tbuckley/cabot-search huggingface dataset:
Do seminoma germ cell elements affect perioperative outcomes following post-chemotherapy retroperitoneal lymph node dissection for metastatic testis cancer?
Authors: Gautum Agarwal, David D. Buethe, Christopher Russell, Patrick Espiritu, Adam Luchey, Philippe E. Spiess, Julio Pow-Sang, Michael Adam Poch, Wade Jeffers Sexton
Journal: Journal of Clinical Oncology (2014)

378 Background: Post-chemotherapy retroperitoneal lymph node dissections (PC-RPLND) performed at high-volume centers are safe and comparable in risk to primary RPLNDs. The desmoplastic reaction encountered during PC-RPLND in patients with seminoma components increases the complexity of surgical dissection. We examined whether the presence of seminoma at diagnosis was associated with more adverse events in the perioperative setting. Methods: A single institution review board approved retrospective review identified 108 patients undergoing PC−RPLND from 1992 to 2012. All patients had received at least first-line cisplatin-based induction chemotherapy. Of these, 11 patients undergoing redo PC-RPLNDs were excluded from analysis. Patients were divided into two groups; those with any seminoma element in their orchiectomy or retroperitoneal specimens and those without seminoma elements. We performed independent t-tests and Chi-squared analysis of the data. Results: Of 97 patients undergoing PC-RPLND, 33 had seminoma components in their diagnostic specimens. Using the Clavien classification system to stratify post-operative complications, the percentage of seminomatous elements (less than 50% compared to more than 50%) within the primary tumor did not correlate with a higher incidence of complications; even when examining only major complications (p=0.673). There was a trend towards higher nephrectomy rate for tumors with seminoma elements compared to those without (27% vs. 8.5%, p = .058). The nephrectomy rate did show a dependence on the pathologic size of the residual mass regardless of histology (31% for more than 10 cm, 6.8% for 5 to 10 cm, 0% for 0 to 5 cm p = 0.021). There was also a trend towards blood loss greater than one liter for patients with seminoma elements compared to those without (63% vs. 43%, p = 0.078), while the transfusion rate was similar between the two groups (p=0.785). Post−operative length of stay was independent of a patient’s histology (p=0.94). Conclusions: PC-RPLND remains a safe and necessary therapeutic procedure. The presence of seminoma germ cell elements in our patient cohort did not result in a more complicated perioperative course surrounding PC-RPLND.
Phase I study of intraperitoneal paclitaxel combined with S-1 plus cisplatin for gastric cancer with peritoneal metastasis.
Authors: Daisuke Kobayashi, Hironori Ishigami, Mitsuro Kanda, Chie Tanaka, Hironori Yamaguchi, Joji Kitayama, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2016)

115 Background: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer (GC) with peritoneal metastasis (PM). Efficacy of IP paclitaxel (PTX) combined with S-1 and intravenous PTX was reported in a phase II study. Attempts to combine IP PTX with other systemic therapies with higher efficacy are warranted. We designed a new regimen combining IP PTX with S-1/cisplatin (SP) which is regarded as the standard first-line treatment of metastatic GC in Japan. We subsequently carried out a dose-escalation study to determine the maximum-tolerated dose (MTD) and recommended dose (RD). Methods: The combination was a five-week regimen. IP PTX was to be administered on days 1, 8 and 22 with an initial dose of 15 mg/m 2 at level 1 and 20 mg/m 2 at level 2. S-1 was to be administered orally at a fixed dose of 80 mg/m 2 bid for 21 days followed by a 14-day rest. Cisplatin was to be administered intravenously at a dose of 60 mg/m 2 on day 8, and was to be decreased to 50 mg/m 2 (level 0) if necessary. Since the dosage of S-1 at the fixed dose and cisplatin at level 1 were identical to SP regimen, no further dose-escalation was planned. Dose-limiting toxicities (DLTs) were defined as Grade 4 (G4) leukopenia, G3 febrile neutropenia, G3 thrombocytopenia, and G3 non-hematological toxicity. The MTD was defined as the dose level at which ≥2 of 3 or 6 patients developed DLTs during the first course of treatment. The RD was defined as one level below the MTD. Results: A total of 9 patients with macroscopic PM were enrolled. No DLTs were observed among the 3 patients at level 1 and 6 patients at level 2. Furthermore, no G3 toxicities were observed in any of the patients enrolled. Anemia in 1 patient at level 2 was the only G2 toxicity observed. No adverse events or technical problems associated with the IP administration were observed. Consequently, the MTD was not reached, and the RD of IP PTX was determined as 20 mg/m 2 (level 2). As for the efficacy, peritoneal lavage cytology turned negative after the first course in 4 of 7 patients who had positive cytology before treatment. Conclusions: Addition of IP PTX at 20 mg/m 2 to the SP regimen at an established dose/schedule was safe and promising, and further evaluation in a phase II trial is underway. Clinical trial information: UMIN000013528.
Overall survival in intermediate-stage hepatocellular carcinoma (HCC) patients after first transarterial chemoembolization (TACE): Proposal of a new scoring system.
Authors: Rodolfo Sacco, Valeria Mismas, Antonio Romano, Barbara Ginanni, Sara Marceglia, Luca Giacomelli, Gianluca Masi, Alfredo Falcone, Giampaolo Bresci, Carlo Bartolozzi, Irene Bargellini
Journal: Journal of Clinical Oncology (2015)

386 Background: TACE is the standard treatment for patients with intermediate-stage HCC (BCLC-B according to the Barcelona Clinic Liver Cancer [BCLC] classification). However, prognostic factors for survival after the first TACE cycle are unclear. We correlated pre-treatment characteristics and response to therapy with overall survival (OS) and time to tumor progression (TTP), in order to propose a scoring system aimed at facilitating clinical decision after the first TACE. Methods: We retrospectively analyzed 149 patients (125 males; mean age 65.1±9.2 years) with BCLC-B HCC who received ≥1 cycle of TACE (Lipidol TACE, n=106; drug-eluting beads TACE, n=43). Univariate and multivariate analysis were used to correlate pre-treatment characteristics and response to TACE with OS and TTP. Identified predictive factors were used to define a score for each patient. Results: Median OS was 23 (95% Confidence interval [CI] 11.5-27) months, and median TTP was 11 months (CI 7-11). Complete response (CR) was reported in 63 patients (42.3%) and partial response (PR) in 71 (47.7%). Age &gt;65 years (Hazard Ratio [HR] 1.77; 95% CI: 1.18-2.67), ascites (HR 2.44; 95% CI 1.32-4.29), total diameter of nodules &gt;61 mm (HR: 1.96; 95% CI 1.28-3.08) and response at 1 month (HR 1.70; 95% CI 1.30-2.20) were predictors of survival and were used to build the scoring system (Table). Three groups of patients with different OS and TTP were then identified. Patients with score 0-1 had a longer OS (57.8 months) and TTP (12.7 months) than those with score 2-3 (21.1 and 8.2 months) or score 4-6 (8.0 and 6.3 months) (p&lt;0.001 for both comparisons). Conclusions: This scoring system may allow the identification of three groups of patients with different prognosis after a first cycle of TACE and may therefore be useful in guiding clinical decisions, in particular whether continuing TACE therapy after a first cycle or moving to different therapies. Validation of this scoring system on a larger population is ongoing. [Table: see text]
Endostar in combination with radiotherapy and paclitaxel/carboplatin in patients with unresectable non-small cell lung cancer of stage III: Preliminary results of a phase II study.
Authors: S. Ma, Y. Xu, X. Sun, Y. Ji, Y. Zheng, S. Wang, J. Chen
Journal: Journal of Clinical Oncology (2011)

7043 Background: A feasibility study was performed to examine the safety and activity proﬁle of Endostar in combination with radiotherapy and Paclitaxel/Carboplatin in patients with unresectable non-small cell lung cancer(NSCLC) of stage III. Methods: Patients with unresectable stage III NSCLC will receive thoracic radiation therapy in 2Gy fractions ﬁve times weekly to a total dose of 60-66 Gy and concurrent with Endostar 7.5 mg/m2 over 3 hours d1-14, paclitaxel 50 mg/m2 weekly over 1 hour, carboplatin AUC=2 mg/mL/min over 30 min weekly. Followed by Endostar 7.5 mg/m2 d1-14, paclitaxel 175 mg/m2 d1 and carboplatin AUC=5 mg/mL/min d1 every 3 weeks for 2 cycles as consolidation treatment. Objective response rate according to the RECIST criteria was recorded and toxicity was evaluated using the NCI Common Toxicity Criteria. Results: 12 eligible patients enrolled in the study received concurrent Endostar, paclitaxel/carboplatin and deﬁnitive thoracic radiation therapy (TRT). Three patients were unable to complete the followed consolidation treatment (two because of pulmonary toxicity and one because of progressive disease). 9 patients (75.0%) had a partial response, while 2 patient’s disease remained stable and 1 patient had progression of the disease. The overall response rate (75.0%,95% confidence interval (CI): 51%-97%) didn’t exceed the goal per study design (85.0%), and the study was therefore closed according to the protocol deﬁnition. Main toxicity (grade 3 or greater, %): neutropenia 5 (41.7%); thrombocytopenia 2 (16.7%); anaemia 2 (16.7%); nausea/vomiting 1 (8.3%); anorexia 2 (16.7%), dysphagia 2 (16.7%), radiation pneumonitis 4 (33.3%) and fatigue 1 (8.3%). Conclusions: Our results do not support further trials of Endostar in combination with radiochemotherapy in patients with Stage III NSCLC. Endostar likely enhances radiation pneumonitis. The impact of Endostar on survival as a ﬁrst-line treatment in combination with radiochemotherapy remains to be determined.
An open label, phase II, multicenter, study to evaluate the efficacy and safety of pertuzumab (P) in chemotherapy naïve patients (pts) with hormone refractory prostate cancer (HRPC)
Authors: J. S. de Bono, J. Bellmunt, J. P. Droz, K. Miller, G. Zugmaier, C. Sternberg, V. Gimenez, C. Parker, M. Mason, J. Graham
Journal: Journal of Clinical Oncology (2005)

4609 Background: P is the 1st of a new class of targeted therapeutics known as HER-dimerization inhibitors (HDI). P is a human monoclonal antibody that blocks ligand-associated heterodimerization of HER2 with other HER kinase family members, thereby inhibiting intracellular signaling. Preclinical activity of P in prostate cancer xenografts has been demonstrated. Methods: P was administered IV once every 3 weeks at 420 mg (with a loading dose of 840 mg) or 1050 mg (without a loading dose) in consecutive cohorts. An interim analysis was performed for each cohort after inclusion of 23 evaluable pts. In case of > 3 responses, 27 additional pts were to be enrolled in that cohort. The 1050 mg cohort was only to be opened, if the 420 mg cohort showed ≤ 3 responses. Eligibility criteria were: progressing chemotherapy naïve HRPC, LVEF ≥ 50%. The primary endpoint in this study was PSA (prostate specific antigen) response rate (RR) at 24 weeks after start of single agent P. Secondary endpoints were safety profile, overall RR by RECIST, time to tumor progression (TTP), and overall survival (OS). Results: 23 evaluable pts in each cohort were included in the interim analysis. No PSA responses were observed with a median TTP (PSA) of 5 weeks. One unconfirmed 75% decrease in PSA was found after the interim analysis. P was well tolerated. Most common adverse event in the 46 pts was grade 1 & 2 diarrhea (48%). Nausea was reported for the 420 mg- and 1050 mg dose level respectively in 22 & 9% and asthenia in 35 & 13%. No LVEF decreases of ≥ 15% and to below 50% were observed in either cohort. No congestive heart failure was reported. Conclusions: P is safe and well tolerated. No difference in toxicity was observed between the two dose levels. There is insufficient evidence of activity in this prostate cancer study. A combination (either chemo or hormonal) or pt selection strategy may be investigated in the future. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche AstraZeneca, Boehringer Ingleheim, Celgene, Novartis
ARMOR2: Galeterone in progressive CRPC patients who have failed oral therapy.
Authors: Mary-Ellen Taplin, Robert B. Montgomery
Journal: Journal of Clinical Oncology (2014)

71 Background: Galeterone is a first-in-class multitargeted oral steroid analog; it suppresses prostate cancer by a combination of AR modulation (antagonism and degradation) and CYP17 inhibition. Safety and proof of concept of galeterone in CRPC was assessed in ARMOR1. Galeterone was reformulated by spray dry dispersion technology (SDD) to optimize PK and remove food effect. ARMOR2 (NCT 01709734) is an open label, 2-part phase 2 trial that evaluates safety and efficacy of SDD galeterone in 4 populations of CRPC patients. These results report Part 1. Methods: Objectives of Part 1: confirm dose equivalence of SDD formulation with evaluation of PK, safety and PSA response. Metastatic (M1) and non-metastatic (M0) treatment naïve CRPC pts enrolled to groups of 1,700, 2,550 or 3,400 mg PO daily. An abiraterone refractory (Abi-R) group of 3 patients opened at 2,550mg. Results: 28 were enrolled in part 1. Safety: All groups were safe by IMC assessment. There were 4 grade 3 adverse events. 2 were unrelated to study drug. 2 had transient G3 ALT elevations (did not recur with rechallenge). There was no AME: supplemental steroids were not required. G4 angioedema occurred in a pt receiving lisinopril (known association with angioedema). Efficacy: PSA response was improved compared to ARMOR1 (AACR 2012. Taplin et al abstract: CT-07). At early follow up Abi-R pts showed improvements in PSA with 1 PSA30% response, 2 with stablized PSA (decline in PSA-V from +0.44 to -0.39 ng/day). Conclusions: Galeterone in SDD formulation is tolerated at doses up to 3,400mg daily. SDD galeterone provides improved PSA response and durability vs. prior formulation. There is evidence of activity in abiraterone refractory patients. Clinical trial information: 01709734. [Table: see text]
End-of-life cancer care: Health service delivery in the last 12 months of life in Calgary, Alberta, Canada.
Authors: Marc Kerba, Ayn Sinnarajah, M Sarah Rose, Lynn Nicholson, Barbara Wheler, Bert Enns
Journal: Journal of Clinical Oncology (2015)

171 Background: In Calgary, Alberta, the Calgary Zone Palliative Care Collaborative (CZPCC) undertook a study to examine the current state of cancer and palliative services and to recommend steps to address gaps in service delivery. We hypothesized that early access to palliative care services would reduce utilization of active cancer treatments and services for individuals nearing the end of life. Our study objectives were to determine the utilization and timing of acute, palliative and oncology-related services in Calgary. Methods: This retrospective study examined cancer registry and administrative data for patients &gt; 18 years, who died in 2012. Measures of aggressive end of life care (EOL) were also collected. A combination of descriptive statistics, tests of association and multivariate regression analysis were conducted. Results: N = 1909 died of cancer in 2012: median age 73 years (IQR: 62-82 years) and median disease duration 364 days (IQR: 92-1114 days). 40.6% of patients received systemic treatment in last 12 months of life. 29.9% received radiotherapy and 13.0% received psychosocial/spiritual care. Palliative care contact was 80.7%, inclusive of 20.6% who had an intensive palliative care unit admission. 5.2% had EOL chemotherapy and 3.8% received EOL radiotherapy. Up to 10.4% of patients had one or more hospital admission. There was no significant effect of age on those who received aggressive EOL care. Men had an increased probability to receive aggressive EOL care (p = 0.015). Tumor group was also associated with receiving aggressive EOL (p &lt; 0.001), with the highest utilization in Head and Neck and hematological malignancies. In patients with a disease duration of &gt; 4 months those who received palliative care at least 2-3 months prior to death were less likely to receive aggressive EOL care (P &lt; 0.001). Patients whose disease duration was &lt; 1 month were less likely to receive aggressive EOL care if they received palliative care services (p = 0.02). Conclusions: The provision of palliative care services at the end of life is most needed among men and certain tumor groups who are the highest users of aggressive EOL care.
Role of overexpressions of ALEX1 gene in human colorectal tumorigenesis.
Authors: Akihiko Takeda
Journal: Journal of Clinical Oncology (2013)

443 Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup within the armadillo family which has several ARM repeat domain. Our studies have revealed that overexpression of ALEX1 suppressed colony formation ability of stable human colorectal carcinoma cell lines. But clinical significance of ALEX1 expression in colorectal cancer patients is largely unknown. Methods: We examined the expression level of ALEX1 mRNA in matched tissue pairs of normal colorectal mucosa and colorectal tumor tissue by quantitative real-time RT-PCR Tumor specimens along with adjacent normal tissues were obtained from 49 patients with primary colorectal cancer undergoing complete surgical resection of tumors and lymph nodes, followed by adjuvant systemic therapy in some cases. All tissue samples were stored at -80°C until use. The 49 colorectal specimens comprised 26 well-differentiated and 23 moderately-differentiated adenocarcinoma. Corresponding extraneoplastic normal colon tissues from the same 49 patients were also examined. The pathological stages of the patients were as follows: stage I, 9 patients; stage II, 16 patients and stage III, 24 patients by pTNM classification. The post-surgical treatment observation period was from 277 to 3,631 days (1625.0 ± 1033.0 days). Results: In 34 cases out of 49 (69%) colorectal tumor tissues, greater than a 50% reduction of the ALEX1 mRNA level was observed in comparison to adjacent normal mucosa tissues. ALEX1 mRNA was significantly reduced in colorectal tumor tissues than those in normal mucosa (p=0.01459, Mann–Whitney U-test). The 17 cases with higher ALEX1 gene expression (tumor/normal value ³a0.20) significantly revealed a better disease-free survival rate than the other 32 cases (&lt; 0.20; p = 0.045, log-rank test), which showed significant correlations between ALEX1 expression and better prognosis. There was no significant relationship between ALEX1 expression and the other clinicopathological features. Conclusions: Our findings may support that ALEX1 functions as a tumor suppressor in colorectal cancer progression. Examination of ALEX1 expression might be helpful for predicting the prognosis of patients with curative resected colorectal cancer.
Post-embolization syndrome: Outcomes regarding the type of embolization.
Authors: W. J. Romero Ubillus, J. Munoz, M. Vekaria, I. S. Wollner, T. Getzen
Journal: Journal of Clinical Oncology (2011)

e14582 Background: Post-embolization syndrome (PES) is characterized by fever, abdominal pain and leukocytosis after embolization of hepatic tumors and is likely caused by an inflammatory response to necrotic tissue. Despite the benign nature of PES, it has been suggested that this entity portends worse prognosis. We examined the outcomes of a large group of patients that underwent embolization with particular emphasis on the type of procedure performed. Methods: Retrospective chart review of 247 cases that underwent embolization procedures of hepatic tumors at our institution from January 2002 to January 2010. Progression-free survival (PFS) and overall survival (OS) were measured in days starting from the day of the first embolization. Results: Out of 247 patients, 173 were men (70%) and 74 were women (30%). The etiology of the hepatic tumors (Algorithm 1) was comprised of 190 cases of hepatocellular carcinoma (HCC), 23 cases of metastatic carcinomas, 12 cases of neuroendocrine tumors, 18 benign tumors, and others (4 cases). PES (Table 1) developed in 16 patients (6.4%) with a median length of hospitalization of 4.4 days (range 1-7 days). Subsequently we examined 190 patients with HCC as a separate group in which chemoembolization with doxorubicin drug eluting beads (DEB) was the most frequent type of procedure in 97 out of 190 HCC patients (51%), followed by bland microspheres in 73 patients (38%), polyvinyl alcohol (PVA) particles in 27 patients and 3 cases of epirubicin DEB embolization. Cox regression indicates that PES was not a statistically significant predictor of either PFS or OS, although the results showed a trend towards worse PFS in PES patients (p = 0.061). Patients that did not undergo liver transplantation had significantly worse PFS and OS (p < 0.001). Both PVA embolization (p = 0.019) and bland microsphere embolization (p = 0.027) patients had significantly worse OS when compared to chemoembolization. Conclusions: PES heralds slight worse outcome albeit likely not directly associated to infectious complications but rather as a surrogate of other poor prognostic features. Despite the fact that most PES cases occurred after chemoembolization, such procedure still fairs favorably when compared to other types of embolization.
Cost-effectiveness analysis of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.
Authors: Scott M. Stevenson, Chris M. Deibert, James M. McKiernan
Journal: Journal of Clinical Oncology (2013)

258 Background: Neoadjuvant chemotherapy (NAC) is an option for treating muscle invasive bladder cancer (MIBC), and is reported to increase survival for patients who obtain a complete response with no residual disease at the time of radical cystectomy (RC). However, NAC has additional costs and side effects. We seek to compare the effectiveness of NAC and RC for MIBC and to report the increase in cost and change in quality adjusted life years (QALYs) for patients who receive NAC. Methods: Patients were retrospectively reviewed from 2004 to 2011 to identify those with MIBC (stage T2 to T4a) who were treated with either RC alone or NAC. Costs for hospital admissions and surgical procedures were estimated from the Healthcare Cost and Utilization Project (HCUP) using specific Diagnosis Related Groups (DRG) or ICD-9-CM identifiers. Costs for outpatient procedures and urology visits were obtained from internal billing departments, and costs for chemotherapy were estimated based on published literature. QALYs were calculated based on clinical events and standard utility weights obtained from the medical literature. Results: 186 patients were identified, of which 64% received RC alone and 36% received NAC. Overall median survival for the RC group and the NAC group was 26.6 months and 38.3 months, respectively (p=0.056). Overall median survival in QALYs for the RC group and NAC group was 21.9 months and 32.9 months, respectively (p=0.057). 5-year overall survival in QALYs was 21.8% for the RC group and 39.8% for the NAC group (p=0.039). The mean total cost of treatment during follow-up for the RC and NAC groups was $42,890 and $52,336, respectively. The absolute increase in cost of therapy for patients receiving NAC compared to RC alone was $9,712. The increased cost per additional QALY gained for patients receiving NAC was $10,317. Conclusions: Neoadjuvant chemotherapy results in an increased overall survival for patients with muscle invasive bladder cancer. This treatment is associated with an increased cost of approximately $10,000/QALY gained. This cost effectiveness compares favorably with other cancer therapies.