tbuckley/cabot-search huggingface dataset:
Third-line therapy in metastatic renal cell carcinoma: Results from the International mRCC Database Consortium.
Authors: Daniel Yick Chin Heng, Connor Wells, Frede Donskov, Brian I. Rini, Jae-Lyun Lee, Georg A. Bjarnason, Benoit Beuselinck, Martin Smoragiewicz, Ajjai Shivaram Alva, Sandy Srinivas, Lori Wood, Haru Yamamoto, D. Scott Ernst, Sumanta Kumar Pal, Takeshi Yuasa, Reuben James Broom, Ravindran Kanesvaran, Aristotelis Bamias, Jennifer J. Knox, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2015)

430 Background: Third-line targeted therapy efficacy in metastatic renal cell carcinoma (mRCC) is not well characterized and many funding bodies do not provide reimbursement for it. Methods: The International mRCC Database Consortium (IMDC) consists of consecutive patient series from 25 cancer centers. It was queried for specific sequences of targeted therapy and third-line therapy. Kaplan Meier estimates were used for survival. Cox proportional hazards models were used to adjust hazard ratios for confounders. Patients that stopped second-line therapy were divided into two groups: those that went onto third-line therapy and those did not. Results: 4,050 patients were treated with first-line targeted therapy, of which 2,011 (49.6%) had second-line therapy and 879 (21.7%) had third-line targeted therapy. The most common third-line therapies were everolimus 25%, sorafenib 14%, sunitinib 13%, temsirolimus 11%, pazopanib 10%, and axitinib 6%. IMDC prognostic groups at third-line therapy initiation were 6% favorable risk, 67% intermediate risk, and 27% poor risk. Overall response rate for third-line therapy was 10.5% and 50.9% had stable disease in those patients that were evaluable. Median PFS was 5.1 months (95% CI, 4.5-5.7) and median OS from third-line therapy initiation was 12.0 months (95% CI, 10.7-12.9). Patients stopping second-line therapy that move on to third-line therapy vs. those that do not receive third line therapy have a median OS from stopping second-line therapy of 13.1 vs. 2.3 mons (p&lt;0.0001). When adjusted for second-line IMDC prognostic criteria and KPS at second-line treatment cessation, patients who do receive third-line therapy have a HR of death of 0.41 (95% CI, 0.32-0.52; p&lt;0.0001) compared to those that do not receive third-line therapy. This may be in part due to patient selection. To further limit bias, when excluding patients that live less than 3 months after second-line therapy cessation, the adjusted HR was similar. Conclusions: Third-line targeted therapy has demonstrated activity and is prevalent in use. Further studies are required to determine appropriate sequencing.
HER2 and HER3 genomic gain increases sensitivity to gefitinib in epidermal growth factor receptor positive advanced non-small cell lung cancer
Authors: F. Cappuzzo, L. Toschi, H. Shigematsu, E. Rossi, G. Ceresoli, L. Crino, P. A. Bunn, A. F. Gazdar, F. R. Hirsch, M. Varella-Garcia
Journal: Journal of Clinical Oncology (2005)

3021 Background: In non-small cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors (TKIs) is associated with activating mutation and genomic gains of the epidermal growth factor receptor (EGFR). HER2 and HER3 overexpression increases sensitivity to TKI in pre-clinical settings. Mutations in the HER2 gene have recently been described, but their role in TKI sensitivity is unclear. Methods: One-hundred one NSCLC patients treated with gefitinib (250mg), and previously evaluated for EGFR status by fluorescence in situ hybridization (FISH) and DNA sequencing, were investigated for HER2 and HER3 genomic gains by FISH, and in frame insertions and duplications in HER2 exon 20 by DNA sequencing. Patients with high polysomy and gene amplification were considered as FISH positive (+). Results: FISH HER2+ and HER3+ patterns were significantly associated with female gender (p=0.03 and 0.02) and never smoking history (p=0.04 and 0.02). HER2+ patients (23%) had significantly better objective response (OR: 35% versus 6%, p=0.001), disease control rate (DCR: 56% versus 33%, p=0.04), time to progression (TTP: 9.05 versus 2.7 months, p=0.02), and a non significant trend toward longer survival (OS: 20.8 versus 8.4 months, p=0.056) than HER2-. EGFR+/HER2+ patients had a significantly better OR, DCR, TTP, and OS than patients EGFR-and/or HER2-. Patients EGFR+/HER2+ had better OR than EGFR+/HER2- (54% versus 21%, p=0.07), while EGFR-/HER2+ had same poor outcome than patients negative for both receptors. Patients HER3+ (26%) had a significant longer TTP (3.7 versus 2.7, p=0.04) than HER3-, but no better response or survival. Patients EGFR+/HER3+ had higher OR (36.4% versus 9.9%, p=0.03) and TTP (7.7 versus 2.7 months, p=0.03) than EGFR- and/or HER3-, while patients EGFR-/HER3- had lower response rate (18.2% versus 81.8%, p=0.02) and TTP (2.6 versus 6.0 months, p=0.002) than EGFR+ and/or HER3+. Mutation was not detected in exon 20 of the HER2 gene in 74 sequenced patients. Conclusions: HER2 and HER3 FISH analyses add to EGFR tests for prediction of clinical benefit to TKI therapy in advanced NSCLC patients. HER2 mutations seem to be infrequent and not clinically relevant. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, ImClone, Ligand, Roche AstraZeneca, Bristol-Myers Squibb, Genentech, ImClone, OSI, Roche
Body mass index at mCRPC, weight change, and survival in advanced prostate cancer.
Authors: Lydia D. Chow, Elisa M. Ledet, Allie E. Steinberger, Jeffrey R. Guccione, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2016)

270 Background: Body mass index (BMI) at diagnosis is associated with increased risk of fatal prostate cancer, but the link between BMI at mCRPC and cancer progression is less clear. Cachexia, often defined as involuntary weight loss &gt; 5% over 6 months, is common in advanced cancers. The goal of this study was to examine the link between BMI at mCRPC and weight change as it relates to cancer progression, the outcomes of survival, and treatment use in a single-institution setting. Methods: 58 mCRPC patients treated at Tulane Hospital were identified, 41 of whom had an overweight BMI at mCRPC (BMI &gt; 25) and 17 with normal BMI at mCRPC (BMI &lt; 25). All patients had a confirmed prostate cancer death. Survival, treatment history, and percent weight change were compared according to BMI status. Rate of percent weight change was defined as the change in weight per day, from date of mCRPC diagnosis to the last treatment stop date or death date (“mCRPC days”). Linear regression, overall survival (OS), and nonparametric analyses were performed. Results: There was no significant difference between the normal and overweight BMI groups in overall survival, from date of diagnosis to death (median = 1835 days vs. 2710 days respectively). Additionally, the difference in survival from mCRPC to death was not statistically significant (median = 630 days vs. 799 days, p = 0.115). Use of Taxotere was not significantly different (47% vs. 68% respectively); however, overweight patients (n = 28) more likely received Abiraterone than normal BMI patients (n = 2) (p-value = 0.0001). The rate of percent weight change was significantly different for normal and overweight patients (mean = –0.050%/day vs. –0.019%/day, p = 0.003). Linear regression analysis showed that mCRPC days had a significant effect on percent weight change (p = 0.0109), and this effect was not significantly different between BMI groups (p = 0.6991). Conclusions: Survival after mCRPC was not significantly different between BMI groups. We observed a significant effect of mCRPC days on percent weight change, with a similar effect for both BMI groups. This outcome is expected, as more time would allow for greater weight changes to occur. Larger studies are needed to fully evaluate these observations.
Differential glycan profile of CEACAM5 expressed by small cell lung carcinoma in comparison with colorectal carcinoma
Authors: L. Liu, L. Agulto, Z. Xie, R. Manteiga, Y. Jiang, C. Gelber
Journal: Journal of Clinical Oncology (2008)

14023 Background: Glycans linked to proteins are important determinants of molecular function in normal and diseased states. Recent studies showed that the glycan perturbation manifested on several tumor markers are directly associated with the cancer development. Targeting the glycan structures is an increasingly important therapeutic strategy. Although CEACAM5 (CEA) is a well known tumor associated glycoprotein overexpressed in many tumors and linked with tumor invasiveness, previous clinical development has not focused on the differential glycosylation patterns exhibited by different tumors. Methods: In this study, we characterized and compared the glycan profiles of CEA antigen extracted from two different sources: liver metastasis of colorectal carcinoma (Fitzgerald Industries) and small cell lung carcinoma (SCLC) cell lines using a high affinity monoclonal antibody developed using DIAAD technology (Krueger P et al. [2003] Cancer Immunol Immunother. 52, 367–377). The glycan profiles were analyzed using QProteome GlycoArray Kit (Qiagen), which allows for a quantitative measurement of the glycosylation moieties present on glycoproteins. Results: Dramatic disparities were observed when comparing the glycan patterns of the CEA from SCLC with the one from colorectal cancer. The signals displayed in the glycan fingerprint analysis indicated that the Mannose 1 is absent in CEA from SCLC, while the Alpha Gal 1 is absent in the CEA prepared from colorectal cancer. The relative abundance of other glycan epitopes including Gal/GalNAc (1–8), Beta Gal (1 and 2), Fucose (4, 5 and 6) and Sialic Acid (1 and 4) were also different in CEA from the two different sources. Conclusions: Previous CEA based therapeutics development has been focused on the protein itself. Our study showed that CEA from two different cancers, i.e. SCLC and colorectal carcinoma possess distinct glycan profile. We propose the characteristic glycans of CEA provides a better target for developing discerning therapeutics with improved efficacy and specificity. In addition, the monoclonal antibody generated by DIAAD technology is an ideal candidate for developing antibody therapeutics as it can bind to the distinct glycans of CEA from SCLC with defined specificity and high affinity. No significant financial relationships to disclose.
Updated Survival Analyses after Prolonged Follow-Up of the Phase 2, Multicenter CREST Study of Bortezomib in Relapsed or Refractory Multiple Myeloma.
Authors: Sundar Jagannath, Bart Barlogie, James R. Berenson, David Siegel, D. Irwin, Paul Richardson, Ruben Niesvizky, Raymond Alexanian, Steven Limentani, Melissa Alsina, Dixie-Lee Esseltine, Kenneth C. Anderson
Journal: Blood (2007)
Randomized phase II trial of S-1 versus S-1 plus irinotecan (IRIS) in patients with gemcitabine-refractory pancreatic cancer.
Authors: Nobumasa Mizuno, Kenji Yamao, Yoshito Komatsu, Masaki Munakata, Atsushi Ishiguro, Taketo Yamaguchi, Shinichi Ohkawa, Mitsuhiro Kida, Tatsuya Ioka, Koji Takeda, Toshihiro Kudo, Masayuki Kitano, Haruo Iguchi, Akihito Tsuji, Tetsuhide Ito, Masao Tanaka, Junji Furuse, Chikuma Hamada, Yuh Sakata
Journal: Journal of Clinical Oncology (2013)

263 Background: Gemcitabine (Gem) monotherapy or Gem-based combination therapy is a standard first-line therapy for advanced pancreatic cancer (PC). There is no consensus on second-line therapy in patients (pts) with disease progression (PD) after Gem-based therapy. S-1, an oral fluoropyrimidine derivative, is commonly used for the second-line treatment of PC in Japan. Shitara et al previously reported that IRIS regimen showed that 44% of response rate (RR), 4.9 mo of median progression free survival (PFS), and 11.3 mo of median overall survival (OS), respectively. Therefore a randomized phase II trial was conducted to evaluate the efficacy and safety of IRIS compared with S-1 alone in the second-line setting. Methods: The inclusion criteria were as follows: (1) histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma; (2) confirmed PD after Gem treatment; (3) ECOG PS, 0-1; (4) measurable metastatic lesion based on RECIST criteria; (5) age ≥ 20 years; (6) total bilirubin &lt; 2.0 mg/dL. Patients were randomized to receive either IRIS (CPT-11 100 mg/m 2 , iv, d1,15 plus S-1 80/100/120 mg/day based on BSA, po, d1-14, q4w; Arm A) or S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w; Arm B). The primary endpoint was to compare PFS in Arm A and Arm B. Results: Of a total of 137 pts enrolled between Nov 2008 and Mar 2011, 127 were eligible (60 randomized to Arm A and 67 to B). Median PFS in Arm A and B was 107 and 58 days, respectively (HR= 0.767; 95% CI, 0.527-1.114; p=0.1750). Median OS in Arm A and B was 208 and 176 days, respectively (HR=0.749; 95% CI, 0.512-1.093; p=0.1338). RR was 18.3% in Arm A (11/60; 95% CI, 9.5-30.4) and 6.0% in Arm B (4/67; 95% CI, 1.7-14.6)(p=0.0311). The incidences of grade 3/4 toxicities were as follows: neutropenia (15.6% and 4.3%), anorexia (23.4% and 17.3%), nausea (6.3% and 2.9%), and diarrhea (3.1% and 2.9%) in Arm A and B, respectively. Both regimens were tolerable. Conclusions: Although IRIS showed no significant improvement in PFS or OS compared with S-1 alone in this study, it showed significant advantage in RR, and favorable HR in both of PFS and OS. IRIS might have potential power to treat second-line PC patients. Further study is warranted. Clinical trial information: JapicCTI-080657.
Relationship of ER, PR, and HER2-neu status with age, menopausal status, and axillary nodal status in early breast cancer.
Authors: E. Ur Rahman, A. Shaharyar, M. Hafeez, A. W. Goraya
Journal: Journal of Clinical Oncology (2011)

e11011 Background: Treatment decisions in early breast cancer are mostly based on age, menopausal status, tumor size, axillary nodal status, hormone receptors status and Her 2 neu expression. Correlation of ER, PR and Her 2 neu expression with other clinical parameters of disease is not clearly defined. This study attempts to identify the relationship of ER, PR and Her 2 neu status with age, menopausal and axillary nodal status. Methods: Data on ER, PR and Her 2 neu expression status of 289 consecutive early breast cancer patients treated during 2008-2010 in Mayo Hospital Lahore was obtained. Relationship of ER, PR and Her 2 neu status with these parameters of disease was studied by finding correlation co efficient. SPSS version 11.5 was used for statistical analysis. Results: HER2 over expression (3+ by IHC or by FISH) was seen in 125/289 (43.25 %), hormone receptor positivity (ER/PR or both) in 133/289 (46.02 %) and 88 patients (30.4 %) were triple negative. Majority of triple negative patients 69/88 (78.4 %) were pre menopausal with a median age of 43.8 years (range; 25-72) and median size of primary of 5.2 cm (range;2-12 cms). Half of these patients were node -ve (44/88) and in remaining patients median number of 2.4 nodes (range; 0-18). Triple negative disease was negatively related to age of patients (r = - 0.75). HER2 +ve / receptor -ve patients were 68 (23.52 % ) and 41 (60.29 %) patients were pre menopausal with a median age of 50.5 years (range; 28-85) and median size of primary of 4.5 cm (range; 1.5-12.5 cms). Fifty patients (73.53%) were node positive with a median number of 4.5 nodes (range;0-23). 133 receptor +ve patients (either ER or PR or both) had an associated Her 2 neu over expression in 57/133. Eighty six patients (64.66 %) were pre menopausal with a median age of 47 years (range; 25-90) and median size of primary of 4.48 cm (range; 1-18 cms). 91patients (68.42 %) were node +ve with a median number of 3.71 nodes (range;0-19). Conclusions: ER, PR and Her 2 neu status doesn’t correlate with clinical parameters of disease. Triple negative, Her 2 enriched or receptor positive molecular subtypes of disease cannot be predicted from clinical parameters. However, triple negative disease tends to be frequent in younger patients.
Treatment outcome of patients with intermediate- and poor-prognosis metastatic testicular cancer in the 2000s: A multicenter experience in Japan.
Authors: Takahiro Kojima, Koji Kawai, Kunihiko Tsuchiya, Takashige Abe, Nobuo Shinohara, Toshiaki Tanaka, Naoya Masumori, Shigeyuki Yamada, Yoichi Arai, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi, Hiroyuki Nishiyama
Journal: Journal of Clinical Oncology (2015)

397 Background: As a risk classification system of metastatic germ cell tumors, the International Germ Cell Consensus (IGCC) classification was proposed in 1997 and has received broad approval. We aimed to clarify the significance of the IGCC classification in the 2000s especially in intermediate and poor-prognosis patients in Japan. Methods: We analyzed 118 patients with intermediate- and poor-prognosis metastatic non-seminomatous germ cell testicular cancer treated at five university hospitals in Japan between 2000 and 2010. Data were collected on age, levels of serum AFP, HCG and LDH, lung metastases, spread to non-pulmonary visceral metastases (NPVM) and on treatment details (first, second and third-line chemotherapy and post-chemotherapy surgery) and survival data. Results: The median age at diagnosis was 31 years (range, 2-54 years). The median follow-up period of all patients was 57 months. Sixty-eight patients were classified as poor prognosis, having LDH elevation in 14 (21%), AFP in 13 (19%), HCG in 27 (40%), presence of NPVM in 44 (65%). As first line chemotherapy, 93 (79%) were treated by BEP (bleomycin, etoposide and cisplatin)-containing regimen. Of 118 patients, 75 (64%) received second-line chemotherapy, in which the most frequently used regimen was taxane-containing regimen, including TIP (paclitaxel, ifosfamide and cisplatin), TIN (paxlitaxel, ifosfamide and nedaplatin) and DIN (docetaxel, ifosfamide and nedaplatin). Third-line chemotherapy was carried out in 33 patients (28%). Eighty-nine patients (75%) underwent post-chemotherapy surgery. The 5-year overall survivals for intermediate (n=50) and poor (n=68) prognosis was 89% and 83% (P=0.23), respectively. In poor prognosis patients, patients with more than 2 poor-prognostic factors had significantly worse survival than those with only one prognostic factor (72% vs 91%, P=0.01). Conclusions: There was a trend of increase in survival for any risk groups and, in particular, large increase in survival for patients with a poor prognosis. Further classification of poor-prognosis patients into two subgroups has a potential to identify a patient group with very poor-prognosis.
An interdisciplinary early simultaneous palliative approach in advanced lung cancer (a-LC): Preliminary data in outpatient setting experience.
Authors: Annamaria Catino, Ferruccio Aloe, Maria Elvira Piccininno, Antonella Daniele, Andrea Misino, Donata Ricci, Basilio Damiani, Claudia Cormio, Antonio Logroscino, Domenico Galetta
Journal: Journal of Clinical Oncology (2015)

138 Background: To integrate Simultaneous Palliative Care with standard cancer care is a growing-interest concept; hence, a global patient-centered care rather than disease-directed intervention is a major issue in advanced Lung Cancer (a-LC). These patients are often characterized by high tumor burden and comorbidities related to smoking history and elderly; furthermore, malnutrition could contribute to worse outcome. Some landmark experiences have demonstrated that a-LC patients benefit from simultaneous palliative care in early phase of treatment. The initial results of a pilot experience on early simultaneous interdisciplinary palliative approach in a-LC patients, referring to the Thoracic Oncology outpatient department of a Clinical Cancer Center, are reported. Methods: From October 2014 to May 2015, 35 patients with stage IV disease, receiving first-line therapy, were accrued. The team includes medical oncologists, a palliative care specialist, a psychologist, a nutritional expert and a research nurse. The baseline assessment comprised the disease status and comorbidities, psychosocial distress, pain and Mini-nutritional assessment (MNA). Smoking habits were recorded and information about smoking cessation programs was provided. A survey about the grade of satisfaction of patients during this multimodal approach was conducted. Results: The main patients’ characteristics are shown in Table.18/35 patients required pain treatment reassessment, while 13/35 patients had severe malnutrition. The most frequent symptoms were pain (24/35), severe psychological distress (24/35), asthenia (23/35) and anorexia (20/35). Conclusions: This approach is suggested due to multiple unmet needs of these patients; these preliminary data confirm that an interdisciplinary early palliative care is feasible in an outpatient setting with good compliance and satisfaction of patients as well as of caregivers. [Table: see text]
The association between statin use and hepatocellular cancer outcome.
Authors: Young Kwang Chae, Ahmed Omar Kaseb, Hesham Mohamed, Ibrahim Halil Sahin, Mohamed Fahd Khalil, Donghui Li, James L. Abbruzzese, Manal Hassan
Journal: Journal of Clinical Oncology (2013)

165 Background: Preclinical evidence supports anti-tumoral activity of statins. Several observational studies have shown inverse association between statin use and hepatocellular cancer (HCC) incidence. However, little is known as to whether statins can delay the progression of HCC. Therefore, we investigated the association between statin use and the outcome of patients with HCC. Methods: 644 patients diagnosed with pathologically confirmed HCC were followed up from 2000 till 2011. Survival analysis was done using Cox regression model. Results: The mean age of the HCC cohort was 63.1 years (SD, ±11.5). 73.4% were men and 65.5% were Caucasians. 70.7% were diagnosed at TNM stage III and IV. 52.6% had no evidence of hepatitis B or C virus infection. 81.7% had local and systemic therapy, while 18.3% underwent surgical resection. The median survival of HCC patients was 19.2 months. 10.7% of patients reported statin use. We observed significant difference in overall survival between statin non-users and users; the median overall survival (95% CI) were 18.5 (16.4-20.5) months and 25.4 (19.8-31.1) months, respectively (log rank test p = 0.04). 30% mortality reduction was observed in statin users versus non-users (HR = 0.7, 95% CI, 0.5-0.9). This significant association was also observed in patients who received systemic and local therapy (p = 0.04). HCC patient without liver cirrhosis showed 40% mortality reduction (HR = 0.6, 95% CI, 0.4-0.9, P = 0.04) while patient with liver cirrhosis did not. History of hepatitis did not affect the association. Even after controlling for various clinical variables including age, sex, race, staging, HCV, HBV, liver cirrhosis, treatment, alcohol use and diabetes, statin use was still associated with favorable overall survival in HCC patients (HR = 0.7, 95% CI, 0.5-0.9, P=0.03). Conclusions: This is the largest study to date to evaluate the effect of statins on the outcomes of HCC patients. We found that statin use may reduce the risk of death in patients with HCC. Validation of our finding is warranted in a large prospective study.