tbuckley/cabot-search huggingface dataset:
Korean population-based external validation of western prognostic models for survival in metastatic renal cell cancer.
Authors: Yongchel Ahn, Kwonoh Park, Seongjoon Park, Inkeun Park, Jae-Lyun Lee, Cheryn Song, Jin-Hee Ahn, Jun Hyuk Hong, Choung-Soo Kim, Hanjong Ahn
Journal: Journal of Clinical Oncology (2012)

464 Background: Prognostic models have been proposed to predict factors affecting survival in metastatic renal cell cancer (RCC). We retrospectively reviewed clinical features and survival data to validate MSKCC and Heng’s models in Korean metastatic RCC patients. Methods: 270 patients with first-line Vascular Endothelial Growth Factor (VEGF) targeted therapy, regardless of prior immunotherapy, were enrolled. We reviewed medical records to find clinical factors affecting overall survival (OS). Predictive accuracy for survival of two models was evaluated by Harrell’s concordance-index (c-index). Results: From 2005 to 2010, 197 males (72.6%) and 73 females received therapy at a median age of 58 years (range, 17 - 86). After median follow-up of 16.0 months (range 0.0 - 78.0), median OS (mOS) was 22.7 months (95% CI, 18.3 - 27.1). 55 patients (20.4%) had prior immune therapies and 162 (60.4%) were initially metastatic. None was treated with bevacizumab, thus 221 (81.9%) were treated with sunitinib and 49 with sorafenib. Multivariate analysis showed 5 of Heng’s factors were independent: Karnofsky scale &lt; 80% (HR = 1.53, 95% CI 1.01 - 2.31, p=0.047), from diagnosis to treatment &lt; 1 year (HR=1.94, 95% CI 1.35 - 2.79, p &lt; 0.001), anemia (HR 1.66, 95% CI 1.13 - 2.43, p = 0.010), hypercalcemia (HR = 1.92, 95% CI 1.21 - 3.05, p=0.006) and neutrophilia (HR = 1.96, 95% CI 1.21 - 3.16, p = 0.006). Validation of MSKCC and Heng’s model showed c-index of 0.836 (95% CI, 0.698 - 0.941) and 0.800 (95% CI, 0.655 - 0.915), each. We further applied each model’s stratification by risk grouping. First with MSKCC (log-rank p &lt; 0.001), mOS in no risk (n = 80), 1 risk (n = 128) and 2 or more risks (n=51) were 35.5 months (95% CI, 24.0 - 47.0), 23.7 months (95% CI, 18.2 - 29.2) and 7.4 months (95% CI, 4.5 - 10.3), respectively. Second with Heng’s (log-rank p &lt; 0.001), mOS in favorable (no adverse factors, n = 37), intermediate (one or two adverse factors, n = 161) and poor (three to six adverse factors, n=61) were respectively 43.8 months (95% CI, 31.8 - 55.8), 25.4 months (95% CI, 21.5 - 29.3) and 7.5 months (95% CI, 4.9 - 10.1). Conclusions: Western prognostic models were accurate and feasible in Korean metastatic RCC patients treated with anti-VEGF therapy.
Recurrence patterns and outcome of patients with stage IIIB-IV(M0) gastric cancer after gastrectomy and adjuvant chemotherapy: A retrospective analysis in one Chinese cancer center.
Authors: Chun-Xia Du, Hai-Tao Zhou, Yu-Xin Zhong, Wei Pei, Yue Yu, Ai-Ping Zhou
Journal: Journal of Clinical Oncology (2016)

160 Background: Gastric cancer is one of the leading causes of cancer-related death in China. Previous data showed 5-year OS rates varied from 10% to 20% in patients with stage IIIb and IV(M0) disease. This study aimedto explore recurrence patterns and outcome of stage IIIB-IV(M0) gastric cancer patients who underwent radical gastrectomy and adjuvant chemotherapy in the Cancer Hospital, Chinese Academy of Medical Center. Methods: Patients with stage IIIB-IV(M0) (AJCC V6) gastric adenocarcinoma were enrolled. All patients received a total or subtotal gastrectomy with at least D1 lymph node dissection. Adjuvant chemotherapy consisting of oxaliplatin, fluoropyrimidines with or without docetaxel was started within 1 month after surgery for maximum of 12 cycles. Results: From January 2006 to December 2011, a total of 137 patients were included (stage IIIB:85, stage IV(M0):52) in the study. The median age was 56 years (20-77) and 96 (70.1%) were male. With a median follow-up time of 40 months, 89 (65%) patients developed recurrence or a second primary malignancy. Peritoneal recurrence (28, 20.4%), locoregional lymph nodes (38, 27.7%) and hematogenous metastases (24, 17.5%) were the most common recurrence patterns. The 5-year DFS rates were 34% and 30% in patients with stage IIIB and stage IV(M0) diseases, respectively. The 5-year OS rates were 46% and 30%, respectively. No statistical difference was observed between stage IIIB and stage IV(M0) patients in terms of median DFS (27.0 m vs 17.4m, p = 0.35). The median OS was in favor of stage IIIB patients compared to stage IV (M0) patients (46.5 m vs 26.1 m, p = 0.02). Multivariate analysis revealed that male (p = 0.02), leather stomach or multiple original diseases (p = 0.02), T4 stage (p = 0.01) and higher lymph node ratio (p &lt; 0.01) were independent negative prognostic factors. Conclusions: Patients with stage IIIB and IV (M0) gastric cancer achieved a better outcome than the historical data in our center. Further investigations are needed to focus on individual and multimodality adjuvant therapy for this group.
Phase I study of biweekly docetaxel, cisplatin, and S-1 combination neoadjuvant chemotherapy for stage III gastric cancer.
Authors: Chikara Kunisaki, Hirochika Makino, Jun Kimura, Takashi Oshima, Mitsuyoshi Ota, Ryo Takagawa, Takashi Kosaka, Hirotoshi Akiyama, Itaru Endo
Journal: Journal of Clinical Oncology (2014)

153 Background: It is unclear neoadjuvant chemotherapy for stage III gastric cancer can provide satisfactory outcomes. Therefore, we conducted a phase I study to clarify recommend dose (RD) of biweekly docetaxel, cisplatin, and S1 combination neoadjuvant chemotherapy for stage III gastric cancer. Methods: A dose escalation method was employed. S1 (80mg/m 2 /day; day1-7, 15-21) and docetaxel (20mg/m 2 /day; day1, 15) were fixed and cisplatin (day1, 15) was increased by 5mg/m 2 from level I (20mg/m 2 /day). Each course was lasted for one month. Toxicity was examined by the CTCAE version 4.0 during two courses. Results: A total of 21 patients (male/female=14/7, mean age=63 years) was enrolled in this study. Of these, nine stage IIIA, nine stage IIIB, and three stage IIIC were included. In level I, There was no DLT case. In level II, we encountered perforation of gastric cancer in one case without any other DLT in the remaining five cases. In level III, IV, V, and VI, we did not encounter any cases with DLT. So, we decided that the RD of cisplatin was 50mg/m 2 /day (Level VI), which is regarded as maximum safety dose in the outpatient clinic. Response status was as follows: one PR case, 19 non CR/non-PD cases and one PD case. Total gastrectomy was performed in 14 cases, and distal gastrectomy in seven cases. Histologically, grade 1a was found in 13 cases, grade 1b in three cases, grade 2 in four cases, and grade 3 was one case. Five cases (23.8%) suffered from postoperative complications (two anastomotic leakage; one pneumonia; one pancreatic fistula; one chyloascites) although all cases recovered conservatively. Conclusions: RD of cisplatin was 50mg/m 2 /day in biweekly docetaxel, cisplatin, and S1 combination neoadjuvant chemotherapy for stage III gastric cancer. Phase II study is now going on to confirm the usefulness of this treatment.
Treatment of locally recurrent or high-risk carcinoma of the breast with radiation therapy and weekly docetaxel given as a radiosensitizer
Authors: E. Tapen, F. E. Halberg, L. A. Champion, B. Davis CRA, S. C. Dutton, S. A. Rosenthal
Journal: Journal of Clinical Oncology (2008)

11538 Background: Uncontrolled breast cancer involving the chest wall continues to be a major source of morbidity. Docetaxel has proven to be a good radiation sensitizer, causing cells to arrest during the most radiation sensitive phase of the cell cycle, G2/M. The goal of this trial is to determine the feasibility of delivering docetaxel during radiation therapy (XRT). Methods: Post-mastectomy patients at high risk of local failure because of tumor size, poor response to induction chemotherapy, extensive nodal involvement, inflammatory breast cancer (IBC) or recurrent disease were eligible. Conventional XRT (1.8 to 2.0 Gy/day, 5 days/week to 50.4 Gy to chest wall/supraclavicular areas), followed by an optional boost to 10 to 12.0 Gy. Docetaxel, 20 mg/M2 was given intravenously weekly. The primary objective was toxicity as defined using Common Toxicity Criteria. Secondary objectives included time to progression (TTP), and response rate. Results: Four centers enrolled 33 women. One patient was excluded after an allergic reaction to docetaxel. Eight patients had measurable disease, nine had recurrent disease, twenty-three were newly diagnosed, and three had IBC. One patient received less than 50 Gy. Five patients received less then 6 cycles of docetaxel. All patients had radiation dermatitis. Four patients (8%) had grade 3 desquamation; none had grade 4 or 5. Chest wall/axillary or arm pain occurred in eleven patients. Grade 1–2 or grade 3 hematologic toxicity occurred in six and two patients respectively. Grade 1 neuropathy in three patients. Grade 1–2 nausea/vomiting occurred in eight patients. Grade 1–2 diarrhea occurred in three patients. Of eight patients with measurable disease all responded, four achieved complete response. Mean TTP was 19.16 months. Five local failures occurred at 13–28 months. Conclusions: The administration of low-dose weekly docetaxel during radiotherapy to the chest wall for is feasible. Further studies are needed to evaluate ideal dosing and impact on PFS. No significant financial relationships to disclose.
The actual accuracy of endoscopic ultrasound for detailed tumor depth determination in nonserosal exposed gastric cancer: What should we do to increase the accuracy of endoscopic ultrasound?
Authors: H. Lee, J. H. Lee
Journal: Journal of Clinical Oncology (2011)

20 Background: The accuracy of endoscopic ultrasound (EUS) for preoperative staging of gastric cancer varies. The aim of this study was to investigate the accuracy of EUS T and N staging in all and non-serosal exposed cases and identify the histopathological factors influencing accuracy. Methods: A total of 309 gastric cancer patients with confirmed pathological staging underwent EUS examination for preoperative staging at Seoul St. Mary's Hospital, Korea, between January and December 2009. Of these, 262 patients were diagnosed with non-serosal exposed gastric cancer. Results: Overall accuracies of EUS for T stage, the detailed T stages of all cases, and the detailed T stage in the non-serosal exposed group were 70.2%, 43.0%, and 41.2%, respectively. In the non-serosal exposed group, tumors greater than 5 cm in diameter were significantly associated with T overstaging (odds ratio [OR], 2.583). The overall accuracies of EUS for N staging in all cases and in the non-serosal exposed group were 71.2% and 76.7%, respectively. Tumor size (2 cm ≤ size &lt; 5 cm; OR, 4.467; and 5 cm ≤ size; OR, 8.668) and tumor depth (submucosa; OR, 3.267; muscular propria; OR, 6.675 and subserosa; OR, 4.831) were significant factors affecting incorrect nodal detection in non-serosal exposed gastric cancer cases. Conclusions: Careful attention is required during EUS examination of large-sized gastric cancers to increase accuracy, especially for T staging. No significant financial relationships to disclose.
Pilot study of adding vincristine, topotecan, and cyclophosphamide to interval-compressed chemotherapy in newly diagnosed patients with localized Ewing sarcoma family of tumors: A Children's Oncology Group trial.
Authors: L. Mascarenhas, J. L. Felgenhauer, M. C. Bond, J. D. Femino, N. N. Laack, S. Ranganathan, M. D. Krailo, N. Marina
Journal: Journal of Clinical Oncology (2011)

9526 Background: Topotecan and cyclophosphamide are active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents to standard interval compressed therapy was investigated. Methods: Patients with biopsy proven previously untreated extra-dural ESFT without distant metastases and < 31 years of age were eligible. Entry criteria were: performance status < 2, adequate organ function and written informed consent. Patients were to receive 17 cycles of intravenous chemotherapy that were to be administered at two week intervals. VCR 1.5 mg/m2 on days 1 and 8, TOPO 0.75 mg/m2 days 1-5 and CYCLO 250 mg/m2 days 1-5 (VTC), VCR identical to VTC, DOX 37.5 mg/m2on days 1-2, CYCLO 1200 mg/m2on day 1 (VDC), and IFOS 1800 mg/m2 days 1-5 and ETOP 100 mg/m2 days 1-5 (IE) were administered for 5, 5 and 7 cycles respectively in an alternating manner. Local control (LC) with surgery, radiation or both modalities occurred after 6 cycles of chemotherapy. Primary endpoints were the ability to deliver chemotherapy cycles in an interval compressed schedule, and the rate of grade >/= 3 non hematologic toxicity and grade 4 hematologic toxicity that delayed the administration of chemotherapy by 2 weeks. Toxicities were evaluated in 4 reporting periods (RP)-weeks 1-12, 13-22, 23-28 and 29-37. Secondary endpoints were event free survival (EFS) and survival (OS). Results: 35 patients (19 male) enrolled. Median age was 11 yrs (0-22). The mean time to last dose of chemotherapy prior to LC was 12.9 +/- 0.2 wks which was significantly different from the corresponding protocol calendar of 11 wks (P<0.0002). 48.6% of the patients received intended chemotherapy without any delay prior to LC. There were no toxic deaths and unexpected toxicities. Targeted toxicity rates were 37%, 32%, 29% and 39% for each RP respectively. EFS and OS are pending the last patient completing 24 months of follow-up off protocol therapy. Conclusions: The addition of VTC to standard therapy was tolerable and provided sufficient interval compression. This regimen is now being investigated in a randomized phase III trial for newly diagnosed localized ESFT by COG.
Justification of more expensive antiemetic use with FOLFOX at an ambulatory cancer center.
Authors: Amanda Manoogian, Leila Rostamnjad, Michael Diviak, David P. Ryan, Gayle C. Blouin
Journal: Journal of Clinical Oncology (2014)

27 Background: According to NCCN, ASCO, and Multinational Association of Supportive Care in Cancer (MASCC) guidelines, palonosetron in combination with dexamethasone is the preferred 5-HT3 antagonist for use with moderately-emetogenic chemotherapy (MEC). NCCN gives all 5-HT3 antagonists a category one recommendation. Currently at the Massachusetts General Hospital (MGH), ondansetron is the 5-HT3 antagonist of choice due to its significant cost advantage and flexibility in dosing. Palonosetron is currently restricted to use in the second-line setting at MGH based on limitations of the evidence currently available supporting its preferred use. The primary objective of this study is to assess antiemetic utilization in patients receiving FOLFOX +/- bevacizumab(B) in an outpatient infusion unit and measure palonosetron and NK-1 antagonist usage. Methods: A retrospective review was conducted of all outpatient chemotherapy orders for FOLFOX +/- B for a six month period from 11/13-4/14. Prophylactic antiemetic use was evaluated over that time period. Data was captured using electronic MARs, prescription records, and drug utilization reports. Results: 184 patients were identified; 858 FOLFOX +/- B treatments were administered during the study period. For emesis prophylaxis, 74.5% received the MGH standard ondansetron and dexamethasone, 10.3% received palonosetron, 9.8% received an NK-1 antagonist, and 5.4% received a combination of palonosetron plus NK-1 antagonist. Mean patient age was 60.8 years; 59.8% of patients were male; 63.6% had a diagnosis of colorectal cancer; 42.9% had metastatic disease. Conclusions: The majority of patients receiving FOLFOX +/- B were well managed on ondansetron and dexamethasone and did not require the use of more costly antiemetics. However 25.5% of patients required alternative/additional antiemetics, suggesting further investigation to determine which patients could benefit from these therapies up-front may be prudent. Study data support continued use of palonosetron as a second line therapy. Larger, pharmacoeconomic comparison studies are necessary to justify frontline use of palonsetron.
Oncologist and patient roles in assessing current and future treatment for metastatic breast cancer: Results of an observational linguistic study
Authors: M. Nelson, D. S. Blum, J. R. Gralow, F. Cardoso, C. Grande, F. M. Palmieri, M. C. Kirk, C. Eagan
Journal: Journal of Clinical Oncology (2008)

1064 Background: The majority of research in office-based breast cancer communication has focused on the adjuvant setting; however, an unmet need exists for insight into dialogue with metastatic breast cancer (MBC) patients. An observational in-office linguistic study was conducted to analyze how oncologists and MBC patients discuss MBC and its treatment, in order to identify gaps in communication and develop recommendations to improve patient-provider dialogue. Methods: 1,000+ community-based oncologists were sent invitation letters; of these, 20 met screening criteria and agreed to participate. Signed consent was obtained from all providers and MBC patients (n=45). Patient-provider discussions were recorded during regularly-scheduled visits. Both parties were interviewed separately post-visit to capture provider intent and patient comprehension. All components were transcribed, analyzed and correlated using validated sociolinguistic models. Results: In-office discussions of MBC treatment have the following characteristics: Oncologists primarily use closed-ended questioning to evaluate symptoms and side effects. Neither party links side effects to patients’ quality of life (QOL). In contrast, post-visit, patients focus on how side effects affect their QOL. Oncologists and patients are often misaligned regarding side effects post-visit, with both parties often referencing side effects not mentioned during the visit. Oncologists’ language surrounding prognosis and treatment goals is largely positive. Although patients are actively engaged in visits through asking questions about MBC and treatment, they are often not aligned with the oncologist on prognosis and treatment goals post-visit. Conclusions: Analysis of in-office dialogue demonstrates that oncologists and patients may be misaligned on multiple facets of treatment decision-making and objectives. New interactional frameworks may help meet the specific needs of oncologists engaging in dialogue with MBC patients, resulting in improved patient care. No significant financial relationships to disclose.
Heterogeneity and Evolution Of DNA Methylation In Chronic Lymphocytic Leukemia
Authors: Christopher C Oakes, Rainer Claus, Lei Gu, Yassen Assenov, Jennifer Hüllein, Manuela Zucknick, David Brocks, Olga Bogatyrova, Christopher R. Schmidt, Laura Rassenti, Thomas J. Kipps, Daniel Mertens, Peter Lichter, Hartmut Döhner, Stephan Stilgenbauer, John C. Byrd, Thorsten Zenz, Christoph Plass
Journal: Blood (2013)
Clinical significance of UDP-glucurosyltransferase 1A1*6 upon toxicities of combination chemotherapy of irinotecan and cisplatin in gynecologic cancers: A preliminary multi-institutional result
Authors: M. Takano, M. Kato, T. Yoshikawa, K. Furuya, M. Takahashi, H. Yokota, N. Kino, K. Horie, T. Goto, K. Ishii, T. Kita
Journal: Journal of Clinical Oncology (2008)

5580 Background: Although the clear impact of UGT1A1*28 on severe irinotecal-related toxicities has been established, the effects of other UGT1A1 polyphisms are not fully understood. Our aim is to investigate the effects of UGT1A1*28, *6, and *27 in the patients (pts) with gynecologic cancer who received combination therapy with irinotecan and cisplatin. Methods: Pts eligible for this study had histologically confirmed uterine cancer or ovarian cancer, who received the combination therapy with irinotecan and cisplatin; a course of therapy consisting of 60 mg/m2 of irinotecan on D1, D8, and D15 and 60 mg/m2 of cisplatin on D1, q4weeks. Pts who met the criteria were enrolled in the study and polymophysms of UGT1A1 were analyzed by Invader assay; UGT1A1*28, *6, and *27. The toxicity profile was determined by National Cancer Institute common toxicity criteria version 2. Results: During August 2006 and December 2007, 27 patients were entered in this study; 21 pts with ovarian carcinoma and 6 pts with uterine cancer. The allele types of UGT1A1 were wild in 15 pts (56%), *28 in 3 pts (11%), *6 in 8 pts (30%), *28*6 in 1 pt (4%) and no case of *27 (0%). The incidences of grade 3/4 neutrocytopenia (N) and thrombocytopenia (T) were significantly higher in *6 pts compared with wild type pts (N, 75% vs 27%, p=0.03; T, 20% vs 0%, p=0.04). Moreover, grade 3/4 diarrhea was more frequently observed in *6 pts in comparison with wild type pts (50% vs 0%, p=0.003). Also, the delay of chemotherapy or skip of irinotecan on D8 or D15 due to toxicities significantly increased in *6 pts. Pts with *28 or *28*6 had similar side effects with pts with *6. Conclusions: The study revealed clinical significance of UGT1A1*6 upon toxicities in combination therapy with irinotecan and cisplatin. In addition to UGT1A1*28, UGT1A1*6 might be a key candidate to determine the dose of combination chemotherapy of irinotecan plus cisplatin. No significant financial relationships to disclose.
Impact of radiation and surgery for intraductal papillary neoplasm of the bile duct: A population-based analysis.
Authors: Sean Szeja, Savita V. Dandapani, Todd A. Swanson
Journal: Journal of Clinical Oncology (2016)

363 Background: Intraductal Papillary Neoplasm of the Bile Duct (IPNB), either in-situ or invasive, is a histological variant with better prognosis then the more common adenocarcinoma. This study’s purpose is to use the Surveillance Epidemiology and End Results (SEER) database to evaluate prognostic factors: histology, stage, location, extent of surgery and the use of radiation therapy (RT). Methods: Cases from 1973-2011 were acquired. Inclusion criteria included intrahepatic (IHD), extrahepatic bile duct (EHD) or ampulla of vater (AoV) locations, first primary, extent of surgery and RT history. Kaplan-Meier and Log-Rank methods measured overall survival (OS) and disease specific survival (DSS) in months (m) and their medians (MOS, MDSS). Cox multivariate regression computed hazard ratios (HR) controlling for stage, treatment, surgical extent and histology. Results: . For non-invasive cases, 14% were IPNB (n = 31). Survival was similar for EHD &amp; AoV cases. Surgery was associated with prolonged MOS of 120m compared to 8m without surgery or RT. A trend suggested better survival with lesser extent of surgery for EHD &amp; AoV cases (p &lt; 0.16, n = 8 at both sites). For invasive cases, 5% were IPNB (n = 1309). For cases not receiving surgery, RT was associated with prolonged OS &amp; DSS from 3 to 7m (p = 0.026) and 4 to 8m (p = 0.074). In T1N0M0 EHD cases, surgery with and without RT had similar OS &amp; DSS. Cox analysis observed similar OS &amp; DSS for surgery with and without RT for EHD and AoV cases. Mucin-producing IPNB was less likely local stage disease (10% vs 39%, p &lt; 0.01), with shorter OS 5m vs 23 m (p &lt; 0.01) and DSS 6m vs 28m (p &lt; 0.01), and for EHD cases, with HR = 2.0 (p &lt; 0.01) compared to papillary type IPNB. Conclusions: For non-invasive IPNB, surgery with less extensive resections was associated with better prognosis. For invasive IPNB cases not amenable to surgery, RT improved short term survival. If high-risk factors such as suboptimal surgical margins, which are not recorded in SEER, correlated with the use of RT, then the outcomes in EHD &amp; AoV locations could be explained by an imparted benefit. As well, mucin-associated IPNB, was associated with worse survival than papillary type. Further work is necessary to validate these findings.