tbuckley/cabot-search huggingface dataset:
Early experience of combination treatment of sorafenib and radiotherapy in patients with advanced hepatocellular carcinoma (HCC).
Authors: J. Seong
Journal: Journal of Clinical Oncology (2011)

320 Background: Although sorafenib has been recognized as a standard therapy for advanced HCC, its antitumor effect as a single modality seems unsatisfactory. In this study, we report our early experience of combination treatment of sorafenib and radiation in locally advanced or metastatic HCC. Methods: From 2007 to 2009, a total of 22 HCC patients were treated with concurrent sorafenib (400 mg/day) and radiation. Nine patients received local radiotherapy 45-54 Gy in 1.8-5 Gy/fraction on the primary tumor with sorafenib (primary group). In the primary group, number of patients in stage III, IVA, and IVB was 1, 4, and 4, respectively. The remaining 13 patients received local radiotherapy 30-58.4 Gy in 1.8-6 Gy/fraction on the metastatic tumor with sorafenib (metastatic group). The metastatic sites involved bones (8 patients), lymph nodes (3 patients), chest wall (1 patient) and pelvic cavity (1 patient). Toxicity and tumor response were evaluated. Results: In toxicity, the primary group presented hand-foot syndrome in 3 patients, grade 2 GI toxicity in 1 patient, and grade 2 thrombocytopenia in 1 patient. The metastatic group showed hand-foot syndrome in 2 patients and grade 1-2 GI toxicity in 4 patients. Grade 3 thrombocytopenia was observed in 2 patients, in whom the initial platelet count was less than 100,000/mm 3 . In tumor response, the primary group presented partial response and stable disease in 6 patients and 1 patient, respectively, among 8 assessable patients (PR rate; 6/8, 75%). Tumor marker AFP decreased from pretreatment 9,710±19,208 ng/mL to post- treatment 1,410±2,866 ng/mL. In the metastatic group, significant pain palliation was shown in 7 among 8 patients (87.5%) in Visual Analogue Scale. In the remaining 5 patients, tumor response was shown as partial response and stable disease in 4 patients and 1 patient, respectively (PR rate; 4/5, 80%). Conclusions: In combination treatment of sorafenib and radiation, toxicity was acceptable. The substantial tumor response was also observed. Although this is the limited experience, the results of this study urge the initiation of a controlled clinical trial to verify the effect of combination treatment of sorafenib and radiotherapy. No significant financial relationships to disclose.
Simultaneous Isolation of Human Bone Marrow Hematopoietic, Endothelial, and Mesenchymal Progenitor Cells by Flow Sorting Based on Aldehyde Dehydrogenase Activity.
Authors: Tracy Gentry, Sandra J. Foster, Lisa Winstead, Erica Deibert, Michelle Fiordalisi, Andrew E. Balber
Journal: Blood (2006)
Phase I study of fixed-dose rate (FDR) gemcitabine with capecitabine in advanced solid malignancies
Authors: S. Attia, J. Eickhoff, K. D. Holen, H. Bailey, D. Alberti, G. Wilding, G. Liu
Journal: Journal of Clinical Oncology (2008)

13509 Background: Combining FDR gemcitabine and capecitabine has potential advantages of non-overlapping mechanisms/toxicity and higher, more efficacious extracellular concentrations of gemcitabine. Methods: Eligible patients (age ≥ 18; biopsy-proven, measurable advanced solid tumor; ECOG performance status (PS) ≤ 2; no brain metastasis; prior chemotherapies ≤ 3; and adequate major organ function) received capecitabine 500 mg/m2 PO BID days 1–14 of 21 with varying concentrations of FDR gemcitabine (400 to 1000 mg/m2 IV escalating by 200 mg/m2 increments) on days 1 & 8 using a 3 by 3 cohort design. The primary endpoint was to find dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD). Secondary endpoints were tolerability and response. Results: Twenty-seven patients (12 women/15 men; median age 59 years (range, 35 to 80 years); median PS 1; cancers: six kidney; four esophageal; two each: bladder, cholangiocarcinoma, soft tissue sarcoma, pancreas and head & neck; and one each: anal, non-small cell lung cancer, ovarian, uterine, rectal, hepatoma and salivary gland) were enrolled between 3/04 and 10/07. Accrual: 400 mg/m2 of gemcitabine, nine patients; 600 mg/m2, six; 800 mg/m2, four; and 1000 mg/m2, eight. Predominant grade ≥ 3 toxicities (123 cycles) were neutropenia (grade 3, nine patients; grade 4, six patients), thrombocytopenia (grade 3, two patients; grade 4, one patient) and rash (grade 3, two patients). DLTs: 400 mg/m2 of gemcitabine, grade 3 rash (one patient) and grade 3 neutropenia (one patient); 600 mg/m2, grade 4 neutropenia (one patient); and at 1000 mg/m2, one patient had grade 4 neutropenia and thrombocytopenia. The MTD and recommended phase II dose is capecitabine 500 mg/m2 PO BID days 1–14 of 21 with FDR gemcitabine 800 mg/m2 IV days 1 & 8. One patient died on treatment from progressive disease. Twenty-five were evaluable for response. There were no complete responses. Three had a confirmed partial response (12.0%; kidney, bladder and esophageal, 95% CI: 4–30%) and 10 (40.0%, 95% CI: 23–59%) had stable disease as a best response. Conclusions: This regimen was moderately tolerated with neutropenia as the primary toxicity. The recommended phase II dose is capecitabine 500 mg/m2 PO BID days 1–14 of 21 with 800 mg/m2 IV FDR gemcitabine days 1 & 8. No significant financial relationships to disclose.
Post-prostatectomy persisting PSA: Correlation with disease progression and survival in pT3 prostate cancer patients of the ARO 96-02 randomized phase III clinical trial—10 years' follow-up.
Authors: Thomas Wiegel, Detlef Bartkowiak, Dirk Bottke, Axel Hinke, Michael Stöckle, Manfred Wirth, Axel Semjonow, Kurt Miller
Journal: Journal of Clinical Oncology (2014)

32 Background: In the ARO 96-02 trial, patients with pT3 prostate cancer were randomly assigned before achieving an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP) to receive a wait and see policy (arm A) or adjuvant radiotherapy (RT) (arm B). If the undetectable PSA level was not achieved, patients were excluded by protocol and received RT with 66 Gy (arm C). Methods: Three hundred eighty eight patients with pT3-4 pN0 prostate cancer with positive or negative surgical margins were recruited; 78 retained a detectable PSA (median 0.6 ng/mL, range 0.05-5.6 ng/mL) after RP; 74 of them were irradiated with 66 Gy to the prostatic fossa. Radiotherapy was applied in median 86 days post-RP. Results: Compared to patients in arm A and B, the patients with persisting PSA after RP had higher preoperative PSA values (p&lt;0.0001), higher tumor stages (p=0.0057), higher grades (more G3 tumors), higher Gleason scores (p=0.0013) and more positive surgical margins (p=0.033). For the 74 patients, the 10 years clinical relapse-free survival rate was 63%. Forty three men had hormonal therapy, 12 developed distant metastases; 23 patients died. Compared to patients who did achieve an undetectable PSA (arms A+B), arm-C patients fared significantly worse with a 10 year overall survival of 68% versus 84% (p=0.0019). The rate of developing distant metastases within 10 year post-RP was 2.5 fold higher (14.6 vs. 5.8%) for men with a persisting PSA compared with the patients in arm A (p=0.0079). Metastasis-free survival after 10 years was 67% in arm C versus 81% in arm B (p=0.01). Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors which should then prompt aggressive treatment. It correlates with a higher rate of distant metastases and with worse overall survival. The results underline the significance of achieving an undetectable PSA after radical prostatectomy.
Unique histopathologic features of brain metastases from hepatocellular carcinoma.
Authors: Yu Yun Shao, Min-Shu Hsieh, Chung-Yi Huang, Li-Chun Lu, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2013)

169 Background: In the era of anti-angiogenic therapy as treatment for advanced hepatocellular carcinoma (HCC), the incidence and importance of brain metastases are increasing. We aimed to study their histopathologic features. Methods: We searched for all patients who were diagnosed to have HCC with brain metastasis from 1999 to 2010 at National Taiwan University Hospital, Taipei, Taiwan. Patients who had HCC with lung metastasis were also included for comparison. Patients with available tissues of both primary and metastatic tumors were enrolled in this study. Tumor slides from paired primary and metastatic HCCs were stained by H and E, and immunohistochemically stained for CK7, p53, Ki67, vimentin, Hes1, and c-Met. The expressions of CK7, p53, and vimentin were graded according to percentages of positive staining, but those of Hes1 and c-Met were recorded as an H score, which was defined as intensity (0, 1, 2, or 3) × percentages of positive staining. Results: A total of 14 patients had available tumor tissues of both primary and metastatic brain tumors. Another 21 patients had tumor tissues of both primary and metastatic lung tumors. The metastatic brain tumors, comparing to the metastatic lung tumors, had significantly more bizarre dilated vessels (86% vs. 14%, p &lt; 0.001), hyaline globules (50% vs. 5%, p = 0.003), higher Hes1 H scores (mean, 245 vs. 131, p = 0.001), and lower c-Met H scores (mean, 15.4 vs. 38.1, p = 0.046). Tumor necrosis also tended to be more common among metastatic brain tumors (93% vs. 62%, p = 0.056). On the contrary, the above differences were not identified between the primary tumors which later developed brain metastasis and those which later developed lung metastasis. When disease progressed from primary liver to brain metastasis, mitosis counts (p = 0.034) and bizarre dilated vessels (p = 0.020) significantly increased, and necrosis (p = 0.059) tended to be more common. Conclusions: Metastatic brain tumors from HCC had unique histopathologic features compared to primary liver tumors or lung metastases. The increased Hes1 expression and decreased c-Met expression in HCC brain metastasis should be further explored. (This study was supported by the grant of NSC101-2314-B-002 -141, 100CAP1020-2 &amp; NTUH.101-N1965.)
Comparison of the long-term toxicities conferred by two different doses of definitive chemoradiotherapy for stage II/III esophageal squamous cell carcinoma.
Authors: Emi Kubo, Ken Kato, Natsuko T. Okita, Atsuo Takashima, Yoshitaka Honma, Satoru Iwasa, Tetsuya Hamaguchi, Yasuhide Yamada, Yasuhiro Shimada, Yoshinori Ito, Jun Itami
Journal: Journal of Clinical Oncology (2014)

96 Background: Deﬁnitive chemoradiotherapy is one of the options for stage II/III esophagealsquamous cell carcinoma (ESCC). RTOG9405 recently reported that a higher dose of radiation did not confer any additional survival benefit over the standard dose (50.4 Gy). We comparedthe long-term toxicities conferred by chemoradiation at a dose of 60 Gy and 50.4 Gy for stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (non-T4) (UICC-TNM, 6 th edition) ESCC, performance status 0-2, and age 20-75 years. The study group comprised 254 patients who received definitive chemoradiotherapy as first-line therapy between January 2000 and August 2010 in our hospital. Group J (n=207) received 2 cycles of cisplatin (40 mg/m 2 on days 1 and 8) with fluorouracil infusion (400 mg/m 2 /day on days 1-5 and 8-12), or 2 cycles of cisplatin(70 mg/m 2 on day 1) with fluorouracil infusion (700 mg/m 2 /day on days 1-4) and concurrent radiotherapy at 60 Gy. Group R (n = 47) received 2 cycles of cisplatin (75 mg/m 2 on day 1) with fluorouracil infusion (1000 mg/m 2 /day on days 1–4) and concurrent radiotherapy at 50.4 Gy. Long-term toxicity was evaluated according to the Common Terminology Criteria for Adverse Event Ver. 3.0. Results: The characteristics of both groups are as follows (J:R group): median age, 64:63; male/female, 178/29:42/5; PS 0/1/2, 90/104/1:33/14/0; stage IIA/IIB/III: 48/58/101:6/20/21. The median follow-up period was more than 60 months for both groups, with 5-year survival rates of 43.6% and 58.6% for the J and R group, respectively. The proportion of patients with grade 3/4 long-term toxicity in each group was as follows (J/R group): pleural effusion, (8.7%/0%; p = 0.036); pericardial effusion, (6.7%/2.1%; p = 0.196); radiation pneumonitis, (2.4%/4.2%); esophagitis, (0.9%/0%); and pericarditis, (2.4%/0%). Grade 3/4 late toxicity was observed more frequently in the J group (15.0%) than in the R group (6.4%) (p = 0.087). Treatment-related death due to pneumonitis was observed in only 1 patient in group J. Conclusions: The RTOG regimen at a dose of 50.4 Gy showed promising results while inducing lower late toxicity rates than when administered at 60 Gy.
Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index
Authors: Heather E. Hoch, Agustin Calatroni, Joseph B. West, Andrew H. Liu, Peter J. Gergen, Rebecca S. Gruchalla, Gurjit K. Khurana Hershey, Carolyn M. Kercsmar, Haejin Kim, Carin I. Lamm, Melanie M. Makhija, Herman E. Mitchell, Stephen J. Teach, Jeremy J. Wildfire, William W. Busse, Stanley J. Szefler
Journal: Journal of Allergy and Clinical Immunology (2017)
Does disease control rate (DCR) at 9 and 18 weeks predict overall survival (OS) in patients with malignant pleural mesothelioma (MPM)? An individual patient data combined analysis of 10 European Organisation for Research and Treatment of Cancer (EORTC) Lung Cancer Group (LCG) studies.
Authors: L. Greillier, B. Hasan, P. Baas, J. J. Welch, J. P. Van Meerbeeck, R. M. Gaafar, R. Sylvester, D. A. Lacombe, M. O'Brien
Journal: Journal of Clinical Oncology (2011)

7025 Background: The development of new drugs is urgently needed in MPM to improve the efficacy of first-line therapy and identify effective second-line treatments. In phase II trials, the biological activity of drugs is generally assessed using the response rate (RR) as the primary endpoint. However, response criteria have always been difficult to apply to MPM, due to its unique pattern of growth. We hypothesized that the DCR could be a better predictor of OS than the RR in MPM patients (pts). Methods: Individual patient data from 10 EORTC LCG studies (9 phase II and 1 phase III trials) of first-line chemotherapy in MPM were pooled. Response to therapy was assessed according to WHO criteria in all trials except the 2 most recent trials, which used RECIST. Landmark analyses (LA) were performed to assess the association of the intermediate endpoints (DCR and RR) with OS. Two different time points, namely 9 weeks and 18 weeks after registration or randomization, were considered. All 10 studies (N=523 pts) were included in the LA of DCR, but only 6 studies (N=369 pts) were suitable for LA of DCR and RR at 9 weeks and 18 weeks. Results: Based on the data from 6 studies, response (vs non-response) at 9 and 18 weeks was associated with longer survival times, with hazard ratios (HR) of 0.51 (95%CI, 0.36-0.72) and 0.55 (95%CI, 0.38-0.78), respectively. In the same population, disease control (vs progression) at 9 and 18 weeks was also associated with longer survival times, but with HR of 0.41 (95%CI, 0.30-0.55) and 0.52 (95%CI, 0.37-0.74), respectively. In the overall population, disease control at 9 and 18 weeks was confirmed as a predictor of OS, with HR of 0.37 (95%CI, 0.30-0.47) and 0.50 (0.38-0.65), respectively. Conclusions: With a smaller HR, the DCR at 9 weeks shows some advantage over the RR in predicting OS in MPM pts. Therefore, it should be taken into consideration as primary endpoint when designing future phase II clinical trials in MPM.
Surgical interventions in cancer patients at the end of life: Experiences at an academic medical center.
Authors: Lynn Jackson Howie, Arif Kamal, Nrupen A Bhavsar, Steve Power, Paul J. Mosca
Journal: Journal of Clinical Oncology (2014)

281 Background: Surgical quality measures look to reduce variation and improve outcomes. Procedure goals can range from cure to symptom improvement. Knowledge of procedures used in this population can inform quality metrics, ensure palliation is included and that metrics do not discourage interventions where benefits are other than traditional measures like mortality. Methods: Clinical and administrative data from 1,343 patients treated at an academic medical center from 2006 to 2013 were obtained. Using CPT codes, procedures were identified. Patients who underwent surgical procedures within 180 days of their death were then evaluated to determine the demographic, clinical and surgical characteristics of these cases. Patients &lt;18 years of age and those with missing data were excluded from the analysis. Descriptive statistics were used to describe interventions among patients in the cohort. Results: From 2006 to 2010, 761 patients with cancer treated at an academic medical center had surgical procedures performed within the last 180 days of life. 38.8% of these patients were female, 82% were Caucasian, 15% were African-American, and 3% were other race. Median age was 67.9 years (interquartile range: 58.1 - 78.1). 158 had procedures performed ≤30 days of death, 295 ≤60 days of death, and 530 ≤120 days of death. The most frequent type of procedure performed ≤30 days from death were thoracic procedures including bronchoscopy, thoracentesis, mediastinoscopy and catheter placement for pleural fluid drainage (20.8%), ≤60 days of death 30.3% underwent thoracic procedures, and ≤120 days of death 24.5% underwent similar thoracic procedures. Conclusions: Surgical quality measures are thought to improve surgical outcomes. Evaluation of surgical data from a academic medical center demonstrates continued use interventional procedures in cancer patients within the last 6 months of life. This may in part be due to the symptom burden associated with these diseases. Further evaluation about the goals of interventional procedures in this patient population can inform the outcomes of primary interest in this population of patients who have high mortality due to their advanced disease.
Clinicopathological features and response to platinum-based chemotherapy in pancreatic neuroendocrine carcinoma: A retrospective multicenter study of 70 patients.
Authors: Susumu Hijioka, Waki Hosoda, Keitaro Matsuo, Makoto Ueno, Masayuki Furukawa, Hideyuki Yoshitomi, Noritoshi Kobayashi, Masafumi Ikeda, Tetsuhide Ito, Shoji Nakamori, Hiroshi Ishii, Yuzo Kodama, Chigusa Morizane, Hiroaki Yanagimoto, Kei Yane, Kenji Notohara, Junji Furuse, Yasushi Yatabe, Nobumasa Mizuno
Journal: Journal of Clinical Oncology (2016)

298 Background: The WHO classified pancreatic neuroendocrine Neoplasms (pNEN) in 2010 as G1, G2, and neuroendocrine carcinoma (NEC). However, pNEC is suspected to include heterogeneous disease entities, but is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. Methods: A total of 100 cases clinical data and pathological slides originally diagnosed as NEC by the WHO in 2010(WHO-NEC) were retrospectively collected from 31 institutes. Expert pathologists were reassessed all cases slide using the designed protocol and reclassified as well differentiated NET (NET-G3), small cell NEC(SCNEC), and large cell NEC(LCNEC) by morphological features. Results: Thirty cases were eliminated mostly because acinar cell carcinoma, NET-G2 and malignant tumor not otherwise specified. Remaining 70 cases were subclassified into 21(30%) NET-G3, 31 (44.3%) SCNEC, 18(25.7%) LCNEC. Comparisons of NET-G3 vs. SCNEC vs. LCNEC revealed the following traits: ENETS stageⅣ: 76%, 81% and 78%; median Ki67 LI: 28.5% (15-53), 85 % (50-100) and 70.0 %(22-90); abnormal Rb expression: 0 %, 59% and 47%; KRAS mutations: 0 %, 48% and 50%; response rates to platinum-based chemotherapy: 0%, 60% and 44.4% ;and median survival(days): 1255, 340 and 196, respectively. When KRAS divided wild (n = 20) and KRAS mutation group (n = 42), response rate to platinum-based chemotherapy was 77% vs 23%.In the same manner, when Rb immune stain divided negative (n = 24) and positive (N = 41), response rate to platinum-based chemotherapy was 80% vs 23.8%. Besides response rate to platinum-based chemotherapy of KRAS mutation(+) and Rb immunopositivity(-) group (n = 7) were 100%, on the other hand, KRAS mutation(-) and Rb immunopositivity(+) group (n = 7) were 18.7%. Conclusions: In this retrospective study, WHO-NEC include 30% NET-G3. NET-G3 are genetically different from SCNEC and LCNEC. As for chemotherapy,Mutated KRAS and/or Rb immunonegativity in tumors with pNEC is associated with response to platinum-based chemotherapy.
TNF-α deficiency as protection against sickness behavior related to external beam radiation of the pelvis in mice.
Authors: Sravana K Chennupati, Faisal A Siddiqui, Tasha L. McDonald, Charles R. Thomas, Arthur Hung, Lisa J Wood
Journal: Journal of Clinical Oncology (2012)

208 Background: Prostate cancer patients undergoing localized external beam radiation therapy (EBRT), experience significant fatigue during treatment, which can affect physical functioning and QOL. We hypothesize that cancer treatment related fatigue (CTRF) is the same as sickness behavior caused, in part, by increases in TNF-α. Our previous data demonstrate that pelvic EBRT induces systemic increases in TNF-α and a decline in voluntary wheel running activity (VWRA) , an objective measure of sickness in mice. A specific aim of this study was to determine the requirement of EBRT for TNF-α for the induction of sickness behavior. Methods: Daily VWRA was monitored in male WT (n=10) and TNF-α−/− (n=10) anesthetized mice undergoing pelvic EBRT at 4.6 Gy/fraction, 5 days per week for 15 fractions for a total dose of 69 Gy [4.6 X 15 = 69, not 70]. Control WT (n=10) and TNF-α−/− (n= 10) mice underwent anesthesia followed by sham EBRT. The effect of treatment on weight and food intake was also determined by calculating change in weight and daily food intake during treatment. A 2 x 2 repeated measure analysis of covariance ANCOVA was used to determine whether there was a significant interaction between treatment group (EBRT or Control) and genotype (WT or TNF-α−/−) on voluntary wheel running activity controlling for baseline differences in this variable. Similarly a 2 x 2 ANOVA was used to determine whether there was a drug x genotype interaction between change in body weight or food intake. Results: There was a significant effect of EBRT on VWRA (p&lt; 0.001), food intake (p0.002), and weight (p&lt;0.001). We did not however observe a significant interaction between EBRT and genotype in VWRA (p= 0.756), food intake (p=0.654), or weight (p= 0.450). Conclusions: Targeting TNF-α using specific cytokine blocking agents has been suggested as a potential strategy for preventing or managing EBRT related fatigue. Although our prior data support that localized EBRT to the pelvis may induce TNF-α and sickness behavior in mice, our latest data do not support a direct role for this cytokine in mediating these effects.