662 results on '"Scher, Hi"'
Search Results
2. Androgen dynamics and serum PSA in patients treated with abiraterone acetate
- Author
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Ryan, Charles, Ryan, CJ, Peng, W, Kheoh, T, Welkowsky, E, Haqq, CM, Chandler, DW, Scher, HI, and Molina, A
- Abstract
Background: We analyzed the potential of abiraterone acetate (henceforth abiraterone) to reduce androgen levels below lower limits of quantification (LLOQ) and explored the association with changes in PSA decline in metastatic castration-resistant prostate
- Published
- 2014
3. What Experts Think About Prostate Cancer Management During the COVID-19 Pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021 (vol 82, pg 6, 2022)
- Author
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Turco, F, Armstrong, A, Attard, G, Beer, TM, Beltran, H, Bjartell, A, Bossi, A, Briganti, A, Bristow, RG, Bulbul, M, Caffo, O, Chi, KN, Clarke, C, Clarke, N, Davis, ID, de Bono, J, Duran, I, Eeles, R, Efstathiou, E, Efstathiou, J, Evans, CP, Fanti, S, Feng, FY, Fizazi, K, Frydenberg, M, George, D, Gleave, M, Halabi, S, Heinrich, D, Higano, C, Hofman, MS, Hussain, M, James, N, Jones, R, Kanesvaran, R, Khauli, RB, Klotz, L, Leibowitz, R, Logothetis, C, Maluf, F, Millman, R, Morgans, AK, Morris, MJ, Mottet, N, Mrabti, H, Murphy, DG, Murthy, V, Oh, WK, Ekeke, ON, Ost, P, O'Sullivan, JM, Padhani, AR, Parker, C, Poon, DMC, Pritchard, CC, Rabah, DM, Rathkopf, D, Reiter, RE, Rubin, M, Ryan, CJ, Saad, F, Sade, JP, Sartor, O, Scher, HI, Shore, N, Skoneczna, I, Small, E, Smith, M, Soule, H, Spratt, D, Sternberg, CN, Suzuki, H, Sweeney, C, Sydes, M, Taplin, M-E, Tilki, D, Tombal, B, Turkeri, L, Uemura, H, van Oort, I, Yamoah, K, Ye, D, Zapatero, A, Gillessen, S, Omlin, A, Turco, F, Armstrong, A, Attard, G, Beer, TM, Beltran, H, Bjartell, A, Bossi, A, Briganti, A, Bristow, RG, Bulbul, M, Caffo, O, Chi, KN, Clarke, C, Clarke, N, Davis, ID, de Bono, J, Duran, I, Eeles, R, Efstathiou, E, Efstathiou, J, Evans, CP, Fanti, S, Feng, FY, Fizazi, K, Frydenberg, M, George, D, Gleave, M, Halabi, S, Heinrich, D, Higano, C, Hofman, MS, Hussain, M, James, N, Jones, R, Kanesvaran, R, Khauli, RB, Klotz, L, Leibowitz, R, Logothetis, C, Maluf, F, Millman, R, Morgans, AK, Morris, MJ, Mottet, N, Mrabti, H, Murphy, DG, Murthy, V, Oh, WK, Ekeke, ON, Ost, P, O'Sullivan, JM, Padhani, AR, Parker, C, Poon, DMC, Pritchard, CC, Rabah, DM, Rathkopf, D, Reiter, RE, Rubin, M, Ryan, CJ, Saad, F, Sade, JP, Sartor, O, Scher, HI, Shore, N, Skoneczna, I, Small, E, Smith, M, Soule, H, Spratt, D, Sternberg, CN, Suzuki, H, Sweeney, C, Sydes, M, Taplin, M-E, Tilki, D, Tombal, B, Turkeri, L, Uemura, H, van Oort, I, Yamoah, K, Ye, D, Zapatero, A, Gillessen, S, and Omlin, A
- Published
- 2022
4. Farnesyl:protein transferase inhibitors as potential agents for the management of human prostate cancer
- Author
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Sepp-Lorenzino, L, Tjaden, G, Moasser, MM, Timaul, N, Ma, Z, Kohl, NE, Gibbs, JB, Oliff, A, Rosen, N, and Scher, HI
- Published
- 2001
- Full Text
- View/download PDF
5. The microtubule-stabilizing agents epothilones A and B and their desoxy-derivatives induce mitotic arrest and apoptosis in human prostate cancer cells
- Author
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Sepp-Lorenzino, L, Balog, A, Su, D-S, Meng, D, Timaul, N, Scher, HI, Danishefsky, SJ, and Rosen, N
- Published
- 1999
- Full Text
- View/download PDF
6. Consensus on molecular imaging and theranostics in prostate cancer
- Author
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Fanti, S, Minozzi, S, Antoch, G, Banks, I, Briganti, A, Carrio, I, Chiti, A, Clarke, N, Eiber, M, De Bono, J, Fizazi, K, Gillessen, S, Gledhill, S, Haberkorn, U, Herrmann, K, Hicks, RJ, Lecouvet, F, Montironi, R, Ost, P, O'Sullivan, JM, Padhani, AR, Schalken, JA, Scher, HI, Tombal, B, van Moorselaar, RJA, Van Poppel, H, Vargas, HA, Walz, J, Weber, WA, Wester, HJ, and Oyen, WJG
- Abstract
Rapid developments in imaging and treatment with radiopharmaceuticals targeting prostate cancer pose issues for the development of guidelines for their appropriate use. To tackle this problem, international experts representing medical oncologists, urologists, radiation oncologists, radiologists, and nuclear medicine specialists convened at the European Association of Nuclear Medicine Focus 1 meeting to deliver a balanced perspective on available data and clinical experience of imaging in prostate cancer, which had been supported by a systematic review of the literature and a modified Delphi process. Relevant conclusions included the following: diphosphonate bone scanning and contrast-enhanced CT are mentioned but rarely recommended for most patients in clinical guidelines; MRI (whole-body or multiparametric) and prostate cancer-targeted PET are frequently suggested, but the specific contexts in which these methods affect practice are not established; sodium fluoride-18 for PET-CT bone scanning is not widely advocated, whereas gallium-68 or fluorine-18 prostate-specific membrane antigen gain acceptance; and, palliative treatment with bone targeting radiopharmaceuticals (rhenium-186, samarium-153, or strontium-89) have largely been replaced by radium-223 on the basis of the survival benefit that was reported in prospective trials, and by other systemic therapies with proven survival benefits. Although the advances in MRI and PET-CT have improved the accuracy of imaging, the effects of these new methods on clinical outcomes remains to be established. Improved communication between imagers and clinicians and more multidisciplinary input in clinical trial design are essential to encourage imaging insights into clinical decision making.
- Published
- 2018
7. Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: Is Real Circulating Tumor Cell Number Superior to Prostate-Specific Antigen? Reply
- Author
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Heller, G, McCormack, R, Kheoh, T, Molina, A, Smith, MR, Dreicer, R, Saad, F, de Wit, Ronald, Aftab, DT, Hirmand, M, Limon-Carrera, A, Fizazi, K, Fleisher, M, de Bono, JS, Scher, HI, and Medical Oncology
- Subjects
SDG 3 - Good Health and Well-being - Published
- 2018
8. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy
- Author
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Beer, Tm, Armstrong, Aj, Rathkopf, De, Loriot, Y, Sternberg, Cn, Higano, Cs, Iversen, P, Bhattacharya, S, Carles, J, Chowdhury, S, Davis, Id, de Bono JS, Evans, Cp, Fizazi, K, Joshua, Am, Kim, Cs, Kimura, G, Mainwaring, P, Mansbach, H, Miller, K, Noonberg, Sb, Perabo, F, Phung, D, Saad, F, Scher, Hi, Taplin, Me, Venner, Pm, Tombal, B, Prevail, Investigators, Scagliotti, Giorgio Vittorio, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), and Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
- Subjects
Male ,Oncology ,Aging ,CASTRATION ,Medical and Health Sciences ,Androgen ,chemistry.chemical_compound ,Prostate cancer ,Receptors ,ANTIANDROGEN ,Neoplasm Metastasis ,Cancer ,Prostate Cancer ,Hazard ratio ,Apalutamide ,Abiraterone acetate ,General Medicine ,MITOXANTRONE ,3. Good health ,Darolutamide ,6.1 Pharmaceuticals ,Benzamides ,Administration ,Disease Progression ,PREDNISONE ,Oral ,Urologic Diseases ,medicine.medical_specialty ,Clinical Trials and Supportive Activities ,INCREASED SURVIVAL ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antineoplastic Agents ,Adenocarcinoma ,Double-Blind Method ,Clinical Research ,General & Internal Medicine ,Intensive care ,Internal medicine ,Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15] ,Nitriles ,Phenylthiohydantoin ,Androgen Receptor Antagonists ,medicine ,Humans ,Enzalutamide ,Hormonal ,business.industry ,Prostatic Neoplasms ,Evaluation of treatments and therapeutic interventions ,ABIRATERONE ,Interim analysis ,medicine.disease ,Survival Analysis ,Surgery ,Radiography ,chemistry ,PREVAIL Investigators ,business - Abstract
Contains fulltext : 137932.pdf (Publisher’s version ) (Open Access) BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. RESULTS: The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P
- Published
- 2014
9. Erratum: Evaluation of molecular forms of PSA and human kallikrein 2 in predicting biochemical failure following radical prostatectomy (International Journal of Cancer (2009) 125 (659-663) DOI:10.1002/ijc.23983)
- Author
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Wenske, S, Korets, R, Cronin, AM, Vickers, AJ, Fleisher, M, Scher, HI, Pettersson, K, Guillonneau, B, Scardino, PT, Eastham, JA, and Lilja, H
- Published
- 2016
10. Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium
- Author
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Grossman, RL, primary, Abel, B, additional, Angiuoli, S, additional, Barrett, JC, additional, Bassett, D, additional, Bramlett, K, additional, Blumenthal, GM, additional, Carlsson, A, additional, Cortese, R, additional, DiGiovanna, J, additional, Davis‐Dusenbery, B, additional, Dittamore, R, additional, Eberhard, DA, additional, Febbo, P, additional, Fitzsimons, M, additional, Flamig, Z, additional, Godsey, J, additional, Goswami, J, additional, Gruen, A, additional, Ortuño, F, additional, Han, J, additional, Hayes, D, additional, Hicks, J, additional, Holloway, D, additional, Hovelson, D, additional, Johnson, J, additional, Juhl, H, additional, Kalamegham, R, additional, Kamal, R, additional, Kang, Q, additional, Kelloff, GJ, additional, Klozenbuecher, M, additional, Kolatkar, A, additional, Kuhn, P, additional, Langone, K, additional, Leary, R, additional, Loverso, P, additional, Manmathan, H, additional, Martin, A‐M, additional, Martini, J, additional, Miller, D, additional, Mitchell, M, additional, Morgan, T, additional, Mulpuri, R, additional, Nguyen, T, additional, Otto, G, additional, Pathak, A, additional, Peters, E, additional, Philip, R, additional, Posadas, E, additional, Reese, D, additional, Reese, MG, additional, Robinson, D, additional, Dei Rossi, A, additional, Sakul, H, additional, Schageman, J, additional, Singh, S, additional, Scher, HI, additional, Schmitt, K, additional, Silvestro, A, additional, Simmons, J, additional, Simmons, T, additional, Sislow, J, additional, Talasaz, A, additional, Tang, P, additional, Tewari, M, additional, Tomlins, S, additional, Toukhy, H, additional, Tseng, HR, additional, Tuck, M, additional, Tzou, A, additional, Vinson, J, additional, Wang, Y, additional, Wells, W, additional, Welsh, A, additional, Wilbanks, J, additional, Wolf, J, additional, Young, L, additional, Lee, JSH, additional, and Leiman, LC, additional
- Published
- 2017
- Full Text
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11. Enzalutamide in European and North American men participating in the AFFIRM trial
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Merseburger, AS, Scher, HI, Bellmunt, J, Miller, K, Mulders, PFA, Stenzl, A, Sternberg, CN, Fizazi, K, Hirmand, M, Franks, B, Haas, GP, De Bono, J, de Wit, Ronald, and Medical Oncology
- Subjects
SDG 3 - Good Health and Well-being ,Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15] - Abstract
Contains fulltext : 155187.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311). PATIENTS AND METHODS: Phase III, double-blind, placebo-controlled, multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis. RESULTS: Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry. CONCLUSION: This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions.
- Published
- 2015
12. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015
- Author
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Gillessen, S, Omlin, A, Attard, G, de Bono, JS, Efstathiou, E, Fizazi, K, Halabi, S, Nelson, PS, Sartor, O, Smith, MR, Soule, HR, Akaza, H, Beer, TM, Beltran, H, Chinnaiyan, AM, Daugaard, G, Davis, ID, De Santis, M, Drake, CG, Eeles, RA, Fanti, S, Gleave, ME, Heidenreich, A, Hussain, M, James, ND, Lecouvet, FE, Logothetis, CJ, Mastris, K, Nilsson, S, Oh, WK, Olmos, D, Padhani, AR, Parker, C, Rubin, MA, Schalken, JA, Scher, HI, Sella, A, Shore, ND, Small, EJ, Sternberg, CN, Suzuki, H, Sweeney, CJ, Tannock, IF, Tombal, B, Gillessen, S, Omlin, A, Attard, G, de Bono, JS, Efstathiou, E, Fizazi, K, Halabi, S, Nelson, PS, Sartor, O, Smith, MR, Soule, HR, Akaza, H, Beer, TM, Beltran, H, Chinnaiyan, AM, Daugaard, G, Davis, ID, De Santis, M, Drake, CG, Eeles, RA, Fanti, S, Gleave, ME, Heidenreich, A, Hussain, M, James, ND, Lecouvet, FE, Logothetis, CJ, Mastris, K, Nilsson, S, Oh, WK, Olmos, D, Padhani, AR, Parker, C, Rubin, MA, Schalken, JA, Scher, HI, Sella, A, Shore, ND, Small, EJ, Sternberg, CN, Suzuki, H, Sweeney, CJ, Tannock, IF, and Tombal, B
- Abstract
The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.
- Published
- 2015
13. A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan Index
- Author
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IMBRIACO, MASSIMO, Larson SM, Yeung HW, Mawlawi OR, Erdi Y, Venkatraman ES, Scher HI, Imbriaco, Massimo, Larson, Sm, Yeung, Hw, Mawlawi, Or, Erdi, Y, Venkatraman, E, and Scher, Hi
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Male ,Observer Variation ,Humans ,Prostatic Neoplasms ,Bone Neoplasms ,Prostate-Specific Antigen ,Radionuclide Imaging ,Severity of Illness Index ,Aged - Abstract
In this report, we describe a method for quantitative bone scan interpretation (the Bone Scan Index or BSI) in advanced prostate cancer. The BSI estimates the fraction of the skeleton that is involved by tumor, as well as the regional distribution of the metastases in the bones. The purpose of this report is to describe the development and validation of this method in terms of reproducibility and the application of BSI for determining extent of disease and monitoring disease progression. We analyzed 263 bone scans from 90 patients being studied under four protocols at Memorial Sloan-Kettering Cancer Center for progressive, androgen-independent prostate cancer (AIPC), who had bone scans as a part of their work-up. We determined: (a) the intraobserver and interobserver variability of the BSI; (b) the comparison between a change in BSI and prostate-specific antigen (PSA); (c) the regional distribution of bony metastases in early stage D prostate cancer (3% skeletal involvement); and (d) the rate of growth of bony metastases from prostate cancer. A cube root transformation of the percentage of involvement of the entire skeleton was used to stabilize the variance over the entire span of values (0-60% tumor involvement). The range of interobserver variability between readers was 0.2-0.5 times the cube root of the BSI (69 scans, 18 patients). Intraobserver variability was minimal when the same reader read the same scans after a 2-year interval, showing a correlation coefficient of 0.97 (reader 1) and 0.99 (reader 2), P0.001. There was a parallel rise in the BSI and the PSA in 24 patients (105 scans) treated for AIPC with hydrocortisone followed by suramin at PSA relapse (Pearson's moment correlation, 0.71). In a group of 27 patients with limited bone involvement by AIPC (i.e.,3% BSI), the distribution of early metastases was not random within the skeleton but was distributed in the central skeleton in a manner that matched the distribution of the normal adult bone marrow. Also, in a group of 21 patients (62 scans), the change in BSI as a function of time after diagnosis was explored graphically. The progression of bone scan changes in AIPC, from early involvement (3%) to late involvement, was fitted to a Gompertzian equation. It showed a rapid exponential growth phase, with an estimated tumor doubling time of 43 days when the BSI was 3.3%. The change in BSI rapidly approached a more gradual slope as the percentage of skeletal involvement increased. The BSI provides a reproducible new parameter for quantitative assessment of bone involvement by AIPC. These results suggest that the BSI will be useful for stratifying patients entering treatment protocols for extent of tumor involvement of bone. Although further study is necessary, serial bone scan BSI appears capable of quantifying both the progression of bony involvement by tumor as well as the response to treatment.
- Published
- 1998
14. Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients with androgen-independent prostate cancer
- Author
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Slovin SF, Scher HI, Divgi CR, Reuter V, Sgouros G, Moore M, Weingard K, Pettengall R, El Shirbiny A, Finn R, Bronstein J, Brett C, Milenic D, Dnistrian A, Shapiro L, Schlom J, Larson SM, IMBRIACO, MASSIMO, Slovin, Sf, Scher, Hi, Divgi, Cr, Reuter, V, Sgouros, G, Moore, M, Weingard, K, Pettengall, R, Imbriaco, Massimo, El Shirbiny, A, Finn, R, Bronstein, J, Brett, C, Milenic, D, Dnistrian, A, Shapiro, L, Schlom, J, and Larson, Sm
- Subjects
Aged, 80 and over ,Male ,Tomography, Emission-Computed, Single-Photon ,Neoplasms, Hormone-Dependent ,Antibodies, Monoclonal ,Pain ,Prostatic Neoplasms ,Middle Aged ,Prostate-Specific Antigen ,Radioimmunotherapy ,Combined Modality Therapy ,Bone and Bones ,Iodine Radioisotopes ,Interferon-gamma ,Treatment Outcome ,Antigens, Neoplasm ,Bone Marrow ,Humans ,Aged ,Glycoproteins ,Tomography, Emission-Computed - Abstract
To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients received 131I-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used. The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects. In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain. No patient showed a50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months. The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity. For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response.
- Published
- 1998
15. Treatment for metastatic urothelial cancer
- Author
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de Wit, Ronald, Bochner, BH, Scher, HI, and Medical Oncology
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SDG 3 - Good Health and Well-being - Published
- 2001
16. Survival of patients with advanced urothelial cancer treated with cisplatin-based chemotherapy
- Author
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Fosså, SD, primary, Sternberg, C, additional, Scher, HI, additional, Theodore, CH, additional, Mead, B, additional, Dearnaley, D, additional, Roberts, JT, additional, and Skovlund, E, additional
- Published
- 1996
- Full Text
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17. Androgen receptor antagonists in castration-resistant prostate cancer.
- Author
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Rathkopf D, Scher HI, Rathkopf, Dana, and Scher, Howard I
- Abstract
Persistent androgen receptor (AR) signaling despite low levels of serum androgens has been identified as a critical target for drug discovery in castration-resistant prostate cancer (CRPC). As proof of principle that the AR remains relevant in CRPC, 2 AR-targeted agents recently approved by the Food and Drug Administration-abiraterone and enzalutamide-have increased overall survival for patients with CRPC in the setting of prior chemotherapy. This review focuses on the AR and 2 direct antagonists, enzalutamide and ARN-509. These next-generation AR antagonists offer great promise for patients with advanced disease. Relative to conventional antiandrogens such as bicalutamide, they bind to the receptor with higher affinity, prevent nuclear translocation and DNA binding, and induce apoptosis without agonist activity in preclinical models. The success of these AR-targeted agents in the clinic has changed the landscape of therapy for patients with CRPC, and further therapeutic options building on this platform are currently in development. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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18. A phase I study of oral panobinostat alone and in combination with docetaxel in patients with castration-resistant prostate cancer.
- Author
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Rathkopf D, Wong BY, Ross RW, Anand A, Tanaka E, Woo MM, Hu J, Dzik-Jurasz A, Yang W, Scher HI, Rathkopf, Dana, Wong, Bryan Y, Ross, Robert W, Anand, Aseem, Tanaka, Erika, Woo, Margaret M, Hu, Jing, Dzik-Jurasz, Andy, Yang, Wei, and Scher, Howard I
- Abstract
Purpose: Histone deacetylase inhibitors have demonstrated anticancer activity against a range of tumors. We aimed to define the maximum tolerated dose, toxicity, activity, and pharmacokinetics of oral panobinostat, a pan-deacetylase inhibitor, alone and in combination with docetaxel for the treatment of castration-resistant prostate cancer (CRPC).Methods: Sixteen patients were enrolled, eight in each arm. Eligible patients had CRPC and adequate organ function. In arm I, oral panobinostat (20 mg) was administered on days 1, 3, and 5 for 2 consecutive weeks followed by a 1-week break. In arm II, oral panobinostat (15 mg) was administered on the same schedule in combination with docetaxel 75 mg/m(2) every 21 days.Results: Dose-limiting toxicities were grade 3 dyspnea (arm I) and grade 3 neutropenia >7 days (arm II). In arm I, all patients developed progressive disease despite accumulation of acetylated histones in peripheral blood mononuclear cells. In arm II, five of eight patients (63%) had a >or=50% decline in prostate-specific antigen (PSA), including one patient whose disease had previously progressed on docetaxel.Conclusions: Oral panobinostat with and without docetaxel is feasible, and docetaxel had no apparent effect on the pharmacokinetics of panobinostat. Since preclinical studies suggest a dose-dependent effect of panobinostat on PSA expression, and other phase I data demonstrate that intravenous panobinostat produces higher peak concentrations (>20- to 30-fold) and area under the curve (3.5x-5x), a decision was made to focus the development of panobinostat on the intravenous formulation to treat CRPC. [ABSTRACT FROM AUTHOR]- Published
- 2010
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19. The Brief Pain Inventory and its 'pain at its worst in the last 24 hours' item: clinical trial endpoint considerations.
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Atkinson TM, Mendoza TR, Sit L, Passik S, Scher HI, Cleeland C, and Basch E
- Published
- 2010
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20. Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer.
- Author
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Morris MJ, Pandit-Taskar N, Carrasquillo J, Divgi CR, Slovin S, Kelly WK, Rathkopf D, Gignac GA, Solit D, Schwartz L, Stephenson RD, Hong C, Delacruz A, Curley T, Heller G, Jia X, O'Donoghue J, Larson S, Scher HI, and Morris, Michael J
- Published
- 2009
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21. Phase II trial of docetaxel with rapid androgen cycling for progressive noncastrate prostate cancer.
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Rathkopf D, Carducci MA, Morris MJ, Slovin SF, Eisenberger MA, Pili R, Denmeade SR, Kelsen M, Curley T, Halter M, Collins C, Fleisher M, Heller G, Baker SD, Scher HI, Rathkopf, Dana, Carducci, Michael A, Morris, Michael J, Slovin, Susan F, and Eisenberger, Mario A
- Published
- 2008
- Full Text
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22. Phase I trial of the prostate-specific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer.
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Galsky MD, Eisenberger M, Moore-Cooper S, Kelly WK, Slovin SF, DeLaCruz A, Lee Y, Webb IJ, Scher HI, Galsky, Matthew D, Eisenberger, Mario, Moore-Cooper, Sandra, Kelly, W Kevin, Slovin, Susan F, DeLaCruz, Anthony, Lee, Yih, Webb, Iain J, and Scher, Howard I
- Published
- 2008
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23. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group.
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Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, and Hussain M
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- 2008
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24. Long-term toxicity monitoring via electronic patient-reported outcomes in patients receiving chemotherapy.
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Basch E, Iasonos A, Barz A, Culkin A, Kris MG, Artz D, Fearn P, Speakman J, Farquhar R, Scher HI, McCabe M, Schrag D, Basch, Ethan, Iasonos, Alexia, Barz, Allison, Culkin, Ann, Kris, Mark G, Artz, David, Fearn, Paul, and Speakman, John
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- 2007
25. Improving the decision to pursue a phase 3 clinical trial by adjusting for patient-specific factors in evaluating phase 2 treatment efficacy data.
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Heller G, Kattan MW, and Scher HI
- Abstract
Phase 2 clinical trials are undertaken to provide evidence of treatment efficacy and safety. A test statistic that accounts for individual patient risk in the patient population is proposed and applied to a phase 2 clinical trial for castrate metastatic prostate cancer. The test statistic is computed to compare, for each patient, the observed 2-year survival outcome to the predicted 2-year survival probability. A logistic regression model, developed using historical data in the same patient population, is used to adjust for patient risk in predicting the 2-year survival probability. Goodness-of-fit procedures are performed to ensure that a proper model is fit to the data. The test result is compared to the score test, the binomial exact test, and Fisher's exact test, all of which use the average 2-year survival probability in the population as the parameter of interest. The results demonstrate the benefit of risk adjustment in determining treatment efficacy in a single-arm phase 2 trial. By adjusting for patient risk, this method can provide a more precise assessment of phase 2 treatment efficacy, thereby improving the decision whether to proceed to a phase 3 clinical trial. [ABSTRACT FROM AUTHOR]
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- 2007
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26. Evaluation of an online platform for cancer patient self-reporting of chemotherapy toxicities.
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Basch E, Artz D, Iasonos A, Speakman J, Shannon K, Lin K, Pun C, Yong H, Fearn P, Barz A, Scher HI, McCabe M, Schrag D, Basch, Ethan, Artz, David, Iasonos, Alexia, Speakman, John, Shannon, Kevin, Lin, Kai, and Pun, Charmaine
- Abstract
The current mechanism for monitoring toxicity symptoms in cancer trials depends on a complex paper-based process. Electronic collection of patient-reported outcomes (PROs) may be more efficient and accurate. An online PRO platform was created including a simple data entry interface, real-time report generation, and an alert system to e-mail clinicians when patients self-report serious toxicities. Feasibility assessment involving 180 chemotherapy patients demonstrated high levels of use at up to 40 follow-up clinic visits per patient over 16 months (85% of patients at any given visit), with high levels of patient and clinician acceptance and satisfaction (>95%). Alerts were used as the basis for delayed chemotherapy treatments, dose modifications, and scheduling changes. These results demonstrate that online patient-reporting is a feasible strategy for chemotherapy toxicity symptom monitoring, and may improve safety and satisfaction with care. Ongoing multi-center research will evaluate the impact of this approach on clinical and administrative outcomes. [ABSTRACT FROM AUTHOR]
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- 2007
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27. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline.
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Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, Middleton R, Sharp SA, Smith TJ, Talcott J, Taplin M, Vogelzang NJ, Wade JL 3rd, Bennett CL, Scher HI, and American Society of Clinical Oncology
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- 2007
28. Second-line chemotherapy for prostate cancer: patient characteristics and survival.
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Beekman KW, Fleming MT, Scher HI, Slovin SF, Ishill NM, Heller G, and Kelly WK
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- 2005
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29. Prostate cancer: a dynamic illness with shifting targets.
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Shaffer DR, Scher HI, Shaffer, David R, and Scher, Howard I
- Abstract
Despite high response rates and palliative clinical benefits, androgen ablation does not cure advanced prostate cancer because of the inevitable emergence of resistant cells. Many new therapies under development for prostate cancer target pathways and molecules that contribute to the growth and survival of these cells. The rational and effective use of targeted therapies to eradicate resistant populations of tumour cells should be grounded on the premise that prostate cancer is a dynamic disease that evolves as it progresses, and that specific molecular determinants mediating sensitivity and resistance may be relevant only during specific states of the disease. Directed approaches must account for this changing dynamic so that clinical outcomes may be improved. [ABSTRACT FROM AUTHOR]
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- 2003
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30. Bone marrow aspiration for disseminated tumor cell detection: a must-have test or is the jury still out?
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Scher HI and Pantel K
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- 2009
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31. Serial transabdominal sonography of bladder cancer
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Dershaw, DD, primary and Scher, HI, additional
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- 1988
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32. New approaches to the treatment of bladder cancer.
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Scher HI
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- 1993
33. Anti-epidermal growth factor receptor monoclonal antibody cetuximab plus doxorubicin in the treatment of metastatic castration-resistant prostate cancer.
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Slovin SF, Kelly WK, Wilton A, Kattan M, Myskowski P, Mendelsohn J, and Scher HI
- Abstract
Purpose: An open-label, dose-escalating phase Ib/IIa trial was performed to establish a safety profile of ascending doses of cetuximab (IMC C225) in combination with doxorubicin administered weekly for 6 treatments in patients with metastatic castration-resistant prostate cancer. The secondary endpoint was to assess the efficacy of cetuximab in combination with doxorubicin as well as to determine the optimal biologic dose and the maximum tolerated dose. Patients and Methods: Patients in 8 groups received escalating doses of cetuximab 20-300 mg/m2 plus doxorubicin 15 or 20 mg/m2 given intravenously weekly for 6 consecutive weeks, followed by a 1-week observation period. A treatment response was defined as a > 50% decline in prostate-specific antigen (PSA) or regression of radiographically measurable disease. Results: Of the 36 treated patients, 25% had grade 2 neutropenia, 39% had leukopenia, and 44% had stomatitis at doxorubicin 20 mg/m2. Erythematous skin exanthema was seen in 38% of the patients. There was no significant regression of bone or soft tissue disease, but stable disease was observed in 20 (65%) of the 31 patients with bone disease and 14 (61%) of the 23 patients with lymph node disease. Declines in PSA were modest in the 36 patients, with 1 (2.7%) with an 80% decline from baseline, 2 (5.6%) with > 50% to < 80% declines, and 14 (39%) with progression. Median survival was approximately 18 months. Conclusion: In a heavily pretreated population of men with metastatic castration-resistant prostate cancer, this study of cetuximab/doxorubicin was associated with minimal PSA declines posttherapy, though median survival was longer compared to historical control groups. Further studies with cetuximab combined with more contemporary chemotherapy for castration-resistant prostate cancer might be warranted. [ABSTRACT FROM AUTHOR]
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- 2009
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34. Trial design for metastatic castration-resistant prostate cancer.
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Sonpavde G, Fleming MT, Hutson TE, Galsky MD, Scher HI, Halabi S, Tannock IF, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak DP, Kantoff P, Basch E, Kelly WK, Figg WD, and Small EJ
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- 2008
35. Psychostimulants for fatigue in prostate cancer.
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Roth AJ, Nelson CJ, Rosenfeld B, O'Shea N, Slovin S, Scher HI, and Breitbart W
- Published
- 2006
36. A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study.
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Ross RW, Galsky MD, Scher HI, Magidson J, Wassmann K, Lee GS, Katz L, Subudhi SK, Anand A, Fleisher M, Kantoff PW, Oh WK, Ross, Robert W, Galsky, Matthew D, Scher, Howard I, Magidson, Jay, Wassmann, Karl, Lee, Gwo-Shu Mary, Katz, Leah, and Subudhi, Sumit K
- Abstract
Background: Survival for patients with castration-resistant prostate cancer is highly variable. We assessed the effectiveness of a whole-blood RNA transcript-based model as a prognostic biomarker in castration-resistant prostate cancer.Methods: Peripheral blood was prospectively collected from 62 men with castration-resistant prostate cancer on various treatment regimens who were enrolled in a training set at the Dana-Farber Cancer Institute (Boston, MA, USA) from August, 2006, to June, 2008, and from 140 patients with castration-resistant prostate cancer in a validation set from Memorial Sloan-Kettering Cancer Center (New York, NY, USA) from August, 2006, to February, 2009. A panel of 168 inflammation-related and prostate cancer-related genes was assessed with optimised quantitative PCR to assess biomarkers predictive of survival.Findings: A six-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A) separated patients with castration-resistant prostate cancer into two risk groups: a low-risk group with a median survival of more than 34·9 months (median survival was not reached) and a high-risk group with a median survival of 7·8 months (95% CI 1·8-13·9; p<0·0001). The prognostic utility of the six-gene model was validated in an independent cohort. This model was associated with a significantly higher area under the curve compared with a clinicopathological model (0·90 [95% CI 0·78-0·96] vs 0·65 [0·52-0·78]; p=0·0067).Interpretation: Transcriptional profiling of whole blood yields crucial prognostic information about men with castration-resistant prostate cancer. The six-gene model suggests possible dysregulation of the immune system, a finding that warrants further study.Funding: Source MDX. [ABSTRACT FROM AUTHOR]- Published
- 2012
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37. Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302
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Brooke E. Wilson, Andrew J. Armstrong, Johann de Bono, Cora N. Sternberg, Charles J. Ryan, Howard I. Scher, Matthew R. Smith, Dana Rathkopf, Christopher J. Logothetis, Kim N. Chi, Robert J. Jones, Fred Saad, Peter De Porre, NamPhuong Tran, Peter Hu, Silke Gillessen, Joan Carles, Karim Fizazi, Anthony M. Joshua, Institut Català de la Salut, [Wilson BE] Princess Margaret Cancer Centre, Toronto, Canada. Faculty of Medicine, University of New South Wales, Kensington, Australia. Kinghorn Cancer Centre, St Vincents Hospital, Darlinghurst, Sydney, Australia. [Armstrong AJ] Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham NC, USA. [de Bono J] The Institute of Cancer Research and Royal Marsden Hospital, London, UK. [Sternberg CN] Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY 10021, USA. [Ryan CJ] Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA. [Scher HI] Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [Carles J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Male ,Cancer Research ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Abiraterone Acetate ,diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Prostate-Specific Antigen ,Pròstata - Càncer - Tractament ,Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant [DISEASES] ,Disease-Free Survival ,Metformin ,Prostatic Neoplasms, Castration-Resistant ,Treatment Outcome ,Metàstasi ,Oncology ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración [ENFERMEDADES] ,Antineoplastic Combined Chemotherapy Protocols ,Avaluació de resultats (Assistència sanitària) ,Humans ,Prednisone ,Castration ,Hydroxymethylglutaryl-CoA Reductase Inhibitors - Abstract
Abiraterone acetate; Metastatic castration-resistant prostate cancer; Metformin Acetato de abiraterona; Cáncer de próstata metastásico resistente a la castración; Metformina Acetat d'abiraterona; Càncer de pròstata resistent a la castració metastàtic; Metformina Background The associations of metformin and statins with overall survival (OS) and prostate specific antigen response rate (PSA-RR) in trials in metastatic castration-resistant prostate cancer remain unclear. Objective To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR. Design, setting and participant COU-AA-301 and COU-AA-302 patients were stratified by metformin and statin use. Cox proportional hazards models were used to estimate hazards ratio (HR) stratified by concomitant medications, and a random effects model was used to pool HR. We compared PSA-RR using Chi χ2 test. Results In COU-AA-301-AAP, metformin was associated with improved PSA-RR (41.1% versus 28.6%) but not prolonged OS. In COU-AA-301-placebo-P, there was no association between metformin and prolonged OS or PSA-RR. In COU-AA-302-AAP, metformin was associated with prolonged OS (adjHR 0.69, 95% CI 0.48–0.98) and improved PSA-RR (72.7% versus 60.0%). In COU-AA-302-P, metformin was associated with prolonged OS (adjHR 0.66, 95% CI 0.47–0.93). In pooled analysis, OS was prolonged among those treated with metformin (pooled HR 0.77, 95% CI 0.62–0.95).In COU-AA-301-AAP, statins were associated with an improved OS (adjHR 0.76, 95% CI 0.62–0.93), while there was no difference in COU-AA-301-P. There was no association with statins and OS in either COU-AA-302 groups. When pooling HR, OS was prolonged among those treated with statins (pooled HR 0.78, 95% CI 0.68–0.88). Conclusion Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP.
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- 2022
38. Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER
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Anthony M. Joshua, Andrew Armstrong, Megan Crumbaker, Howard I. Scher, Johann de Bono, Bertrand Tombal, Maha Hussain, Cora N. Sternberg, Silke Gillessen, Joan Carles, Karim Fizazi, Ping Lin, William Duggan, Jennifer Sugg, David Russell, Tomasz M. Beer, Institut Català de la Salut, [Joshua AM, Crumbaker M] Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, NSW, Australia. [Armstrong A] Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA. [Scher HI] Memorial Sloan Kettering Cancer Center, New York, NY, USA. [de Bono J] The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK. [Tombal B] Cliniques Universitaires Saint-Luc, Brussels, Belgium. [Carles J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, and UCL - (SLuc) Service d'urologie
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Male ,Cancer Research ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Antineoplastic Agents ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Disease-Free Survival ,Organic Chemicals::Amidines::Guanidines::Biguanides::Metformin [CHEMICALS AND DRUGS] ,Nitriles ,Phenylthiohydantoin ,Enzalutamide ,Humans ,Overall survival ,Prospective Studies ,Other subheadings::/therapeutic use [Other subheadings] ,Radiographic progression-free survival ,Castration-resistant prostate cancer ,Randomized Controlled Trials as Topic ,Retrospective Studies ,Otros calificadores::/uso terapéutico [Otros calificadores] ,compuestos orgánicos::amidinas::guanidinas::biguanidas::metformina [COMPUESTOS QUÍMICOS Y DROGAS] ,nutritional and metabolic diseases ,Statin ,diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Pròstata - Càncer - Tractament ,Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant [DISEASES] ,Metformin ,Prostatic Neoplasms, Castration-Resistant ,Treatment Outcome ,Oncology ,Metformina - Ús terapèutic ,neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración [ENFERMEDADES] ,Benzamides ,Avaluació de resultats (Assistència sanitària) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors - Abstract
Castration-resistant prostate cancer; Metformin; Overall survival Càncer de pròstata resistent a la castració; Metformina; Supervivència global Cáncer de próstata resistente a la castración; Metformina; Supervivencia global Background: Statins and metformin are commonly prescribed for patients, including those with prostate cancer. Preclinical and epidemiologic studies of each agent have suggested anti-cancer properties. Methods: Patient data from three randomised, double-blind, placebo-controlled, phase III studies evaluating enzalutamide (AFFIRM, PREVAIL and PROSPER) in patients with castration-resistant prostate cancer were included in this analysis. This post hoc, retrospective study examined the association of statin and metformin on radiographic progression-free survival (rPFS), metastasis-free survival (MFS), toxicity and overall survival (OS). After adjusting for available clinical prognostic variables, multivariate analyses were performed on pooled data from AFFIRM and PREVAIL, all three trials pooled, and each trial individually, to assess differential efficacy in these end-points associated with the baseline use of these medications. Results: In the multivariate analysis of the individual trials, OS and rPFS/MFS were not significantly influenced by statin or metformin use in AFFIRM or PROSPER. However, in PREVAIL, OS was significantly influenced by statin (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.59-0.89) and rPFS was significantly influenced by metformin (HR, 0.48; 95% CI 0.34-0.70). In pooled analyses, improved OS was significantly associated with statin use but not metformin use for AFFIRM+PREVAIL trials (HR 0.83; 95% CI 0.72-0.96) and AFFIRM+PREVAIL+PROSPER (HR 0.75; 95% CI 0.66-0.85). Conclusions: The association between statin or metformin use and rPFS, MFS and OS was inconsistent across three trials. Analyses of all three trials pooled and AFFIRM+PREVAIL pooled revealed that statin but not metformin use was significantly associated with a reduced risk of death in enzalutamide-treated patients. Additional prospective, controlled studies are warranted. This study was sponsored by Pfizer Inc. (New York, NY, USA) and Astellas Pharma, Inc. (Northbrook, IL, USA), the co-developers of enzalutamide. Medical writing and editorial support funded by the sponsors were provided by Stephanie Vadasz, PhD, and Dena McWain of Ashfield MedComms (an Ashfield Health company), Lauren Rainer, BSc, and Julie B. Stimmel, PhD, of Onyx (a Prime Global agency).
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- 2022
39. Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019
- Author
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Charles G. Drake, Matthew R. Smith, Almudena Zapatero, Charles J. Ryan, Philip W. Kantoff, Piet Ost, Inge M. van Oort, Ian D. Davis, Nicolas James, Matthew R. Sydes, Vedang Murthy, Martin E. Gleave, Maha Hussain, Michael S Hofman, Susan Halabi, Ignacio Duran, Oliver Sartor, Raya Leibowitz, Christopher P. Evans, Anders Bjartell, Ros Eeles, Mack Roach, Hiroyoshi Suzuki, Colin C. Pritchard, Levent Türkeri, Daniel Heinrich, Fred Saad, William Oh, Karim Fizazi, Himisha Beltran, Declan G. Murphy, Joe M. O'Sullivan, Thomas Steuber, Raja B. Khauli, Axel Heidenreich, Silke Gillessen, Eric J. Small, Robert E. Reiter, Juan Pablo Sade, Chris Logothetis, Tomasz M. Beer, Alberto Briganti, Mary-Ellen Taplin, Johann S. de Bono, Howard I. Scher, Eleni Efstathiou, Stefano Fanti, Darren M.C. Poon, Felix Y. Feng, Aurelius Omlin, Hind Mrabti, Chris Parker, Anwar R. Padhani, Kim N. Chi, Mark A. Rubin, Neal D. Shore, Nicolas Mottet, Alicia K. Morgans, Christopher Sweeney, Mark Frydenberg, Robert G. Bristow, Fernando C. Maluf, Robin Millman, Cora N. Sternberg, Ravindran Kanesvaran, Michael J. Morris, Noel W. Clarke, Gerhardt Attard, Alberto Bossi, Bertrand Tombal, Celestia S. Higano, Howard R. Soule, Acibadem University Dspace, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, and Gillessen S, Attard G, Beer TM, Beltran H, Bjartell A, Bossi A, Briganti A, Bristow RG, Chi KN, Clarke N, Davis ID, de Bono J, Drake CG, Duran I, Eeles R, Efstathiou E, Evans CP, Fanti S, Feng FY, Fizazi K, Frydenberg M, Gleave M, Halabi S, Heidenreich A, Heinrich D, Higano CTS, Hofman MS, Hussain M, James N, Kanesvaran R, Kantoff P, Khauli RB, Leibowitz R, Logothetis C, Maluf F, Millman R, Morgans AK, Morris MJ, Mottet N, Mrabti H, Murphy DG, Murthy V, Oh WK, Ost P, O'Sullivan JM, Padhani AR, Parker C, Poon DMC, Pritchard CC, Reiter RE, Roach M, Rubin M, Ryan CJ, Saad F, Sade JP, Sartor O, Scher HI, Shore N, Small E, Smith M, Soule H, Sternberg CN, Steuber T, Suzuki H, Sweeney C, Sydes MR, Taplin ME, Tombal B, Türkeri L, van Oort I, Zapatero A, Omlin A.
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Male ,Oncology ,Aging ,Advanced prostate cance ,Hormone-sensitive prostate cancer ,Imaging ,SALVAGE RADIATION-THERAPY ,Prostate cancer ,QUALITY-OF-LIFE ,Medicine and Health Sciences ,Overall survival ,Neoplasm Metastasis ,DISSECTION ,Cancer ,Castration-resistant prostate cancer ,Tumour genomic profiling ,Advanced prostate cancer ,Prostate Cancer ,RADICAL PROSTATECTOMY ,Consensus conference ,Progression-free survival ,TESTOSTERONE MEASUREMENTS ,Urology & Nephrology ,High-risk localised prostate cancer ,Prostate cancer treatment ,Local ,Practice Guidelines as Topic ,PHASE-II ,Overall ,profiling ,CLINICAL-TRIALS ,Urologic Diseases ,medicine.medical_specialty ,Urology ,Clinical Sciences ,Bone Neoplasms ,HOT FLASHES ,survival ,All institutes and research themes of the Radboud University Medical Center ,Internal medicine ,Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15] ,Castration-naïve prostate cancer ,Genetics ,medicine ,Humans ,LYMPH-NODE ,Neoplasm Staging ,business.industry ,Tumour genomic ,Prostatic Neoplasms ,Prostate-Specific Antigen ,medicine.disease ,Oligometastatic prostate cancer ,LYMPH-NODE DISSECTION ,Hormone sensitive prostate cancer ,Neoplasm Recurrence ,Good Health and Well Being ,ANDROGEN-DEPRIVATION THERAPY ,Neoplasm Recurrence, Local ,FREE SURVIVAL ,business - Abstract
Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence. Objective: To present the results from the APCCC 2019. Design, setting, and participants: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naive prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process. Results and limitations: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material. Conclusions: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.
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- 2020
40. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial.
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Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, Jones RJ, Goodman OB, Mainwaring PN, Sternberg CN, Efstathiou E, Gagnon DD, Rothman M, Hao Y, Liu CS, Kheoh TS, Haqq CM, Scher HI, de Bono JS, and Logothetis, Christopher J
- Abstract
Background: Bone metastases are a major cause of morbidity in metastatic castration-resistant prostate cancer. Abiraterone acetate potently disrupts intracrine androgen receptor signalling pathways implicated in the progression of the disease, including bone metastases. We assessed data for pain control and skeletal-related events prospectively collected as part of the randomised, phase 3 COU-AA-301 trial of abiraterone acetate plus prednisone versus placebo plus prednisone in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy.Methods: The COU-AA-301 trial enrolled patients with metastatic castration-resistant prostate cancer in whom one or two lines of chemotherapy (one docetaxel based) had been unsuccessful and who had Eastern Cooperative Oncology Group performance statuses of 2 or less. Pain intensity and interference of pain with daily activities were assessed with the Brief Pain Inventory-Short Form questionnaire at baseline, day 15 of cycle 1, and day 1 of each treatment cycle thereafter until discontinuation. We assessed, with prospectively defined response criteria that incorporated analgesic use, clinically meaningful changes in pain intensity and interference with daily living. We measured time to first occurrence of skeletal-related events, which we defined as pathological fracture, spinal cord compression, palliative radiation to bone, or bone surgery, and regularly assessed them throughout the study. Pain palliation was assessed in patients who had clinically significant baseline pain, whereas all other analyses were done in the overall intention-to-treat population. COU-AA-301 is registered with ClinicalTrials.gov, number NCT00638690.Findings: Median follow-up was 20·2 months (IQR 18·4-22·1). In patients with clinically significant pain at baseline, abiraterone acetate and prednisone resulted in significantly more palliation (157 of 349 [45·0%] patients vs 47 of 163 [28·8%]; p=0·0005) and faster palliation (median time to palliation 5·6 months [95% CI 3·7-9·2] vs 13·7 months [5·4-not estimable]; p=0·0018) of pain intensity than did prednisone only. Palliation of pain interference (134 of 223 [60·1%] vs 38 of 100 [38·0%], p=0·0002; median time to palliation of pain interference 1·0 months [95% CI 0·9-1·9] vs 3·7 months [2·7-not estimable], p=0·0004) and median duration of palliation of pain intensity (4·2 months [95% CI 3·0-4·9] vs 2·1 months [1·4-3·7]; p=0·0056) were significantly better with abiraterone acetate and prednisone than with prednisone only. In the overall population, median time to occurrence of first skeletal-related event was significantly longer with abiraterone acetate and prednisone than with prednisone only (25·0 months [95% CI 25·0-not estimable] vs 20·3 months [16·9-not estimable]; p=0·0001).Interpretation: In patients with metastatic castration-resistant prostate cancer previously treated with docetaxel, abiraterone acetate and prednisone offer significant benefits compared with prednisone alone in terms of pain relief, delayed pain progression, and prevention of skeletal-related events.Funding: Janssen Research & Development and Janssen Global Services. [ABSTRACT FROM AUTHOR]- Published
- 2012
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41. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study.
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Basch E, Iasonos A, McDonough T, Barz A, Culkin A, Kris MG, Scher HI, Schrag D, Basch, Ethan, Iasonos, Alexia, McDonough, Tiffani, Barz, Allison, Culkin, Ann, Kris, Mark G, Scher, Howard I, and Schrag, Deborah
- Abstract
Background: The Common Terminology Criteria for Adverse Events (CTCAE) are used as standard practice in trials of cancer treatments by clinicians to elicit and report toxic effects. Alternatively, patients could report this information directly as patient-reported outcomes, but the accuracy of these reports compared with clinician reports remains unclear. We aimed to compare the reporting of symptom severity reported by patients and clinicians.Methods: Between March and May, 2005, a questionnaire with 11 common CTCAE symptoms was given to consecutive outpatients and their clinicians (physicians and nurses) in lung and genitourinary cancer clinics in the Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Patients completed a version that used language adapted from the CTCAE for patient self-reporting. The results from the questionnaire were compared with clinician reporting of the same symptoms.Findings: Of 435 patients and their clinicians asked to take part in the study, 400 paired surveys were completed. For most symptoms, agreement between patient and clinician was high, and most discrepancies were within a grade difference of one point. Agreement was higher for symptoms that could be observable directly, such as vomiting and diarrhoea, than for more subjective symptoms, such as fatigue and dyspnoea. Differences in symptom reporting rarely would have changed treatment decisions or dosing, and patients assigned greater severity to symptoms more than did clinicians. No significant differences were recorded between the results when the questionnaire was completed by the patient before or after the clinician.Interpretation: Patient reporting of symptoms could add to the current approach to symptom monitoring in cancer treatment trials. Future research should assess the effect of self reporting on clinical outcomes and efficiency, and the use of real-time collection of patient-reported outcomes for early detection of potentially serious adverse events. [ABSTRACT FROM AUTHOR]- Published
- 2006
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42. Consensus on molecular imaging and theranostics in prostate cancer
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Frédéric Lecouvet, Hebert Alberto Vargas, Silke Gillessen, Ken Herrmann, Piet Ost, Sam Gledhill, Anwar R. Padhani, Silvia Minozzi, Hans-Jürgen Wester, Alberto Briganti, Ian Banks, Wim J.G. Oyen, Heindrik Van Poppel, Karim Fizazi, Jack A. Schalken, Noel W. Clarke, R. Jeroen A. van Moorselaar, Arturo Chiti, Rodney J. Hicks, Howard I. Scher, Bertrand Tombal, Uwe Haberkorn, Rodolfo Montironi, Gerald Antoch, Matthias Eiber, Ignasi Carrió, Wolfgang A. Weber, Johann S. de Bono, Stefano Fanti, Jochen Walz, Joe M. O'Sullivan, Fanti, S., Minozzi, S., Antoch, G., Banks, I., Briganti, A., Carrio, I., Chiti, A., Clarke, N., Eiber, M., De Bono, J., Fizazi, K., Gillessen, S., Gledhill, S., Haberkorn, U., Herrmann, K., Hicks, R. J., Lecouvet, F., Montironi, R., Ost, P., O'Sullivan, J. M., Padhani, A. R., Schalken, J. A., Scher, H. I., Tombal, B., van Moorselaar, R. J. A., Van Poppel, H., Vargas, H. A., Walz, J., Weber, W. A., Wester, H. -J., Oyen, W. J. G., and Fanti S, Minozzi S, Antoch G, Banks I, Briganti A, Carrio I, Chiti A, Clarke N, Eiber M, De Bono J, Fizazi K, Gillessen S, Gledhill S, Haberkorn U, Herrmann K, Hicks RJ, Lecouvet F, Montironi R, Ost P, O'Sullivan JM, Padhani AR, Schalken JA, Scher HI, Tombal B, van Moorselaar RJA, Van Poppel H, Vargas HA, Walz J, Weber WA, Wester HJ, Oyen WJG.
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Male ,Biochemical recurrence ,medicine.medical_specialty ,Consensus ,Delphi Technique ,medicine.medical_treatment ,Medizin ,Delphi method ,MEDLINE ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Theranostic Nanomedicine ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Predictive Value of Tests ,Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15] ,Biomarkers, Tumor ,medicine ,Humans ,Medical physics ,prostate cancer, theranostics ,medicine.diagnostic_test ,business.industry ,Clinical study design ,Prostatic Neoplasms ,medicine.disease ,Molecular Imaging ,Radiation therapy ,Treatment Outcome ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Cancer biomarkers ,business - Abstract
Contains fulltext : 200014.pdf (Publisher’s version ) (Closed access) Rapid developments in imaging and treatment with radiopharmaceuticals targeting prostate cancer pose issues for the development of guidelines for their appropriate use. To tackle this problem, international experts representing medical oncologists, urologists, radiation oncologists, radiologists, and nuclear medicine specialists convened at the European Association of Nuclear Medicine Focus 1 meeting to deliver a balanced perspective on available data and clinical experience of imaging in prostate cancer, which had been supported by a systematic review of the literature and a modified Delphi process. Relevant conclusions included the following: diphosphonate bone scanning and contrast-enhanced CT are mentioned but rarely recommended for most patients in clinical guidelines; MRI (whole-body or multiparametric) and prostate cancer-targeted PET are frequently suggested, but the specific contexts in which these methods affect practice are not established; sodium fluoride-18 for PET-CT bone scanning is not widely advocated, whereas gallium-68 or fluorine-18 prostate-specific membrane antigen gain acceptance; and, palliative treatment with bone targeting radiopharmaceuticals (rhenium-186, samarium-153, or strontium-89) have largely been replaced by radium-223 on the basis of the survival benefit that was reported in prospective trials, and by other systemic therapies with proven survival benefits. Although the advances in MRI and PET-CT have improved the accuracy of imaging, the effects of these new methods on clinical outcomes remains to be established. Improved communication between imagers and clinicians and more multidisciplinary input in clinical trial design are essential to encourage imaging insights into clinical decision making.
- Published
- 2018
43. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015
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Anwar R. Padhani, Susan Halabi, Avishay Sella, Stefano Fanti, Himisha Beltran, Bertrand Tombal, Rosalind A. Eeles, M. De Santis, Christopher Sweeney, David Olmos, Sten Nilsson, Charles G. Drake, Ian D. Davis, Matthew R. Smith, Nicholas D. James, Hideyuki Akaza, Oliver Sartor, Martin E. Gleave, Maha Hussain, Ken Mastris, Arul M. Chinnaiyan, Christopher J. Logothetis, Peter S. Nelson, Howard R. Soule, Gerhardt Attard, Hiroyoshi Suzuki, Jack A. Schalken, Gedske Daugaard, Chris Parker, Axel Heidenreich, Karim Fizazi, Ian F. Tannock, Silke Gillessen, Cora N. Sternberg, Tomasz M. Beer, Eleni Efstathiou, Mark A. Rubin, William Oh, Howard I. Scher, N. Shore, Frédéric Lecouvet, Aurelius Omlin, J.S. de Bono, Eric J. Small, Gillessen S, Omlin A, Attard G, de Bono JS, Efstathiou E, Fizazi K, Halabi S, Nelson PS, Sartor O, Smith MR, Soule HR, Akaza H, Beer TM, Beltran H, Chinnaiyan AM, Daugaard G, Davis ID, De Santis M, Drake CG, Eeles RA, Fanti S, Gleave ME, Heidenreich A, Hussain M, James ND, Lecouvet FE, Logothetis CJ, Mastris K, Nilsson S, Oh WK, Olmos D, Padhani AR, Parker C, Rubin MA, Schalken JA, Scher HI, Sella A, Shore ND, Small EJ, Sternberg CN, Suzuki H, Sweeney CJ, Tannock IF, Tombal B., UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - SSS/IREC/IMAG - Pôle d'imagerie médicale, UCL - (SLuc) Service de radiologie, and UCL - (SLuc) Service d'urologie
- Subjects
Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,MEDLINE ,Disease ,RC0254 ,Prostate cancer ,Internal medicine ,Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15] ,therapeutics ,medicine ,castration-resistant prostate cancer ,health care economics and organizations ,Gynecology ,business.industry ,Prostatectomy ,Consensus conference ,Hematology ,prostate cancer ,medicine.disease ,Clinical trial ,Prostate-specific antigen ,advanced prostate cancer ,Annals ,Docetaxel ,consensus ,Family medicine ,Special Articles ,Cancer biomarkers ,business ,castration-naïve prostate cancer ,medicine.drug - Abstract
The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed available evidence for the ten most important areas of controversy in advanced prostate cancer management. Recommendations based on expert opinion are presented. Detailed decisions on treatment will involve clinical consideration of disease extent and location, prior treatments, host factors, patient preferences and logistical and economic constraints., The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.
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- 2015
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44. Detection of bony metastases of androgen-independent prostate cancer by PET-FDG
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Hovanes Kalaigian, Steven M. Larson, Steven M. Horowitz, Dahlia Garza, Samuel D.J. Yeh, David Ready, Massimo Imbriaco, Howard I. Scher, Ronald D. Finn, Stanley J. Goldsmith, Jiaju Zhang, Yeh, Sd, Imbriaco, Massimo, Larson, Sm, Garza, D, Zhang, Jj, Kalaigian, H, Finn, Rd, Reddy, D, Horowitz, Sm, Goldsmith, Sj, and Scher, Hi
- Subjects
Male ,Cancer Research ,Fluorine Radioisotopes ,Neoplasms, Hormone-Dependent ,Bone Neoplasms ,Newly diagnosed ,Deoxyglucose ,Technetium Tc 99m Medronate ,Metastasis ,Prostate cancer ,Androgen independent prostate cancer ,Prostate ,Fluorodeoxyglucose F18 ,Carcinoma ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Fluorodeoxyglucose ,business.industry ,Prostatic Neoplasms ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Evaluation Studies as Topic ,Androgens ,Molecular Medicine ,business ,Nuclear medicine ,Increased Glycolysis ,Glycolysis ,medicine.drug ,Tomography, Emission-Computed - Abstract
Fourteen F-18 fluorodeoxyglucose (FDG) studies were carried out in 13 patients known to have bony metastases from carcinoma of the prostate. One patient was newly diagnosed. The remaining patients had various types of therapy and were considered hormonally resistant. The average age was 67. All patients had extensive bony metastases shown on the conventional Tc99m-MDP bone scans. Only about 18% of bony lesions apparent on the conventional bone scans showed corresponding increase of FDG uptake. Anatomical correlation was performed by using co-registered images of SPECT and PET in the same area. The positive FDG uptake was not related to the duration of illness, level of PSA, previous therapy, and magnitude of disease involvement. It appears that only a small percentage of bony metastases is associated with increased glycolysis. It is possible that other metabolic processes are more important than glycolysis for providing prostate cancer with a source of energy and nutrients.
- Published
- 1996
45. Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer
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Massimo Imbriaco, P. Ouyang, Zuo-Feng Zhang, C. Ding, I. D. Horak, Howard I. Scher, Wm. Kevin Kelly, Maxine Sun, Steven M. Larson, Henry Yeung, Paul Sabbatini, M. Conolly, A. B. Kremer, Sabbatini, P, Larson, Sm, Kremer, A, Zhang, Zf, Sun, M, Yeung, H, Imbriaco, Massimo, Horak, I, Conolly, M, Ding, C, Ouyang, P, Kelly, Wk, and Scher, Hi
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,medicine.drug_class ,Bone Neoplasms ,Technetium Tc 99m Medronate ,law.invention ,Metastasis ,Prostate cancer ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Prostate ,Prednisone ,Internal medicine ,medicine ,Humans ,Liarozole ,Radionuclide Imaging ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Performance status ,business.industry ,Prostatic Neoplasms ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Androgen ,Prognosis ,Survival Analysis ,medicine.anatomical_structure ,chemistry ,Androgens ,business ,Algorithms ,medicine.drug - Abstract
PURPOSE: To evaluate the prognostic significance of a bone scan index (BSI) based on the weighted proportion of tumor involvement in individual bones, in relation to other factors and to survival in patients with androgen-independent prostate cancer. PATIENTS AND METHODS: Baseline radionuclide bone scans were reviewed in 191 assessable patients with androgen-independent disease who were enrolled onto an open, randomized trial of liarozole versus prednisone. The extent of skeletal involvement was assessed by scoring each scan using the BSI and independently according to the number of metastatic lesions. The relationship of the scored bone involvement to other known prognostic factors was explored in single- and multiple-variable analyses. RESULTS: In single-variable analyses, the pretreatment factors found to be associated with survival were age (P = .0446), performance status (P = .0005), baseline prostate-specific antigen (P = .0001), hemoglobin (P = .0001), alkaline phosphatase (P = .0002), AST (P = .0021), lactate dehydrogenase (P = .0001), and treatment (P = .0098). The extent of osseous disease was significant using both the BSI (P = .0001) and the number of lesions present (P = .0001). In multiple-variable proportional hazards analyses, only BSI, age, hemoglobin, lactate dehydrogenase, and treatment arm were associated with survival. When the patient population was divided into three equal groups, with BSI values of < 1.4%, 1.4% to 5.1%, and > 5.1%, median survivals of 18.3, 15.5, and 8.1 months, respectively, were observed (P = .0079). CONCLUSION: The BSI quantifies the extent of skeletal involvement by tumor. It allows the identification of patients with distinct prognoses for stratification in clinical trials. Further study is needed to assess the utility of serial BSI determinations in monitoring treatment effects. The BSI may be particularly useful in the evaluation of agents for which prostate-specific antigen changes do not reflect clinical outcomes accurately.
46. Two decades of advances in clinical oncology - lessons learned and future directions.
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Banerjee S, Booth CM, Bruera E, Büchler MW, Drilon A, Fry TJ, Ghobrial IM, Gianni L, Jain RK, Kroemer G, Llovet JM, Long GV, Pantel K, Pritchard-Jones K, Scher HI, Tabernero J, Weichselbaum RR, Weller M, and Wu YL
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- 2024
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47. Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer.
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Liu SY, Erazo T, Jee J, Arfe A, Gupta A, Pike LRG, Santini FC, Daly B, Schoenfeld A, Eichholz J, Johnson K, Martinez A, Sui J, Riaz N, Chang J, Yang SR, Travis W, Arcila ME, Guo J, Gagne E, Garg K, Baehner F, Lee NY, Drilon A, Kris MG, Scher HI, Razavi P, Gomez DR, Jones DR, Rudin CM, Chandarlapaty S, Isbell JM, and Li BT
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- Humans, Female, Male, Middle Aged, Aged, Retrospective Studies, Adult, Biomarkers, Tumor genetics, Aged, 80 and over, Lung Neoplasms genetics, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Circulating Tumor DNA genetics, Circulating Tumor DNA blood, Receptor, ErbB-2 genetics, Mutation, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology
- Abstract
Introduction: No definitive answers currently exist regarding optimal first-line therapy for HER2-mutant NSCLC. Access to rapid tissue sequencing is a major barrier to precision drug development in the first-line setting. ctDNA analysis has the potential to overcome these obstacles and guide treatment., Methods: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing and received systemic therapy at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx LungTM assay. Primary endpoints were time to the next treatment (TTNT) and overall survival (OS)., Results: Sixty-three patients were included in the primary analysis. Chemoimmunotherapy (33/63, 52.4 %) was the predominant first-line treatment with a median TTNT of 5.1 months (95 %CI 4.1 - 6.1) whereas 55.0 % (22/40) of patients who received second-line T-DXd obtained a median TTNT of 9.2 m (95 % CI, 0-22.2). Plasma ctDNA was tested before first-line therapy in 40 patients with a median OS of 28.0 months (95 % CI 21-34), in whom 31 patients (78.0 %) had detectable ctDNA. HER2 mutations were detected on ctDNA with a median turnaround time of 13 days, occasionally co-occurred with EGFR and MET alterations and were tracked longitudinally correlating with treatment response. Patients with detectable baseline ctDNA had significantly shorter OS (hazard ratio (HR), 5.25; 95 % CI, 1.2-23.9; p = 0.019)., Conclusion: Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bob T. Li has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly. He has received research grants to his institution from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Jiangsu Hengrui Pharmaceuticals, Lilly, Nuvalent, and Revolution Medicines. He has received academic travel support from Amgen. He is an inventor on three institutional patents at MSK (US62/685,057, US62/514,661, US63/424,813) and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. Alexander Drilon declared as follows: Honoraria: 14ner/Elevation Oncology, Amgen, Abbvie, ArcherDX, AstraZeneca, Beigene, BergenBio, Blueprint Medicines, Bristol Myers Squibb, Chugai Pharmaceutical, EcoR1, EMD Serono, Entos, Exelixis, Helsinn, Hengrui Therapeutics, Ignyta/Genentech/Roche, Janssen, Loxo/Bayer/Lilly, Merus, Monopteros, MonteRosa, Novartis, Nuvalent, Pfizer, Prelude, Regeneron, Repare RX, Springer Healthcare, Takeda/Ariad/Millenium, Treeline Bio, TP Therapeutics, Tyra Biosciences, Verastem. Advisory Boards: Bayer, MonteRosa, Abbvie, EcoR1 Capital, LLC, Amgen, Helsinn, Novartis, Lilly, AnHeart Therapeutics. Consulting: MonteRosa, Innocare, Boundless Bio, Treeline Bio, Nuvalent, 14ner/Elevation Oncology, Entos, Prelude. Associated Research Paid to Institution: Foundatin Medicine, GlaxoSmithKlein, Teva, Taiho, PharmaMar. Equity: mBrace. Copyright: Selpercatinib-Osimertinib (filed/pending). Royalties: Wolters Kluwer; Other (Food/Beverage): Merck, Puma, Merus, Boehringer Ingelheim; CME Honoraria: Answers in CME, Applied Pharmaceutical Science, Inc, AXIS, Clinical Care Options, Doc Congress, EPG Health, Harborside Nexus, I3 Health, Imedex, Liberum, Medendi, Medscape, Med Learning, MedTalks, MJH Life Sciences, MORE Health, Ology, OncLive, Paradigm, Peerview Institute, PeerVoice, Physicians Education, Projects in Knowledge, Resources, Remedica Ltd, Research to Practice, RV More, Targeted Oncology, TouchIME, WebMD. Sarat Chandarlapaty has received institutional grant/funding from Daiichi-Sankyo, AstraZeneca, and Lilly, Shares/Ownership interests in Odyssey Biosciences, Effector Therapeutics, and Totus Medicines, and consultation/Ad board/Honoraria from AstraZeneca, Daiichi-Sankyo, Novartis, Neogenomics, Nuvalent, Blueprint, SAGA Diagnostics, and Effector Therapeutics. Jiannan Guo is a former employee of Resolution Bioscience. Eric Gagne, Kavita Garg and Frederick Baehner are employees of Exact Sciences. All remaining authors have declared no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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48. Androgen Deprivation Therapy Drives a Distinct Immune Phenotype in Localized Prostate Cancer.
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Dallos MC, Obradovic AZ, McCann P, Chowdhury N, Pratapa A, Aggen DH, Gaffney C, Autio KA, Virk RK, De Marzo AM, Antonarakis ES, Scher HI, Drake CG, and Rathkopf DE
- Abstract
Purpose: Androgen deprivation therapy (ADT) remains the backbone of prostate cancer treatment. Beyond suppression of testosterone and tumor cell growth, emerging evidence suggests ADT also modulates the immune tumor microenvironment (TME). However, a more precise understanding of the timing and intricacies of these immunological shifts is needed., Experimental Design: Here we analyzed 49 primary prostate cancers, comparing those surgically removed either without treatment or following treatment with degarelix at 4, 7, and 14 days pre-surgery. Utilizing next-generation DNA and RNA sequencing, and multiplexed immunofluorescence, we examined alterations in immune phenotypes in the presence or absence of ADT., Results: Our findings reveal that ADT rapidly transforms the typically bland prostate TME into an inflamed environment within days. Notably, we observed an increase in activated CD8 T-cells along with an increase in suppressive regulatory T-cells (Tregs). We also found an expansion of the myeloid compartment, particularly pro-inflammatory M1-like tumor-associated macrophages. Intriguingly, discernable changes which have not previously been described also occurred in tumor cells, including upregulation of antigen presentation by MHC class I and II and, unexpectedly, a decrease in the "don't eat me" signal CD47., Conclusions: These observations underscore the critical role of timing and disease context in order to optimize the therapeutic efficacy of immune modulators combined with androgen ablation, for which the presurgical neoadjuvant setting may be ideal. Our findings warrant future prospective validation, which is currently underway.
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- 2024
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49. Neoadjuvant androgen deprivation therapy with or without Fc-enhanced non-fucosylated anti-CTLA-4 (BMS-986218) in high risk localized prostate cancer: a randomized phase 1 trial.
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Ager CR, Obradovic A, McCann P, Chaimowitz M, Wang ALE, Shaikh N, Shah P, Pan S, Laplaca CJ, Virk RK, Hill JC, Jugler C, DeFranco G, Bhattacharya N, Scher HI, DeCastro GJ, Anderson CB, McKiernan JM, Spina CS, Stein MN, Runcie K, Drake CG, Califano A, and Dallos MC
- Abstract
Men with high-risk localized prostate cancer exhibit high rates of post-surgical recurrence. In these patients, androgen deprivation therapy (ADT) is immunomodulatory, however increased infiltration of regulatory T cells (Tregs) may limit the antitumor immune effects of ADT. We designed a neoadjuvant clinical trial to test whether BMS-986218 - a next-generation non-fucosylated anti-CTLA-4 antibody engineered for enhanced antibody-dependent cellular cytotoxicity or phagocytosis (ADCC/P) - depletes intratumoral Tregs and augments the response to ADT. In this single-center, two-arm, open-label study, 24 men with high-risk localized prostate cancer were randomized to receive a single dose of ADT with or without two pre-operative doses of BMS-986218 (anti-CTLA4-NF) prior to radical prostatectomy. Treatment was well tolerated and feasible in the neoadjuvant setting. A secondary clinical outcome was the rate of disease recurrence, which was lower than predicted in both arms. Mechanistically, anti-CTLA4-NF reduced ADT-induced Treg accumulation through engagement of CD16a/ FCGR3A on tumor macrophages, and depth of Treg depletion was quantitatively associated with clinical outcome. Increased intratumoral dendritic cell (DC) frequencies also associated with lack of recurrence, and pre-clinical data suggest ADCC/P-competent anti-CTLA-4 antibodies elicit activation and expansion of tumor DCs. Patients receiving anti-CTLA4-NF also exhibited phenotypic signatures of enhanced antitumor T cell priming. In total, this study provides the first-in-human evidence of Treg depletion by glycoengineered antibodies targeting CTLA-4 in humans and their potential in combination with ADT in prostate cancer patients with high-risk of recurrence., Competing Interests: Conflicts of Interest: C.G.D is a co-inventor on patents licensed from Johns Hopkins University to BMS and Janssen. He is currently a paid employee of JnJ Innovative Medicine. A.C. is founder, equity holder, consultant, and director of DarwinHealth Inc., which has licensed IP related to these algorithms from Columbia University. Columbia University is an equity holder in DarwinHealth Inc.
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- 2024
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50. Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer.
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Lenis AT, Ravichandran V, Brown S, Alam SM, Katims A, Truong H, Reisz PA, Vasselman S, Nweji B, Autio KA, Morris MJ, Slovin SF, Rathkopf D, Danila D, Woo S, Vargas HA, Laudone VP, Ehdaie B, Reuter V, Arcila M, Berger MF, Viale A, Scher HI, Schultz N, Gopalan A, Donoghue MTA, Ostrovnaya I, Stopsack KH, Solit DB, and Abida W
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- Humans, Male, Aged, Middle Aged, Biomarkers, Tumor genetics, Aged, 80 and over, DNA Mismatch Repair, Antibodies, Monoclonal, Humanized therapeutic use, Microsatellite Instability, Immune Checkpoint Inhibitors therapeutic use, Prostatic Neoplasms genetics, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology, Prostatic Neoplasms immunology, Prostatic Neoplasms mortality, Mutation
- Abstract
Purpose: Patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, and response to immune checkpoint blockade (ICB) in patients with MSI-H/dMMR and TMB-H prostate cancers without MSI [TMB-H/microsatellite stable (MSS)]., Experimental Design: We sequenced 3,244 tumors from 2,257 patients with prostate cancer. MSI-H/dMMR prostate cancer was defined as an MSIsensor score ≥10 or MSIsensor score ≥3 and <10 with a deleterious MMR alteration. TMB-H was defined as ≥10 mutations/megabase. PSA50 and RECIST responses were assigned. Overall survival and radiographic progression-free survival (rPFS) were compared using log-rank test., Results: Sixty-three (2.8%) men had MSI-H/dMMR, and 33 (1.5%) had TMB-H/MSS prostate cancers. Patients with MSI-H/dMMR and TMB-H/MSS tumors more commonly presented with grade group 5 and metastatic disease at diagnosis. MSI-H/dMMR tumors had higher TMB, indel, and neoantigen burden compared with TMB-H/MSS. Twenty-seven patients with MSI-H/dMMR and 8 patients with TMB-H/MSS tumors received ICB, none of whom harbored polymerase epsilon (polE) catalytic subunit mutations. About 45% of patients with MSI-H/dMMR had a RECIST response, and 65% had a PSA50 response. No patient with TMB-H/MSS had a RECIST response, and 50% had a PSA50 response. rPFS tended to be longer in patients with MSI-H/dMMR than in patients with TMB-H/MSS who received immunotherapy. Pronounced differences in genomics, TMB, or MSIsensor score were not detected between MSI-H/dMMR responders and nonresponders., Conclusions: MSI-H/dMMR prostate cancers have greater TMB, indel, and neoantigen burden than TMB-H/MSS prostate cancers, and these differences may contribute to profound and durable responses to ICB., (©2024 American Association for Cancer Research.)
- Published
- 2024
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- View/download PDF
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