteria and utilized Rivaroxaban in primary VTE prophylaxis, published from 1-1-06 to 12-21-11. The data was abstracted by 2 independent reviewers in accordance with PRISMA guidelines. We used R [R Meta package v 0.8-2] for analysis. The OR estimates were done with Mantel-Hanzel fixed estimates method and with random effect model by DerSimonian and Liard. Results: We identified 335 records, screened 15 and 9 trials (n=21,035) were included in the analysis. There were 3 knee replacement, 5 hip replacement, and 1 medically ill prophylaxis trials. All compared to LMWH prophylaxis. Although no heterogeneity was detected [I2=0%, p=0.9], we present a conservative random effect model. The odds of major bleed were 1.98 [95%CI 1.3-3.0] times higher for Rivaroxaban compared to LMWH. Individual omission of each of the publications had no significant effect on the overall significance of the findings. When only those manuscripts using a Rivaroxaban dose of 10 mg daily were analyzed, the major bleeding OR was 1.98 [95%CI 1.3-3.1]. Conclusion: Rivaroxaban is associated with a higher incidence of major bleeding compared to LMWH when used for VTE prophylaxis. This information will be instrumental in calculating risks and benefits of patients who need VTE prophylaxis.
ALTERNATIVE (EGF114299): A study of lapatinib, trastuzumab, and endocrine therapy in patients who received neo-/adjuvant trastuzumab (IV) and endocrine therapy.
Authors: William John Gradishar, Zsuzsanna Kahan, Janice Tsang, Constanta Timcheva, Sergei Tjulandin, Fatima Cardoso, Ruta Grigiene, Hiroji Iwata, Maccon Keane, Kristina Luebbe, Zora Neskovic-Konstantinovic, Sergio D. Simon, Salomon Stemmer, Damir Vrbanec, Tammy Arbani, Allison M. Florance, Yingjie Huang, Meggan Leigh, Susan Wroblewski, Stephen R. D. Johnston
Journal: Journal of Clinical Oncology (2012)

TPS661 Background: Approximately 50% of human epidermal growth factor receptor 2 positive (HER2+) breast cancers are also hormone receptor-positive (HR+). For patients with HER2+/HR+ disease, combining the aromatase inhibitor (AI) letrozole with the dual tyrosine kinase inhibitor lapatinib (L) has been shown to improve outcomes vs letrozole alone. Similar results were found for the combination of trastuzumab (T; a humanized monoclonal antibody targeting HER2) and anastrozole vs anastrozole alone. Finally, the combination of L and T has been shown to improve outcomes vs L alone. Methods: This phase III, randomized, open-label, multicenter trial (ALTERNATIVE) will enroll postmenopausal female patients with HER2+/HR+ metastatic breast cancer (MBC) who have not received prior treatment for MBC, have received neo/adjuvant T and endocrine therapy, and are not candidates for chemotherapy. Patients will be randomized 1:1:1 to 1 of 3 treatment arms: L plus T plus an AI; T plus an AI; or L plus an AI. The AI can be letrozole, anastrozole, or exemestane, to be selected by the investigator. The primary objective of ALTERNATIVE is to examine the efficacy of L/T/AI compared with T/AI alone. The primary efficacy endpoint is overall survival (OS; time from randomization until death due to any cause) for L/T/AI vs T/AI. Secondary efficacy objectives include: comparisons of OS between T/AI and L/AI as well as between T/L/AI and L/AI, comparisons of progression-free survival, overall response rate, time to response, duration of response, safety, and tolerability for all 3 treatment groups. The study is powered to detect a 42% reduction in risk of death (hazard ratio=0.70) in patients who receive L/T/AI (median 28.5 months) vs T/AI (median 20 months) using a 1-sided test for superiority with α=0.025. The required number of total events to achieve a power of 80% is 249. Secondary comparisons are not powered and will be based on the ITT population. This study is currently recruiting, with a target of 525 patients. If its objectives are reached, it will provide a valuable, chemotherapy-free treatment option for HER2+/HR+ MBC patients. Clinical trial registry number: NCT01160211.
Abstract 9391: Artery Cell Contraction Regulated by ROS and NO Balance Directly Visualized by in vivo Multi-Photon Imaging Technique
Authors: Satoshi Nishimura
Journal: Circulation (2014)

Aim:  The blood pressure is regulated dynamically by arterial wall tensions in vivo, but the previous methods did not clarify their detailed mechanisms in living animals due to the lack of visualization technique. Thus we aimed to visualize cell kinetics during artery contractions processes by combining in vivo multi-photon imaging and photochemical reaction technique by laser injuries.   Methods:  We recently developed the in vivo fluorescent imaging technique based on two photon microscopy, which enabled us to directly visualize the femoral artery in living animals. In addition, by combining with the visualization technique with laser induced injury models, we could visualize transient artery contraction in response to ROS (Figure a).   Results:  We induced transient relaxation and following contractions stimulated by ROS production inside the artery. First relaxation was regulated by eNOS. And, ROS and NO production was counter-balanced in artery contraction phases, which was directly confirmed by fluorescent indicators (Figure b and c). As for the molecular mechanisms, we confirmed that this contraction is via PKC and NADPH signaling. The contraction was inhibited by Ca blocker, isosorbide, sildenafile, and angiotension II blockers administrations.  In addition, by treating the artery with CaCl solution, the aneurysm formation can be induced and visualized. In the early phase, the hyper-responsiveness of artery wall, and transient thrombus formation was observed. In the later, the wall was stiffened, collagen contents were increased, and aneurysm was observed in last.   Conclusions:  These results indicated the ROS and NO counter balances dynamically regulate artery contractions. eNOS also contributed to these contractions, and imaging can visualize various dynamic signaling. .In sum, our imaging system can be a powerful tool to analyze the molecular mechanisms of hypertension and artery aneurysm.
Reply to N. Osazuwa-Peters et al
Authors: Jolie Ringash
Journal: Journal of Clinical Oncology (2016)

Osazuwa-Peters et al highlight the importance of suicide as a competing risk for patients with head and neck cancer. I appreciate the opportunity to address this topic. The authors cite work from Kendal, reporting US SEER data from patients with cancer diagnoses between 1973 and 2001. The frequency of completed suicide was 0.05% in females and 0.32% in males with head and neck cancer. In contrast, our own data from The Princess Margaret Cancer Centre (Toronto, Canada), show two known and one suspected completed suicide among 7,550 patients with head and neck cancer (69%male) diagnosed between 2003 and 2013, for a rate of approximately 0.03% to 0.04%. We can only speculate whether universal health care, province-wide cancer distress screening, and other supports, provided within and without our Head and Neck Cancer Survivorship Program, contribute to the different rates seen between countries and during a time span of more than a decade. Do three deaths during a decade warrant a comprehensive suicide-prevention strategy? Although tragic, from a population perspective such an initiative is unlikely to be cost effective. Suicide in patients with cancer may often (but not always) reflect inadequate recognition of, or support for, psychosocial concerns. Unquestionably, longstanding physical impairments and associated disability contribute to psychosocial health. Efforts to improve rehabilitation, distress screening, community support, and psychosocial services for patients and family members in need should indeed be incorporated into survivorship care strategies. Future research evaluating such approaches could include cause of death as well as quality-of-life end points.
Current trend in incidence of severe interstitial lung disease (ILD) due to gefitinib in Japan
Authors: K. Goto, H. Kenmotsu, Y. Nishiwaki, K. Kubota, H. Ohmatsu, S. Niho, K. Yoh, K. Nagai, N. Saijo
Journal: Journal of Clinical Oncology (2009)

e19075 Background: Although gefitinib is a promising agent for the treatment of advanced non-small cell lung cancer, ILD occurs in Japanese patients and sever ILD sometimes becomes fatal toxicity. ILD has been reported to be associated with preexisting ILD, smoking, and poor performance status. On the other hand, it has been reported that female gender, adenocarcinoma, non-smoker, and EGFR mutation are associated with sensitivity to gefitinib. Methods: To investigate the trend in incidence of severe ILD and patient characteristics receiving gefitinib, a total of 751 patients who were administered gefitinib in National Cancer Center Hospital East between 2002 and 2008 were retrospectively reviewed. To investigate how oncologists avoid administering gefitinib to patients with preexisting ILD, pretreatment chest CT films of all patients were also reviewed by two thoracic radiologists. Results: The patient number who received gefitinib in 2002/2003/2004/2005/2006/2007/2008 were 134/141/88/93/125/98/72, respectively. In these patients, percentages of female were 36/43/42/55/59/52/54%, adenocarcinoma 76/78/93/88/95/93/92%, non-smoker 35/30/40/53/49/48/46%, respectively. Almost all of the patient receiving gefitinib was recently restricted to adenocarcinoma. Grade 3–5 severe ILD was observed in 1.9% of all patients. However, the incidence rate of sever ILD were decreased as 3.0/2.8/2.3/1.1/0.8/1.0/1.4%, respectively. The rates of patients with preexisting ILD were also decreased as 22/14/15/5/2/3/6%, respectively. Conclusions: The correct information about efficacy and severe ILD about gefitinib influenced patient selection by oncologists, and it is reasonable to select more effective and safe patients in Japan. It is estimated that the incidence rate of severe ILD should be consequently controlled by the spread of these information. No significant financial relationships to disclose.
Clonality of bladder tumors following radical nephroureterectomy: Against the field defect hypothesis.
Authors: Eugene K. Cha, John Sfakianos, Sasinya N. Scott, Paari Murugan, Gopa Iyer, Aditya Bagrodia, Ronak Shah, Dean F. Bajorin, Jonathan E. Rosenberg, Michael F. Berger, Hikmat Al-Ahmadie, Bernard H. Bochner, Jonathan A. Coleman, David B. Solit
Journal: Journal of Clinical Oncology (2015)

301 Background: Urothelial carcinoma is characterized by multifocal and metachronous tumors. To explain this phenomenon, two hypotheses have been proposed: the ‘field defect’ hypothesis - urothelial cells are primed to undergo transformation by exposure to carcinogens, and the clonal, or ‘single progenitor cell,’ hypothesis - tumors arise from intraluminal seeding of transformed cells. Methods: To examine their clonal relationships, we compared the genomic profiles of primary upper tract urothelial carcinoma (UTUC) tumors and metachronous bladder tumors (intravesical recurrences) in patients treated with radical nephroureterectomy (RNU) and subsequent transurethral resection. Specimens were analyzed using a next-generation, targeted sequencing assay designed to identify point mutations, indels, and copy number alterations in 341 cancer-associated genes. Results: We analyzed 16 primary UTUC tumors and 41 intravesical recurrences in patients treated with RNU. The median number of intravesical recurrences per patient was 2 (range 1-7) and the interval from RNU to intravesical recurrence ranged from 3.5 months to 129 months. With an average sequencing coverage of 516x, we found strong evidence delineating the clonal relationship between primary UTUC tumors and subsequent bladder tumors. The majority of somatic mutations present in the primary UTUC tumors (median=7, range 4-39) were detected in all subsequent bladder tumors (128/146, 88%). In an illustrative case, one patient followed with periodic cystoscopy/cytology who had been NED for 5.5 years then developed 7 bladder tumors over the next 44 months, each with the identical mutation profile (8 mutations) as the primary tumor. Conclusions: We demonstrate that bladder tumors following RNU represent true intravesical recurrences, with almost all tumors sharing the same somatic mutation profile as the primary UTUC tumor. This has important implications for surgical techniques to minimize the risk of intraluminal seeding, the delivery of intravesical therapy following RNU, and the development of strategies employing systemic chemotherapy or targeted agents.
Risk of late relapse after surveillance for stage I mixed (M) or non seminomatous (NS) testicular germ cell tumors (TGCT)
Authors: C. Theodore, S. Droupy, A. Laplanche, P. Wibault, K. Fizazi, M. Terrier-Lacombe
Journal: Journal of Clinical Oncology (2006)

14576 Background: Surveillance is an alternative to retroperitoneal lymph node dissection or adjuvant chemotherapy for stage I M or NS TGCT. It has been shown to be associated with a low mortality rate of about 1%, similar to that of the other therapeutic options. However, there are few reports of long-term results. The aim of this retrospective study was to investigate late relapses in this setting. Methods: Screening of the computerized database from 1984 to 2005 for patients (pts) treated for a relapse of a M or NS TGCT at 10 years or more after an orchidectomy. Results: From 1994 to 2006, the files of 5 pts were retrieved. Two pts were referred from other institutions whereas 3 pts had initially been included in the surveillance program of the Institution out of a total of 88 from 1984 to 1996. (3.4% CI 95% 0.7–9.6). Initial histology was available in 4pts: it was pure mature and immature teratoma in one pt and mixed GCT with seminoma in 3 pts. There was no vascular invasion in any of the tumors. Relapse occurred between 10 and 13 years after orchidectomy (median 11 years). The diagnosis of relapse was made based on a systematic 10-year follow-up CT scan in one pt. The 4 other pts who relapsed presented with symptoms: abdominal and back pain due to retroperitoneal involvement in 2 pts, walking disability due to a spinal cord compression in one pt and acute respiratory distress syndrome due to massive metastatic lung involvement in one pt respectively. All 4 pts had bulky retroperitoneal masses. According to the IGCCCG classification, the prognosis was poor in 2 pts and intermediate in 2pts. One pt died of disease despite cisplatin-based chemotherapy. Conclusion: These data demonstrate that there is a small but clinically significant risk of late relapse of stage I M or NS GCT after orchidectomy alone and support the need for long-term surveillance and patient information. No significant financial relationships to disclose.