1,632 results on '"Goldberg, Richard M."'
Search Results
2. Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis
- Author
-
Cohen, Romain, Raeisi, Morteza, Chibaudel, Benoist, Shi, Qian, Yoshino, Takayuki, Zalcberg, John R., Adams, Richard, Cremolini, Chiara, Van Cutsem, Eric, Heinemann, Volker, Tabernero, Josep, Punt, Cornelis J.A., Arnold, Dirk, Hurwitz, Herbert I., Douillard, Jean-Yves, Venook, Alan P., Saltz, Leonard B., Maughan, Timothy S., Kabbinavar, Fairooz, Bokemeyer, Carsten, Grothey, Axel, Mayer, Robert J., Kaplan, Richard, Tebbutt, Niall C., Randolph Hecht, J., Giantonio, Bruce J., Díaz-Rubio, Eduardo, Sobrero, Alberto F., Peeters, Marc, Koopman, Miriam, Goldberg, Richard M., Andre, Thierry, and de Gramont, Aimery
- Published
- 2024
- Full Text
- View/download PDF
3. Standardizing data collection in adjuvant colon cancer trials: A consensus project from the IDEA and ACCENT international consortia and national experts
- Author
-
Taieb, Julien, Basile, Debora, Seligmann, Jenny, Argiles, Guillem, André, Thierry, Gallois, Claire, Goldberg, Richard M., Yothers, Greg, Sobrero, Alberto, Meyerhardt, Jeffrey A., Souglakos, John, Labianca, Roberto, Iveson, Tim, Church, David N., Arnold, Dirk, Tie, Jeanne, Gill, Sharlene, Laurent-Puig, Pierre, Yoshino, Takayuki, Lonardi, Sara, and Shi, Qian
- Published
- 2024
- Full Text
- View/download PDF
4. Predictive value of CDC37 gene expression for targeted therapy in metastatic colorectal cancer
- Author
-
Arai, Hiroyuki, Yang, Yan, Baca, Yasmine, Millstein, Joshua, Denda, Tadamichi, Ou, Fang-Shu, Innocenti, Federico, Takeda, Hiroyuki, Kubota, Yohei, Doi, Ayako, Horie, Yoshiki, Umemoto, Kumiko, Izawa, Naoki, Wang, Jingyuan, Battaglin, Francesca, Jayachandran, Priya, Algaze, Sandra, Soni, Shivani, Zhang, Wu, Goldberg, Richard M., Hall, Michael J., Scott, Aaron James, Hwang, Jimmy J., Lou, Emil, Weinberg, Benjamin A., Marshall, John, Goel, Sanjay, Xiu, Joanne, Michael Korn, W., Venook, Alan P., Sunakawa, Yu, and Lenz, Heinz-Josef
- Published
- 2024
- Full Text
- View/download PDF
5. Optimal First-Line Therapy for Metastatic Adenocarcinoma of the Esophagus
- Author
-
Malla, Midhun, Fuqua, Jacob, Mukherjee, Sarbajit, and Goldberg, Richard M.
- Published
- 2022
- Full Text
- View/download PDF
6. Characterization of necroptosis activators in colorectal cancer.
- Author
-
Ashouri, Karam, primary, Xiu, Joanne, additional, Yang, Yan, additional, Millstein, Joshua, additional, Soni, Shivani, additional, Algaze, Sandra, additional, Mittal, Pooja, additional, Wong, Alexandra, additional, Lo, Jae Ho, additional, Torres-Gonzalez, Lesly, additional, Shields, Anthony F., additional, Goldberg, Richard M., additional, Lou, Emil, additional, Weinberg, Benjamin Adam, additional, Marshall, John, additional, Hoffmann, Alexander, additional, Zhang, Lin, additional, Yu, Jian, additional, Battaglin, Francesca, additional, and Lenz, Heinz-Josef, additional
- Published
- 2024
- Full Text
- View/download PDF
7. Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon reveals potential new therapeutic targets
- Author
-
Puccini, Alberto, Poorman, Kelsey, Catalano, Fabio, Seeber, Andreas, Goldberg, Richard M., Salem, Mohamed E., Shields, Anthony F., Berger, Martin D., Battaglin, Francesca, Tokunaga, Ryuma, Naseem, Madiha, Zhang, Wu, Philip, Philip A., Marshall, John L., Korn, W. Michael, and Lenz, Heinz-Josef
- Published
- 2022
- Full Text
- View/download PDF
8. A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)
- Author
-
Tabernero, Josep, Argilés, Guillem, Falcone, Alfredo, Ciardiello, Fortunato, Goldberg, Richard, Bennouna, Jaafar, Argilés, Tabernero, J., Mulet, N., Limón, M.L., Valladares, M., Jiménez, P., Vieitez, J. M<ce:sup loc='post">a</ce:sup>, Grávalos, C., García-Alfonso, P., Santos, C., Páez, D., Tobeña, M., Sastre, J., García Paredes, B., Benavides, M., Aranda, E., Cano, M.T., Loupakis, F., Rguez Garrote, M., Guillén, C., Rivera, Ma F., Safont, J., Hiret, S., Bennouna, J., Pannier, D., Malka, D., Falcone, A., Cremolini, C., Mulet, Nuria, Valladares-Ayerbes, Manuel, Viéitez, José M., Grávalos, Cristina, García-Alfonso, Pilar, Santos, Cristina, Tobeña, María, García-Paredes, Beatriz, Benavides, Manuel, Cano, María T., Loupakis, Fotios, Rodríguez-Garrote, Mercedes, Rivera, Fernando, Goldberg, Richard M., Cremolini, Chiara, Tabernero, Josep M., and Aranda, Enrique
- Published
- 2022
- Full Text
- View/download PDF
9. Associations of Physical Activity With Survival and Progression in Metastatic Colorectal Cancer: Results From Cancer and Leukemia Group B (Alliance)/SWOG 80405.
- Author
-
Guercio, Brendan J, Zhang, Sui, Ou, Fang-Shu, Venook, Alan P, Niedzwiecki, Donna, Lenz, Heinz-Josef, Innocenti, Federico, O'Neil, Bert H, Shaw, James E, Polite, Blase N, Hochster, Howard S, Atkins, James N, Goldberg, Richard M, Sato, Kaori, Ng, Kimmie, Van Blarigan, Erin, Mayer, Robert J, Blanke, Charles D, O'Reilly, Eileen M, Fuchs, Charles S, and Meyerhardt, Jeffrey A
- Subjects
Cancer ,Digestive Diseases ,Clinical Research ,Colo-Rectal Cancer ,Good Health and Well Being ,Aged ,Antineoplastic Combined Chemotherapy Protocols ,Clinical Trials ,Phase III as Topic ,Cohort Studies ,Colorectal Neoplasms ,Disease Progression ,Exercise ,Female ,Humans ,Male ,Middle Aged ,Prospective Studies ,Randomized Controlled Trials as Topic ,Surveys and Questionnaires ,United States ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeRegular physical activity is associated with reduced risk of recurrence and mortality in patients with nonmetastatic colorectal cancer. Its influence on patients with advanced/metastatic colorectal cancer (mCRC) has been largely unexplored.Patients and methodsWe conducted a prospective cohort study nested in Cancer and Leukemia Group B (Alliance)/SWOG 80405 (ClinicalTrials.gov identifier: NCT00265850), a National Cancer Institute-sponsored phase III trial of systemic therapy for mCRC. Within 1 month after therapy initiation, patients were invited to complete a validated questionnaire that reported average physical activity over the previous 2 months. On the basis of responses, we calculated metabolic equivalent task (MET) hours per week to quantify physical activity. The primary end point of the clinical trial and this companion study was overall survival (OS). Secondary end points included progression-free survival (PFS) and first grade 3 or greater treatment-related adverse events. To minimize confounding by poor and declining health, we excluded patients who experienced progression or died within 60 days of activity assessment and used Cox proportional hazards regression analysis to adjust for known prognostic factors, comorbidities, and weight loss.ResultsThe final cohort included 1,218 patients. Compared with patients engaged in less than 3 MET hours per week of physical activity, patients engaged in 18 or more MET hours per week experienced an adjusted hazard ratio for OS of 0.85 (95% CI, 0.71 to 1.02; PTrend = .06) and for PFS of 0.83 (95% CI, 0.70 to 0.99; PTrend = .01). Compared with patients engaging in less than 9 MET hours per week, patients engaging in 9 or more MET hours per week experienced an adjusted hazard ratio for grade 3 or greater treatment-related adverse events of 0.73 (95% CI, 0.62 to 0.86; PTrend < .001).ConclusionAmong patients with mCRC in Cancer and Leukemia Group B (Alliance)/SWOG 80405, association of physical activity with OS was not statistically significant. Greater physical activity was associated with longer PFS and lower adjusted risk for first grade 3 or greater treatment-related adverse events.
- Published
- 2019
10. Age and comorbidity association with survival outcomes in metastatic colorectal cancer: CALGB 80405 analysis
- Author
-
McCleary, Nadine J., Zhang, Sui, Ma, Chao, Ou, Fang-Shu, Bainter, Tiffany M., Venook, Alan P., Niedzwiecki, Donna, Lenz, Heinz-Josef, Innocenti, Federico, O'Neil, Bert H., Polite, Blase N., Hochster, Howard S., Atkins, James N., Goldberg, Richard M., Ng, Kimmie, Mayer, Robert J., Blanke, Charles D., O'Reilly, Eileen M., Fuchs, Charles S., and Meyerhardt, Jeffrey A.
- Published
- 2022
- Full Text
- View/download PDF
11. Molecular characteristics and clinical outcomes of patients with Neurofibromin 1-altered metastatic colorectal cancer
- Author
-
Arai, Hiroyuki, Elliott, Andrew, Millstein, Joshua, Xiu, Joanne, Ou, Fang-Shu, Innocenti, Federico, Wang, Jingyuan, Battaglin, Francesca, Jayachandran, Priya, Kawanishi, Natsuko, Soni, Shivani, Zhang, Wu, Sohal, Davendra, Goldberg, Richard M., Hall, Michael J., Scott, Aaron J., Khushman, Mohd, Hwang, Jimmy J., Lou, Emil, Weinberg, Benjamin A., Lockhart, Albert Craig, Shields, Anthony Frank, Abraham, Jim P., Magee, Daniel, Stafford, Phillip, Zhang, Jian, Venook, Alan P., Korn, W. Michael, and Lenz, Heinz-Josef
- Published
- 2022
- Full Text
- View/download PDF
12. Personalizing Survival Predictions in Advanced Colorectal Cancer: The ARCAD Nomogram Project
- Author
-
Sjoquist, Katrin M, Renfro, Lindsay A, Simes, R John, Tebbutt, Niall C, Clarke, Stephen, Seymour, Matthew T, Adams, Richard, Maughan, Timothy S, Saltz, Leonard, Goldberg, Richard M, Schmoll, Hans-Joachim, Van Cutsem, Eric, Douillard, Jean-Yves, Hoff, Paulo M, Hecht, Joel Randolph, Tournigand, Christophe, Punt, Cornelis JA, Koopman, Miriam, Hurwitz, Herbert, Heinemann, Volker, Falcone, Alfredo, Porschen, Rainer, Fuchs, Charles, Diaz-Rubio, Eduardo, Aranda, Enrique, Bokemeyer, Carsten, Souglakos, Ioannis, Kabbinavar, Fairooz F, Chibaudel, Benoist, Meyers, Jeffrey P, Sargent, Daniel J, de Gramont, Aimery, and Zalcberg, John R
- Subjects
Patient Safety ,Colo-Rectal Cancer ,Digestive Diseases ,Prevention ,Clinical Research ,Cancer ,Aged ,Colorectal Neoplasms ,Disease Progression ,Female ,Humans ,Male ,Middle Aged ,Neoadjuvant Therapy ,Neoplasm Metastasis ,Nomograms ,Precision Medicine ,Prognosis ,Progression-Free Survival ,Survival Analysis ,Fondation Aide et Recherche en Cancerologie Digestive Group ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundEstimating prognosis on the basis of clinicopathologic factors can inform clinical practice and improve risk stratification for clinical trials. We constructed prognostic nomograms for one-year overall survival and six-month progression-free survival in metastatic colorectal carcinoma by using the ARCAD database.MethodsData from 22 674 patients in 26 randomized phase III clinical trials since 1997 were used to construct and validate Cox models, stratified by treatment arm within each study. Candidate variables included baseline age, sex, body mass index, performance status, colon vs rectal cancer, prior chemotherapy, number and location of metastatic sites, tumor mutation status (BRAF, KRAS), bilirubin, albumin, white blood cell count, hemoglobin, platelets, absolute neutrophil count, and derived neutrophil-to-lymphocyte ratio. Missing data (50% vs 50% vs
- Published
- 2018
13. Optimising the use of cetuximab in the continuum of care for patients with metastatic colorectal cancer
- Author
-
Goldberg, Richard M, Montagut, Clara, Wainberg, Zev A, Ronga, Philippe, Audhuy, François, Taieb, Julien, Stintzing, Sebastian, Siena, Salvatore, and Santini, Daniele
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Biotechnology ,Digestive Diseases ,Colo-Rectal Cancer ,Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,cetuximab ,continuum of care ,metastatic colorectal cancer ,ras ,retreatment ,Oncology and carcinogenesis - Abstract
The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD on a combination of chemotherapy and targeted agents implies resistance to both components. Here, we propose that some patients may gain additional clinical benefit from the reuse of cetuximab after having PD on regimens including cetuximab in an earlier treatment line. We conducted a non-systematic literature search in PubMed and reviewed published and ongoing clinical trials, focusing on later-line cetuximab reuse in patients with mCRC. Evidence from multiple studies suggests that cetuximab can be an efficacious and tolerable treatment when continued or when fit patients with mCRC are retreated with it after a break from anti-EGFR therapy. Furthermore, on the basis of available preclinical and clinical evidence, we propose that longitudinal monitoring of RAS status may identify patients suitable for such a strategy. Patients who experience progression on cetuximab plus chemotherapy but have maintained RAS wt tumour status may benefit from continuation of cetuximab with a chemotherapy backbone switch because they have probably developed resistance to the chemotherapeutic agents rather than the biologic component of the regimen. Conversely, patients whose disease progresses on cetuximab-based therapy due to drug-selected clonal expansion of RAS-mutant tumour cells may regain sensitivity to cetuximab following a defined break from anti-EGFR therapy. Looking to the future, we propose that RAS status determination at disease progression by liquid, needle or excisional biopsy may identify patients eligible for cetuximab continuation and rechallenge. With this approach, treatment benefit can be extended, adding to established continuum-of-care strategies in patients with mCRC.
- Published
- 2018
14. Adjuvant Chemoradiotherapy With Epirubicin, Cisplatin, and Fluorouracil Compared With Adjuvant Chemoradiotherapy With Fluorouracil and Leucovorin After Curative Resection of Gastric Cancer: Results From CALGB 80101 (Alliance)
- Author
-
Fuchs, Charles S, Niedzwiecki, Donna, Mamon, Harvey J, Tepper, Joel E, Ye, Xing, Swanson, Richard S, Enzinger, Peter C, Haller, Daniel G, Dragovich, Tomislav, Alberts, Steven R, Bjarnason, Georg A, Willett, Christopher G, Gunderson, Leonard L, Goldberg, Richard M, Venook, Alan P, Ilson, David, O'Reilly, Eileen, Ciombor, Kristen, Berg, David J, Meyerhardt, Jeffrey, and Mayer, Robert J
- Subjects
Clinical Trials and Supportive Activities ,Cancer ,Clinical Research ,Patient Safety ,Digestive Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adenocarcinoma ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Chemoradiotherapy ,Adjuvant ,Cisplatin ,Combined Modality Therapy ,Epirubicin ,Esophagogastric Junction ,Female ,Fluorouracil ,Humans ,Leucovorin ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Neoplasm Staging ,Risk Factors ,Stomach Neoplasms ,Survival Rate ,Treatment Outcome ,United States ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Purpose After curative resection of gastric or gastroesophageal junction adenocarcinoma, Intergroup Trial 0116 (Phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and gastroesophageal junction adenocarcinoma: Demonstrated superior survival for patients who received postoperative chemoradiotherapy with bolus fluorouracil (FU) and leucovorin (LV) compared with surgery alone. CALGB 80101 (Alliance; Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma) assessed whether a postoperative chemoradiotherapy regimen that replaced FU plus LV with a potentially more active systemic therapy could further improve overall survival. Patients and Methods Between April 2002 and May 2009, 546 patients who had undergone a curative resection of stage IB through IV (M0) gastric or gastroesophageal junction adenocarcinoma were randomly assigned to receive either postoperative FU plus LV before and after combined FU and radiotherapy (FU plus LV arm) or postoperative epirubicin, cisplatin, and infusional FU (ECF) before and after combined FU and radiotherapy (ECF arm). Results With a median follow-up duration of 6.5 years, 5-year overall survival rates were 44% in the FU plus LV arm and 44% in the ECF arm ( Plogrank = .69; multivariable hazard ratio, 0.98; 95% CI, 0.78 to 1.24 comparing ECF with FU plus LV). Five-year disease-free survival rates were 39% in the FU plus LV arm and 37% in the ECF arm ( Plogrank = .94; multivariable hazard ratio, 0.96; 95% CI, 0.77 to 1.20). In post hoc analyses, the effect of treatment seemed to be similar across all examined patient subgroups. Conclusion After a curative resection of gastric or gastroesophageal junction adenocarcinoma, postoperative chemoradiotherapy using a multiagent regimen of ECF before and after radiotherapy does not improve survival compared with standard FU and LV before and after radiotherapy.
- Published
- 2017
15. Oxaliplatin-Based Adjuvant Chemotherapy in Older Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 12 Trials
- Author
-
Gallois, Claire, primary, Shi, Qian, additional, Pederson, Levi D., additional, André, Thierry, additional, Iveson, Timothy J., additional, Sobrero, Alberto F., additional, Alberts, Steven, additional, de Gramont, Aimery, additional, Meyerhardt, Jeffrey A., additional, George, Thomas, additional, Schmoll, Hans-Joachim E., additional, Souglakos, Ioannis, additional, Harkin, Andrea, additional, Labianca, Roberto, additional, Sinicrope, Frank A., additional, Oki, Eiji, additional, Shields, Anthony F., additional, Boukovinas, Ioannis, additional, Kerr, Rachel, additional, Lonardi, Sara, additional, Yothers, Greg, additional, Yoshino, Takayuki, additional, Goldberg, Richard M., additional, Taieb, Julien, additional, and Papamichael, Demetris, additional
- Published
- 2024
- Full Text
- View/download PDF
16. Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer
- Author
-
Dotan, Efrat, Cohen, Steven J, Starodub, Alexander N, Lieu, Christopher H, Messersmith, Wells A, Simpson, Pamela S, Guarino, Michael J, Marshall, John L, Goldberg, Richard M, Hecht, J Randolph, Wegener, William A, Sharkey, Robert M, Govindan, Serengulam V, Goldenberg, David M, and Berlin, Jordan D
- Subjects
Cancer ,Clinical Research ,Clinical Trials and Supportive Activities ,Colo-Rectal Cancer ,Digestive Diseases ,5.1 Pharmaceuticals ,6.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,6.2 Cellular and gene therapies ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,Aged ,80 and over ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Agents ,Camptothecin ,Colorectal Neoplasms ,Disease Progression ,Disease-Free Survival ,Drug Administration Schedule ,Drug Resistance ,Neoplasm ,Female ,Half-Life ,Humans ,Infusions ,Intravenous ,Irinotecan ,Male ,Middle Aged ,Neoplasm Metastasis ,Survival Analysis ,Treatment Outcome ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer. Patients and Methods Eligible patients with at least one prior irinotecan-containing therapy received labetuzumab govitecan once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles. End points were safety, response, pharmacokinetics, and immunogenicity. Results Eighty-six patients who had undergone a median of five prior therapies (range, one to 13) were each enrolled into one of the four cohorts. On the basis of Response Evaluation Criteria in Solid Tumors 1.1, 38% of these patients had a tumor as well as plasma carcinoembryonic antigen reduction from baseline after labetuzumab govitecan treatment; one patient achieved a partial response with a sustained response spanning > 2 years, whereas 42 patients had stable disease as the best overall response. Median progression-free survival and overall survival were 3.6 and 6.9 months, respectively. The major toxicities (grade ≥ 3) among all cohorts were neutropenia (16%), leukopenia (11%), anemia (9%), and diarrhea (7%). The antibody-drug conjugate's mean half-life was 16.5 hours for the four cohorts. Anti-drug/anti-antibody antibodies were not detected. The two once-weekly dose schedules, showing comparable toxicity and efficacy, were chosen for further study. Conclusion Monotherapy with labetuzumab govitecan demonstrated a manageable safety profile and therapeutic activity in heavily pretreated patients with metastatic colorectal cancer, all with prior irinotecan therapy. Further studies of labetuzumab govitecan treatment alone or in combination with other therapies in earlier settings are indicated.
- Published
- 2017
17. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial
- Author
-
Venook, Alan P, Niedzwiecki, Donna, Lenz, Heinz-Josef, Innocenti, Federico, Fruth, Briant, Meyerhardt, Jeffrey A, Schrag, Deborah, Greene, Claire, O'Neil, Bert H, Atkins, James Norman, Berry, Scott, Polite, Blase N, O'Reilly, Eileen M, Goldberg, Richard M, Hochster, Howard S, Schilsky, Richard L, Bertagnolli, Monica M, El-Khoueiry, Anthony B, Watson, Peter, Benson, Al B, Mulkerin, Daniel L, Mayer, Robert J, and Blanke, Charles
- Subjects
Cancer ,Clinical Trials and Supportive Activities ,Clinical Research ,Colo-Rectal Cancer ,Digestive Diseases ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,Aged ,80 and over ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,Bevacizumab ,Camptothecin ,Canada ,Cetuximab ,Colorectal Neoplasms ,Disease-Free Survival ,Female ,Fluorouracil ,Genes ,ras ,Humans ,Kaplan-Meier Estimate ,Leucovorin ,Male ,Middle Aged ,Organoplatinum Compounds ,Treatment Outcome ,United States ,Medical and Health Sciences ,General & Internal Medicine - Abstract
ImportanceCombining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown.ObjectiveTo determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer.Design, setting, and participantsPatients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015.InterventionsCetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient.Main outcomes and measuresThe primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response.ResultsAmong 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0-110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77-1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84-1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13).Conclusions and relevanceAmong patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment.Trial registrationclinicaltrials.gov identifier: NCT00265850.
- Published
- 2017
18. A Study of Thymidylate Synthase Expression as a Biomarker for Resectable Colon Cancer: Alliance (Cancer and Leukemia Group B) 9581 and 89803.
- Author
-
Niedzwiecki, Donna, Hasson, Rian M, Lenz, Heinz-Josef, Ye, Cynthia, Redston, Mark, Ogino, Shuji, Fuchs, Charles S, Compton, Carolyn C, Mayer, Robert J, Goldberg, Richard M, Colacchio, Thomas A, Saltz, Leonard B, Warren, Robert S, and Bertagnolli, Monica M
- Subjects
Humans ,Colonic Neoplasms ,Fluorouracil ,Thymidylate Synthase ,Neoplasm Staging ,Prognosis ,Disease-Free Survival ,Treatment Outcome ,Combined Modality Therapy ,Gene Expression Regulation ,Neoplastic ,Aged ,Middle Aged ,Female ,Male ,Microsatellite Instability ,Biomarkers ,Tumor ,Adjuvant therapy ,Biomarkers ,Colon cancer ,Microsatellite instability ,Mismatch repair deficiency ,Thymidylate synthase ,Gene Expression Regulation ,Neoplastic ,Tumor ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeTumor levels of thymidylate synthase (TS), a target of 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer, have been studied as a predictive or prognostic biomarker with mixed results.Patients and methodsTumor TS levels were prospectively evaluated in two adjuvant therapy trials for patients with resected stage II or III colon cancer. TS expression was determined by standard immunohistochemistry and by automated quantitative analysis. Tumor mismatch repair deficiency (MMR-D) and BRAF c.1799T > A (p.V600E) mutation status were also examined. Relationships between tumor TS, MMR-D, and BRAF mutation status, overall survival (OS), and disease-free survival (DFS) were investigated in the subset of stage III patients.ResultsPatients whose tumors demonstrated high TS expression experienced better treatment outcomes, with DFS hazard ratio (HR) = 0.67, 95% confidence interval (CI) = 0.53, 0.84; and OS HR = 0.68, 95% CI = 0.53, 0.88, for high versus low TS expression, respectively. No significant interaction between TS expression and stage was observed (DFS: interaction HR = 0.94; OS: interaction HR = 0.94). Tumors with high TS expression were more likely to demonstrate MMR-D (22.2% vs. 12.8%; p = .0003). Patients whose tumors demonstrated both high TS and MMR-D had a 7-year DFS of 77%, compared with 58% for those whose tumors had low TS and were non-MMR-D (log-rank p = .0006). Tumor TS expression did not predict benefit of a particular therapeutic regimen.ConclusionThis large prospective analysis showed that high tumor TS levels were associated with improved DFS and OS following adjuvant therapy for colon cancer, although tumor TS expression did not predict benefit of 5-FU-based chemotherapy. The Oncologist 2017;22:107-114Implications for Practice: This study finds that measurement of tumor levels of thymidylate synthase is not helpful in assigning specific adjuvant treatment for colorectal cancer. It also highlights the importance of using prospective analyses within treatment clinical trials as the optimal method of determining biomarker utility.
- Published
- 2017
19. Large-scale analysis of KMT2 mutations defines a distinctive molecular subset with treatment implication in gastric cancer
- Author
-
Wang, Jingyuan, Xiu, Joanne, Baca, Yasmine, Battaglin, Francesca, Arai, Hiroyuki, Kawanishi, Natsuko, Soni, Shivani, Zhang, Wu, Millstein, Joshua, Salhia, Bodour, Goldberg, Richard M., Philip, Philip A., Seeber, Andreas, Hwang, Jimmy J., Shields, Anthony F., Marshall, John L., Astsaturov, Igor, Craig Lockhart, A., Gatalica, Zoran, Michael Korn, W., and Lenz, Heinz-Josef
- Published
- 2021
- Full Text
- View/download PDF
20. Immunoscore Is Prognostic in Low-Risk and High-Risk Stage III Colon Carcinomas Treated With Adjuvant Infusional Fluorouracil, Leucovorin, and Oxaliplatin in a Phase III Trial
- Author
-
Sinicrope, Frank A., Shi, Qian, Catteau, Aurelie, Poage, Graham M., Zemla, Tyler J., Mlecnik, Bernhard, Benson, Al B., Gill, Sharlene, Goldberg, Richard M., Kahlenberg, Morton S., Nair, Suresh G., Shields, Anthony F., Smyrk, Thomas C., Galon, Jerome, and Alberts, Steven R.
- Published
- 2022
- Full Text
- View/download PDF
21. Genetic Variant Associated With Survival of Patients With Stage II-III Colon Cancer
- Author
-
Penney, Kathryn L., Banbury, Barbara L., Bien, Stephanie, Harrison, Tabitha A., Hua, Xinwei, Phipps, Amanda I., Sun, Wei, Song, Mingyang, Joshi, Amit D., Alberts, Steven R., Allegra, Carmen J., Atkins, James, Colangelo, Linda H., George, Thomas J., Goldberg, Richard M., Lucas, Peter C., Nair, Suresh G., Shi, Qian, Sinicrope, Frank A., Wolmark, Norman, Yothers, Greg, Peters, Ulrike, Newcomb, Polly A., and Chan, Andrew T.
- Published
- 2020
- Full Text
- View/download PDF
22. HER2 Gene Expression Levels Are Predictive and Prognostic in Patients With Metastatic Colorectal Cancer Enrolled in CALGB/SWOG 80405.
- Author
-
Battaglin, Francesca, Ou, Fang-Shu, Qu, Xueping, Hochster, Howard S., Niedzwiecki, Donna, Goldberg, Richard M., Mayer, Robert J., Ashouri, Karam, Zemla, Tyler J., Blanke, Charles D., Venook, Alan P., Kabbarah, Omar, Lenz, Heinz-Josef, and Innocenti, Federico
- Published
- 2024
- Full Text
- View/download PDF
23. Data‐driven optimization of version 9 American Joint Committee on Cancer staging system for anal cancer.
- Author
-
Janczewski, Lauren M., Browner, Amanda, Cotler, Joseph, Nelson, Heidi, Ballman, Karla V., LeBlanc, Michael, Gollub, Marc J., Eng, Cathy, Brierley, James D., Palefsky, Joel M., Goldberg, Richard M., Goodman, Karyn A., Washington, M. Kay, Asare, Elliot A., and Palis, Bryan
- Subjects
ANAL cancer ,TUMOR classification ,PROPORTIONAL hazards models ,OVERALL survival - Abstract
INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data‐driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach. METHODS: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan–Meier methods analyzed 5‐year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings. RESULTS: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1‐2N1M0, whereas Stage IIIA was redefined as T3N0‐1M0. Reevaluation of 5‐year survival based on data‐informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models. CONCLUSION: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data‐driven optimization approach can be implemented for staging revisions across all disease sites moving forward. Evaluation of the 8th edition American Joint Committee on Cancer staging system demonstrated a lack of hierarchical prognostic order for anal cancer. Thus, the version 9 American Joint Committee on Cancer staging system for anal cancer was revised through a validated and data‐driven approach and should similarly be applied across all disease sites moving forward. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
24. Arti Hurria, M.D.: A tribute to her shining legacy in the Alliance for Clinical Trials in Oncology
- Author
-
Adjei, Araba, Buckner, Jan C., Cathcart-Rake, Elizabeth, Chen, Hongbin, Cohen, Harvey J., Dao, Dyda, De Luca, Jo-Ellen, Feliciano, Josephine, Freedman, Rachel A., Goldberg, Richard M., Hopkins, Judith, Hubbard, Joleen, Jatoi, Aminah, Karuturi, Meghan, Kemeny, Margaret, Kimmick, Gretchen G., Klepin, Heidi D., Krok-Schoen, Jessica L., Lafky, Jacqueline M., Le-Rademacher, Jennifer G., Li, Daneng, Lichtman, Stuart M., Maggiore, Ronald, Mandelblatt, Jeanne, Morrison, Vicki A., Muss, Hyman B., Ojelabi, Michael O., Sedrak, Mina S., Subbiah, Niveditha, Sun, Virginia, Tuttle, Susan, VanderWalde, Noam, Wildes, Tanya, Wong, Melisa L., and Woyach, Jennifer
- Published
- 2020
- Full Text
- View/download PDF
25. Molecular characteristics of BRCA1/2 and PALB2 mutations in pancreatic ductal adenocarcinoma
- Author
-
Seeber, Andreas, Zimmer, Kai, Kocher, Florian, Puccini, Alberto, Xiu, Joanne, Nabhan, Chadi, Elliott, Andrew, Goldberg, Richard M., Grothey, Axel, Shields, Anthony F., Battaglin, Francesca, El-Deiry, Wafik S., Philip, Philip A., Marshall, John L., Hall, Michael, Korn, W. Michael, Lenz, Heinz-Josef, Wolf, Dominik, Feistritzer, Clemens, and Spizzo, Gilbert
- Published
- 2020
- Full Text
- View/download PDF
26. Molecular profile of BRCA-mutated biliary tract cancers
- Author
-
Spizzo, Gilbert, Puccini, Alberto, Xiu, Joanne, Goldberg, Richard M., Grothey, Axel, Shields, Anthony F., Arora, Sukeshi Patel, Khushman, Moh’d, Salem, Mohamed E., Battaglin, Francesca, Baca, Yasmine, El-Deiry, Wafik S., Philip, Philip A., Nassem, Madiha, Hall, Michael, Marshall, John L., Kocher, Florian, Amann, Arno, Wolf, Dominik, Korn, W. Michael, Lenz, Heinz-Josef, and Seeber, Andreas
- Published
- 2020
- Full Text
- View/download PDF
27. Identification and characterization of immunogenic neoantigens in colorectal cancer (CRC).
- Author
-
Battaglin, Francesca, primary, Elliott, Andrew, additional, Xiu, Joanne, additional, Algaze, Sandra, additional, Wang, Jingyuan, additional, Jayachandran, Priya, additional, Soni, Shivani, additional, Ashouri, Karam, additional, Wong, Alexandra, additional, Mittal, Pooja, additional, Lo, Jae Ho, additional, Torres-Gonzalez, Lesly, additional, Zhang, Wu, additional, Weinberg, Benjamin Adam, additional, Shields, Anthony F., additional, Goldberg, Richard M., additional, Marshall, John, additional, Lou, Emil, additional, and Lenz, Heinz-Josef, additional
- Published
- 2024
- Full Text
- View/download PDF
28. Genomic analysis of oesophageal carcinoma (EC) to identify recurrent mutations in histone methyltransferases as a distinctive subset.
- Author
-
Wang, Jingyuan, primary, Xiu, Joanne, additional, Oberley, Matthew James, additional, Battaglin, Francesca, additional, Arai, Hiroyuki, additional, Soni, Shivani, additional, Zhang, Wu, additional, Goldberg, Richard M., additional, Shields, Anthony F., additional, Grothey, Axel, additional, Hwang, Jimmy J., additional, Marshall, John, additional, Astsaturov, Igor A., additional, Weinberg, Benjamin Adam, additional, Lou, Emil, additional, Hall, Michael J., additional, Shroff, Rachna T., additional, Khushman, Moh'd M., additional, Sohal, Davendra, additional, and Lenz, Heinz-Josef, additional
- Published
- 2024
- Full Text
- View/download PDF
29. LMTK3 gene expression and the molecular landscape of colorectal cancer (CRC).
- Author
-
Torres-Gonzalez, Lesly, primary, Battaglin, Francesca, additional, Soni, Shivani, additional, Baca, Yasmine, additional, Xiu, Joanne, additional, Walker, Phillip, additional, Lo, Jae Ho, additional, Algaze, Sandra, additional, Jayachandran, Priya, additional, Mittal, Pooja, additional, Zhang, Wu, additional, Weinberg, Benjamin Adam, additional, Lou, Emil, additional, Shields, Anthony F., additional, Goldberg, Richard M., additional, Marshall, John, additional, Goel, Sanjay, additional, Stebbing, Justin, additional, Giamas, Georgios, additional, and Lenz, Heinz-Josef, additional
- Published
- 2024
- Full Text
- View/download PDF
30. Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)
- Author
-
Niedzwiecki, Donna, Frankel, Wendy L, Venook, Alan P, Ye, Xing, Friedman, Paula N, Goldberg, Richard M, Mayer, Robert J, Colacchio, Thomas Anthony, Mulligan, Jude Marie, Davison, Timothy S, O'Brien, Eamonn, Kerr, Peter, Johnston, Patrick G, Kennedy, Richard D, Harkin, D Paul, Schilsky, Richard L, Bertagnolli, Monica M, Warren, Robert S, and Innocenti, Federico
- Subjects
Clinical Research ,Colo-Rectal Cancer ,Stem Cell Research - Nonembryonic - Human ,Stem Cell Research ,Digestive Diseases ,Cancer ,Aged ,Antibodies ,Monoclonal ,Antibodies ,Monoclonal ,Murine-Derived ,Clinical Trials ,Phase III as Topic ,Cohort Studies ,Colonic Neoplasms ,Disease-Free Survival ,Female ,Gene Expression Profiling ,Humans ,Kaplan-Meier Estimate ,Male ,Middle Aged ,Multicenter Studies as Topic ,Neoplasm Recurrence ,Local ,Neoplasm Staging ,Oligonucleotide Array Sequence Analysis ,Randomized Controlled Trials as Topic ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeConventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.Patients and methodsC9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables.ResultsFifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk.ConclusionColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis.
- Published
- 2016
31. Mesothelin expression correlates with elevated inhibitory immune activity in patients with colorectal cancer
- Author
-
malla, Midhun, primary, Deshkmukh, Sachin Kumar, additional, Wu, Sharon, additional, Samec, Timothy, additional, Olevian, Dane, additional, Naili, Reima, additional, Bassel, El-Rayes, additional, Xiu, Joanne, additional, Farrell, Alex, additional, Lenz, Heinz-Josef, additional, Lou, Emil, additional, Goel, Sanjay, additional, Spetzler, David, additional, Goldberg, Richard M., additional, and Hazlehurst, Lori, additional
- Published
- 2023
- Full Text
- View/download PDF
32. Data‐driven optimization of version 9 American Joint Committee on Cancer staging system for anal cancer
- Author
-
Janczewski, Lauren M., primary, Browner, Amanda, additional, Cotler, Joseph, additional, Nelson, Heidi, additional, Ballman, Karla V., additional, LeBlanc, Michael, additional, Gollub, Marc J., additional, Eng, Cathy, additional, Brierley, James D., additional, Palefsky, Joel M., additional, Goldberg, Richard M., additional, Goodman, Karyn A., additional, Washington, M. Kay, additional, Asare, Elliot A., additional, and Palis, Bryan, additional
- Published
- 2023
- Full Text
- View/download PDF
33. Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D₃ levels and survival among patients with metastatic colorectal cancer
- Author
-
Yuan, Chen, Renfro, Lindsay, Ambadwar, Pratibha B., Ou, Fang-Shu, McLeod, Howard L., Innocenti, Federico, Meyerhardt, Jeffrey A., Wolpin, Brian M., Goldberg, Richard M., Grothey, Axel, Fuchs, Charles S., and Ng, Kimmie
- Published
- 2019
34. Molecular differences between lymph nodes and distant metastases compared with primaries in colorectal cancer patients
- Author
-
Puccini, Alberto, Seeber, Andreas, Xiu, Joanne, Goldberg, Richard M., Soldato, Davide, Grothey, Axel, Shields, Anthony F., Salem, Mohamed E., Battaglin, Francesca, Berger, Martin D., El-Deiry, Wafik S., Tokunaga, Ryuma, Naseem, Madiha, Zhang, Wu, Arora, Sukeshi Patel, Khushman, Moh’d M., Hall, Michael J., Philip, Philip A., Marshall, John L., Korn, W. Michael, and Lenz, Heinz-Josef
- Published
- 2021
- Full Text
- View/download PDF
35. Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database
- Author
-
Shi, Qian, de Gramont, Aimery, Grothey, Axel, Zalcberg, John, Chibaudel, Benoist, Schmoll, Hans-Joachim, Seymour, Matthew T, Adams, Richard, Saltz, Leonard, Goldberg, Richard M, Punt, Cornelis JA, Douillard, Jean-Yves, Hoff, Paulo M, Hecht, Joel Randolph, Hurwitz, Herbert, Díaz-Rubio, Eduardo, Porschen, Rainer, Tebbutt, Niall C, Fuchs, Charles, Souglakos, John, Falcone, Alfredo, Tournigand, Christophe, Kabbinavar, Fairooz F, Heinemann, Volker, Van Cutsem, Eric, Bokemeyer, Carsten, Buyse, Marc, and Sargent, Daniel J
- Subjects
Clinical Trials and Supportive Activities ,Digestive Diseases ,Clinical Research ,Cancer ,Colo-Rectal Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,Aged ,80 and over ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Biomedical Research ,Colorectal Neoplasms ,Databases ,Factual ,Digestive System ,Disease-Free Survival ,ErbB Receptors ,Humans ,Middle Aged ,Neoplasm Metastasis ,Neoplasms ,Outcome Assessment ,Health Care ,Prognosis ,Protein Kinase Inhibitors ,Randomized Controlled Trials as Topic ,Young Adult ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeProgression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination.MethodsIndividual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models.ResultsForty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy.ConclusionIn modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.
- Published
- 2015
36. Aspirin and COX-2 Inhibitor Use in Patients With Stage III Colon Cancer
- Author
-
Ng, Kimmie, Meyerhardt, Jeffrey A, Chan, Andrew T, Sato, Kaori, Chan, Jennifer A, Niedzwiecki, Donna, Saltz, Leonard B, Mayer, Robert J, Benson, Al B, Schaefer, Paul L, Whittom, Renaud, Hantel, Alexander, Goldberg, Richard M, Venook, Alan P, Ogino, Shuji, Giovannucci, Edward L, and Fuchs, Charles S
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prevention ,Genetics ,Colo-Rectal Cancer ,Cancer ,Digestive Diseases ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Age Factors ,Aged ,Anti-Inflammatory Agents ,Non-Steroidal ,Antineoplastic Combined Chemotherapy Protocols ,Aspirin ,Camptothecin ,Chemotherapy ,Adjuvant ,Colonic Neoplasms ,Cyclooxygenase 2 Inhibitors ,Disease-Free Survival ,Female ,Fluorouracil ,Humans ,Irinotecan ,Leucovorin ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Neoplasm Staging ,Odds Ratio ,Prospective Studies ,Sex Factors ,Treatment Outcome ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
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.
- Published
- 2015
37. Adjuvant Chemotherapy
- Author
-
Zeger, Erik L., Goldberg, Richard M., Dapri, Giovanni, editor, and Marks, John H, editor
- Published
- 2018
- Full Text
- View/download PDF
38. CpG Island Methylator Phenotype Is Associated With Response to Adjuvant Irinotecan-Based Therapy for Stage III Colon Cancer
- Author
-
Shiovitz, Stacey, Bertagnolli, Monica M, Renfro, Lindsay A, Nam, Eunmi, Foster, Nathan R, Dzieciatkowski, Slavomir, Luo, Yanxin, Lao, Victoria Valinluck, Monnat, Raymond J, Emond, Mary J, Maizels, Nancy, Niedzwiecki, Donna, Goldberg, Richard M, Saltz, Leonard B, Venook, Alan, Warren, Robert S, Grady, William M, and Oncology, Alliance for Clinical Trials in
- Subjects
Cancer ,Genetics ,Colo-Rectal Cancer ,Digestive Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adenocarcinoma ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Camptothecin ,Chemotherapy ,Adjuvant ,Colectomy ,Colonic Neoplasms ,CpG Islands ,DNA Methylation ,DNA Mismatch Repair ,Disease-Free Survival ,Female ,Fluorouracil ,Humans ,Irinotecan ,Kaplan-Meier Estimate ,Leucovorin ,Male ,Middle Aged ,Neoplasm Staging ,Phenotype ,Proportional Hazards Models ,Risk Assessment ,Risk Factors ,Time Factors ,Treatment Outcome ,Young Adult ,CALGB (Alliance) 89803 ,CRC ,Epigenetic Factors ,Chemotherapy ,Alliance for Clinical Trials in Oncology ,Clinical Sciences ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology - Abstract
Background & aimsThe CpG island methylator phenotype (CIMP), defined by a high frequency of aberrantly methylated genes, is a characteristic of a subclass of colon tumors with distinct clinical and molecular features. Cohort studies have produced conflicting results on responses of CIMP-positive tumors to chemotherapy. We assessed the association between tumor CIMP status and survival of patients receiving adjuvant fluorouracil and leucovorin alone or with irinotecan (IFL).MethodsWe analyzed data from patients with stage III colon adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or IFL after surgery, from April 1999 through April 2001. The primary end point of the trial was overall survival and the secondary end point was disease-free survival. DNA isolated from available tumor samples (n = 615) was used to determine CIMP status based on methylation patterns at the CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1 loci. The effects of CIMP on survival were modeled using Kaplan-Meier and Cox proportional hazards; interactions with treatment and BRAF, KRAS, and mismatch repair (MMR) status were also investigated.ResultsOf the tumor samples characterized for CIMP status, 145 were CIMP positive (23%). Patients with CIMP-positive tumors had shorter overall survival times than patients with CIMP-negative tumors (hazard ratio = 1.36; 95% confidence interval: 1.01-1.84). Treatment with IFL showed a trend toward increased overall survival for patients with CIMP-positive tumors, compared with treatment with fluorouracil and leucovorin (hazard ratio = 0.62; 95% CI: 0.37-1.05; P = .07), but not for patients with CIMP-negative tumors (hazard ratio = 1.38; 95% CI: 1.00-1.89; P = .049). In a 3-way interaction analysis, patients with CIMP-positive, MMR-intact tumors benefited most from the addition of irinotecan to fluorouracil and leucovorin therapy (for the interaction, P = .01). CIMP was more strongly associated with response to IFL than MMR status. Results for disease-free survival times were comparable among all analyses.ConclusionsPatients with stage III, CIMP-positive, MMR-intact colon tumors have longer survival times when irinotecan is added to combination therapy with fluorouracil and leucovorin.
- Published
- 2014
39. Physical activity in recurrent colon cancer: Cancer and Leukemia Group B/SWOG 80702 (Alliance)
- Author
-
Brown, Justin C., primary, Ma, Chao, additional, Shi, Qian, additional, Zemla, Tyler, additional, Couture, Felix, additional, Kuebler, Philip, additional, Kumar, Pankaj, additional, Tan, Benjamin, additional, Krishnamurthi, Smitha, additional, Chang, Victor, additional, Goldberg, Richard M., additional, Venook, Alan P., additional, Blanke, Charles D., additional, O’Reilly, Eileen M., additional, Shields, Anthony F., additional, and Meyerhardt, Jeffrey A., additional
- Published
- 2023
- Full Text
- View/download PDF
40. Evaluation of Intratumoral Response Heterogeneity in Metastatic Colorectal Cancer and Its Impact on Patient Overall Survival: Findings from 10,551 Patients in the ARCAD Database
- Author
-
Ou, Fang-Shu, primary, Ahn, Daniel H., additional, Dixon, Jesse G., additional, Grothey, Axel, additional, Lou, Yiyue, additional, Kasi, Pashtoon M., additional, Hubbard, Joleen M., additional, Van Cutsem, Eric, additional, Saltz, Leonard B., additional, Schmoll, Hans-Joachim, additional, Goldberg, Richard M., additional, Venook, Alan P., additional, Hoff, Paulo, additional, Douillard, Jean-Yves, additional, Hecht, J. Randolph, additional, Hurwitz, Herbert, additional, Punt, Cornelis J. A., additional, Koopman, Miriam, additional, Bokemeyer, Carsten, additional, Fuchs, Charles S., additional, Diaz-Rubio, Eduardo, additional, Tebbutt, Niall C., additional, Cremolini, Chiara, additional, Kabbinavar, Fairooz F., additional, Bekaii-Saab, Tanios, additional, Chibaudel, Benoist, additional, Yoshino, Takayuki, additional, Zalcberg, John, additional, Adams, Richard A., additional, de Gramont, Aimery, additional, and Shi, Qian, additional
- Published
- 2023
- Full Text
- View/download PDF
41. Genome‐wide study of genetic polymorphisms predictive for outcome from first‐line oxaliplatin‐based chemotherapy in colorectal cancer patients
- Author
-
Park, Hanla A., primary, Edelmann, Dominic, additional, Canzian, Federico, additional, Seibold, Petra, additional, Harrison, Tabitha A., additional, Hua, Xinwei, additional, Shi, Qian, additional, Silverman, Allison, additional, Benner, Axel, additional, Macauda, Angelica, additional, Schneider, Martin, additional, Goldberg, Richard M., additional, Alberts, Steven R., additional, Hoffmeister, Michael, additional, Brenner, Hermann, additional, Chan, Andrew T., additional, Peters, Ulrike, additional, Newcomb, Polly A., additional, and Chang‐Claude, Jenny, additional
- Published
- 2023
- Full Text
- View/download PDF
42. Prognostic and Predictive Blood-Based Biomarkers in Patients with Advanced Pancreatic Cancer: Results from CALGB80303 (Alliance)
- Author
-
Nixon, Andrew B, Pang, Herbert, Starr, Mark D, Friedman, Paula N, Bertagnolli, Monica M, Kindler, Hedy L, Goldberg, Richard M, Venook, Alan P, Hurwitz, Herbert I, and Oncology, for the Alliance for Clinical Trials In
- Subjects
Digestive Diseases ,Clinical Research ,Pancreatic Cancer ,Rare Diseases ,Cancer ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Adult ,Aged ,Aged ,80 and over ,Antibodies ,Monoclonal ,Humanized ,Bevacizumab ,Biomarkers ,Tumor ,Chemokine CXCL12 ,Clinical Trials ,Phase III as Topic ,Deoxycytidine ,Female ,Humans ,Kaplan-Meier Estimate ,Male ,Middle Aged ,Neoplasm Staging ,Pancreatic Neoplasms ,Prognosis ,Proportional Hazards Models ,Vascular Endothelial Growth Factor D ,Vesicular Transport Proteins ,Gemcitabine ,Alliance for Clinical Trials In Oncology ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeCALGB80303 was a phase III trial of 602 patients with locally advanced or metastatic pancreatic cancer comparing gemcitabine/bevacizumab versus gemcitabine/placebo. The study found no benefit in any outcome from the addition of bevacizumab to gemcitabine. Blood samples were collected and multiple angiogenic factors were evaluated and then correlated with clinical outcome in general (prognostic markers) and with benefit specifically from bevacizumab treatment (predictive markers).Experimental designPlasma samples were analyzed via a novel multiplex ELISA platform for 31 factors related to tumor growth, angiogenesis, and inflammation. Baseline values for these factors were correlated with overall survival (OS) using univariate Cox proportional hazard regression models and multivariable Cox regression models with leave-one-out cross validation. Predictive markers were identified using a treatment by marker interaction term in the Cox model.ResultsBaseline plasma was available from 328 patients. Univariate prognostic markers for OS were identified including: Ang2, CRP, ICAM-1, IGFBP-1, TSP-2 (all P < 0.001). These prognostic factors were found to be highly significant, even after adjustment for known clinical factors. Additional modeling approaches yielded prognostic signatures from multivariable Cox regression. The gemcitabine/bevacizumab signature consisted of IGFBP-1, interleukin-6, PDGF-AA, PDGF-BB, TSP-2; whereas the gemcitabine/placebo signature consisted of CRP, IGFBP-1, PAI-1, PDGF-AA, P-selectin (both P < 0.0001). Finally, three potential predictive markers of bevacizumab efficacy were identified: VEGF-D (P < 0.01), SDF1 (P < 0.05), and Ang2 (P < 0.05).ConclusionThis study identified strong prognostic markers for pancreatic cancer patients. Predictive marker analysis indicated that plasma levels of VEGF-D, Ang2, and SDF1 significantly predicted for benefit or lack of benefit from bevacizumab in this population.
- Published
- 2013
43. Association of TP53 Mutational Status and Gender with Survival after Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803
- Author
-
Warren, Robert S, Atreya, Chloe E, Niedzwiecki, Donna, Weinberg, Vivian K, Donner, David B, Mayer, Robert J, Goldberg, Richard M, Compton, Carolyn C, Zuraek, Marlene B, Ye, Cynthia, Saltz, Leonard B, and Bertagnolli, Monica M
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Human Genome ,Cancer Genomics ,Precision Medicine ,Colo-Rectal Cancer ,Clinical Research ,Women's Health ,Rare Diseases ,Genetics ,Cancer ,Digestive Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Antineoplastic Combined Chemotherapy Protocols ,Chemotherapy ,Adjuvant ,Colonic Neoplasms ,DNA ,Female ,Genotype ,Humans ,Male ,Microsatellite Instability ,Models ,Molecular ,Molecular Conformation ,Mutation ,Neoplasm Staging ,Protein Binding ,Sex Factors ,Tumor Suppressor Protein p53 ,Zinc ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
PurposeThe TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer.Experimental designThe impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL).ResultsTP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc- or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc- or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men.ConclusionsThe presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men.
- Published
- 2013
44. Prognostic Impact of Deficient DNA Mismatch Repair in Patients With Stage III Colon Cancer From a Randomized Trial of FOLFOX-Based Adjuvant Chemotherapy
- Author
-
Sinicrope, Frank A, Mahoney, Michelle R, Smyrk, Thomas C, Thibodeau, Stephen N, Warren, Robert S, Bertagnolli, Monica M, Nelson, Garth D, Goldberg, Richard M, Sargent, Daniel J, and Alberts, Steven R
- Subjects
Clinical Research ,Genetics ,Clinical Trials and Supportive Activities ,Digestive Diseases ,Colo-Rectal Cancer ,Cancer ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Chemotherapy ,Adjuvant ,Colonic Neoplasms ,DNA Mismatch Repair ,Female ,Fluorouracil ,Humans ,Leucovorin ,Male ,Middle Aged ,Neoplasm Staging ,Organoplatinum Compounds ,Prognosis ,Proto-Oncogene Proteins ,Proto-Oncogene Proteins B-raf ,Proto-Oncogene Proteins p21(ras) ,ras Proteins ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeThe association of deficient DNA mismatch repair (dMMR) with prognosis in patients with colon cancer treated with adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy remains unknown.Patients and methodsResected, stage III colon carcinomas from patients (N = 2,686) randomly assigned to FOLFOX ± cetuximab (North Central Cancer Treatment Group N0147 trial) were analyzed for mismatch repair (MMR) protein expression and mutations in BRAF(V600E) (exon 15) and KRAS (codons 12 and 13). Association of biomarkers with disease-free survival (DFS) was determined using Cox models. A validation cohort (Cancer and Leukemia Group B 88903 trial) was used.ResultsdMMR was detected in 314 (12%) of 2,580 tumors, of which 49.3% and 10.6% had BRAF(V600E) or KRAS mutations, respectively. MMR status was not prognostic overall (adjusted hazard ratio [HR], 0.82; 95% CI, 0.64 to 1.07; P = .14), yet significant interactions were found between MMR and primary tumor site (P(interaction) = .009) and lymph node category (N1 v N2; P(interaction) = .014). Favorable DFS was observed for dMMR versus proficient MMR proximal tumors (HR, 0.71; 95% CI, 0.53 to 0.94; P = .018) but not dMMR distal tumors (HR, 1.71; 95% CI, 0.99 to 2.95; P = .056), adjusting for mutations and covariates. Any survival benefit of dMMR was lost in N2 tumors. Mutations in BRAF(V600E) (HR, 1.37; 95% CI, 1.08 to 1.70; P = .009) or KRAS (HR, 1.44; 95% CI, 1.21 to 1.70; P < .001) were independently associated with worse DFS. The observed MMR by tumor site interaction was validated in an independent cohort of stage III colon cancers (P(interaction) = .037).ConclusionThe prognostic impact of MMR depended on tumor site, and this interaction was validated in an independent cohort. Among dMMR cancers, proximal tumors had favorable outcome, whereas distal or N2 tumors had poor outcome. BRAF or KRAS mutations were independently associated with adverse outcome.
- Published
- 2013
45. Comparison of Dietary and Lifestyle Habits Among Stage III and Metastatic Colorectal Cancer Patients: Findings from CALGB 89803 and CALGB 80405
- Author
-
Van Loon, Katherine, Wigler, Devin, Niedzwiecki, Donna, Venook, Alan P, Fuchs, Charles, Blanke, Charles, Saltz, Leonard, Goldberg, Richard M, and Meyerhardt, Jeffrey A
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Nutrition ,Colo-Rectal Cancer ,Behavioral and Social Science ,Digestive Diseases ,Cancer ,Women's Health ,Prevention ,Oral and gastrointestinal ,Good Health and Well Being ,Alcohol Drinking ,Cohort Studies ,Colorectal Neoplasms ,Dietary Supplements ,Feeding Behavior ,Health Behavior ,Humans ,Life Style ,Motor Activity ,Neoplasm Metastasis ,Neoplasm Staging ,Nutrition Policy ,Prevalence ,Smoking ,Surveys and Questionnaires ,Vitamin D ,Vitamins ,Colon cancer ,Chemotherapy ,Exercise ,Behavioral patterns ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
UnlabelledSelf-administered questionnaires were completed by patients undergoing chemotherapy for stage III colon cancer (n=1095) and metastatic colorectal cancer (n=875). We describe the prevalence of a wide-range of health-related dietary patterns and lifestyle behaviors among colorectal cancer patients with stage III and metastatic disease and report notable similarities in these 2 cohorts.BackgroundCancer patients often pursue lifestyle and dietary changes with the aim to improve outcomes. Using data from 2 large National Cancer Institute-sponsored clinical trials, we report on the dietary and lifestyle practices of patients receiving therapy for stage III colon or metastatic colorectal cancer.Patients and methodsSelf-administered questionnaires were completed by patients undergoing chemotherapy for stage III colon cancer (n=1095) and metastatic colorectal cancer (n=875). Descriptive statistical analyses were performed to evaluate anthropometrics, diet, and lifestyle in each cohort.ResultsMedian body mass index was comparable for stage III and metastatic patients (27.3 vs. 26.5 kg/m2). Stage III patients reported a modestly higher median level of physical activity than metastatic patients (4.6 vs. 3.4 metabolic equivalent task-hours per week). Ten percent of stage III and 9% of metastatic patients reported ongoing cigarette use. Avoidance of alcohol was reported by 47% of stage III and 43% of metastatic patients. Dietary patterns for both groups were comparable with more than 80% of stage III and metastatic patients failing to meet the recommended daily intake of vegetables, fruits, and milk products. Usage of at least 2 multivitamins per week was reported by 49% of stage III and 40% of metastatic patients. Two percent of stage III and 5% of metastatic patients reported vitamin D supplement use.ConclusionsWe observed notable similarities in dietary and lifestyle behaviors between stage III colon and metastatic colorectal cancer patients actively receiving chemotherapy. Future research should aim to elucidate the effect of these behaviors on patient outcomes.
- Published
- 2013
46. Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581
- Author
-
Venook, Alan P, Niedzwiecki, Donna, Lopatin, Margarita, Ye, Xing, Lee, Mark, Friedman, Paula N, Frankel, Wendy, Clark-Langone, Kim, Millward, Carl, Shak, Steven, Goldberg, Richard M, Mahmoud, Najjia N, Warren, Robert S, Schilsky, Richard L, and Bertagnolli, Monica M
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Digestive Diseases ,Genetics ,Colo-Rectal Cancer ,Cancer ,Adult ,Aged ,Antibodies ,Monoclonal ,Antibodies ,Monoclonal ,Murine-Derived ,Antineoplastic Agents ,Colonic Neoplasms ,DNA Mismatch Repair ,Female ,Humans ,Leukemia ,Lymphatic Metastasis ,Male ,Middle Aged ,Multivariate Analysis ,Neoplasm Grading ,Neoplasm Recurrence ,Local ,Neoplasm Staging ,Proportional Hazards Models ,Randomized Controlled Trials as Topic ,Reverse Transcriptase Polymerase Chain Reaction ,Risk Assessment ,Risk Factors ,Clinical Sciences ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
PurposeA greater understanding of the biology of tumor recurrence should improve adjuvant treatment decision making. We conducted a validation study of the 12-gene recurrence score (RS), a quantitative assay integrating stromal response and cell cycle gene expression, in tumor specimens from patients enrolled onto Cancer and Leukemia Group B (CALGB) 9581.Patients and methodsCALGB 9581 randomly assigned 1,713 patients with stage II colon cancer to treatment with edrecolomab or observation and found no survival difference. The analysis reported here included all patients with available tissue and recurrence (n = 162) and a random (approximately 1:3) selection of nonrecurring patients. RS was assessed in 690 formalin-fixed paraffin-embedded tumor samples with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously validated algorithm. Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression.ResultsContinuous RS was significantly associated with risk of recurrence (P = .013) as was mismatch repair (MMR) gene deficiency (P = .044). In multivariate analyses, RS was the strongest predictor of recurrence (P = .004), independent of T stage, MMR, number of nodes examined, grade, and lymphovascular invasion. In T3 MMR-intact (MMR-I) patients, prespecified low and high RS groups had average 5-year recurrence risks of 13% (95% CI, 10% to 16%) and 21% (95% CI, 16% to 26%), respectively.ConclusionThe 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581. This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence. RS appears to be most discerning for patients with T3 MMR-I tumors, although markers such as grade and lymphovascular invasion did not add value in this subset of patients.
- Published
- 2013
47. Prospective Statewide Study of Universal Screening for Hereditary Colorectal Cancer: The Ohio Colorectal Cancer Prevention Initiative
- Author
-
Pearlman, Rachel, Frankel, Wendy L., Swanson, Benjamin J., Jones, Dan, Zhao, Weiqiang, Yilmaz, Ahmet, Miller, Kristin, Bacher, Jason, Bigley, Christopher, Nelsen, Lori, Goodfellow, Paul J., Goldberg, Richard M., Paskett, Electra, Shields, Peter G., Freudenheim, Jo L., Stanich, Peter P., Lattimer, Ilene, Arnold, Mark, Prior, Thomas W., Haut, Mitchell, Kalady, Matthew F., Heald, Brandie, Paquette, Ian, Draper, David J., Brell, Joanna M., Mahesh, Sameer, Weeman, Kisa, Bastola, Shyamal, Zangmeister, Jeffrey, Gowda, Aruna, Kencana, Filix, Malcolm, Albert, Liu, Yinong, Cole, Sharon, Bane, Charles, Li, Chaoyang, Rehmus, Esther, Pritchard, Colin C., Shirts, Brian H., Jacobson, Angela, Cummings, Shelly A., de la Chapelle, Albert, and Hampel, Heather
- Published
- 2021
- Full Text
- View/download PDF
48. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
- Author
-
Le, Dung T., Durham, Jennifer N., Smith, Kellie N., Wang, Hao, Bartlett, Bjarne R., Aulakh, Laveet K., Lu, Steve, Kemberling, Holly, Wilt, Cara, Luber, Brandon S., Wong, Fay, Azad, Nilofer S., Rucki, Agnieszka A., Laheru, Dan, Donehower, Ross, Zaheer, Atif, Fisher, George A., Crocenzi, Todd S., Lee, James J., Greten, Tim F., Duffy, Austin G., Ciombor, Kristen K., Eyring, Aleksandra D., Lam, Bao H., Joe, Andrew, Kang, S. Peter, Holdhoff, Matthias, Danilova, Ludmila, Cope, Leslie, Meyer, Christian, Zhou, Shibin, Goldberg, Richard M., Armstrong, Deborah K., Bever, Katherine M., Fader, Amanda N., Taube, Janis, Housseau, Franck, Spetzler, David, Xiao, Nianqing, Pardoll, Drew M., Papadopoulos, Nickolas, Kinzler, Kenneth W., Eshleman, James R., Vogelstein, Bert, Anders, Robert A., and Diaz, Luis A.
- Published
- 2017
49. Supplementary Methods S1 from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
- Author
-
Wang, Qiao-Li, primary, Ma, Chao, primary, Yuan, Chen, primary, Shi, Qian, primary, Wolpin, Brian M., primary, Zhang, Yin, primary, Fuchs, Charles S., primary, Meyer, Jeffrey, primary, Zemla, Tyler, primary, Cheng, En, primary, Kumthekar, Priya, primary, Guthrie, Katherine A., primary, Couture, Felix, primary, Kuebler, Philip, primary, Kumar, Pankaj, primary, Tan, Benjamin, primary, Krishnamurthi, Smitha, primary, Goldberg, Richard M., primary, Venook, Alan, primary, Blanke, Charles, primary, Shields, Anthony F., primary, O'Reilly, Eileen M., primary, Meyerhardt, Jeffrey A., primary, and Ng, Kimmie, primary
- Published
- 2023
- Full Text
- View/download PDF
50. Supplementary Figure S2 from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
- Author
-
Wang, Qiao-Li, primary, Ma, Chao, primary, Yuan, Chen, primary, Shi, Qian, primary, Wolpin, Brian M., primary, Zhang, Yin, primary, Fuchs, Charles S., primary, Meyer, Jeffrey, primary, Zemla, Tyler, primary, Cheng, En, primary, Kumthekar, Priya, primary, Guthrie, Katherine A., primary, Couture, Felix, primary, Kuebler, Philip, primary, Kumar, Pankaj, primary, Tan, Benjamin, primary, Krishnamurthi, Smitha, primary, Goldberg, Richard M., primary, Venook, Alan, primary, Blanke, Charles, primary, Shields, Anthony F., primary, O'Reilly, Eileen M., primary, Meyerhardt, Jeffrey A., primary, and Ng, Kimmie, primary
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.