Casey W Williamson1, Igor Sirák2, Ronghui Xu3, Lorraine Portelance4, Lichun Wei5, Rafal Tarnawski6, Umesh Mahantshetty7, Elena S Heide8, Catheryn M Yashar1, Michael T McHale3, Walter Bosch9, Jessica Lowenstein10, Cheryl C Saenz3, Steve Plaxe3, Ramez Eskander3, John Einck1, Arno J Mundt1, Jyoti Mayadev11, Loren K Mell12. 1. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California. 2. Department of Oncology and Radiotherapy, University Hospital, Hradec Kralove, Czech Republic. 3. University of California San Diego, La Jolla, California. 4. University of Miami, Miami, Florida. 5. Xijing Hospital, Xian, China. 6. Marie Sklodowska Cancer Center and Institute of Oncology, Gliwice, Poland. 7. Tata Memorial Centre, Parel, Mumbai, India. 8. University of California Irvine, Irvine, California. 9. Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri. 10. University of Texas MD Anderson Cancer Center, Houston, Texas. 11. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California; La Jolla Center for Precision Radiation Medicine, La Jolla, California. 12. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California; La Jolla Center for Precision Radiation Medicine, La Jolla, California. Electronic address: lmell@ucsd.edu.
Abstract
PURPOSE: To test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS. RESULTS: In total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P = .048) and in the combined cohort (13% vs 35%, χ2P = .01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P = .216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group. CONCLUSIONS: PET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.
PURPOSE: To test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS. RESULTS: In total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P = .048) and in the combined cohort (13% vs 35%, χ2P = .01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P = .216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group. CONCLUSIONS: PET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.
Authors: Tahir Yusufaly; Austin Miller; Ana Medina-Palomo; Casey W Williamson; Hannah Nguyen; Jessica Lowenstein; Charles A Leath; Ying Xiao; Kevin L Moore; Katherine M Moxley; Carlos M Chevere-Mourino; Tony Y Eng; Tarrick Zaid; Loren K Mell Journal: Int J Radiat Oncol Biol Phys Date: 2020-07-03 Impact factor: 7.038
Authors: Nan Li; Sonal S Noticewala; Casey W Williamson; Hanjie Shen; Igor Sirak; Rafal Tarnawski; Umesh Mahantshetty; Carl K Hoh; Kevin L Moore; Loren K Mell Journal: Radiother Oncol Date: 2017-05 Impact factor: 6.280
Authors: Tsz Him So; Sik Kwan Chan; Wing Lok Chan; Horace Choi; Chi Leung Chiang; Victor Lee; Tai Chung Lam; Ian Wong; Simon Law; Dora Kwong; Feng Ming Spring Kong; Jian Yue Jin; Ka On Lam Journal: Adv Radiat Oncol Date: 2020-04-19
Authors: Loren K Mell; Ronghui Xu; Catheryn M Yashar; Michael T McHale; John P Einck; Jyoti Mayadev; Euyhyun Lee; Pratibha Binder; Dominique Rash; Ramez Eskander; Elena S Heide; Steven C Plaxe; Arno J Mundt; Cheryl C Saenz Journal: Int J Radiat Oncol Biol Phys Date: 2020-04-22 Impact factor: 8.013
Authors: Zhenfeng Yu; Yuanyuan He; Timo Schomann; Kefan Wu; Yang Hao; Ernst Suidgeest; Hong Zhang; Christina Eich; Luis J Cruz Journal: Pharmaceutics Date: 2022-04-11 Impact factor: 6.525