Abstract：
UNASSIGNED: The standard treatment for locally advanced cervical cancer (LACC) is concurrent chemoradiation (CRT) followed by brachytherapy (BRT). The addition of chemotherapy (ChT) to radiotherapy (RT) is associated with a 7.5% improvement in overall survival but with more grade 3-4 acute toxicities (16.4% vs 4.9%, CRT vs RT alone). The risk-benefit ratio could be less favorable in advanced disease with renal dysfunction secondary to tumor-related hydronephrosis; borderline cardiac function; and frail patients. RT alone followed by BRT achieves long-term locoregional control <62%. Hypofractionated RT (HF-RT) using older techniques result in comparable disease control and low late toxicity rates (4-8%). Dose-adapted HF-RT using intensity-modulated RT with nodal simultaneous integrated boost (nSIB) could improve tumor control and toxicity, when ChT is contraindicated.
UNASSIGNED: The HYACINCT study is a two-phase study to determine the effectiveness and safety of HF-RT with nSIB in LACC when ChT is contraindicated. Phase 1 is a dose-escalation study using standard 3 + 3 design, to determine the maximum tolerated dose (MTD) for nSIB in combination with pelvic HF-RT (2.67 Gy x 15 fractions). Phase 2 is a single-arm clinical trial using Simon\'s two-stage design, to assess the efficacy of HF-RT with nSIB in terms of tumor response. Adult women with biopsy-proven, untreated LACC, with contraindication to ChT will be included in this trial.
UNASSIGNED: For the phase 1, the primary endpoint is dose-limiting toxicity (DLT), or any grade ?3 acute or sub-acute toxicity. The dose level at which incidence of DLT is ?33% is defined as the maximum tolerance dose (MTD). For the phase 2, the primary endpoint is complete response at 3 months post-treatment. Secondary outcomes are progression-free and overall survival, acute and late toxicity, and patient-reported outcomes (EPIC, EORTCQLQ C30 + CX24, PGIC, PCIS). Trial registration: NCT05210270.
UNASSIGNED: The HYACINCT study is a two-phase study to determine the effectiveness and safety of HF-RT with nSIB in LACC when ChT is contraindicated. Phase 1 is a dose-escalation study using standard 3 + 3 design, to determine the maximum tolerated dose (MTD) for nSIB in combination with pelvic HF-RT (2.67 Gy x 15 fractions). Phase 2 is a single-arm clinical trial using Simon\'s two-stage design, to assess the efficacy of HF-RT with nSIB in terms of tumor response. Adult women with biopsy-proven, untreated LACC, with contraindication to ChT will be included in this trial.
UNASSIGNED: For the phase 1, the primary endpoint is dose-limiting toxicity (DLT), or any grade ?3 acute or sub-acute toxicity. The dose level at which incidence of DLT is ?33% is defined as the maximum tolerance dose (MTD). For the phase 2, the primary endpoint is complete response at 3 months post-treatment. Secondary outcomes are progression-free and overall survival, acute and late toxicity, and patient-reported outcomes (EPIC, EORTCQLQ C30 + CX24, PGIC, PCIS). Trial registration: NCT05210270.
摘要：
UNASSIGNED：局部晚期宫颈癌（LACC）的标准治疗方法是同步放化疗（CRT），然后进行近距离放射治疗（BRT）。在放疗（RT）中增加化疗（ChT）与总生存率提高7.5％相关，但具有更多的3-4级急性毒性（16.4％vs4.9％，单独CRT与RT)。在患有继发于肿瘤相关肾积水的肾功能不全的晚期疾病中，风险收益比可能较差；临界心功能；和虚弱的患者。单独RT后BRT实现长期局部控制<62%。使用较旧技术的低分割RT（HF-RT）可实现可比的疾病控制和低的晚期毒性率（4-8％）。剂量适应的HF-RT使用强度调节的RT与节点同步整合增强（nSIB）可以改善肿瘤控制和毒性，当ChT是禁忌的。
UNASSIGNED：HYACINCT研究是一项两阶段研究，旨在确定在ChT禁忌时在LACC中使用nSIB的HF-RT的有效性和安全性。第一阶段是使用标准3+3设计的剂量递增研究，确定nSIB联合盆腔HF-RT的最大耐受剂量（MTD）（2.67Gyx15分）。第二阶段是使用Simon的两阶段设计的单臂临床试验，评估HF-RT与nSIB在肿瘤反应方面的疗效。经活检证实的成年女性，未经处理的LACC，与ChT的禁忌症将包括在本试验中。
未经评估：对于第一阶段，主要终点是剂量限制性毒性（DLT），或任何3级急性或亚急性毒性。DLT发生率为33％的剂量水平定义为最大耐受剂量（MTD）。对于2期，主要终点是治疗后3个月的完全反应。次要结局是无进展和总生存期，急性和晚期毒性，和患者报告的结果(EPIC，EORTCQLQC30+CX24、PGIC、PCIS）。试用注册：NCT05210270。
UNASSIGNED：HYACINCT研究是一项两阶段研究，旨在确定在ChT禁忌时在LACC中使用nSIB的HF-RT的有效性和安全性。第一阶段是使用标准3+3设计的剂量递增研究，确定nSIB联合盆腔HF-RT的最大耐受剂量（MTD）（2.67Gyx15分）。第二阶段是使用Simon的两阶段设计的单臂临床试验，评估HF-RT与nSIB在肿瘤反应方面的疗效。经活检证实的成年女性，未经处理的LACC，与ChT的禁忌症将包括在本试验中。
未经评估：对于第一阶段，主要终点是剂量限制性毒性（DLT），或任何3级急性或亚急性毒性。DLT发生率为33％的剂量水平定义为最大耐受剂量（MTD）。对于2期，主要终点是治疗后3个月的完全反应。次要结局是无进展和总生存期，急性和晚期毒性，和患者报告的结果(EPIC，EORTCQLQC30+CX24、PGIC、PCIS）。试用注册：NCT05210270。
