Advances in Radiation Oncology for the Treatment of Cervical Cancer
Abstract
:1. Introduction
2. Material and Methods
2.1. Advances in External Beam Radiotherapy
2.1.1. From 2D Radiotherapy to 3D-Conformal Radiotherapy (3DCRT)
2.1.2. Intensity Modulated Radiotherapy (IMRT) for the Treatment of Locally Advanced Cervical Cancer
2.1.3. Adaptive External Beam Radiotherapy
2.2. Advances in Brachytherapy for the Treatment of Locally Advanced Cervical Cancer
2.2.1. From 2D-Brachytherapy (2D-BT) to 3D Image Guided Adaptive Brachytherapy (3D-IGABT)
2.2.2. Outcomes of 3D Image-Guided Brachytherapy (3D-IGABT)
2.3. Stereotactic Body Radiotherapy in the Treatment of Locally Advanced Cervical Cancer
2.4. Immunotherapy as an Adjunct to Chemoradiation
3. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Trial ID | Design | Eligibility | Intervention | Details | Outcome Measures | Status |
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NCT04221945 (KEYNOTE-A18/ENGOT-cx11/GOG-3047) | Randomized Phase III | FIGO 2014 Stage IB2–IIB (with N+ disease) or FIGO 2014 Stages III–IVA cervical cancer | Pembrolizumab + CRT + BT vs. Placebo + CRT + BT | Pembrolizumab 200 mg IV vs. placebo q3 weeks × 5 cycles, followed by Pembrolizumab 400 mg IV vs. placebo q6 weeks × 15 cycles + Cisplatin qweek during EBRT + BT (to a total RT dose of 80 Gy for volume directed and 75 Gy for point directed | Primary: PFS (RECIST 1.1), OS Secondary: 2-year PFS, 3-year OS, CR at 12 weeks, ORR, PFS and OS in PD-L1+ patients, PFS after next line treatment, EORTC QLQ-C30, QLQ-CX24, and safety | Recruiting |
NCT02635360 | Randomized Phase II | Confirmed cervical Cancer (excluded: distant metastases) | Pembrolizumab following CRT vs. Pembrolizumab concurrent with CRT | CRT followed by Pembrolizumab 200 mg IV q21 days × 3 months Vs Pembrolizumab 200 mg IV q21 days at the same time as CRT | Primary: Change in immunologic markers, Incidence of DLTs Secondary: Metabolic Response Rate on PET/CT, Incidence of distant metastases, PFS, OS | Active, not recruiting |
NCT03738228 | Multi-arm Phase I | Stage IB2, II, IIIB, or IVA cervical cancer | Atezolizumab + CRT + BT | Arm A: Atezolizumab IV on days -21, 0, and 21 + Cisplatin qweek concurrent with EBRT (Monday–Friday) × 5 weeks + IGBT at week 4 or 5 Arm B: Atezolizumab IV on days -21, 0, and 42 + Cisplatin qweek concurrent with EBRT (Monday-Friday) × 5 weeks + IGBT at week 4 or 5 | Primary: T cell receptor beta (TCRB) clonal expansion in peripheral blood Secondary: Incidence of DLTs, Frequency and severity of AEs as per CTCAE v5, TCR clonality, diversity, and frequency in peripheral blood and tissue, PD-L1 expression in tissue | Active, not recruiting |
NCT03612791 (ATEZOLACC) | Randomized Phase II | FIGO 2009 stage IB1–IIA (N+) or stage IIB–IVA cervical cancer | Atezolizumab + SoC CRT + BT vs. SoC CRT + BT | Atezolizumab 1200 mg IV q3 week starting on week1 and continued as adjuvant treatment for a max of 20 cycles + Cisplatin qweek concurrent with pelvic +/− para-aortic EBRT by IMRT (45Gy/25Fx) + BT starting at week 7 (85 Gy EQD2 to HR-CTV) vs concurrent CRT +BT alone as above | Primary: PFS (RECIST 1.1) | Recruiting |
NCT03527264 (BrUOG 355) | Non-randomized Phase II | Cervical cancer | Nivolumab induction + Nivolumab concurrent with chemoradiation + Nivolumab maintenance | Cohort 1A: Nivolumab induction (240 mg IV × 2 doses) + Nivolumab 240 mg IV q14 days for 3 doses concurrent on day 1 with Cisplatin qweek and EBRT (45 Gy/25 Fx) Cohort 1B: As above but with EFRT Cohort 2: Nivolumab induction as above + CRT w/o Nivolumba + Maintenance Nivolumab (480 mg IV q4weeks × 2 years) Cohort 3: Nivolumab induction + Nivolumab with CRT + Maintenance Nivolumab | Primary: Feasibility of the incorporation of nivolumab with weekly cisplatin and EFRT or WPRT in women with cervical cancer (acute toxicities as per CTCAE v4.0), PFS | Active, not recruiting |
NCT03298893 (NiCOL) | Single arm Phase I/II | Stage IB2–IVA squamous-cell carcinoma or adenocarcinoma of the cervix | Nivolumab + CRT followed by 5 months of Nivolumab alone | Nivolumab IV q2 weeks + Cisplastin + EBRT (45Gy/25Fx by IMRT/VMAT +/− SIB to 54Gy/25Fx) | Primary: rate of DLT Secondary: ORR, PFS, DFS, Incidence of SAEs and AEs, molecular alterations, ctDNA heterogeneity, tumour microenvironment description, tumour PD-L1 IHC | Active, not recruiting |
NCT03830866 (CALLA) | Phase III RCT | FIGO (2009) Stages IB2 to IIB N+ or FIGO (2009) IIIA–IVA any node cervical adenoCa or SCC | Durvalumab + SoC CRT + BT followed by Durvalumab monotherapy up to 24 months or until progression of disease, vs. Placebo + SoC CRT + BT | Durvalumab IV q4 weeks + Cisplatin (or Carboplatin) qweek concurrent with EBRT + BT | Primary: PFS (RECIST 1.1) Secondary: OS, CR (RECIST 1.1), duration of response, QoL (EORTC QLQ-C30, EORTC CX24), 3-year PFS, PFS and OS in PD-L1+ patients | Active, not recruiting |
NCT01711515 | Single arm Phase I | Stage IB2–IIA with positive PA LNs, IIB/IIB/IVA with positive pelvic or PA LNs cervical cancer | CRT + BT+ adjuvant Ipilimumab | Cisplatin qweek + EBRT × 6 weeks + BT followed by Ipilimumab IV q3weeks for 12 weeks | Primary: DLTs occurring during adjuvant ipilimumab in the dose escalation phase, DLTs occurring in the feasibility phase, AEs Secondary: Response rate (RECIST 1.1), PFS, OS, location of recurrence (locoregional versus distant), chronic toxicities | Completed |
NCT01158248 | Phase II | Stage IB–IIIB cervical cancer with no PA LNs | Panitumumab + CRT + BT | Panitumumab + CRT+ BT | Primary: PFS at 4 months by MRI according to RECIST, Rate of skin and/or gastrointestinal toxicity CTCAE grade 4 at 4 months Secondary: ORR at 4 months according to RECIST criteria, PFS and OS at 12 and 24 months, rate of SAEs at 4, 12, 24 months, Rate of SAEs of panitumumab monotherapy at day 14 | Unknown |
NCT04580771 (IMMUNOCERV) | Single arm Phase II | Stage IB3–IVA cervical cancer | Liposomal HPV-16 E6/E7 Multipeptide Vaccine (PDS0101) + SoC CRT (Cisplatin + RT) | RT (Monday–Friday) for 5–7 weeks _ Cisplatin IV qweek during the 5 weeks of RT + PDS0101 SC on days -10, 7, 28, 49, and 170 in the absence of disease progression or unacceptable toxicity. | Primary: Rate of grade ≥ 3 acute toxicity Secondary: complete metabolic response rate of ≥ 90% GTV reduction, LC, PFS, OS at 12 and 18 months, Long term safety (rate of grade ≥3 chronic toxicity) | Recruiting |
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Faye, M.D.; Alfieri, J. Advances in Radiation Oncology for the Treatment of Cervical Cancer. Curr. Oncol. 2022, 29, 928-944. https://doi.org/10.3390/curroncol29020079
Faye MD, Alfieri J. Advances in Radiation Oncology for the Treatment of Cervical Cancer. Current Oncology. 2022; 29(2):928-944. https://doi.org/10.3390/curroncol29020079
Chicago/Turabian StyleFaye, Mame Daro, and Joanne Alfieri. 2022. "Advances in Radiation Oncology for the Treatment of Cervical Cancer" Current Oncology 29, no. 2: 928-944. https://doi.org/10.3390/curroncol29020079