tbuckley/cabot-search huggingface dataset:
A phase II open-label trial of dacomitinib monotherapy in patients with HER2-positive advanced gastric cancer after failure of at least one prior chemotherapy regimen.
Authors: Do-Youn Oh, Keun-Wook Lee, Jae Yong Cho, Won Ki Kang, Sun Young Rha, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2012)

54 Background: HER2 is a clinically relevant therapeutic target in gastric cancer. Trastuzumab plus chemotherapy has improved patients’ survival in HER2 (+) advanced gastric cancer (AGC). Pan-HER inhibitor shows significant antitumor effects in in vitro and xenograft model of HER2 (+) gastric cancer. The aim of this study was to find the efficacy/safety of dacomitinib, a irreversible pan-HER tyrosine kinase inhibitor by Pfizer, in HER2 (+) AGC patients. Methods: We enrolled AGC patients with HER2 FISH (+) or HER2 IHC 3+ who were treated with at least one prior palliative chemotherapy regimen and with ECOG PS 0-2, normal cardiac ejection fraction. Patients were treated with dacomitinib 45 mg once daily continuously every 4 weeks. Response was evaluated every 8 weeks using RECIST v1.1 and safety was assessed with CTCAE v4.0. The primary endpoint was 4 month-progression free survival rate (4m-PFS). PK and PD study were also conducted. Results: A total of 27 patients were enrolled. The median age was 61 (range: 43-80). Twenty two patients were male. The ECOG PS was 0 in 9 patients, 1 in 16, and 2 in 2. The number of prior palliative chemotherapy regimen was 1 in 7 patients (25.9%), 2 in 9 (33.3%), more than 3 in 11 (40.7%). Six patients received prior anti-HER2 therapy (trastuzumab 2, lapatinib 2, lapatinib or placebo in clinical trial 2) A total of 80 cycles were delivered (median 2 cycles per patient, range: 1-6). The 4m-PFS was 22.2 % and median progression-free survival was 2.1 months (95% CI: 2.3-3.4) There was 2 PR, 9 SD and 16 PD, resulting in 7.4 % response rate (95% CI: 0-17.5%) and 40.7 % disease control rate (95% CI: 21.9-59.6%). Median overall survival was 7.1 months (95% CI: 4.4-9.8). The most common toxicities were skin rash, diarrhea, and fatigue, but most of them were grade ½. Grade 3 skin rash was observed in 3 patients. There was no treatment-related death. Conclusions: Considering the heavily pretreated nature of enrolled patients, the dacomitinib is active and safe treatment option in HER2 (+) AGC patients. The results of PK and PD studies will be also presented at the meeting. (ClinicalTrials.gov: NCT01152853 )
Positive surgical margins after partial nephrectomy for renal cell carcinoma: Results from Canadian Kidney Cancer Information System database.
Authors: Rahul K. Bansal, Anil Kapoor, Antonio Finelli, Ricardo A. Rendon, Ronald Brian Moore, Rodney H. Breau, Louis Lacombe, Jun Kawakami, Darrel E Drachenberg, Peter C. Black, Stephen E. Pautler, Zhihui Liu, Simon Tanguay
Journal: Journal of Clinical Oncology (2014)

420 Background: Partial nephrectomy (PN) is the standard of care for small renal masses (SRMs) whenever feasible. The occurrence of a positive surgical margin (PSM) on a pathological specimen is not uncommon and an ideal management is unknown. We conducted this study to examine the rate of PSM, predictors of PSM and their oncological outcomes after PN for renal cell carcinoma (RCC), using the Canadian Kidney Cancer information system (CKCis) database. Methods: We accessed the prospectively maintained CKCis database for 1066 patients who underwent PN for RCC in major academic centers all across Canada. Demographics, clinical, pathological and follow-up data were noted for patients with PSM and negative surgical margins (NSM). Multivariate logistic regression analysis was performed to assess predictors of PSM. Results: Out of 1066 patients, 59 (5.5%) had PSM, 928 (87%) had NSM and records of 79 (7.4%) patients were not available. Mean patient age was 61 years and 59 years in the PSM and NSM group respectively, and in each group 63% of the patients were males. Mean tumor size was 3.6cm (range 1.1 – 9.5) and 3.3cm (range 0.5 – 16.2) in PSM and NSM group respectively. PSM group had 5 (8%) grade 1, 28 (47%) grade 2, 16 (27%) grade 3 and 5 (8%) grade 4 tumors as compared to 127 (14%), 458 (50%), 207 (23%) and 27 (3%) respectively in NSM group. Four (6.7%) patients from the PSM group and 49 (5.3%) patients from the NSM group had local and/or systemic progression of disease. There were two cancer specific deaths in NSM group and none in PSM group. Fifty two (88%) and 861 (93%) patients were alive at mean follow-up of 18.5 (range 0 – 91.7) and 28.9 months (range 0 – 315.5) in PSM and NSM group respectively. For the multivariate logistic regression analysis; Fuhrman grade 4 predicted presence of PSM whereas age, operative technique, tumor size, tumor stage did not. Conclusions: Results from the CKCis database suggest that PSM after PN are common but does not result in adverse oncological outcomes. Presence of Fuhrman grade 4 may be associated with PSM on final pathological specimen.
Parathyroid carcinoma: A rare case with mandible brown tumor
Authors: P. Samareh Pahlavan
Journal: Journal of Clinical Oncology (2005)

5610 Background: Parathyroid carcinoma (PC) constitutes less than 1% of primary hyperparathyroidism. Prior radiation to neck, chronic renal failure and genetic factors play roles. The m/f is one. The mean age is 40. In half a palpable cervical mass is evident. Serum calcium levels are >14 mg/dl. Methods: A 21-year-old man with right sided non-mobile 1X1 cm mandible bulging without tenderness came to the TM center. Other presentations include fatigue, recent weight loss, hoarseness, polydipsia, polyuria, hematuria, recurrent renal stones and constipation - diarrhea. In mandible biopsy brown tumor was confirmed. In x-ray ground glass appearance of the skull and in 99mTc-MDP, Tc absorption was low in mandible. Serum Ca level was more than 15.4 mg/dl. In cervical sonography, a hypoecho area with suspicious of parathyroid adenoma (PA) was detected. During operation, a capsular mass with attachment to the surrounding tissue was excised. In pathology PC was detected and en bloc resection was performed. Hypercalcemia was controlled. During a two-year follow up, there was no evidence of tumor recurrence and/or hypercalcemia. Results: PC is a slowly progressive disease with frequent recurrence and late local metastasis. The combinations of young age, palpable neck mass, concomitant renal and skeletal disease, and extremely high iPTH level in PTH-dependent hypercalcemia is highly suggestive of PC. Etiologically deletion of q13 of chromosome 11 and loss of tumor suppressor genes RB and BRCA2 were recognized. Clinical manifestations are mainly due to hypercalcemia per se. Diagnosis is based on lymph node or distant metastasis, capsular or vascular invasion, presence of fibrotic networks or frequent mitosis. Early surgery with en bloc resection is the only potentially curative treatment. Bisphosphonates, calcitonin, dacarbazine and in-situ alcohol instillation is advocated. The 5-year survival is between 50–85%. Conclusions: This unique case of PC in attention to the brown tumor in mandible is the second worldwide. Second operation was performed due to lack of attention of rare causes of hyperparathyroidism. Comprehensive multidisciplinary approach with surgery, radiation therapy, and medical treatment for hypercalcemia is needed to optimize patient outcome. No significant financial relationships to disclose.
A phase I dose-escalation study using three-dimensional conformal radiotherapy with concurrent cisplatin and S-1 in patients with stage III non-small cell lung cancer.
Authors: T. Kozuka, H. Harada, M. Nishio, H. Murakami, F. Ohyanagi, S. Ishikura, A. Horiike, J. Eba, T. Nishimura, N. Yamamoto
Journal: Journal of Clinical Oncology (2010)

7086 Background: Concurrent chemoradiotherapy with the total radiation dose of 60 Gy is standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In our previous phase II trial, 60 Gy of thoracic radiotherapy concurrent with cisplatin and S-1 was a promising regimen with good survival rates (MST 33 months) and mild toxicities (Br J Cancer 2009;101,225), but the local failure rate was not preferable. According to this result, a dose-escalation study using 3-dimensional conformal radiotherapy (3D-CRT) up to 74 Gy was performed with the same chemotherapy regimen. Here, we report the feasibility and the late toxicities at 74 Gy dose level of this concurrent chemoradiotherapy. Methods: The eligibility criteria were: histologically or cytologically proven NSCLC, 20-75 years old, and performance status 0-1. Cisplatin (60 mg/m2 on day 1) and S-1 (orally at 40 mg/m2/dose b.i.d., on days 1-14) were administered every 4 weeks for 4 cycles and radiotherapy was started on day 1. Radiation dose was escalated from 66 Gy/33fxs (Level I) to 70Gy/35fxs (Level II), and then to 74 Gy/37 fxs (Level III). The target volume included the primary tumor and involved lymph nodes. Elective nodal irradiation was not performed. Dose constraints were as follows: the lung, V20 < 30%; the esophagus, mean dose ≤ 34 Gy and V55 ≤ 30%; the spinal cord, max dose ≤ 50 Gy. Each escalation process was validated when dose limiting toxicities (DLTs) were observed in only 2 or less patients among 6 patients in each dose level. After evaluation of acute toxicities at all levels, additional 6 patients were enrolled in level III to confirm the feasibility and the late toxicities of 74 Gy. Results: Among 24 patients at level I, II, and III, 2 DLTs were observed at level I (grade 3 febrile neutropenia, mucositis, and diarrhea) and 1 DLT (grade 3 vasospastic angina pectoris) in 1 of the newly registered 6 patients at level III. At the median follow-up time of 9 months, no severe late toxicities were observed in 12 patients at level III. Conclusions: By using 3D-CRT, the radiation dose could be escalated to 74 Gy without increase of severe late toxicities when concurrently combined with cisplatin and S-1. No significant financial relationships to disclose.
<i>RAS</i> testing awareness amongst oncologists and panitumumab prescription for metastatic colorectal cancer: A European physician survey and medical records review.
Authors: Jorg Trojan, George Kafatos, James Bennett, Gaston Demonty, Gerry Downey, Laurent Mineur, Jiri Tomasek, Etienne Rouleau, Pavel Fabian, Giovanna De Maglio, Pilar Garcia Alfonso, Giuseppe Aprile, J. Han van Krieken
Journal: Journal of Clinical Oncology (2016)

530 Background: Patients with metastatic colorectal cancer (mCRC) must have a confirmed RAS wild-type status before starting panitumumab (pmab). Two studies, a physician survey and a medical records review (MRR), were carried out to evaluate physician awareness of the need for biomarker testing in mCRC. Methods: Both studies were carried out in three rounds. Rounds 1 and 2 (2012–14) examined KRAS testing only as they were completed before guidelines changed, and have been published previously. Round 3 (2014–15), reported here, was performed after guidelines changed and covered full RAS testing. Participants were from nine European countries:France, Germany, Italy, Spain, the Czech Republic, the Netherlands, Belgium, Denmark, and Sweden. For the survey, oncologists who had prescribed pmab to mCRC patients in the previous 6 months were interviewed by telephone using a standard questionnaire.For the MRR,oncologists were asked to provide clinical information extracted from their patients’ medical records. Results: 152 oncologists and 131 patients’ records were included in Round 3 of the physician survey and the MMR, respectively, compared with 301 oncologists and 306 records in Rounds 1 and 2. In Round 3 of the physician survey, 95.4% (n = 145) of participants correctly reported that pmab should be prescribed in RAS wild-type mCRC only, compared with 99.0% (n = 298) in Rounds 1 and 2, responding to the same question about KRAS testing. In Round 3 of the MRR, 100% (n = 131) of patients had a confirmed RAS or KRAS wild-type status prior to initiation of pmab. Of those patients, 83.2% (n = 109) were tested for RAS status and 16.8% (n = 22) were tested for KRAS status only. Conclusions: Round 3 of the survey demonstrated a high level of knowledge amongst oncologists about the need for RAS testing in mCRC. The MRR supported these findings, showing that this knowledge is being applied to clinical practice. Comparisons between Round 3 and Rounds 1 and 2 show that physician awareness and adherence to prescribing guidelines remained high over time, despite recommendations changing with RAS testing replacing KRAS testing.
Folfoxiri with or without cetuximab as first-line treatment of patients with non-resectable liver, only metastatic colorectal cancer and KRAS/NRAS wild type (FOCULM study).
Authors: Yanhong Deng, Lei Wang, Guanjian Liu, Huabin Hu, Yue Cai
Journal: Journal of Clinical Oncology (2015)

TPS798 Background: For liver limited metastatic colorectal cancers, complete resection of liver metastases is the only potentially curative treatment and can significantly improve overall survival. The current goal of medical treatment for colorectal cancer with initially unresectable liver metastases is to maximize the rate of secondary resection. This phase II study is to explore whether cetuximab in combination with FOLFOXIRI as first treatment could improve radical resectability in patients with KRAS/NRAS wild-type, unresectable liver - only metastases of colorectal cancer. Methods: The primary aim is to evaluate the percentage of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be completely resected and/or ablated with no evidence of residual malignant disease. Secondary aims include safty, objective response rate, overall survival, progression free survival, quality of life and an assessment of predictive molecular markers of response. 138 cases of patients met inclusion criteria and enrolled in the trial will be randomized to two therapy groups: experimental arm A (Chemotherapy with FOLFOXIRI + Cetuximab) or standard arm B (Chemotherapy with FOLFOXIRI). All patients will receive the study treatment regimen every 2 weeks, and a total of the maximum of 8 cycles. CT scan or MRI of the abdomen will be performed after 2 or 3 cycles of therapy to assess clinical response and resectability of liver metastases by multidisciplinary team including hepatic surgeon. If liver metastases are not deemed to be resectable at this assessment, but tumor assessment demonstrates stable disease or partial response, therapy will continue with re-assessment for clinical response and resectability after the next cycle. Clinical trial information: NCT02063529.
Quantifying decreased radiation exposure from modern CT scan surveillance programs of germ cell tumors.
Authors: Stephanie Anne Holler Howard, Michael Rosenthal, Lei Qin, Brandon David Bernard, Clair Beard, Christopher Sweeney
Journal: Journal of Clinical Oncology (2016)

478 Background: Active surveillance (AS) is increasingly used to manage clinical stage I testicular cancer (CS1TC,) but has the risk of radiation exposure from CT scans. Modern CT scanners with iterative reconstruction techniques (IRT) produce equivalent image quality with less radiation dose compared with traditional filtered back projection (FBP). Data examining timing of CS1TC relapses on AS have suggested it is safe to decrease CT scanning of abdomen and pelvis from the NCCN 2009 guideline of approximately 16 scans over 5 years to 7 scans. We examine the impact of the CT upgrade and decreased scans on radiation dose and associated risks. Methods: This IRB-approved study enrolled 24 CS1TC patients who had CT scans on the same Toshiba Aquilion 64 CT before and after IRT software installation. Dose-length product and CT dose index volume were recorded. A medical physicist calculated effective doses. Radiation doses were compared using the Wilcoxon signed rank test. Median effective dose per scan was multiplied by scan number based on 16 and 7 scan 5 year AS protocols to calculate an estimated cumulative dose (ECD). Lifetime attributable risk (LAR) of dying of a radiation-associated solid tumor was estimated for a single exposure at age 35 using the excess absolute risk transport model from the Biological Effects of Ionizing Radiation VII analysis of long-term atomic bomb survivors. Results: Median pre and post upgrade doses were 12.5 mSv and 7.7 mSv respectively (p &lt; 0.0001). A linear regression model with a constrained zero intercept fit to the data found that IRT dose was best estimated as 61% of FBP dose (95% CI 0.56 – 0.66). Table 1 lists ECD and LAR data for both AS regimens pre and post upgrade. Conclusions: IRT, as part of an integrated approach to optimize patient outcome, should reduce CT-related risks by about 39%. This reduction, combined with the scan reduction of newer AS regimens, further significantly lowers the already small potential mortality of imaging associated cancers. [Table: see text]
A phase I, dose-finding study of orally administered S-1 in combination with epirubicin and oxaliplatin (EOS) in patients (pts) with advanced or metastatic gastrointestinal cancer (AGIC) and chemonaïve advanced esophagogastric cancer (AEGC).
Authors: Markus Hermann Moehler, Volker Heinemann, Radka Obermannova, Eugen Kubala, Bohuslav Melichar, Rolf Mahlberg, Arndt Weinmann, Paul Scigalla, Marietta Tesarova, Petr Janda, Fabienne Biville-Hedouin, Wasat Mansoor
Journal: Journal of Clinical Oncology (2015)

140 Background: S-1 (Teysuno), an oral fluoropyrimidine registered in Europe since 2011, provides a good efficacy and safety profile for the treatment (trt) of AEGC in combination with cisplatin. (FLAGS Study; J.A. Ajani. EJC2013). Because triplets with platinum compounds and anthracyclines are commonly used in AEGC, a phase I evaluating S-1 with fixed doses of oxaliplatin (130 mg/m² D1) and epirubicin (50 mg/m² D1) q3w in AGIC pts [cohorts 1 (C1) and 2 (C2)] and in chemonaïve AEGC pts [cohort 3 (C3)] was performed. Methods: Pts &gt;18 years, ECOG/PS 0/1 were enrolled. Standard dose-limiting toxicity (DLT) evaluation was used. The maximum tolerate dose (MTD) was defined as the highest dose level at which less than &lt;2/6 of pts experienced a DLT during Cycle 1. Once MTD was established, the cohort was expanded up to 12 pts. C1 and C2: S-1 dose was defined in cohort of pts (3+3 design): C1 20mg/m² BID (40 mg/m²/day); C2 25 mg/m² BID (50 mg/m²/d). Escalation to dose level (DL) 2 occurred only after DL1 (20mg/m²/BID) was safe according to DLT criteria. In C3 pts received S-1 25mg/m² BID. Results: 23 pts were evaluated. C1 and C2 included AGIC pts at all lines of trt. As in C1: 3 pts had no DLT, dose was increased and 3 pts were included in C2: after 1 DLT (≥Gr3 non-hematological toxicity), 2 more pts were included in C2 with a second DLT (febrile neutropenia). These 2 DLTs occurred in heavily pre-treated pts (3rd line) and led to closing of C2 and 3 additional pts were enrolled in expanded C1. MTD of S-1 was established 20 mg/m² BID. No DLT reported for chemo-naïve pts treated. Since EOS is used to treat AEGC in first line, a new C3 cohort with chemo-naïve pts was opened to again determine MTD of S-1: 6 pts in C3 were included. Here no DLT occurred and additional 6 pts confirmed dose of 25 mg/m² as the MTD. Conclusions: Based on these results, the recommended doses of S-1 in EOS regimen are 20 mg/m²/BID in heavily pre-treated AGIC pts and 25 mg/m²/BID in chemo-naïve AEGC pts. The triplets EOS could represent a well-tolerated alternative first line trt for AEGC pts. Clinical trial information: 2011-003471-11.
Pegfilgrastim for treatment of chemotherapy associated myelosuppression in pediatric patients with solid tumor malignancies
Authors: J. A. Pollard, L. Winter, S. Borinstein, D. S. Hawkins
Journal: Journal of Clinical Oncology (2008)

10022 Background: Filgrastim (G-CSF) reduces the duration of severe neutropenia and incidence of febrile neutropenia following cytotoxic chemotherapy. Pegfilgrastim, a long acting form of G-CSF, has similar efficacy to G-CSF in adults, but studies in pediatrics are limited. We report our institutional experience with pegfilgrastim following dose intensive chemotherapy for solid tumors. Methods: Thirty-nine pediatric patients diagnosed with solid tumors between 1/1/07 and 11/14/07 who received dose intensive chemotherapy and pegfilgrastim therapy (100 mcg/kg; 6 mg maximum dose) were included in this retrospective review. Demographic data at diagnosis, treatment characteristics, frequency and duration of severe neutropenia (absolute neutrophil count < 0.2 ×109/L), and frequency of neutropenic fever were recorded. Results: The median age of patients evaluated was 12 yrs (range 0.17–23 years) and the median weight was 50 kg (range 4–107 kg); 13/39 (33×) weighed < 20 kg and 19/39 (49×) were less than 45 kg. Primary diagnoses included: osteosarcoma (6), Ewings sarcoma (5), rhabdomyosarcoma (9), soft tissue sarcoma (2), neuroblastoma (6), Hodgkin disease (6) and other solid tumors (5). In total, 141 chemotherapy courses with pegfilgrastim support were administered (median 4 courses per patient); no adverse events secondary to pegfilgrastim were recorded. Severe neutropenia occurred in 46× of courses. Overall, the median duration of severe neutropenia was 0 days (range 0–8 days). Febrile neutropenia occurred in 28× of courses. Of particular interest were 8 patients treated with interval-compressed (every 14 days) sarcoma chemotherapy. Of 51 courses administered, the median course duration was 15 days (range 14–28 days). Conclusions: Our study demonstrates that pegfilgrastim administration following dose intensive chemotherapy for solid tumors is safe and feasible in children, including those < 45 kg. The frequency and duration of severe neutropenia, as well as incidence of febrile neutropenia, were similar to G-CSF historic data. Pegfilgrastim is a suitable alternative to G-CSF therapy even in young children. No significant financial relationships to disclose.
Safety, Efficacy and Rituximab Levels Following Chemoimmunotherapy (Rituximab + FAB Chemotherapy) in Children and Adolescents with Mature B-Cell Non-Hodgkin Lymphoma (B-NHL): A Children’s Oncology Group Report
Authors: Mitchell S. Cairo, James Lynch, Lauren Harrison, Carmella van de Ven, Thomas Gross, Bruce Shiramizu, Warren Sanger, Sherrie L. Perkins, Stanton Goldman
Journal: Blood (2008)