Impact of interfractional target motion in locally advanced cervical cancer patients treated with spot scanning proton therapy using an internal target volume strategy

Background and purpose: The more localized dose deposition of proton therapy (PT) compared to photon therapy might allow a reduction in treatment-related side effects but induces additional challenges to address. The aim of this study was to evaluate the impact of interfractional motion on the target and organs at risk (OARs) in cervical cancer patients treated with spot scanning PT using an internal target volume (ITV) strategy. Methods and materials: For ten locally advanced cervical cancer patients, empty and full bladder planning computed tomography (pCT) as well as 25 daily cone beam CTs (CBCTs) were available. The Clinical Target Volume (CTV), the High Risk CTV (CTVHR) (gross tumor volume and whole cervix), the non-involved uterus as well as the OARs (bowel, bladder and rectum) were contoured on the daily CBCTs and transferred to the pCT through rigid bony match. Using synthetic CTs derived from pCTs, four-beam spot scanning PT plans were generated to target the patient-specific ITV with 45 Gy(RBE) in 25 fractions. This structure was defined based on pre-treatment MRI and CT to anticipate potential target motion throughout the treatment. D98% of the targets and V40Gy(RBE) of the OARs were extracted from the daily anatomies, accumulated and analyzed. In addition, the impact of bladder volume deviations from planning values on target and bowel dose was investigated. Results: The ITV strategy ensured a total accumulated dose >42.75 Gy(RBE) to the CTVHR for all ten patients. Two patients with large bladder-related uterus motion had accumulated dose to the non-involved uterus of 35.7 Gy(RBE) and 41.1 Gy(RBE). Variations in bowel V40Gy(RBE) were found to be correlated (Pearson r = −0.55; p-value <0.0001) with changes in bladder volume during treatment. Conclusion: The ITV concept ensured adequate dose to the CTVHR, but was insufficient for the non-involved uterus of patients subject to large target interfractional motion. CBCT monitoring and occasional replanning is recommended along the same lines as with photon radiotherapy in cervical cancer

Evaluation of a New Prognostic Tumor Score in Locally Advanced Cervical Cancer Integrating Clinical Examination and Magnetic Resonance Imaging

Purpose: The integral results of clinical examination and magnetic resonance imaging (MRI) of patients with locally advanced cervical cancer may provide prognostic information that cannot readily be placed in current staging systems, such as proximal versus distal parametrial invasion, unilateral versus bilateral involvement, or organ infiltration on MRI. The aim was to develop and investigate the performance of a simple but comprehensive tumor score for reporting and prognostication. Methods and Materials: In the present study, 400 consecutive patients with locally advanced cervical cancer treated 2005 to 2018 with chemoradiation and image guided adaptive brachytherapy (IGABT) were analyzed. The diagnostic workup included clinical examination, positron emission tomography/computed tomography, and MRI. International Federation of Gynecology and Obstetrics 2009 stage distribution was IB to IIA 9%, IIB 61%, and III to IV 30%. Involvement of 8 anatomic locations (cervix, left parametrium, right parametrium, vagina, bladder, ureter, rectum, and uterine corpus) was scored according to a ranked ordinal scale with 0 to 3 points. The total sum of points constituted the tumor score (T-score). Results: The median T-score was 6 (range, 0-20). Based on the frequency distribution of the T-score, 4 equally sized groups were formed: 0 to 4, 5 to 6, 7 to 9, and >9 points. The T-score grouping was highly significant in both univariate and multivariable analysis and outperformed International Federation of Gynecology and Obstetrics stage for both survival and local control enabling also intrastage prognostication. Used as a linear variable, the T-score was correlated with IGABT target volume (high-risk clinical target volume, CTVHR), use of interstitial needles, dose (D90 of CTVHR), and total reference air kerma. Conclusions: The T-score is a simple instrument for combining clinical findings and imaging into a powerful prognostic factor for survival and local control with capabilities surpassing traditional staging. In addition, the T-score may already at diagnosis predict essential IGABT parameters and may be used for audit and comparison of results in multicenter settings

Impact of bowel gas and body outline variations on total accumulated dose with intensity-modulated proton therapy in locally advanced cervical cancer patients

<p><b>Introduction:</b> Density changes occurring during fractionated radiotherapy in the pelvic region may degrade proton dose distributions. The aim of the study was to quantify the dosimetric impact of gas cavities and body outline variations.</p> <p><b>Material and methods:</b> Seven patients with locally advanced cervical cancer (LACC) were analyzed through a total of 175 daily cone beam computed tomography (CBCT) scans. Four-beams intensity-modulated proton therapy (IMPT) dose plans were generated targeting the internal target volume (ITV) composed of: primary tumor, elective and pathological nodes. The planned dose was 45 Gy [Relative-Biological-Effectiveness-weighted (RBE)] in 25 fractions and simultaneously integrated boosts of pathologic lymph nodes were 55–57.5 Gy (RBE). In total, 475 modified CTs were generated to evaluate the effect of: 1/gas cavities, 2/outline variations and 3/the two combined. The anatomy of each fraction was simulated by propagating gas cavities contours and body outlines from each daily CBCT to the pCT. Hounsfield units corresponding to gas and fat were assigned to the propagated contours. D98 (least dose received by the hottest 98% of the volume) and D99.9 for targets and V43Gy(RBE) (volume receiving ≥43 Gy(RBE)) for organs at risk (OARs) were recalculated on each modified CT, and total dose was evaluated through dose volume histogram (DVH) addition across all fractions.</p> <p><b>Results:</b> Weight changes during radiotherapy were between −3.1% and 1.2%. Gas cavities and outline variations induced a median [range] dose degradation for ITV45 of 1.0% [0.5–3.5%] for D98 and 2.1% [0.8–6.4%] for D99.9. Outline variations had larger dosimetric impact than gas cavities. Worst nodal dose degradation was 2.0% for D98 and 2.3% for D99.9. The impact on bladder, bowel and rectum was limited with V43Gy(RBE) variations ≤3.5 cm³.</p> <p><b>Conclusion:</b> Bowel gas cavities and outline variations had minor impact on accumulated dose in targets and OAR of four-field IMPT in a LACC population of moderate weight changes.</p

Cone beam computed tomography-based monitoring and management of target and organ motion during external beam radiotherapy in cervical cancer

Background and purpose: Organ motion is a challenge during high-precision external beam radiotherapy in cervical cancer, and improved strategies for treatment adaptation and monitoring of target dose coverage are needed. This study evaluates a cone beam computed tomography (CBCT)-based approach. Materials and methods: In twenty-three patients, individualized internal target volumes (ITVs) were generated from pre-treatment MRI and CT scans with full and empty bladders. The target volumes encompassed high-risk clinical target volume (CTV-T HR) (gross tumor volume + remaining cervix) and low risk (LR) CTV-T (CTV-T HR + uterus + parametriae + upper vagina). Volumetric Modulated Arc Therapy (VMAT) was used to deliver a dose of 45 Gy in 25 fractions. CBCTs were used for setup and for radiation therapists (RTTs) to evaluate the target coverage (inside/outside the planning target volume). CBCTs were reviewed offline. Estimates of the dose delivered with minimum (point) doses across all fractions to CTV-T HR (aim 42.75 Gy) and CTV-T LR (aim 40 Gy) were assessed. In patients with insufficient dose coverage, re-plans were generated based on previous imaging. Results: Median (range) of the ITV-margins (mean of anterior-posterior margins) related to uterus and cervix was 1.2 (0.5–2.2 and 1.0–2.1) cm. RTTs were able to assess the target coverage in 90% of all CBCTs (505/563). With re-planning, one patient had considerable benefit (12.7 Gy increase of minimum dose) to CTV-T LR_vagina, four patients had improved dose to the CTV-T LR_uterus (1.2–1.8 Gy), and 3 patients did not benefit from re-planning. Conclusions: Daily CBCT-based monitoring of target coverage by the RTTs has proven safe with limited workload. It allows for reduction in the treated volumes without compromising the target dose coverage. Keywords: Image guidance, External beam radiotherapy, Adaptive radiotherapy, Cervical cancer, Cone-beam computed tomography, Interfraction motio