BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes. METHODS: We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration's RoB tool. Random-effects models were used for the meta-analysis. RESULTS: A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes. CONCLUSIONS: The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.

• Klíčová slova
• Bone marrow, Chemoradiotherapy, Cisplatin, Haematologic toxicity, Pelvic bones,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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.

• MeSH
• cisplatina terapeutické užití   MeSH
• kostní dřeň účinky záření   MeSH
• lidé MeSH
• nádory děložního čípku * diagnostické zobrazování   farmakoterapie   patologie   radioterapie   MeSH
• pozitronová emisní tomografie MeSH
• radioterapie řízená obrazem MeSH
• radioterapie s modulovanou intenzitou * škodlivé účinky   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• cisplatina MeSH

BACKGROUND: Three-weekly high-dose cisplatin (100 mg/m2) is considered the standard systemic regimen given concurrently with postoperative or definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, due to unsatisfactory patient tolerance, various weekly low-dose schedules have been increasingly used in clinical practice. The aim of this meta-analysis was to compare the efficacy, safety, and compliance between these two approaches. MATERIALS AND METHODS: We systematically searched literature for prospective trials of patients with LA-SCCHN who received postoperative or definitive conventionally fractionated concurrent chemoradiation. Radiation doses were usually 60-66 gray (Gy) in the postoperative setting and 66-70 Gy in the definitive setting. Standard, three-weekly high-dose cisplatin (100 mg/m2, 3 doses) was compared with the weekly low-dose protocol (≤50 mg/m2, ≥6 doses). The primary endpoint was overall survival. Secondary outcomes comprised response rate, acute and late adverse events, and treatment compliance. RESULTS: Fifty-two studies with 4,209 patients were included in two separate meta-analyses according to the two clinical settings. There was no difference in treatment efficacy as measured by overall survival or response rate between the chemoradiation settings with low-dose weekly and high-dose three-weekly cisplatin regimens. In the definitive treatment setting, the weekly regimen was more compliant and significantly less toxic with respect to severe (grade 3-4) myelosuppression (leukopenia p = .0083; neutropenia p = .0024), severe nausea and/or vomiting (p < .0001), and severe nephrotoxicity (p = .0099). Although in the postoperative setting the two approaches were more equal in compliance and with clearly less differences in the cisplatin-induced toxicities, the weekly approach induced more grade 3-4 dysphagia (p = .0026) and weight loss (p < .0001). CONCLUSION: In LA-SCCHN, current evidence is insufficient to demonstrate a meaningful survival difference between the two dosing regimens. Prior to its adoption into routine clinical practice, the low-dose weekly approach needs to be prospectively compared with the standard three-weekly high-dose schedule. IMPLICATIONS FOR PRACTICE: Given concurrently with conventional radiotherapy in locally advanced head and neck cancer, high-dose three-weekly cisplatin has often been replaced with weekly low-dose infusions to increase compliance and decrease toxicity. The present meta-analysis suggests that both approaches might be equal in efficacy, both in the definitive and postoperative settings, but differ in toxicity. However, some toxicity data can be influenced by unbalanced representation, and the conclusions are not based on adequately sized prospective randomized studies. Therefore, low-dose weekly cisplatin should not be used outside clinical trials but first prospectively studied in adequately sized phase III trials versus the high-dose three-weekly approach.

• Klíčová slova
• Cisplatin, Head and neck cancer, Radiotherapy, Survival, Toxicity,
• MeSH
• adherence pacienta statistika a číselné údaje   MeSH
• chemoradioterapie škodlivé účinky   metody   MeSH
• cisplatina aplikace a dávkování   MeSH
• dávka záření MeSH
• dlaždicobuněčné karcinomy hlavy a krku MeSH
• frakcionace dávky záření MeSH
• klinické zkoušky jako téma MeSH
• leukopenie chemicky indukované   epidemiologie   MeSH
• lidé MeSH
• nádory hlavy a krku mortalita   patologie   terapie   MeSH
• nauzea chemicky indukované   epidemiologie   MeSH
• neutropenie chemicky indukované   epidemiologie   MeSH
• rozvrh dávkování léků MeSH
• spinocelulární karcinom mortalita   patologie   terapie   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvracení chemicky indukované   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• srovnávací studie MeSH
• systematický přehled MeSH
• Názvy látek
• cisplatina MeSH