tbuckley/cabot-search huggingface dataset:
Chemotherapy compared to surgery: Quality-of-life analysis of the German prospective multicenter trial in clinical stage I NSGCT (AUO AH 01/94).
Authors: Peter Albers, Florian Fischer, Henning Flechtner, Michael Hartmann, Roswitha Siener
Journal: Journal of Clinical Oncology (2014)

4563 Background: Although the superiority of one course of BEP over RPLND and surveillance in terms of recurrence rate has been shown, studies providing validated prospective quality of life (QoL) data in patients (pts) with NSGCT I treated with only one cycle of BEP are lacking. Therefore, the objective of the present trial was to examine long-term QoL issues in pts with clinical stage I NSGCT randomized after orchiectomy to either RPLND or one cycle of PEB chemotherapy. Methods: Results of the EORTC QLQ C30 plus additional scales questionnaire (QLQ C30+) were reviewed in 382 pts included in a prospective trial, which have been randomly assigned to receive either RPLND (n=191) or one course of BEP (n=191) after orchidectomy [AH 01/94, JCO 2008]. Pts with completed QLQ C30 and available data on treatment response were eligible for analysis. Pts with recurrences or 2nd malignancies were excluded. Treatment related changes of QoL in the no-event population were evaluated for the first 5 years after the end of treatment. A difference of >= 17% on the global item about “strain by treatment and/or tumor” was considered a clinically relevant difference between both treatment arms. Statistical comparisons between groups were performed using the Mann–Whitney U-test for nonparametric unpaired data. Results: The hazard ratio to experience a tumour recurrence with surgery as opposed to chemotherapy was 7.937 (95% CI, 1.808 to 34.48), i.e. 15 versus 2 recurrences. QoL results of pts with no event after the 1styear were available from 138 pts with BEP and 126 pts with RPLND. For year 5, still 83 BEP pts had QoL assessments compared to 72 pts in the RPLND group. No significant differences between treatment groups in any of the QoL domains occurred during 5 years, not even at the time of treatment. Neither physical, nor emotional or global domains revealed any difference between the two approaches. As expected, hair loss reflected the side effects of chemotherapy during years 1 and 2, but recovered fully thereafter. Conclusions: This large randomized trial was not able to detect significant short- or long-term differences in QoL scores between RPLND and PEB. Clinical trial information: Number 141 / AH 01/94.
Cancer immunotherapy of patients with the biochemical relapse of the prostate cancer using dendritic cell-based vaccine DCVAC/PCa.
Authors: Radek Spisek, Michal Podrazil, Ladislav Jarolim, Daniela Rozkova, Jitka Fucikova, Anna Fialova, Jirina Bartunkova
Journal: Journal of Clinical Oncology (2014)

3099 Background: Effect of cancer immunotherapy at the minimal residual disease stage can be evaluated in patients with the biochemical relapse of the prostate cancer. We performed a Phase I/II clinical trial in patients with the biochemical relapse of the prostate cancer using autologous mature dendritic cells pulsed with killed LNCap prostate cancer cell line, DCVAC/PCa. Methods: Eligible patients had a biochemical relapse of the prostate cancer after primary prostatectomy or after radical prostatectomy and salvage radiotherapy. Absence of hormonal therapy was required. DCVAC/PCa treatment consisted of twelve doses of 1x107dendritic cells injected s.c. Treatment comprised of initial 2 doses in 2 weeks interval and DCVAC/PCa was then administered every four weeks for a total of twelve doses. Patients experiencing significant prolongation/stabilization of PSA-DT were eligible for an additional treatment cycle. Primary goal of the study was to assess safety. Secondary goals were PSA kinetics and presence of tumor specific immunity. Results: Twenty one patients were evaluated after receiving 12 doses of DCVAC/PCa. Administration of DCVAC/PCa did not lead to any significant side effects. Continuous cancer immunotherapy by DCVAC/PCa significantly prolonged the PSA doubling time (PSA-DT) in all treated patients. Median PSA-DT increased from 7,86 months prior to the treatment, to 26,08 months after completing 12 doses of DCVAC/PCa, p<0.001. Eight of 21 patients had stable PSA levels during the treatment duration (PSA-DT>36 months) and PSA-DT remained stable during the additional cycle of the treatment (average PSA-DT of 48,13 months). Long-term administration of DCVAC/PCa led to the induction and maintenance of T cells specific against multiple tumor antigens including PSA, MAGE-A1 and MAGE-A3. Conclusions: This study indicates that the cancer immunotherapy with DCVAC/PCa represents a promising approach for prostate cancer patients with biochemical relapse. This study supports the use of immunotherapy early in the course of the disease, provided that relevant surrogate endpoints predictive of improved prognosis of early stage patients will be identified. Clinical trial information: 2009-017259-91.
Clinical and Genomic Characteristics in De Novo Blastoid/Pleomorphic (dnMCL) and Transformed Blastoid/Pleomorphic (t-MCL) Mantle Cell Lymphoma (MCL) in the Ibrutinib Era: Comprehensive Analysis of 168 Patients
Authors: Preetesh Jain, Rashmi Kanagal-Shamanna, Shaojun Zhang, Chi Young Ok, Graciela M. Nogueras González, Makhdum Ahmed, Gonzalez-Pagan Omarya, Ahmad Ghorab, Prajwal C Boddu, Wendy Chen, Hun Ju Lee, Maria Badillo, Krystle Nomie, Luis Fayad, Loretta J. Nastoupil, Richard E Champlin, Sattva S. Neelapu, Keyur Patel, L. Jeffrey Medeiros, Jorge Enrique Romaguera, Nathan H. Fowler, Linghua Wang, Michael Wang
Journal: Blood (2018)
Tolerability of epirubicin, oxaliplatin, and capecitabine chemotherapy in advanced esophagogastric cancer.
Authors: Christina Rigby, Manon Evans, Kevin Chan, Andrea Spencer-Shaw, Vikki Owen-Holt, Wasat Mansoor
Journal: Journal of Clinical Oncology (2014)

e15078 Background: Oesophago-gastric cancer is the fifth commonest malignancy in the UK, and its incidence is rising. Less than 30% of patients at diagnosis are suitable for curative treatment. Randomised data supports the use of palliative chemotherapy to reduce cancer related symptoms and improve both quality of life and life expectancy in those with incurable disease. Epirubicin, oxaliplatin and capecitabine (EOX) is an established regimen. Its toxicities are well documented and of significant relevance in this patient population where prognosis is limited. Methods: We conducted a retrospective review of patients with advanced oesophago-gastric adenocarcinoma treated with at least 1 cycle of EOX chemotherapy at our institution since 2011. Patient characteristics, toxicities, and need for dose reductions or discontinuation of treatment were analysed. Results: 249 patients were identified; 124 lower oesophageal, 78 gastric, 40 gastro-oesophageal junction and 8 of undefined origin. Patients were predominantly male (184 v 74), median age of 65 and over 92% were of WHO PS 1 or better. 47% of patients completed all 6 recommended cycles of chemotherapy with 53% of these needing a dose reduction of at least one cytotoxic drug. 133 patients discontinued treatment; 41 due to disease progression and 92 due to intolerable toxicities. Significant toxicities reported were: haematological (17%), neurological 11%, and gastrointestinal 13%. 56% reported deterioration in their performance status or profound fatigue. 3 patients discontinued treatment due to cardiac complications. 1 with established myocardial infarction and 2 with non-troponin elevated chest pain. There were no treatment related fatalities. Conclusions: Palliative chemotherapy with EOX improves cancer related symptoms and survival in advanced oesophago-gastric malignancies. In this population tolerance of treatment and avoidance of toxicity is essential.
Patterns of care and overall survival in the Medicare ovarian cancer population.
Authors: Larissa Meyer, Weiguo He, Hui Zhao, Charlotte C. Sun, Thomas A. Buchholz, Karen H. Lu, Sharon Hermes Giordano
Journal: Journal of Clinical Oncology (2014)

5587 Background: Tumor reductive surgery and combination chemotherapy is the standard of care for advanced ovarian cancer. Comorbid conditions and poor performance status can affect treatment options. Population level outcomes data in the geriatric population is lacking for women with ovarian cancer. The objective of this study is to characterize the patterns of care and overall survival in women over the age of 65 with epithelial ovarian cancer. Methods: Using the SEER-Medicare database, a cohort of patients who died of epithelial ovarian cancer between 2002-2009 was identified. All patients had pathologic confirmation of disease to be included in the cohort. Charlson comorbidity score was used to estimate health status. Kaplan-Meier analysis, Chi-square and ANOVA test were utilized. Results: A total of 4,672 women were included in the analysis and stratified into 4 groups based on previous therapy: No chemotherapy or surgery (NoCS), surgery only (S), chemotherapy only (C) or surgery and chemotherapy (CS). Mean age for the groups were 81 years (NoCS), 79 years (S), 78 years (C) and 74 years (CS). 1026 women (22%) received no treatment for their ovarian cancer (NoCS). 627 women (13.4%) underwent surgery but no chemotherapy. 988 women (21%) received chemotherapy but never underwent surgery. 2,031 women (44%) of the cohort underwent surgery and chemotherapy. 9.6% of women in the (CS) group had a comorbidity index of > 2 compared to 21% (C) group, 18% (S) group and 23% of the (NoCS) group (p<0.0001). There was a significant difference in survival between the groups with median survival time of 1.2 months for women who received no treatment, 1.8 months for surgery alone, 7.9 months for chemotherapy alone, and 21.2 months for patients who underwent the standard of care treatment of surgery and chemotherapy (p<0.05). Conclusions: Over half of patients over 65 do not or are not able to receive optimal therapy for epithelial ovarian cancer. Younger age and lower Charlson comorbidity index are associated with ability to undergo surgery and chemotherapy. This subset of patients is able to reach a significantly improved median survival time of 21 months compared to <2 months for patients who do not receive chemotherapy.
Mechanism underlying increased serum iron levels during FOLFOX/FOLFIRI therapy.
Authors: Takumi Ochiai, Kazuhiko Nishimura, Tomoo Watanabe, Masayuki Kitajima, Akinori Nakatani, Tsuyoshi Sato, Kennji Kishine, Isao Nagaoka
Journal: Journal of Clinical Oncology (2014)

e14608 Background: We previously reported a significant transient increase in serum iron levels during FOLFOX and FOLFIRI therapies in advanced colorectal cancer (CRC) patients. Moreover, serum iron levels offer potential as an extremely useful and convenient predictive factor for chemotherapy (ASCO2013:#e14651). However, the mechanism underlying this increase in serum iron levels during chemotherapy remains to be clarified. The aim of this study was to investigate the mechanism underlying increased serum iron levels during chemotherapy. Methods: Twenty advanced CRC patients undergoing treatment between September 2012 and July 2013 were included in the study. Serum iron, ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), hepcidin 25 (Hepc), interleukin-6 (IL-6), and soluble transferrin receptor (sTfR) levels were measured at before and 48 hour after treatment. Results: Serum iron levels and Hepc significantly increased after treatment (p<0.0001), whereas IL-6 significantly decreased (p=0.0073); no significant change was observed in ferritin, AST, ALT, Hb, or sTfR. Conclusions: No significant change in AST, ALT, or Hb level indicates that increased serum iron levels were not due to destruction of hepatocytes or erythrocytes. sTfR level reflects the number of erythroblasts, so no change indicates no destruction of erythroblasts. Hepc is a key regulator in the metabolism of iron, decreasing serum iron levels. It is increased by iron loading and IL-6, and decreased by anemia or hypoxia. Erythropoiesis consumes the largest amount of iron in the body, and its suppression leads to increased serum iron levels. Chemotherapy suppresses erythropoiesis. In this study, serum iron levels and Hepc showed a significant increase and IL-6 a significant decrease, with no significant change in sTfR. This suggests that increased serum iron levels during chemotherapy are due reduced iron consumption by erythropoiesis, which leads to an increase in expression of Hepc. Such an increase in expression of Hepc leads to a decrease in expression of Il-6 as negative feedback. The results suggest that increased serum iron levels during chemotherapy are due to reduced iron consumption by erythropoiesis.
Multidisciplinary treatment for stage IIIA non-small cell lung cancer (NSCLC): Does institution matter?
Authors: Pamela Parker Samson, Aalok Patel, Traves Crabtree, Daniel Morgensztern, Cliff Grant Robinson, Graham A. Colditz, Saiama Naheed Waqar, Daniel Kreisel, G Alexander Patterson, Alexander Sasha Krupnick, Stephen R. Broderick, Bryan F Meyers, Varun Puri
Journal: Journal of Clinical Oncology (2014)

7512 Background: It has been reported that survival is improved for early stage NSCLC when surgery is performed at high volume academic centers. However, the impact of institution has not been well described in the setting of surgery for stage IIIA NSCLC, in which a wide variety of neo-/adjuvant therapies are often employed. Methods: Treatment data of clinical stage IIIA NSCLC patients undergoing resection was obtained from the National Cancer Database (NCDB). Information on patient and tumor-related variables, therapy modalities, 30-day mortality, and survival was abstracted. Multivariable regression models were fitted to evaluate variables influencing 30-day mortality and overall survival (OS). Results: From 1998-2010, 11,492 clinical stage IIIA NSCLC patients were treated at community centers, while 7,743 patients were treated at academic centers. Academic center patients were more likely to be younger, female, non-Caucasian, live in an urban area, have a lower Charlson Comorbidity Index (CCI), and have a higher income and travel distance (all p < 0.001). Academic center patients were more likely to receive neoadjuvant chemotherapy (49.6% vs. 40.6%, p <0.001). Increased 30-day mortality was associated with increasing age, male gender, pre-operative radiation therapy, increased CCI, and pneumonectomy. Patients undergoing surgery at academic centers experienced decreased 30-day mortality (OR 0.75, 95% CI 0.60 – 0.93, 3.3% vs. 4.5%, p <0.001). Decreased long term survival was associated with increasing age, male gender, increased CCI, larger tumors, and pre-operative radiation therapy. Neoadjuvant chemotherapy (HR 0.66, 95% CI 0.62-0.70), surgery at an academic center (HR 0.92, 95% CI 0.88 – 0.97), and surgical treatment with lobectomy (HR 0.72, 95% CI 0.67 – 0.77) were associated with improved OS. Median OS for academic center patients was longer (33.8 vs. 28.9 months, p <0.001). Conclusions: Stage IIIA NSCLC patients treated with pulmonary resection at academic centers had a lower 30-day mortality rate and increased OS compared to patients treated at community centers. Possible contributing factors include high-volume surgical centers and an increased rate of neoadjuvant chemotherapy.
Tolerability of capecitabine in postoperative adjuvant chemotherapy in colon cancer: A single center study.
Authors: Esat Namal, Pelin Altinok Sut, Bulent Askaroglu, Betul Yildiz, Ozgul Pamukcu
Journal: Journal of Clinical Oncology (2014)

e14633 Background: According to Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial, capecitabine has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, we have seen more side effects of capecitabine in our practice. Methods: In our study, we retrospectively examined treatment continuation, and adverse events that occurred during eight cycles of post-operative adjuvant chemotherapy with capecitabine in 89 patient with colon cancer who had underwent curative resection. Results: 89 patients who had undergone curative resection and had treatment of capecitabine were taken to the study. 82 of 89 patients completed the treatment (92%); 3 of them left the treatment after 6 cycles and 2 of them after 3 cycles. FOLFOX regimen was initiated in 2 patients. At one of these two patients capecitabin could be given for 3 cycles and other patient could have 4 cycle capecitabine. None of patients failed to complete the initial dose. The doses were reducted in all of our patients. 44/ 89 (49%) patients with grade 1-2 mucositis, 9/89 (10%) patients with grade 3 mucositis, 16/ 89 (17%) patients with grade 1-2 hand foot syndrome, 5/89 (5,6%) patients with grade 3 hand foot syndrome, 23/89 (25%) patients with grade 1-2 diarrhea, 4 (4,4%) of which had to be hospitalized; 60/89 (67%) patients with grade 1-2 fatique; 4 (4,4%) with grade 3 fatique which needed hospitalization; 3/89 (3,3%) patients with grade 3 hyperbilirubinemia, 21/89 (23%) patients with grade 1-2 hyperbilirubinemia; 5/89 (0.05%) patients with febrile neutropenia were observed. Conclusions: In this study, we have observed that none of patients could receive the recommended doses of capecitabine due to capecitabine related toxicities. Although X-ACT Study suggests that capecitabine is associated with fewer adverse events, in our study side effects are observed more common.
Oncology clinical pathway: Adoption of a Web-based decision support tool.
Authors: Bruce A. Feinberg, Jason Drenning, Tim Olson
Journal: Journal of Clinical Oncology (2014)

e17542 Background: The unsustainable cost curve of cancer care has been the focus of much debate. Pathway programs have been suggested as a means to decrease treatment variability, thereby making cost more predictable and improving quality of care. Integration of pathways into electronic medical records (EMR) has been considered critical to adoption and influence, but myriad health information technology platforms make this problematic. Web-based non-EMR-integrated decision support tools (DST) represent an alternative, but workflow redundancy is a concern for adoption. We report initial experience with the adoption of a pathway program that incorporated a DST and the impact of the DST on pathway compliance. Methods: Medical oncologists participating in a large regional insurance network in the Southeastern region of the United States signed voluntary participation amendments for a pathway program managed by Cardinal Health that encouraged use of a web-based DST (Pathware). Enhanced reimbursement was offered to mitigate increased workflow requirements. Payer claims data was applied to a treatment algorithm to identify regimens administered, which was then matched to the patient regimen inventory created within the DST. Results: A total of 24 physicians from 10 practices agreed to participate in year 1 of the pathway; an additional 14 physicians from 5 practices signed participation agreements during the course of the year. Claims data revealed 311 treatment regimens for the 24 physicians who completed a full year in the program. Of these, 111 (36%) could be matched to a DST selection. An additional 109 regimen selections were found in DST for patients not found in network claims data. Of the entire 420 chemotherapy regimens identified, compliance to the pathway was consistently higher with regimen selection using the DST than with those found only in claims, 91% vs 84%, respectively. DST adoption rates were disparate among providers and ranged from 0% to 100%, with a mean of 48%. Conclusions: Non-EMR integrated web-based DSTs can be successfully deployed across disparate provider networks to facilitate pathway program compliance. Barriers to adoption need to be identified and overcome as DST use has favorable impact on compliance.
DNA Methylation and Genetic Profiles in 320 Patients with Myelodysplastic Syndromes
Authors: Suguru Morimoto, Hideki Makishima, Yasunobu Nagata, Niroshan Nadarajah, Constance Baer, Tamara Alpermann, Genta Nagae, Yasuhito Nannya, Yasushi Miyazaki, Kenichi Yoshida, Tetsuichi Yoshizato, Masahiro Marshall Nakagawa, Ryosaku Inagaki, June Takeda, Yoichi Fujii, Yasuhide Takeuchi, Hiroo Ueno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Masashi Sanada, Satoru Miyano, Claudia Haferlach, Wolfgang Kern, Hiroyuki Aburatani, Torsten Haferlach, Seishi Ogawa
Journal: Blood (2018)
Dynamic changes in epithelial to mesenchymal composition and prognostic relevance of circulating cancer cells (CTCs) in head and neck squamous cell carcinoma (HNSCC).
Authors: Elena Mihal Vagia, George Koutsodontis, Areti Strati, Athina Giagini, Spiros Siolos, Nikolaos Charalambakis, Kostas Tsigaridas, Giannis Kotsantis, Panagiota Economopoulou, Vasileios Stephanos Ramfidis, Christos Perisanidis, Clarence Sasaki, Evi Lianidou, Valentina Bartzi, Amanda Psyrri, Alexios Strimpakos
Journal: Journal of Clinical Oncology (2014)

6076 Background: Epithelial-mesenchymal transtition (EMT) of adherent epithelial cells to migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in HNSCC, we characterized EMT in circulating tumor cells (CTCs) from HNSCC patients. Methods: We quantified by RT-qPCR EGFR, TWIST1, stem cell marker gene transcripts in immunomagnetically positively selected CTCs from 27 locally advanced HNSCC , 8 recurrent/metastatic HNSCC, and 20 healthy individuals. Patients with locally advanced disease were treated with cisplatin chemoradiotherapy +/- TPF induction chemotherapy. To assess the univariate differences of study parameters according to the expression of EGFR,TWIST1 and CD24-/low/CD44+ and/or CD24-/low/ALDH1high stem cell markers standard statistical procedures were used, as appropriate (Chi-square test for categorical data and Fisher’s Exact test for categorical data with limited number of frequencies). Subsequently, survival curves were generated by Kaplan-Meier analysis and tested for significance using the Mantel-Cox log rank test. Results: Thirteen of 27 (48%) primary HNSCC and six of 8 (75%) metastatic HNSCC harbored CTCs in peripheral blood. Mesenchymal cells were highly enriched in CTCs. Significant correlations could be found for stem cell-like CTCs and TNM stage (p=0.046,Fisher’s exact test). Detection of EGFR+ CTCs at baseline in primary HNSCC was associated with recurrence or death (p=0.041,Fisher’s exact test). Conclusions: These data support a role for EMT in cancer progression in human HNSCC. Liquid biopsies may identify patients at high risk for relapse in need for adjuvant therapy in locally advanced disease setting.