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

Role of Brachytherapy in the Postoperative Management of Endometrial Cancer: Decision-Making Analysis among Experienced European Radiation Oncologists.

BACKGROUND There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT. METHODS Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology. RESULTS The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1-2 LVSI-negative disease. For 74-84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT. CONCLUSIONS There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1-2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic

Differences in Administration of Methotrexate and Impact on Outcome in Low-Risk Gestational Trophoblastic Neoplasia

Methotrexate (MTX) is frequently used as first-line treatment for low-risk gestational trophoblastic neoplasia (GTN). Intravenous and intramuscular (im) routes of administration are the most common methods, although oral administration is used by some Scandinavian centers. The primary aim of this study was to assess the impact of form of administration (im/oral) on resistance to methotrexate (MTX-R) treatment in low-risk GTN. Secondary aims were time to hCG normalization, rates of toxicity-induced treatment switch, and rates of complete remission and recurrence. In total, 170 women treated at Karolinska University Hospital in Sweden and Aarhus University Hospital in Denmark between 1994 and 2018 were included, of whom 107 were given im and 63 oral MTX. MTX-R developed in 35% and 54% in the im and oral groups, respectively (p = 0.01). There was no difference in days to hCG normalization (42 vs. 41 days, p = 0.50) for MTX-sensitive women. Toxicity-induced treatment switch was only seen in the im group. Complete remission was obtained in 99.1% and 100% (p = 0.44), and recurrence rate within one year was 2.8% and 1.6% (p = 0.29). The form of administration of MTX had a significant impact on development of MTX-R and treatment-associated toxicity, but does not affect rates of complete remission, recurrence or survival

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