tbuckley/cabot-search huggingface dataset:
Phase I study of sorafenib in combination with low-dose cisplatin and fluorouracil intra-arterial infusion chemotherapy.
Authors: K. Ueshima, M. Kudo, M. Tanaka, T. Kumada, T. Sakurai, H. Chung, S. Hagiwara, Y. Minami, T. Inoue, N. Yada, S. Kitai, M. Takita, S. Hayaishi
Journal: Journal of Clinical Oncology (2011)

e14563 Background: This study aimed to determine the recommended dose for combination therapy of sorafenib with hepatic arterial infusion of low dose cisplatin and fluorouracil in patients with advanced hepatocellular carcinoma (HCC). Methods: Cohorts of 3 to 6 patients received an escalated dose of cisplatin and fluorouracil until the maximum tolerated dose was reached. Sorafenib was administered orally at a dose of 400 mg bid for 28 days. Cisplatin at a dose of 10-20 mg/m2 was administered at day 1 and day 8, and fluorouracil at a dose of 170-330 mg/m2 was administered continuously at days 1-5 and days 8-12 via an implanted catheter system. A cycle was defined as 28 days and 3 cycles of this combination therapy was continued. At the end of the first cycle, adverse effects were evaluated and dose escalation was determined. Results: Eighteen patients with advanced HCC were enrolled in this study. The dose-limiting toxicity was observed in 2 patients at dose level 1 (erythema multiforme and grade 4 thrombocytopenia) and in 1 patient at dose level 2 (erythema multiforme). Seven of 18 patients achieved a partial response, 7 achieved stable disease, 2 achieved progressive disease, and 2 were not assessable. The response rate was 38.9% and the disease control rate was 77.8%. The time to progression was 9.7 months (95%C.I., 5.4-14.0) and 1-year survival was 88.2%. Conclusions: According to protocol, sorafenib orally at a dose of 400 mg bid, intra-arterial infusion of cisplatin at a dose of 20 mg/m2, and 5-FU at a dose of 330 mg/m2 were decided as the recommended dose of this combination therapy. This combination therapy is well tolerated and efficacious, and it is a promising therapy for patients with advanced HCC. In order to confirm the efficacy of this therapy, the large cohort study is now currently investigated (n=190; Clinicaltrials NCT01214343).
Long-term treatment outcome of nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT).
Authors: M. K. Kam, S. Leung, K. Yu, A. D. King, R. M. Chau, K. Cheung, B. Ma, E. P. Hui, A. T. Ahuja, A. T. Chan
Journal: Journal of Clinical Oncology (2010)

5582 Background: A number of centers have reported promising early results of treating NPC patients using IMRT, in terms of locoregional control and parotid sparing. This study evaluated the sustainability of early favorable results, and late events. Methods: 231 consecutive NPC patients were treated with IMRT between 2000 and 2005. The proportion of stage I, IIA, IIB, III, IVA, and IVB disease was 8%, 5%, 14%, 32%, 28%, and 13% respectively. The prescribed dose was 66 Gy over 33 daily fractions to the gross tumor, 60 Gy to the planning target volume, and 54–60 Gy to the clinically negative neck. Majority of T1-2a patients received brachytherapy boost (12 Gy/ 4 fractions), and T2b-T4 patients received conformal or IMRT boost (6-8 Gy/ 3-4 fractions). Stage III–IVB patients also received concurrent chemotherapy, with or without neoadjuvant chemotherapy. Results: The median follow-up period was 59 months. The overall 6-year local failure-free survival (LFFS), regional failure-free survival (RFFS), distant metastasis-free survival (DMFS), and overall survival (OS) was 82%, 91%, 75%, and 66% respectively. Between 3 to 6 years there was a drop in LFFS, RFFS, and OS, while DMFS plateaued. Local failure was dominated by within-field failure (85%). 68% of local failure involved the skull base and intracranial region (rT3/4). Only two patients developed visual impairment despite a proportion of T3/4 patients had received > 54Gy to the optic nerves or chiasm. Radiation-induced malignancy occurred in 3 patients (2 in oral tongue, 1 in nasal cavity). The 5-year cumulative incidence of radiation-induced tongue cancer was 1.43%, higher than that seen after 2-dimensional radiotherapy. Conclusions: Although IMRT at a dose between 66-74 Gy achieves good early response and promising late toxicity profile, further locoregional recurrence can be seen on longer follow-up, especially at or above skull-base region. More vigorous use of adaptive and image-guidance radiotherapy may be needed to overcome potential setup error and volumetric changes during treatment course. The incidence of radiation-induced oral tongue cancer warrants further assessment. No significant financial relationships to disclose.
Survival analysis by pooling risk factors in AVAGAST: First-line capecitabine and cisplatin plus bevacizumab (bev) or placebo (pla) in patients (pts) with advanced gastric cancer (AGC).
Authors: Y. Kang, A. Ohtsu, E. Van Cutsem, L. Roman, J. Nunes, C. Li, D. Otero, F. Rivera, G. Aprile, P. R. Pimentel Alvarez, M. H. Moehler, J. Wu, B. Langer, M. A. Shah
Journal: Journal of Clinical Oncology (2011)

4119 Background: A difference in median overall survival (OS) of 2 months between treatment arms was observed in AVAGAST, but the result was not significant. However, significant differences in OS between regions were seen, with more benefit in the region with poorer survival. Furthermore, multiple Cox-regression analysis for OS revealed 5 covariates with significant prognostic value. A simple prognostic index with 3 risk groups (RG) was created to test impact of RG and region on OS. Methods: Multiple Cox regression showed (apart from regional differences) significant impact on outcome for: ECOG PS >1 (HR=1.95; p=0.0003), prior gastrectomy (0.66; 0.0005), bone mets (1.71; 0.0097), intestinal type histology (0.74; 0.003) and peritoneal mets (1.39; 0.0015). 774 pts were sorted by number of negative prognostic factors present at baseline and pooled into 3 different RGs: low (no covariates involved); moderate (1 covariate); high (>1 covariate). Because of the large prognostic impact, ECOG PS >1 and bone mets received a score of 2. OS survival analysis was performed by RG and region. Results: Approx. 10% of pts belonged to the low RG, 30% to the moderate RG and the remaining 60% to the high RG. OS by RG and region are shown in the table. Conclusions: Outside of Asia, high-risk pts with AGC may benefit from the addition of bev to cisplatin/capecitabine. This predictive effect was not observed for pts with ≤1 risk factors, although there were few pts with 0 or 1 risk factors. The lack of efficacy of treatment in Asian pts with AGC cannot be explained by the number of prognostic factors at baseline. Risk group Region Patients per arm (bev/pla) Hazard ratio 95% CI P value Low All 27/31 1.60 0.67–3.81 0.2869 Asia 8/17 2.38 0.50–11.32 0.2621 Europe 13/8 1.07 0.29–4.00 0.9170 Americas 6/6 2.62 0.24–29.02 0.4135 Moderate All 101/108 0.96 0.68–1.37 0.8428 Asia 43/47 0.95 0.54–1.66 0.8611 Europe 43/39 1.23 0.72–2.10 0.4468 Americas 15/22 0.63 0.26–1.51 0.2967 High All 259/248 0.80 0.65–0.98 0.0307 Asia 137/124 0.99 0.74–1.33 0.9604 Europe 68/78 0.59 0.41–0.85 0.0043 Americas 54/46 0.60 0.38–0.94 0.0246
Genetic Susceptibility to Therapy-Related Leukemia (t-MDS/AML) After Hodgkin Lymphoma (HL) or Non-Hodgkin Lymphoma (NHL).
Authors: Yan Ding, Can-Lan Sun, Liton Francisco, Melanie Sabado, Liang Li, Brian Hahn, Garrett Larson, Stephen J. Forman, Ravi Bhatia, Smita Bhatia
Journal: Blood (2009)
In vitro and in vivo antitumor activities of a small and novel synthetic molecule: A potential therapy for hepatocellular carcinoma.
Authors: K. I. Batarseh
Journal: Journal of Clinical Oncology (2011)

300 Background: A small (molecular weight of 275) and novel pharmaceutically silver (I)-tartaric acid complex given the title name aliargentumycine was recently synthesized and the results on its in vitro cytotoxicity and mechanism of action on solid and hematopoietic malignancies were reported. Here the therapeutic potential of aliargentumycine on hepatocellular carcinoma was investigated. Methods: The in vitro and in vivo antitumor activities of aliargentumycine were studied on human HepG-2 xenograft model grown subcutaneously in female immunodeficient mice. Aliargentumycine was administered intratumorally, intravenously and orally twice a week at various concentrations. Results: The IC 50 of aliargentumycine was found to be 1.49 ± 0.067 mg/ml, which is comparable to the value of 1.04 ± 0.07 mg/ml for doxorubicin, and almost half the value of 2.87 ± 1.02 mg/ml for sorafenib tosylate. The in vivo results demonstrated excellent statistically significant antitumor activities for the intratumoral, intravenous and oral routes of administration with P i.t. &lt; 0.00001, P i.v. &lt; 0.005 and P p.o. &lt; 0.003, respectively. Some animals showed complete tumor remission (tumor-free), and no tumor re-growth was observed even after treatment was stopped. Nonlinear regression on the data revealed that aliargentumycine results in significant tumor growth delay. All treated animals did not show any commonly observed signs of toxicity, including no body weight loss (p &gt; 0.05). Mantel-Cox statistical tests revealed that there were significant tumor growth delays (p &lt; 0.05) and survival advantages (p &lt; 0.05). Conclusions: These promising findings might have great therapeutic potential on the future clinical treatment of hepatocellular carcinoma using aliargentumycine. No significant financial relationships to disclose.
Allogeneic Hematopoietic Stem Cell Transplantation Overcomes the Adverse Prognostic Impact of Minimal Residual Disease in Acute Myeloid Leukemia
Authors: Betul Oran, Timothy Singleton, Pablo A. Ramirez, Ryan Shanley, Claudio Brunstein, Celalettin Ustun, Erica D Warlick, Daniel J. Weisdorf
Journal: Blood (2011)
Association of modern era adjuvant chemotherapy with improved survival in patients with stage II colon cancer.
Authors: Leigh Casadaban, Dana Villenes, Garth Rauscher, Mebea Aklilu, Ajay V. Maker
Journal: Journal of Clinical Oncology (2015)

671 Background: Patients are often selected for adjuvant therapy after resection of stage II colon cancer based on the presence of poor risk factors. However, the survival advantage of chemotherapy in this population is unclear and there remains variation in clinical practice. Methods: The National Cancer Data Base was analyzed for colon cancer patients treated 1998-2006. The primary outcome was OS between patients who did or did not receive adjuvant chemotherapy. Additional stratification variables included high-risk disease features, age, multi-agent chemotherapy, and diagnosis after 2004 when oxaliplatin was approved for adjuvant therapy. Demographic and disease information was compared using the Pearson Chi-squared test and binary logistic regression, effect size with Cramer's V/Phi for categorical variables, and survival data with Cox regression. Propensity score weighting was utilized to account for the possibility of selection bias. Results: Of 1,078,091 patients with colorectal cancer, 153,110 stage II colon cancer patients met inclusion criteria. Mean age was 72, 46% were male, 84% stage IIA (AJCC 6 th ed.), 9% stage IIB, and 20% received adjuvant chemotherapy. Predictors of receiving treatment included age&lt;65, male gender, community treatment facility, geographical location, non-Medicare insurance, education level, and diagnosis before 2004. All patient sub-groups analyzed experienced improved OS with adjuvant chemotherapy regardless of the number of high-risk features, age, multi-agent chemotherapy, or adjustment for covariates. Median OS was 13.2 years in the chemotherapy group and 7.0 years in the no-chemotherapy group (p&lt; 0.001). Median and 5-year OS was improved in both high and low-risk patients who received chemotherapy compared to those who did not with a median follow-up &gt;5 years. Conclusions: This large-scale study with long-term follow-up demonstrated that adjuvant chemotherapy was associated with a clinically relevant improvement in OS regardless of treatment regimen, patient age, or high-risk features in patients with resected stage II colon cancer. The results of this retrospective analysis warrant further investigation in prospective trials.
Surface applicator high-dose-rate fractionated brachytherapy for conservative definitive management of extramammilary Paget’s disease of the penis, scrotum, and mons pubis.
Authors: Phillip M. Devlin
Journal: Journal of Clinical Oncology (2013)

333 Background: This case is of a 70 yo Asian male who had suffered for many years from a painful eroding, oozing, bleeding lesion that started on the mons and over time had spread the full length of the penis and onto the anterior scrotum. A surface mold applicator fractionated computer-optimized high-dose rate (HDR) brachytherapy to 50Gy given in 2 Gy/day 5 days/week for 5 weeks. Methods: For the mons and the anterior scrotum a flat plate of aquaplast was molded with an aperture through which to pass the penis. For the penis a soft wrap, make of two layers of 5mm superflab was created with 15 truguide catheters embedded between. The wrapped penis was then supported with towels and tapes. Using radio-opaque dummy markers a CT was generated and an optimized treatment plan using Oncentra Brachytherapy. Because of the need for daily setups and the intrinsically elastic nature of the penis and scrotum, effort was made to keep the dwell times even so as to minimize any effect from day to day variation in set up. The prescription isodose line was manually adjusted so that where possible there was sparing of deep tissue of the urethra, bladder and testes. When QA was approved the patient began with daily treatments and successfully completed 25 without a treatment break. Results: Sustained local control was observed. Discussion: Surface mold applicator brachytherapy provides the most conformal of radiation therapy to complex superficial targets. For these targets it compares most favorably with all external beam approaches including electron, photon, IMRT and proton therapy. Conclusions: This modality optimally treated these lesions. The depth of the dose can be modulated. The treatment plan can be adapted to deal with swelling late in the course of therapy. The chance of a geographic miss of therapy is low because of the direct application to the affected area.
Laparoscopic hepatic resection: Favorable short-term outcomes for colorectal cancer metastases of the left hemiliver.
Authors: C. K. Enestvedt, B. S. Diggs, B. C. Sheppard, S. Orloff, K. G. Billingsley
Journal: Journal of Clinical Oncology (2011)

347 Background: Recent reports demonstrate the feasibility of laparoscopic liver resection for patients with benign and malignant conditions. We hypothesized that patients who underwent laparoscopic resections for colorectal cancer (CRC) metastases of the left liver would have short-term outcomes similar to those who had open surgery. Methods: A retrospective review compared laparoscopic left liver resections for CRC metastases to open controls for the years 2005-2010. There were two anatomic left hepatectomies in each group, with lesser segmentectomies in the remainder. Demographic information, pathology, tumor characteristics, procedure related factors, complications, and mortality were assessed. Univariate analysis was performed with significance of p&lt;0.05. Results: Nine patients had laparoscopic resection during the study period, with 1 case converted to open (11%). There were no differences in demographics, tumor factors, margins, or major complications (Table). The laparoscopy group had significantly lower intraoperative blood loss and shorter length of stay compared to the open group. There were no deaths in either group. Conclusions: In this select group of patients undergoing resection of the left hemi-liver for CRC metastases, short-term outcomes favored the laparoscopic approach. Long- term data regarding disease recurrence and survival are needed in this group of patients. These results indicate that surgeons should consider laparoscopic resection of the left liver whenever technically feasible in the setting of CRC metastases. [Table: see text] No significant financial relationships to disclose.
Phase I trial of personalized peptide vaccine for HLA-A24 positive patients with advanced cancer
Authors: M. Terasaki, M. Noguchi, S. Naito, H. Uemura, H. Akaza, S. Sibui, T. Fujimaki, T. Aoki, K. Itoh
Journal: Journal of Clinical Oncology (2008)

3079 Background: A personalized selection of the right peptides for each patient could be a novel approach of cancer vaccine for boosting anti-cancer immunity in the majority of patients. Our approach is a pre-vaccination measurement of peptide-specific IgG in cancer patients reactive to 14 kinds of vaccine candidates (ITK-1) with the ability to induce CTLs, followed by administration of only reactive peptides (personalized peptide vaccine). Methods: To evaluate safety, tolerability and immune responses of the vaccination, 27 HLA-A24 positive patients with advanced cancer, 12 recurrent glioblastoma multiforme (GBM) and 15 advanced hormone-refractory prostate cancer (HRPC) patients, were enrolled in a phase I clinical trial. Pre-vaccination plasma was measured for their IgG levels to each of ITK-1 peptides followed by weekly subcutaneous administration of the top four peptides showing the strongest antibody responses for 6 times at the 3 different dose settings (1mg, 3mg, and 5mg per peptide). The protocol was approved by each ethics committee. Results: There were no severe adverse events, but grade 2 skin reactions at the injection sites were observed in 3 of 12 patients receiving 1mg/peptide, and 8 of 12 patients receiving 3mg. Vaccination schedule was skipped or disconnected in 3 of 3 patients receiving 5mg because of both grade 2 skin reactions in wider regions and patients’ claim. The recommended dose of ITK-1 peptides is 3mg/peptide in patients with advanced cancer. In the post (6th)-vaccination samples, CTL responses measured by IFN-γ release assay were boosted in 8 of 12 patients with 1mg/peptide and 9 of 11 patients with 3mg/peptide tested, while IgG responses were boosted in 5 of 12 and 5 of 11 pts, respectively. After the 6th vaccination, a prostate-specific antigen decline of at least 30 percent occurred in 1 and 3 of each 6 HRPC patients with 1mg and 3 mg/peptide, respectively. Two recurrent GBM patients showed partial response by RECIST criteria when received continuing vaccination. Conclusions: This personalized vaccine with ITK-1 peptides could be recommended for further stages of clinical trials because of safety, higher frequency of immune responses with potential clinical benefits. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GreenPeptide GreenPeptide GreenPeptide GreenPeptide GreenPeptide GreenPeptide
Genome-wide interaction study of gemcitabine treatment and genotype on survival in pancreatic cancer.
Authors: R. R. McWilliams, W. R. Bamlet, M. Matsumoto, G. P. Kim, P. A. Burch, D. Grendahl, G. M. Petersen
Journal: Journal of Clinical Oncology (2011)

4022 Background: Gemcitabine (gem) is commonly given for all stages of pancreatic adenocarcinoma (PC). However, it is not known a priori which patients will benefit from gem treatment compared to other treatments such as FOLFIRINOX. It is possible that germline variation may influence the efficacy of gem. Therefore, we performed a treatment-benefit interaction study of gem exposure with genome-wide single nucleotide polymorphisms (SNPs) on PC survival. Methods: We performed a two-stage cohort survival study of PC patients from the Mayo Clinic Pancreas Biospecimen Resource from 2000-08. In the first stage, we assessed data on 550,000 SNPs from 413 pts [median age 68, 56% male, 35%/34%/31% resected/locally advanced/metastatic (R/LA/M)] with PC for a Cox regression analysis assessing the interaction of gem treatment (Y/N) and genotype on survival, adjusted for age, stage, sex, and BMI. SNPs were also correlated with treatment toxicity. The 100 most significant SNPs from this first stage were used for a replication study of another 527 pts (median age 65, 53% male, 34%/32%/33% R/LA/M). Survival was assessed from first diagnosis to death (84% had died), and only patients with complete treatment records were included. Results: Nine SNPs interact with the same direction of effect (Table), including genes affecting apoptosis, reactive oxygen species, and other genes. PYCARD and MAPRE2 were strongly significant in both stages. MAPRE2, EPHB1, and NOX4 expression have previously been reported to affect chemosensitivity in pancreatic cancer cells in vitro. Conclusions: In a two-stage study, multiple SNPs appear to be predictive of the efficacy of gem therapy. No effects on gem toxicity were identified. SNP Gene Adjusted p value for interaction variable of genotype and gem exposure on survival Stage I (N=413) Stage II (N=527) Combined (N=940) rs6507115 MAPRE2 1.81 x 10-6 1.5 x 10-3 4.8 x 10-9 rs497279 NOX4 1.6 x 10-5 0.02 5.8 x 10-8 rs8056505 PYCARD 6.1 x 10-5 9.1 x 10-4 1.97 x 10-7 rs4889426 PLCG2 4.0 x 10-6 0.04 3.1 x 10-7 rs1021584 LOC100131418 4.5 x 10-5 0.03 5.9 x 10-7 rs7243052 PARD6G 2.5 x 10-4 0.01 2.7 x 10-6 rs1457784 KCNQ3 2.4 x 10-6 0.03 4.0 x 10-6 rs11130399 CACNA2D3 1.9 x 10-5 0.02 5.5 x 10-6 rs36064 EPHB1 3.6 x 10-4 0.04 1.5 x 10-5
Intervention model for cancer control in a low-income African area.
Authors: N. Masalu, A. Farolfi, P. Serra, L. Faustine, B. Kopf, C. R. Majinge, D. Amadori
Journal: Journal of Clinical Oncology (2011)

e16539 Background: Cancer outcome is an emergency in low-income areas (LIAs) such as Tanzania, where incidence is 84 and 91 per 100,000 males and females, respectively. Prior to 2008, an Oncology Department (OD) did not exist at Bugando Medical Center (BMC), Mwanza, Tanzania (catchment area of 14 million people). Methods: Thanks to an agreement between BMC, Association Tison, IRST, and Istituto Oncologico Romagnolo, a Pathology Laboratory and an OD were instituted in 2000 and 2008, respectively. The oncology team comprises a multidisciplinary staff of 13, including 1 physician and 3 nurses who received cancer training at IRST. Volunteer Italian oncologists provide support for the Tanzanian team each month. Results: Between Jan 2009 and Dec 2010, 1610 patients were admitted to BMC OD, of whom 511 were children and 1099 adults (670, 61% females; 429, 39% males). The majority of children (70%) had Burkitt’s lymphoma, 20% retinoblastoma and the remaining, acute leukemias, Wilm’s and brain tumors.The highest rate of cancer in adults was cervical cancer in females (32%) and hepatocarcinoma (HCC) in males (30%). Out of 562 women screened for breast and cervical cancer, only 3% had stage I breast cancer, treated with curative intent. Among patients screened for cervical cancer, 18% showed alterations at colposcopy, and biopsy confirmed cancer. One third of these were inoperable locally advanced cervical tumors. Conclusions: Cancer epidemiological patterns in Tanzania differ from those of high-income areas (HIAs) due to the high prevalence of infection-related cancers. Several challenges exist: inadequate or poorly accessible diagnostics; drug availability and cost; patients lost to follow up; lack of palliative care culture; and bureaucracy. This transnational collaboration aims to improve the quality of oncology care and to foster no-profit trials on tumors with a low incidence in HIAs, but with greater relevance in LIAs. Number of patients (%) admitted to the BMC OD. Cervix HCC Breast Kaposi’s sarcoma Esophagus Hodgkin lymphoma Prostate Ovary Others Total Males – 129 (30) – 64 (15) 77 (18) 38 (9) 73 (17) – 48 (11) 429 (39) Females 214 (32) – 141 (21) 47 (7) 34 (5) 67 (10) – 20 (3) 147 (22) 670 (61) All adults 214 (32) 129 (30) 141 (21) 111 (10) 111 (10) 105 (9) 73 (7) 20 (2) 195 (18) 1099