tbuckley/cabot-search huggingface dataset:
The efficacy of PEG-Asp-argase-based chemotherapy for nasal-type extranodal NK/T-cell lymphoma.
Authors: Jing-Yun Wen, Mai Li, Xing Li, Qu Lin, Min Dong, Dan-Yun Ruan, Xiang-Yuan Wu
Journal: Journal of Clinical Oncology (2013)

e19504 Background: Nasal-type extranodal NK/T-cell lymphoma (ENKL) is a highly invasive disease with quite poor prognosis.Pegaspargase (PEG-Asp) displays a similar anti-cancer mechanism as that of L-asparaginase (L-ASP), but exhibits lighter antigenicity. The aim of the present research was to evaluate efficacy and safty of PEG-Asp-based regimen in ENKL. Methods: Data were collected from 23 patients with histologically confirmed ENKL who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to March 2012. Each patient received PEG-Asp 2500 IU/m2/IM on day 1 of each 21-day chemo-cycle. Among them, 8 received combination chemotherapy with CHOP regimen, 11 with EPOCH, and 4 with a CHOP-like regimen (CHOP + bleomycin). The CHOP regimen consisted of cyclophosphamide 750mg/m2, IV (day 1), pirarubicin 40mg/m2, IV (day 1), vincristine 1.4 mg/m2, IV (day 1), and prednisone 100mg, oral (days 1- 5). The EPOCH regimen consisted of etoposide 50mg/m2, epidoxorubicin 12 mg/m2 and vincristine 0.4mg/m2 dissolved in 500mL saline and administered as a continuous IV drip for 24 hours on days 1- 4. Cyclophosphamide 750mg/m2, IV (day 5) and prednisone 60mg/m2, oral (days 1-5), were also administered. In the CHOP-like regimen, bleomycin 15mg was added on days 1-3. Stage I-II patients received local radiotherapy after the chemotherapy. Results: The patients received the PEG-Asp-based chemotherapy for 2-5 cycles (median, 4 cycles). Eleven (47.8%) achieved complete response (CR), and the overall response rate (ORR) was 82.6%. The median time to progression (TTP) was 5 months (range, 2-6 months) and the median OS was 16 months (range, 5-38 months). The 1-year and 2-year survival rate were 82.6% (19/23) and 56.5% (13/23) , respectively. A minor glutamic-pyruvic transaminase (GPT) elevation was observed in 3 patients (13.0%), slight decrease of albumin in 3 (13.0%), reduced fibrinogen level in 2 (8.7%), grade I-II WBC bone marrow suppression in 8 (34.8%), and grade III-IV WBC bone marrow suppression in 3 (13.0%). No allergic incidences were witnessed. Conclusions: Our results suggested PEG-Asp-based chemotherapy presented potential effects in treating nasal-type ENKL with acceptable side effects profile.
Comparision of adefovir and lamivudine for patients with hepatitis B virus-related hepatocellular carcinoma after hepatic resection.
Authors: Xiao Xiang, Jian-Hong Zhong, Yang Ke, Xue-Mei You, Ning-Fu Peng, Liang Ma, Le-Qun Li
Journal: Journal of Clinical Oncology (2017)

257 Background: Lamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few studies have directly compared their therapeutic efficacy and treatment cost. This study aims to compare LAM with ADV head-to-head in these patients. Methods: We retrospectively analyzed 201 patients with HBV-related HCC who underwent radical resection and subsequently received LAM (n = 155) or ADV (n = 46). The two groups were compared in terms of HBV-DNA levels, liver function, antiviral resistance, recurrence-free and overall survival, as well as antiviral medication costs. Results: Despite significant improvement in HBV-DNA and ALT level in the LAM group after 1 year of antiviral therapy, these parameters did not differ significantly between the two groups over the following 2 years. Incidence of antiviral resistance after 1, 2 and 3 years of antiviral treatment was significantly higher in the LAM group (19.5%, 45.7%, 56.4%) than in the ADV group (0%, 3.3%, 14.5%; P &lt; 0.001). Overall survival at 1, 2, 3 years after resection was similar for the LAM group (84.5%, 69.3%, 64.6%) and the ADV group (84.1%, 77.8%, 63.4%; P = 0.905). Recurrence-free survival at the three follow-up points was also similar for the LAM group (71.7%, 58.3%, 43.9%) and the ADV group (81.1%, 66.1%, 53.0%; P = 0.452). Cox regression analysis confirmed that both nucleos(t)ide analogues were associated with similar overall and recurrence-free survival. However, the average medication costs after 1, 2, 3 years of antiviral treatment were significantly higher in the LAM group (€3.0, €4.8, €5.6 per person per day) than in the ADV group (€2.2, €2.4, €3.1 per person per day; all P &lt; 0.05). Conclusions: ADV and LAM are associated with similar survival benefit in patients with HBV-related HCC after radical resection, but ADV is more cost-effective.
Prognostic implications of serum crosslinked-n-terminal telopeptide of type I collagen (NTx) for patients with initial prostate carcinoma.
Authors: Fernando Jablonka, Marcelo L. Wroclawski, Fernando L. A. Fonseca, Marcelo Szwarc, Marcos Tobias Machado, Webster de Oliveira Vitoria, Auro Del Giglio
Journal: Journal of Clinical Oncology (2013)

e16030 Background: NTx is a metabolite of type I collagen, the main constituent of bone matrix, which has been previously shown to be increased in patients with bone metastasis. We wanted to evaluate NTx role in sample PCa patients at diagnosis when most of them have no overt bone involvement. Methods: Men with a histologic diagnosis of PCa at diagnosis were included. Serum Ntx was measured serially every 3 months up to two years by ELISA with the osteomark NTx Serum kit. Results: 55 PCa patients with a median age of 67 years (51 – 83), 86% with stage I, 4% with stage II, 2% with stage III and 10% with stage IV were included. At entry median NTx was of 14.65 nM and it did not correlate with age, Gleason score or PSA but we observed a significant direct correlation with stage (p = 0.0094). With a median follow up of 23 months, at diagnosis, Seum Ntx correlated significantly with biochemical recurrence (p = 0.012) as did Gleason score (p = 0.00056), Stage (p = 0.012) and PSA (p &lt; 0.0001). By multivariate analysis the only 2 independent variables significantly correlated with biochemical recurrence were PSA (p = 0.046) and NTx (p = 0.021). Conclusions: We conclude that Serum Ntx has potential prognostic value in PCa patients at diagnosis and may improve current prognostic models. These data stress the potential prognostic importance of bone metabolism biomarkers for PCa patients even in the absence of overt bone involvement. Supported by: FAPESP.
mTOR inhibitor-associated noninfectious pneumonitis in patients with metastatic renal cell cancer: A single-center experience.
Authors: Diana H. Cauley, Bradley J. Atkinson, Chaan S. Ng, Randall E. Millikan, Lianchun Xiao, Paul Gettys Corn, Eric Jonasch, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2013)

e15612 Background: Noninfectious pneumonitis (NIP) is a known adverse effect of mTOR inhibitors, with a reported incidence of 25-45%. The goal of this review was to characterize the incidence, onset, management, and clinical outcomes of pts with mRCC who experienced mTOR inhibitor-associated NIP at our tertiary cancer center. Methods: Retrospective review of 310 mRCC pts who received everolimus and/or temsirolimus between 6/1/2007 and 10/1/2010. Clinical correlation was made in conjunction with serial radiologic imaging studies. Results: 36 mRCC pts (12%) treated with an mTOR inhibitor developed NIP with a median time to symptom onset of 65 d (21-855) and radiographic appearance of 62.5 d (35-736). 23 pts (21%) received everolimus compared to 13 pts (6%) who received temsirolimus (P&lt;0.0001). Median time to onset, radiographic appearance, and NCI CTCAE pneumonitis grade did not differ significantly between treatments (P=NS). Increased age (OR 1.04; 95% CI: 1.004-1.08) and everolimus (OR 4.106; 95% CI: 1.96-8.6) were associated with a greater risk of NIP. NCI CTCAE grade 2 NIP severity was most common (78%). mTOR inhibitor therapy was discontinued in 9 pts (25%); continued at same dose in 7 pts (19%), dose reduced in 2 pts (6%); held and resumed at lower dose in 2 pts (6%), and held and then resumed at same dose in 1 pt (3%). Median time on treatment was greater for pts who developed NIP; 4.1 vs 2 mo (P=0.035). Median OS was significantly greater for NIP pts; 15.4 vs 7.4 mo (P&lt;0.0001). 3-yr survival of NIP pts was 35.4% vs 7.2% (P&lt;0.0001). Predictors of improved OS included NIP (HR 0.315; 95% CI: 0.2-0.495; P&lt;0.0001). Conclusions: A higher incidence of NIP was observed in mRCC pts treated with everolimus than temsirolimus. The finding of improved OS in pts who developed NIP is intriguing and should be further investigated.
Long-term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom macroglobulinemia.
Authors: Irene M. Ghobrial, Morie A. Gertz, Betsy LaPlant, John Kelly Camoriano, Suzanne R. Hayman, Martha Lacy, Stacey Chuma, Brianna Harris, Erica Boswell, Ranjit Banwait, Patricia Sheehy, Stephen Maxted Ansell, Daniel J DeAngelo, Angela Dispenzieri, Leif Bergsagel, Craig B. Reeder, Kenneth Carl Anderson, Paul Gerard Guy Richardson, Steven P. Treon, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2012)

8043 Background: The mammalian target of rapamycin (mTOR) signal pathway controls cell proliferation and survival. The trial's goal was to determine the anti-tumor activity and safety of single-agent everolimus (TORC1 inhibitor) in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM). Methods: Eligible patients had measurable disease (IgM monoclonal protein &gt;1000 mg/dL with &gt;10% marrow involvement or nodal masses &gt;2 cm), a platelet count ≥75,000 x 10 6 /L, a neutrophil count ≥1,000 x 10 6 /L. Patients received everolimus 10 mg PO daily. Tumor response was assessed after cycles 2 and 6 and then every 3 cycles until progression. Results: 60 pts were treated. The median age was 64 years (range, 43-85). The median number of prior therapies was 3 (range, 1-11). All but two patients (97%) had received prior rituximab based therapy and 64% of patients had received prior alkylator based therapies. The overall response rate (complete response CR+ partial response PR+ minimal response MR) was 73% (95% CI: 60-84%), with a PR of 50% and 23% MR. The median time to progression (TTP), progression-free survival (PFS), and overall survival (OS) for the entire study population is 28 months (mos), (95% CI: 18-not reached (NR)), 22 mos (95% CI: 12 0-NR), and 55 mos (95% CI: 55-NR), respectively. The estimated PFS at 12 and 24 months is 62% (95%CI: 51-75%), and 48% (95%CI: 37-63%), respectively. The 30 patients who achieved a PR responded after a median of 2 months (range, 1-26) of treatment. The median duration of response (DR) for these patients has not yet been reached and 19 of these patients remain in response after a median follow up of 31 months (range, 3-54). All but two patients had a decrease in their serum IgM. Grade 3 or higher related toxicities were observed in 67% of patients. The most common were hematological toxicities with cytopenias. Pulmonary toxicity occurred in 5% of patients. Dose reductions due to toxicity occurred in 63% of patients. Conclusions: Everolimus has high single-agent activity with an overall response rate of 73% and manageable toxicity in patients with relapsed WM, and offers a potential new therapeutic strategy for this patient population.
End-of-life care: Empowering cancer patients with information and choices
Authors: K. Tucker
Journal: Journal of Clinical Oncology (2009)

e20739 Background: Terminally ill patients want information and choices, including aid in dying, as they confront death due to cancer and other terminal illnesses. Physicians treating such patients want to feel safe in having candid conversations with patients about their wishes and to provide aid in dying when appropriate. Methods: Review the law governing end of life decision making, including aid in dying. Review the data from Oregon, which has more than 10 years experience with a regulated practice. Review what has been learned in OR, and how that is transferring to other states making aid in dying an end of life option. Results: Oregon's experience shows that when aid in dying is a legal option for mentally competent terminally ill patients overall end of life care improves. Conversations between physicians and patients are more open and candid; Referrals to hospice increase and occur earlier; clinician enrollment in CE for pain and symptom management increase; rx of strong pain medication increase; more patients die at home; patients are comforted to have aid in dying as an option; there is no negative impact on the practice of medicine. Conclusions: Terminally ill patients should be able to recieve comprehensive counseling about all end of life options. There is a growing trend of support for expanding end of life options to include aid in dying for mentally competent terminally ill patients who find themselves trapped in an unbearable dying process. No significant financial relationships to disclose.
Association of perioperative venous thromboembolism with long-term oncologic outcomes following radical cystectomy.
Authors: Harras B. Zaid, Matthew K. Tollefson, Igor Frank, William P. Parker, Robert Houston Thompson, Robert F. Tarrell, Prabin Thapa, John C. Cheville, Stephen A. Boorjian
Journal: Journal of Clinical Oncology (2017)

364 Background: Venous thromboembolism (VTE) has been reported to occur in 2-5% of patients undergoing radical cystectomy (RC). While VTE is an important cause of perioperative morbidity, the association of these events with long-term cancer prognosis has not been established. Herein, we evaluated the association of perioperative VTE with patients’ risk of subsequent disease recurrence and mortality. Methods: We reviewed 2889 patients undergoing RC between 1980−2009 at the Mayo Clinic to identify patients diagnosed with a VTE within 90 days of RC. These cases were then matched in a 1:2 fashion to control patients undergoing RC who did not develop VTE. Matching was performed on the basis of age, BMI, receipt of neoadjuvant chemotherapy, and pathologic T and N stages. Recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were estimated utilizing the Kaplan-Meier method and compared with the log-rank test. Results: A total of 132 patients with a VTE within 90 days of RC were identified, accounting for 4.6% of all patients analyzed. These cases were matched to 257 controls per criteria noted above, and were overall well-matched. Of the 389 patients in this study, median follow-up after RC was 9.2 years, during which time 152 (39%) patients experienced recurrence and 306 (78%) died, including 157 (40%) who died of bladder cancer. We found no significant difference in 5-year RFS (59% versus 61%; p = 0.75); CSS (57% versus 64%; p = 0.13); or OS (45% versus 50%; p = 0.15) between patients with versus without perioperative VTE, respectively. Conclusions: We found that VTE within 90 days of RC did not significantly impact long-term cancer outcomes. While these events represent an important cause of perioperative morbidity, no interaction with oncologic control was noted, and patients may be counseled accordingly.
CGTG-102 (Ad5/3-D24-GMCSF), a novel oncolytic adenovirus, in patients with refractory solid tumors: Experience from an advanced therapy access program.
Authors: Mikael Von Euler, Anna Kanerva, Petri Nokisalmi, Anniina Koski, Iulia Diaconu, Vincenzo Cerullo, Timo K. Joensuu, Minna Oksanen, Sari Pesonen, Lotta Kangasniemi, Tuuli Ranki, Raita Heiskanen, Akseli Hemminki
Journal: Journal of Clinical Oncology (2012)

e13035 Background: Following preclinical testing CGTG-102, a 5/3 chimeric oncolytic adenovirus armed with human GMCSF, has been used to treat 115 refractory cancer patients. Methods: Eligibility criteria included refractory advanced solid tumors, no major organ deficiencies and written informed consent. Patients were treated with either a single treatment or serial treatments with one or more viruses. Intra tumoral administration was performed under ultrasound guidance. The initial dose, 8 x 10 10 Viral Particles (VP), was based on published safety results and preclinical testing and escalated in later patients. A routinely tolerated dose of 3 x 10 11 VP was deemed optimal and is the target dose for clinical development. To reduce regulatory T-cells, low-dose cyclophosphamide 50 mg/day was given. Adverse Reactions (AR) were scored according to CTCAE 3.0. Imaging was done by CT before and ~2 months after treatment. Response was scored according to RECIST 1.1, including injected and non-injected lesions. Decrease not fulfilling PR was scored as minor response (MR). Results: The most common ARs were pain (82%), fever (81%), fatigue (79%), nausea (54%) and hemoglobin decrease (48%). Pain is mostly tumor pain or pain in the injected tumor, which may be causally related to the MOA of the therapy. Most ARs were G1 or G2; 6 were G4: 2 Hb decrease, 2 pulmonary embolism and single reports of thrombocytopenia and pericardial effusion, most probably due to the underlying disease.Imaging was performed when clinically useful. 65/115 are evaluable by imaging: 3% PR, 11% MR, 40% SD and 46% PD. Best results were obtained in Breast Cancer, Melanoma, Soft Tissue Sarcoma, Mesothelioma and Ovarian Cancer. Median survival in this heavily pre-treated refractory population is 164d, 95% CI 122d – 206d. Mean survival is 281d reflecting that approx. 30% survive more than 300d and 15% up to 600d. A wide range of samples are being analyzed to further characterize the viral and immunological aspects of the therapy. Conclusions: CGTG-102 is a novel oncolytic adenovirus with good safety profile and encouraging signs of efficacy. Formal clinical studies are underway in several tumor types in both US and EU.
Maintenance erlotinib (E) following first-line treatment with docetaxel, carboplatin and erlotinib in patients with ovarian carcinoma
Authors: P. A. Vasey, J. Paul, G. Rustin, R. Wilson, J. Guastalla, E. Pujade-Lauraine, M. Gore, H. Gabra, K. Carty, S. Kaye
Journal: Journal of Clinical Oncology (2007)

5560 Background: We previously reported on the feasibility of a combination of erlotinib (E; a HER1/EGFR tyrosine-kinase inhibitor) with platinum and taxane chemotherapy (Agarwal et al, Ann Oncol 2004) and reported that almost 1/3rd patients (pts) stopped E during treatment due to toxicities which included intolerable rash, diarrhea and neutropenic sepsis. This update reports on those pts who then received E at 150mg daily as maintenance treatment. Methods: 48 pts initially received docetaxel (75 mg/m 2 ) and carboplatin (AUC 5) following surgery q21d for 6 cycles in combination with daily oral E (50–100 mg) in dose-escalating cohorts. After 6 cycles, pts could continue with E alone (150mg/d) until progression. Results: 27 pts (56%) continued E beyond chemotherapy for a median of 8.6 months (mo) (range 2.3–32.5 mos), and 23/27 were escalated as planned to daily. Subsequently, 12/27 (44%) pts had their dose either reduced or interrupted for toxicity, which was cutaneous in 10/12 (83%) pts. However, the incidence of = grade 2 toxicity was low apart from alopecia (24%), rash (18%) and fatigue (15%). During follow-up (36 mo) 22/27 (81%) pts stopped E due to progressive disease and 3/27 (11%) stopped E due to cutaneous toxicity. Only 2/27 (7%) pts continue to receive E without evidence of progression, both at doses less than 150mg, again due to cutaneous toxicity. Pts receiving maintenance E had a median progression-free survival of 14.8 mo (95% CI 12.6–17.1 mo) and median overall survival 37.0 mo (95% ci 31.6–42.4 mo); for all pts these figures were 12.5 mo (95% CI 9.1–15.9 mo) respectively, and 37.0 mo (95% ci 27.3–46.7 mo). Conclusions: Maintenance E at 150mg daily following initial treatment with E plus docetaxel-carboplatin for ovarian carcinoma is associated with cutaneous toxicity which limits the dose and duration of treatment in a proportion of pts. The potential benefit of this approach can only be addressed in a randomized trial, and this is now underway under the auspices of the EORTC. A parallel translational study will examine the possibility that patients most likely to benefit can be predicted by molecular tumor analysis. [Table: see text]
Frequency of TLE3 overexpression in breast carcinoma subtypes including a large cohort of triple-negative patients.
Authors: Gargi D. Basu, Anatole Ghazalpour, David Arguello, Raheela Ashfaq, Zoran Gatalica, Matthew Jerome McGinniss, Richard Blevins, Kathleen D Danenberg
Journal: Journal of Clinical Oncology (2012)

1040 Background: The taxanes are an important class of agents for the treatment of a broad range of malignancies including breast cancer. They improve survival in patients with early stage and metastatic breast cancer. Transducin-like enhancer of split 3 (TLE3) is a transcriptional repressor which influences growth and microtubule stability and its expression has been implicated in response to taxane therapy in breast cancer. We investigated the tumor expression of TLE3 in breast cancer patients, including a large cohort of the triple negative subtype. Methods: We analyzed TLE3 (M-201), ER(1D5), PR(PgR636) and HER2/neu(Polyclonal) expression by immunohistochemistry in 978 breast cancer patients. Immunoreactivity was assessed by scoring the percentage of cells stained in each field and by the intensity of staining. Results: To sub-classify the 978 breast cancer patients, we utilized hormone receptors (ER and PR) and HER2 expression/amplification. Overall, 36% of the total breast cancer patients were hormone receptor positive, 15% were HER2 positive and 49% were triple negative. The percentage of triple negative patients was higher in our cohort, given the fact that molecular profiling services are used more frequently for this subtype. A total of 477 patients were triple negative of which 61% stained positive for TLE3 expression. Of the 150 HER2 positive patients, 73% stained positive for TLE3 expression as compared with 82% TLE3 positivity in the 351 hormone receptor positive patients. By pairwise comparison, the hormone receptor positive vs triple-negative subtype showed the highest statistical significance in ratios of TLE3 positives (p =2.5e-10). Conclusions: Our results show that TLE3 is over-expressed in the majority of HER2 positive and hormone receptor positive breast cancer patients. Interestingly, the frequency of over-expression of TLE3 was lowest in the triple negative subtype thereby making it more important to identify those patients in this group who are most likely to respond to taxanes prior to therapy. To our knowledge, this is the first study providing a comprehensive review of TLE expression in breast cancer subtypes.