Radiotherapy for Gynecologic Cancer With Up to 10 Active Metastatic Lesions

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to more than 5 total active metastatic lesions, diffuse or uncountable disease, or death. Evaluated only in participants with 1-5 active metastatic lesions at the qualifying oligometastatic disease assessment (T0-OMD). The threshold uses total active metastatic burden, not only newly detected lesions.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to more than 10 total active metastatic lesions, diffuse or uncountable disease, or death. Evaluated in the positron emission tomography (PET)-defined cohort with 1-10 lesions. The expanded positron emission tomography-defined polymetastatic progression threshold (PMD-E10) status is indeterminate when follow-up imaging cannot assess the threshold, unless more than 10 lesions or diffuse disease is unequivocal.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to loss of the oligometastatic state through progression to the applicable polymetastatic threshold or diffuse disease. Death is treated as a competing event in the disease-state estimand.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to initiation of systemic anticancer treatment, a change in treatment line, escalation of the systemic strategy, or death. Event rules depend on the baseline systemic-treatment setting.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to death from any cause.

Time from the first radiotherapy fraction or brachytherapy application to the individual lesion to unequivocal in-field progression. Death without lesion progression is treated as a competing event. Lesions are assessed individually.

Description of first progression by anatomical site, number of active lesions, detection modality, local feasibility of subsequent metastasis-directed therapy, and oligometastatic or polymetastatic disease status.

Among participants without active systemic treatment at the first qualifying radiotherapy fraction or brachytherapy application (T0-RT), time to initiation of any systemic anticancer treatment or death.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to the first new systemic treatment line after the index strategy. Continuation of a regimen started as part of the index strategy is not an event until treatment is changed or escalated.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to initiation or change of cytotoxic chemotherapy. Continuation of non-cytotoxic treatment is not an event.

Among participants receiving maintenance or continuing therapy, time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to permanent discontinuation, escalation or change of that strategy because of progression, an adverse event or a clinical decision. A temporary hold followed by resumption of the same therapy is not an event.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to subsequent metastasis-directed treatment, particularly a subsequent course of radiotherapy.

Complete response assessed separately for treated lesions at approximately 3 and 6 months after completion of radiotherapy, according to local practice, preferably Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), supplemented by metabolic criteria when positron emission tomography (PET) is used.

Complete response at participant level assessed at approximately 3 and 6 months after completion of radiotherapy, according to local practice, preferably Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), supplemented by metabolic criteria when positron emission tomography (PET) is used.

Acute adverse events characterized by term, grade, dates, seriousness, attribution, intervention, hospitalization, treatment interruption and outcome. Baseline events are recorded separately. The Common Terminology Criteria for Adverse Events, version 6.0 (CTCAE v6.0) are used for prospectively collected data; historical data retain the source version and are mapped only when reliable.

Adverse events occurring more than 90 days after completion of radiotherapy, characterized by term, grade, dates, seriousness, attribution, intervention and outcome. The Common Terminology Criteria for Adverse Events, version 6.0 (CTCAE v6.0) are used for prospectively collected data; historical data retain the source version and are mapped only when reliable.

Reclassification of the number of active metastatic lesions between 1-5, 6-10, and more than 10 or diffuse-disease categories after incorporating fluorodeoxyglucose positron emission tomography (FDG-PET). Paired computed tomography/magnetic resonance imaging (CT/MRI)-PET comparisons require scans no more than 28 days apart without intervening treatment that changes disease burden.

Positron emission tomography (PET)-associated changes in eligibility, treatment intent, target selection, radiation fields or systemic-treatment strategy for the index episode.

Differences between computed tomography/magnetic resonance imaging (CT/MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) in the number and anatomical location of active metastatic lesions, assessed in the paired-imaging population.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to the first radiographically documented new lesion or unequivocal progression of an existing lesion outside the prespecified disease-specific locoregional compartment. This includes progression of distant metastases present at baseline. Compartments are defined relative to the primary tumor, independently of the radiation fields.

Time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to the first radiographically documented new lesion or unequivocal progression within the primary tumor or operative bed and the regional nodal basins prespecified for the primary gynecological site. Locoregional status is anatomical and is not defined by whether a lesion lies within a radiation field.

Only where the optional patient-reported outcome (PRO) module has been approved and activated, and the required participant consent has been obtained, time from the first qualifying radiotherapy fraction or brachytherapy application (T0-RT) to the first observed decrease of at least 10 points from a valid pre-radiotherapy baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/quality of life (QoL) scale (items 29-30; range 0-100; higher scores indicate better health/QoL). The event date is the questionnaire date; confirmation at a later assessment is not required.

Only where the optional patient-reported outcome (PRO) module has been approved and activated, and the required participant consent has been obtained, mean change from a valid pre-radiotherapy baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/quality of life (QoL) scale (items 29-30; range 0-100), assessed separately at approximately 3 and 6 months after completion of radiotherapy. Positive change indicates improvement and negative change indicates deterioration. No binary preservation threshold is applied.

Only where the optional patient-reported outcome (PRO) module has been approved and activated, and the required participant consent has been obtained, response-category distributions and changes from pre-radiotherapy baseline are reported separately for General pain frequency, severity and interference, and Fatigue severity and interference, using the five corresponding Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) items with a 7-day recall. No combined score, conversion to Common Terminology Criteria for Adverse Events (CTCAE) grades or clinically meaningful responder threshold is used.

During the first 180 calendar days beginning on the first qualifying radiotherapy fraction or brachytherapy application (T0-RT), report separately per participant the number of unplanned inpatient admission episodes, urgent or unscheduled visits, and unique days spent in unplanned inpatient care. Transfers during one continuous inpatient stay do not constitute a new admission. Components are not combined into a single score.

Number of calendar days alive and not in inpatient care during days 0-179 beginning on the first qualifying radiotherapy fraction or brachytherapy application (T0-RT); range 0-180. Both planned and unplanned inpatient stays count as hospital days. A day with any inpatient care counts once; outpatient-only visits do not subtract a day. The date of death and subsequent days contribute zero. A value is calculated only when vital status and inpatient dates are adequately documented.