tbuckley/cabot-search huggingface dataset:
Impact of disease progression on patient reported outcomes, hospitalization, and death in patients with stage IV, renal cell carcinoma.
Authors: Junji Lin, Ronda Copher, Debanjana Chatterjee, Prashant Ramesh Joshi, Maxine D. Fisher, Mark S. Walker, Jiandong Kerr, Yousef Zakharia
Journal: Journal of Clinical Oncology (2018)

e16550 Background: Targeted therapy is widely used as 1st and 2nd line treatment in metastatic renal cell carcinoma (mRCC). This study assessed the impact of disease progression (DP) on patient reported outcomes (PROs), hospitalization and death in patients receiving targeted therapy for mRCC in community oncology setting. Methods: Retrospective medical records data from adults diagnosed with stage IV/metastatic RCC (ICD-9, 189; ICD 10, C64, C65) between 7/11/2000 and 3/29/2016 were collected from a network of community oncology practices across US. Linear mixed models were used to evaluate longitudinal PROs collected from the Patient Care Monitor survey. Time-varying Cox models were used to assess the impact of DP on risk of hospitalization and death, where DP was considered as a time-varying covariate. In patients with at least one DP, standard Cox model was used to assess the impact of time to the first disease progression (TTFP) on death after first DP. Results: Among 417 patients, 65.7% were male, 75.8% white, and median age was 65 years (range 27-93 years). Of 355 patients with 1st line systemic treatment, 278 (78.3%) received tyrosine kinase inhibitors (TKIs), and 52 (14.6%) received mammalian target of rapamycin inhibitors (mTORs). Comparing patients on mTORs to those on TKIs, index scores were nominally higher (worse) for General Physical Symptoms, Acute Distress, Impaired Performance, and significantly higher for Impaired Ambulation (p = 0.01). DP was significantly (p < 0.001) associated with increase in index scores for both Treatment Side Effects and Despair. Time-varying Cox models showed a 42.5% increases in risk of hospitalization and a 72.7% increase in risk of death associated with each additional DP. In patients with at least one DP, longer TTFP was associated with a 4% (p = 0.003) decrease in risk of death for all treated patients. Conclusions: In this study, among mRCC patients treated with TKIs and mTORs, DP was associated with worsening PROs, and increased risk of hospitalization and death. Longer TTFP was associated with decreased risk of death. Future studies should investigate impact of DP for mRCC patients beyond community oncology setting.
Role of circulating tumor cells by rare cell enumeration system in predicting response of non-small cell lung cancers to therapy.
Authors: Midhun Malla, Roberto Bernardo, Crista Horton, Mohamed Kamal, Leslie Macall, Takemi Tanaka, Mohammad Abdul Razaq
Journal: Journal of Clinical Oncology (2018)

e24058 Background: We aim to investigate role of circulating tumor cells (CTC) as supplementary marker to imaging to predict response to therapy in non-small cell lung cancer (NSCLC) patients (pt). We hypothesized “CTC rise post therapy is associated with radiologic progression or progression of NSCLC in near future”. We used a new CTC enumeration system (Rare Cell), which collects epithelial and mesenchymal CTC from blood, instead of Cell search. Methods: CTC were collected from whole blood of Stage III and IV NSCLC pt before and after therapy. Data was correlated with radiologic response. Chi-square and t-test analysis were performed as appropriate. Results: 9 pt with stage IV and 1 with stage IIIB NSCLC were analyzed. In 4 pt with response & 3 with progression Δ in CTC correlated with images. 3 pt had discordant results (see table). Pt with higher baseline CTC had greater radiologic response. Baseline CTC > 4 also resulted in higher CTC response (-2.50±1.00 vs 2.33±1.21, p<0.001). Conclusions: Radiologic findings and ΔCTC correlated well in majority of NSCLC pt. Higher response rate with higher baseline CTC might suggest aggressiveness of the disease, making it more sensitive to therapy. In pt with discrepancy between imaging and CTC, increase in CTC was predictive of disease progression in near future. Trending CTC helps augment response assessed by routine imaging. Oncologists can consider imaging in short intervals (4-6 weeks) for pt with CTC increase despite radiologic response. Table 1. Subject Pathology Pre therapy CTC Post therapy CTC CTC Responders Radiological Responders Comment 1 Adenocarcinoma 4 3 Yes Yes 2 Squamous 6 3 Yes Yes 3 Squamous 3 5 No Mixed Post treatment imaging showed 36% shrinkage of primary tumor but increase in pleural nodules. Scans in 4 weeks showed progression. Pt died within 8 weeks of CTC rise 4 Squamous 1 2 No No 5 Adenosquamous 2 5 No No 6 Adenocarcinoma 3 7 No Mixed Post therapy scans showed response but CTC increased. Scans in 3 months showed progression of disease. However, pleurodesis was done prior to 2nd CTC 7 Adenocarcinoma 4 1 Yes Yes 8 Adenocarcinoma 2 3 No No 9 Squamous 4 1 Yes Yes 10 Adenosquamous 2 5 No Yes Pt developed liver metastases within 6 months of rise in CTC
Prognostic value of Mesenchymal Circulating Tumour Cells: Dynamic monitoring in patients with colorectal cancer.
Authors: Bin Xiong, Dongdong Shi, Shuyi Wang, Liang Zheng, Chunxiao Zhang, Chaogang Yang, Tangxi Guo, Fangfang Chen
Journal: Journal of Clinical Oncology (2018)

e24052 Background: Circulating tumor cell (CTC) could indicate residual disease and epithelial-mesenchymal transition (EMT) of CTC plays an important role in tumour recurrence and drug resistance. Thus, detection of CTCs exhibiting phenotypic hallmarks of EMT may provide a source for predicting relapse and evaluating the therapeutic response. Methods: CTC was isolated by size of epithelial tumour cells (ISET) and identified by Wright staining. Epithelial and mesenchymal markers of CTC were labelled using immunocytochemistry. Eighty-nine CRC patients were monitored at three different time points: before surgery, after surgery, and after two cycles of postoperative chemotherapy. Factors of prognostic significance were investigated using the univariate and multivariate Cox regression model. Results: Kaplan–Meier survival and Cox regression analyses revealed that mesenchymal phenotype CTC(M+CTC) positive before surgery was an independent factor for poor progression-free survival and overall survival (P < 0.001). After two cycles of chemotherapy, M+CTC positivity remained an independent prognostic factor for poor PFS (P < 0.001), but not for OS. The presence of CTCs is positively correlated with poor prognosis, M+CTC positivity before surgery predicts poorer survival; when taking before surgery and after two cycles of chemotherapy CTC counts and M+CTC ratio into account, PFS for patients in bad prognosis group were pooer than that in good prognosis group (P < 0.001), PFS for patients in good prognosis group and bad prognosis group were 29.9 and 15.8 months (P < 0.001). . Conclusions: CTC detection was correlated with advanced disease stage. The presence of M+CTC was correlated with CRC disease stage and lower grade of differentiation. The presence of CTC (CTC or M+CTC) both before surgery and after two cycles of chemotherapy was a strong independent prognostic factor for PFS. In addition, only M+CTC-positivity before surgery was associated with worse OS. our findings prompt that M+CTCs could be a potential prognostic factor in CRC patients with a high risk of relapse factors and could be useful for studying CTC-targeting therapies.
Utility of CT texture for identification of FGFR2 fusion in cholangiocarcinoma: A radiogenomic pilot study.
Authors: Thomas DeLeon, Mitesh J. Borad, Teresa Wu, Jing Li, Christine M. Zwart, George Yang, Scott Holeman, Alvin C. Silva
Journal: Journal of Clinical Oncology (2017)

e15626 Background: FGFR2 fusions are found in 10-15% of intrahepatic cholangiocarcinomas. Individuals with FGFR2 fusions have a better prognosis and more indolent natural history. More recently FGFR2 fusions have been described as a predictive marker for tyrosine kinase inhibitors targeting the FGFR2 pathway. Texture analysis from CT imaging has been used in the past to estimate degree of fibrosis and angiogenesis in various tumors types; however, texture analysis has not been used in the past to detect FGFR2 rearrangements. Methods: This is a retrospective study of 33 patients with intrahepatic cholangiocarcinoma who were previously tested for FGFR2 fusions with either a FISH break apart assay or with clinically available next generation sequencing assays. All patients had a contrast enhanced CT performed. To address physiological and pathological variations, matched-size regions of interest (ROIs) over areas of non-necrotic tumor and unaffected liver during the portal venous phase were drawn. The paired ROIs for each patient were then processed via an imaging analytic pipeline for (1) ROI normalization, (2) texture panel creation, and (3) machine learning predictive model development. Results: Fifteen patients with FGFR2 fusions and 18 patients without FGFR2 fusions were included in the study. Using the developed predictive model, accurate FGFR2 fusion classification in 90% of cases was achieved (sensitivity = 87%, specificity = 94%). Conclusions: Utilizing advanced analytics with machine learning techniques, multi-textural data obtained from conventional CT images has the capability to detect genetic aberrations in intrahepatic cholangiocarcinoma, including FGFR2 gene fusions. Radiogenomic evaluation has several attractive benefits including the cost effective and expeditious detection of actionable mutations such as FGFR2 fusions as well as avoidance of invasive procedures such as percutaneous core biopsies. [Table: see text]
A multicenter, randomized, double-blind, placebo-controlled phase III study of monosialoganglioside (GM1) preventing neurotoxicity induced by cisplatin-based chemotherapy in non-small cell lung cancer patients.
Authors: Li Zhang, Ting Zhou, Yuxiang Ma, Yunpeng Yang, Wenfeng Fang, Yuangyuan Zhao, Shaodong Hong, Chan Fang, Jiexia Zhang, Hongyu Zhang, Hongyun Zhao, Yan Huang
Journal: Journal of Clinical Oncology (2016)

TPS10142 Background: The peripheral neurotoxicity induced by cisplatin is a common adverse event in non-small cell lung cancer (NSCLC) patients. This phase III trial will evaluate the efficacy and safety of monosialoganlioside (GM1) preventing neurotoxicity induced by chemotherapy contained cisplatin in patients with NSCLC. Methods: The population consists of NSCLC patients that received cispaltin-based doublet chemotherapy as. Eligible patients will be randomized in a 1:1 ratio to receive either GM1 or placebo (80mg on days 0-3, every 3 weeks), concomitant with cisplatin-based chemotherapy (cisplatin 75 mg/m2 on day 1 or on days 1-3, every 3 weeks) for 4 or 6 cycles. The neurotoxicity evaluation will be conducted every cycle and 3w/11w/19w after the cispaltin-based chemotherapy. The primary endpoint is incidence rate of neurotoxicity adverse events. Secondary endpoints include eurotoxicity the safety and quality of life and adverse events alleviation time. According to previously reported, it was assumed that the incidence rate of neurotoxicity would be 50% in the placebo group and 30% in the GM1 group. To detect a 20% reduction in incidence rate of neurotoxicity in GM1 group at a two-sided significant level of 0.05 and power of 0.08, allowing for a drop-out rate of 10%, the sample size was calculated to be 150 patients per group. 300 patients will be enrolled in the trial at 10 sites in China. So far, 200 patients have been enrolled. Clinical trial information: NCT01882621.
Mobile game for management in metastatic breast cancer patients receiving cytotoxic chemotherapy.
Authors: Hee Jun Kim, Min-suk Kwon, Jae-hyun Tae, Song-Ee Park, Sun Mi Kim, Hee-Chul Shin, Doug Hyun Han
Journal: Journal of Clinical Oncology (2016)

6515 Background: Mobile games were blamed for provoking aggressions and physical harms and reducing pro-social behaviors. However, recent studies suggested well-designed pro-social games may increase sociality and help brain activity in specific subset of patients. A smartphone-based multiplayer mobile game, called ILOVEBREAST (CLGAMES, Seoul, Korea), was invented in purpose to improve self-management and reduce side effects related with chemotherapeutic drugs. We hypothesized that a 3-week program with the online social networking game would be helpful in patients who are receiving chemotherapy for metastatic breast cancer. Methods: A total of 82 patients with pathologically proven clinical stage IV metastatic breast cancer were enrolled in a single tertiary center between 2013 and 2014. The patients were randomly assigned to the game group or the education group in a 1:1 ratio. Patients in the control group were given a brochure explaining coping strategies for side effects of chemotherapy, and recommended to read them regularly. Results: The game group experienced lower rates of chemotherapy-induced side effects than the education group did: fatigue (50% vs. 77.5%, p<0.01), numbness (0% vs. 62.5%, p<0.01), stomatitis (0% vs. 7.5%, p<0.01), hair loss (0% vs. 25%, p<0.01), and total side effects (53% vs. 79%, p<0.01). The decrease in quality of life, and the increase in anxiety levels after 3 weeks were also lower in the game group than in the education only group. After the 3-week program, 41% of the subjects in the game group were satisfied with the contents. Conclusions: The smartphone-based multiplayer mobile game reduced chemotherapy-induced side effects and the level of anxiety, and enhanced quality-of-life compared to the conventional measures based on education. This study suggests that a carefully designed social network-based mobile game may help patients who receive cytotoxic chemotherapy.
Prognostic influence of BRCA 1 somatic mutations in African Amercian versus Caucasian ovarian cancer patients.
Authors: Sareena Singh, Karen Swarer, Analisa DiFeo, Joram Sawady, Susanna Syriac, Kimberly Erin Resnick
Journal: Journal of Clinical Oncology (2017)

e17054 Background: Racial disparities in outcomes exist between African-American (AA) and Caucasian (C) patients (pts) with high grade epithelial ovarian cancer (EOC). Not all disparity is explained by socio-economic and access related issues. Many argue that differences in tumor biology also play a role. Germline BRCA mutations confer a protective effect in these pts. Immunohistochemistry (IHC) for BRCA 1 is being developed to detect somatic BRCA1 mutations. Parp-inhibitors have been approved for use in pts with germline and/or somatic BRCA mutations. We describe the first comparison of the prognostic implications of BRCA1 somatic mutation status in tumor samples taken from AA and C EOC pts who underwent primary surgery followed by systemic chemotherapy. Methods: IHC staining of whole tumor sections from AA and C pts was performed using a commercially available monoclonal antibody against BRCA1 (Calbiochem). Staining was scored as: loss, retention, or equivocal in the presence of a positive control. Retention was described as wild-type and loss or equivocal as mutation. Standard statistical analyses were used to correlate race, BRCA1 status, and survival. Results: Tumor from 33 pts (16AA and 17C) was stained and scored. Most pts had Stage III (66.7%) disease and high grade serous subtype (82%). Stage, histology, and debulking status did not differ between groups. Overall, loss of BRCA 1 occurred 16/33 (48.5%) tumors. BRCA1 was mutated more frequently in tumors from AA pts (11/16) compared to C pts (5/17) (p=.024). BRCA 1 mutation conferred a protective effect, with a trend towards improved progression free survival: 9.5 vs 15.8 mos in AA (p=0.44) and 16.5 vs. 21 mos in C pts (p=0.97). No statistically significant difference in OS was seen. Conclusions: We demonstrate that IHC for BRCA 1 mutation is feasible in a standard hospital pathology laboratory. Race based differences in somatic BRCA 1 mutation exist; mutational differences are associated with a trend in improved PFS. A larger cohort is needed to elucidate the true effect of this status on outcome. Conceivably, knowledge of BRCA 1 tumor status could be used to improve outcomes in AA pts who may be able to achieve survival numbers comparable to C pts.
Cisplatin and gemcitabine versus carboplatin and gemcitabine in metastatic bladder cancer: Survival analysis of veterans' health care data.
Authors: Anuradha Kunthur, Eric R Siegel, Rangaswamy Govindarajan
Journal: Journal of Clinical Oncology (2017)

e16023 Background: Background: Cisplatin and gemcitabine combination chemotherapy is the standard regimen used for the treatment of metastatic bladder cancer. Most Veterans Administration (VA) patients with metastatic bladder cancer are elderly or with poor renal function, and are considered not good candidates for cisplatin administration. It is a common practice to substitute carboplatin for cisplatin in this population. Methods: Methods: We identified stage IV bladder cancer patients treated initially with cisplatin plus gemcitabine (Ci+G) or carboplatin plus gemcitabine (Ca+G) at VA medical centers from 2000 to 2010. The data was obtained via the VA central cancer registry from all VA medical centers across the country. Overall survival (OS) was summarized as Kaplan-Meier medians and compared for difference between platinum groups via Cox regression. Results: Results: 196 subjects () with stage IV bladder cancer were identified. There were 194 males , 78 received Ca+G, 118 received Ci+G. 149 deaths occurred during 197.49 person-years of follow up, for a median OS of 10.35 months. Median OS was 11.14 months with Ca+G versus 10.35 months with Ci+G. Cox regression revealed nearly equal group mortality rates, with Ca+G having a hazard ratio (90% confidence limits) of 1.02 (0.77–1.34) compared to Ci+G ( P= 0.93). Conclusions: Conclusion: Patients treated with Ca+G and Ci+G regimens had similar median OS, supporting the substitution of carboplatin for cisplatin with gemcitabine in this patient population.
Mutational Profile of Aggressive, Localised Prostate Cancer from African Caribbean Men Versus European Ancestry Men
Authors: Laurie Tonon, Gaëlle Fromont, Sandrine Boyault, Emilie Thomas, Anthony Ferrari, Anne-Sophie Sertier, Janice Kielbassa, Vincent Le Texier, Aurélie Kamoun, Nabila Elarouci, Jacques Irani, Luc Multigner, Ivo Glynne Gut, Marta Gut, Pascal Blanchet, Aurélien De Reynies, Géraldine Cancel-Tassin, Alain Viari, Olivier Cussenot
Journal: European Urology (2018)
Porocarcinoma expression of high EGFR levels and sensitivity to EGFR or/and MEK inhibition.
Authors: Friedegund Elke Meier, Mildred Sergon, Marlene Garzarolli, Arno Ruetten, Sophia Blum, Michael Laniado, Selma Ugurel, Jan Maschke, Stefan Beissert, Dagmar Kulms, Dana Westphal
Journal: Journal of Clinical Oncology (2016)

9545 Background: Eccrine porocarcinoma (EPC) is a rare skin cancer arising from the intraepidermal sweat duct. EPCs metastasize to regional lymph nodes in approx. 20% of cases with a mortality rate of 67%, due to subsequent distant metastasis. Whereas surgery is effective as first line treatment, optimal management of metastatic porocarcinoma has not yet been defined. Targeting the epidermal growth factor receptor (EGFR) or/and the downstream RAF-MEK-ERK (MAPK) signaling pathway may be a potential treatment for metastatic EPC since EGFR is expressed in more than 81% of skin adnexal tumors. Methods: Immunohistochemical analyses (IHC) of ten primary EPCs and of skin metastases derived from one patient with EPC were performed. EGFR and the downstream signal transduction molecules ERK, p-ERK, AKT and p-AKT were analysed. To study the in vitro effects of EGFR or/and MEK inhibition in EPC, we isolated tumor cells from a skin metastasis of a patient with EPC who was resistant to chemotherapy. Results: All primary tumors and metastases were highly positive for the epidermal growth factor receptor and positive for the signal transduction molecules ERK, p-ERK and AKT but negative for p-AKT. Isolated cutaneous metastatic EPC cells strongly expressed p-EGFR and p-ERK. Treatment of these cells with the anti-EGFR antibody cetuximab or the MEK inhibitor trametinib inhibited tumor growth and moderately induced apoptosis. Moreover, combined EGFR and MEK inhibition significantly enhanced the antiproliferative and proapoptotic effects. This patient underwent surgery for rapidly progressing skin and lymph node metastases and was treated with cetuximab. The patient remained progression-free for 6 months. Conclusions: These data suggest that EPC cells express high levels of EGFR that activates the MAPK pathway thus rendering tumor cells susceptible to EGFR or/and MEK inhibition. Our data provide a strong rationale for targeting EGFR or/and MEK in patients with metastatic EPC.
Clinicopathological features and prognosis of pregnancy associated breast cancer at Instituto Nacional de Cancerología of Mexico.
Authors: Wendy Rossemary Munoz Montano, Paula Cabrera-Galeana, Alberto Alvarado Miranda, Fernando Lara, Rafael Vazquez, Enrique Bargallo, Nereida Esparza, Alejandro Olvera, Cynthia Villarreal-Garza, Juan Wolfgang Zinser, Abelardo Meneses
Journal: Journal of Clinical Oncology (2018)

e13099 Background: Pregnancy-associated breast cancer (PABC) includes breast cancer diagnosed during pregnancy or within one or two years after delivery. PABC is the second most common malignancy diagnosed in pregnancy. There is controversial information about outcomes in this setting. Methods: We conducted a retrospective case-control study to evaluate overall survival (OS) and progresion free survival (PFS) of pregnant versus non-pregnant women with breast cancer, matched for age, inmunohistochemical subtype and stage of disease. Results: Median age was 35 years, there were no differences between cases and controls regarding clinical stage, tumor grading, IHC subtype (p = 1.0), Ki67 and histological type. Highlight that 31% were triple negative. Cases and controls were followed over 48 months. Kaplan–Meier survival showed no significant difference in OS and PFS between cases and controls (p = 0.892 and 0.121 respectivily). But if we analized the population by the time breast cancer takes place, the percentage of patients free of progresión at 24 months were: during pregnancy 46.4 (CI 95% 27.9-64.8); 12 months-postpartum 29.6 (CI 95% 12.3-46.8) and non-pregnancy patients 26.7 (CI 95% 17.2-36.1), log-rank test showed significance difference between these population PFS curves p = 0.045. Conclusions: We confirm previous reports that patients with breast cancer after delivery had worst PFS and PABC it is not associated with poor OS. As far as we know this is the first hispanic report in this setting. PABC %(n/N) Non-PABC %(n/N) P Clinical stage 1.0 I 1.7 (2/116) 1.7 (4/232) II 29.3 (34/116) 29.3 (68/232) III 48.3 (56/116) 48.3 (112/232) IV 20.7 (24/116) 20.7 (48/232) Histological type n (%) 0.171 Canalicular carcinoma 76.7 (89/116) 85.3 (198/232) Lubulillar carcinoma 12.1 (14/116) 6.0 (14/232) Mix 6.0 (7/116) 3.9 (9/232) Other 5.2 (6/116) 4.7 (11/232) Subtype 1.0 Triple Negative 31.0 (36/116) 31.0 (72/232) HER2+ 27.6 (32/116) 27.6 (64/232) RH+ 41.4 (48/116) 41.4 (96/232) Ki-67 n (%) 0.470 < 20 45.8 (44/96) 44.6 (100/224) > 20 54.2 (52/96) 55.4 (124/224) SBR CCI y CLI n (%)* 0.802 Low 9.1 (10/110) 8.1 (18/221) Medium 37.4 (41/110) 34.4 (76/221) High 53.6 (59/110) 57.5 (127/221)