Ng K.,Dana-Farber Cancer Institute |
Ogino S.,Dana-Farber Cancer Institute |
Ogino S.,Harvard University |
Meyerhardt J.A.,Dana-Farber Cancer Institute |
And 16 more authors.
Journal of the National Cancer Institute | Year: 2011
Background Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown. Methods We conducted a prospective observational study of 842 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival. Disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status (n = 394), and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables. All statistical tests were two-sided. Results Among 842 patients, 134 (15.9%) reported statin use after completing adjuvant chemotherapy. DFS among statin users and nonusers was similar (hazard ratio [HR] of cancer recurrence or death = 1.04, 95% confidence interval [CI] = 0.73 to 1.49). RFS and OS were also similar between statin users and nonusers (adjusted HR of cancer recurrence = 1.14, 95% CI = 0.77 to 1.69; adjusted HR of death = 1.15, 95% CI = 0.77 to 1.71). Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis (Ptrend =. 63,. 63, and. 59 for DFS, RFS, and OS, respectively). The impact of statin use did not differ by tumor KRAS mutation status, with similar DFS, RFS, and OS for statin use among mutant and wild-type subgroups (Pinteraction =. 84,. 67, and. 98 for DFS, RFS, and OS, respectively). Conclusion Statin use during and after adjuvant chemotherapy was not associated with improved DFS, RFS, or OS in patients with stage III colon cancer, regardless of KRAS mutation status. © The Author 2011. Published by Oxford University Press.
Ng K.,Dana-Farber Cancer Institute |
Meyerhardt J.A.,Dana-Farber Cancer Institute |
Chan A.T.,Massachusetts General Hospital |
Chan A.T.,Brigham and Women's Hospital |
And 17 more authors.
Journal of the National Cancer Institute | Year: 2015
We conducted a prospective, observational study of aspirin and COX-2 inhibitor use and survival in stage III colon cancer patients enrolled in an adjuvant chemotherapy trial. Among 799 eligible patients, aspirin use was associated with improved recurrence-free survival (RFS) (multivariable hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.28 to 0.95), disease-free survival (DFS) (HR = 0.68, 95% CI = 0.42 to 1.11), and overall survival (OS) (HR = 0.63, 95% CI = 0.35 to 1.12). Adjusted HRs for DFS and OS censored at five years (in an attempt to minimize misclassification from noncancer death) were 0.61 (95% CI = 0.36 to 1.04) and 0.48 (95% CI = 0.23 to 0.99). Among 843 eligible patients, those who used COX-2 inhibitors had multivariable HRs for RFS, DFS, and OS of 0.53 (95% CI = 0.27 to 1.04), 0.60 (95% CI = 0.33 to 1.08), and 0.50 (95% CI = 0.23 to 1.07), and HRs of 0.47 (95% CI = 0.24 to 0.91) and 0.26 (95% CI = 0.08 to 0.81) for DFS and OS censored at five years. Aspirin and COX-2 inhibitor use may be associated with improved outcomes in stage III colon cancer patients. © The Author 2014. Published by Oxford University Press.
Jeon J.,Dana-Farber Cancer Institute |
Jeon J.,Yonsei University |
Sato K.,Dana-Farber Cancer Institute |
Niedzwiecki D.,Duke University |
And 14 more authors.
Clinical Colorectal Cancer | Year: 2013
Background The impact of physical activity on survival outcomes in patients with recurrent colon cancer has not been studied. We tested the association between the level of postdiagnosis physical activity and survival outcomes of patients with recurrent colon cancer. Patients and Methods We conducted a prospective observational study of 237 patients with stage III colon cancer who had recurrence of disease. Physical activity was measured approximately 6 months after the completion of therapy (14 months after surgical resection) but before detection of recurrent disease. The primary end point of the study was survival time after recurrence. Results The hazard ratio comparing patients who reported at least 18 metabolic equivalent task (MET) hours per week of physical activity with those engaging in < 3 MET hours per week was 0.71 (95% confidence interval, 0.46-1.11). Increasing total MET hours of physical activity per week was associated with a borderline statistical significance trend for improved survival after recurrence (P =.052). The benefit of physical activity on survival was not significantly modified by sex, body mass index (BMI), number of positive lymph nodes, age, baseline performance status, adjuvant chemotherapy regimen, or recurrence-free survival period. Conclusion To our knowledge, this is the first study investigating the association of physical activity with survival outcome of patients with recurrent colon cancer. Although the association exceeded our predefined P trend <.05 for statistical significance, these findings warrant further studies of physical activity in patients with recurrent colorectal cancer. © 2013 Elsevier Inc. All rights reserved.
Livingston R.B.,Arizona Cancer Center |
Barlow W.E.,Cancer Research and Biostatistics |
Kash J.J.,Edward Cancer Center |
Albain K.S.,Loyola University Chicago |
And 5 more authors.
Breast Cancer Research and Treatment | Year: 2011
SWOG trial S0102 showed significant activity of the combination of docetaxel and vinorelbine in HER2- negative metastatic breast cancer (MBC). For HER2- positive patients, additional benefit may occur with the addition of trastuzumab due to its synergy with docetaxel and vinorelbine. Patients with HER2-positive MBC, but without prior chemotherapy for MBC or adjuvant taxane, were eligible. Docetaxel (60 mg/m2) was given intravenously on Day 1, vinorelbine (27.5 mg/m2) intravenously on Days 8 and 15, and filgrastim (5 μg/kg) on Days 2-21 of a 21-day cycle. In addition, patients received weekly infusions of trastuzumab (2 mg/kg) after an initial bolus of 4 mg/kg. The primary outcome was 1 year overall survival (OS), with secondary outcomes of progression-free survival (PFS), response rate, and toxicity. Due to slow accrual (February 2003-December 2006), enrollment was stopped after 76 of 90 planned patients. There have been 32 deaths and 51 progressions among the 74 eligible patients who received treatment. The estimated 1 year OS was 93% (95% CI 84-97%) with a median of 48 months. One-year PFS was 70% (95% CI 58-79%) with a median of 20 months. Response rate for measurable disease was 84%. No deaths were attributed to treatment. Grade 4 toxicities were reported for 19% with neutropenia the most common (15%). The most common grade 3 toxicities (33%) were leucopenia (14%) and fatigue (10%). The combination of trastuzumab, docetaxel, and vinorelbine is effective as first-line chemotherapy in HER2-positive MBC with minimal toxicity. One-year survival estimates are among the highest reported in this population. © Springer Science+Business Media, LLC. 2011.
Ogino S.,Dana-Farber Cancer Institute |
Ogino S.,Harvard University |
Liao X.,Dana-Farber Cancer Institute |
Imamura Y.,Dana-Farber Cancer Institute |
And 17 more authors.
Journal of the National Cancer Institute | Year: 2013
Background Somatic mutations in PIK3CA (phosphatidylinositol-4,5- bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer. Methods We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided. Results Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, diseasefree, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (Pinteraction > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (Pinteraction > .16). Conclusions Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy. © The Author 2013.
PubMed | Abington Hospital, University of Houston, Dana-Farber Cancer Institute, Hightstown and 12 more.
Type: Journal Article | Journal: Gynecologic oncology | Year: 2016
To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer.The Society of Gynecologic Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature.Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality.All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to <1cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to <1cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.
McGovern-Phalen A.M.,Edward Cancer Center
Clinical Journal of Oncology Nursing | Year: 2015
As a participant in the ONS Foundation–supported Breast Cancer Care Quality Measures Set in 2010, the Edward Cancer Center (ECC) identified gaps in patient assessment. Sleep-wake disturbance and distress were two common areas that were lacking consistent assessment when nurses saw patients during their visits. Another issue is the lack of standard methods of practice or a standardized tool. The ECC, in collaboration with Edward Diabetes Center, Linden Oaks Hospital, and other outpatient offices, adopted the use of the Patient Health Questionnaire-9 depression screening tool. The ECC also modified the intervention recommendations to meet the needs of the oncology population. As a result of the findings in the pilot, the ECC was able to implement an evidence-based practice change to improve the overall quality of patient care and provide earlier intervention in an effort to further improve patient outcomes. © 2015 by the Oncology Nursing Society.
Bhagwandin S.,University of Illinois at Chicago |
Naffouje S.,University of Illinois at Chicago |
Salti G.,University of Illinois at Chicago |
Salti G.,Edward Cancer Center
Annals of Surgical Oncology | Year: 2015
Purpose: Our aim was to evaluate the utility of in vitro drug sensitivity testing in patients with peritoneal surface malignancies undergoing cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: We found data for 27 patients who underwent CRS plus HIPEC from September 2009 to May 2012 and whose tumors were submitted for in vitro drug sensitivity (ChemoFx®). Intraperitoneal chemotherapy agents included mitomycin C, cisplatin + doxorubicin, or cisplatin alone. Results: There were 12 (44.4 %) appendiceal adenocarcinomas, 5 (18.5 %) colon cancers, 4 (14.8 %) sarcomas, 3 (11.1 %) ovarian cancers, 2 (7.4 %) mesotheliomas, and one (3.7 %) gastric cancer. In all, 15 patients (55.5 %) underwent complete cytoreduction (CC ≤ 1). Seventeen tumors (63 %) displayed in vitro sensitivity to the agents used. Mean overall (OS) and progression-free (PFS) survivals for the entire group were 34.4 ± 4.5 months (median 41 months) and 12.5 ± 2.1 months (median 8 months), respectively. There were no significant differences in OS and PFS for patients whose tumors displayed in vitro drug sensitivity versus those whose tumors did not (p = 0.101 and p = 0.403, respectively). These results also did not differ when evaluating only the patients who underwent complete cytoreduction. In vitro, the drug sensitivity did not correlate with primary tumor pathology or preoperative systemic chemotherapy administration. In vitro drug sensitivity correlated with the drug used at the time of HIPEC (p = 0.003). None of the tumors tested showed in vitro sensitivity to cisplatin and/or doxorubicin. Eight nonresponsive tumors, however, showed in vitro activity to other agents. Conclusions: Data indicate a high rate of in vitro resistance to the intraperitoneal chemotherapeutic agents used. In vitro drug sensitivity is not useful in patients undergoing CRS plus HIPEC. © 2015, Society of Surgical Oncology.
PubMed | Advocate Christ Medical Center, Edward Cancer Center, University of Illinois at Chicago and Loyola University
Type: Journal Article | Journal: Medical physics | Year: 2015
A multi-institutional planning study was performed to evaluate the frequency that current guidelines established by Radiation Therapy Oncology Group (RTOG) protocols and other literature for lung stereotactic body radiotherapy (SBRT) treatments are followed.A total of 300 patients receiving lung SBRT treatments in four different institutions were retrospectively reviewed. The treatments were delivered using Linac based SBRT (160 patients) or image guided robotic radiosurgery (140). Most tumors were located peripherally (250/300). Median fractional doses and ranges were 18 Gy (8-20 Gy), 12 Gy (6-15 Gy), and 10 Gy (5-12 Gy) for three, four, and five fraction treatments, respectively. The following planning criteria derived from RTOG trials and the literature were used to evaluate the treatment plans: planning target volumes, PTVV 100 95% and PTVV 95 99%; conformality indices, CI100% < 1.2 and CI50% range of 2.9-5.9 dependent on PTV; total lung-ITV: V20Gy < 10%, V12.5Gy < 15%, and V5Gy < 37%; contralateral lung V5Gy < 26%; and maximum doses for spinal cord, esophagus, trachea/bronchus, and heart and great vessels. Populations were grouped by number of fractions, and dosimetric criteria satisfaction rates (CSRs) were reported.Five fraction regimens were the most common lung SBRT fractionation (46%). The median PTV was 27.2 cm(3) (range: 3.8-419.5 cm(3)). For all plans: mean PTVV 100 was 94.5% (5.6%, planning CSR: 69.8%), mean PTVV 95 was 98.1% (4.1%, CSR: 69.5%), mean CI100% was 1.14 (0.21, CSR: 79.1%, and 16.5% within minor deviation), and mean CI50% was 5.63 (2.8, CSR: 33.0%, and 28.0% within minor deviation). When comparing plans based on location, peripherally located tumors displayed higher PTVV 100 and PTVV 95 CSR (71.5% and 71.9%, respectively) than centrally located tumors (61.2% and 57.1%, respectively). Overall, the planning criteria were met for all the critical structure such as lung, heart, spinal cord, esophagus, and trachea/bronchus for at least 85% of the patients.Among the various parameters that were used to evaluate the SBRT plans, the CI100% and CI50% were the most challenging criteria to meet. Although the CSRs of organs at risk were higher among all cases, their proximity to the PTV was a significant factor.
PubMed | Edward Cancer Center
Type: | Journal: Clinical journal of oncology nursing | Year: 2014
As a participant in the ONS Foundation-supported Breast Cancer Care Quality Measures Set in 2010, the Edward Cancer Center (ECC) identified gaps in patient assessment. Sleep-wake disturbance and distress were two common areas that were lacking consistent assessment when nurses saw patients during their visits. Another issue is the lack of standard methods of practice or a standardized tool. The ECC, in collaboration with Edward Diabetes Center, Linden Oaks Hospital, and other outpatient offices, adopted the use of the Patient Health Questionnaire-9 depression screening tool. The ECC also modified the intervention recommendations to meet the needs of the oncology population. As a result of the findings in the pilot, the ECC was able to implement an evidence-based practice change to improve the overall quality of patient care and provide earlier intervention in an effort to further improve patient outcomes.