Johannes Knoth

Oncologic outcome of metachronous oligometastatic recurrence in advanced cervical cancer patients after primary radio-chemotherapy

Systemic chemotherapy in recurrent cervical cancer is a palliative treatment approach with limited oncologic outcome. As emerging evidence supports favorable prognosis following radical local treatment strategies for oligometastatic recurrence in gynecologic malignancies, there is an unmet clinical need to define prognostic implications of surgical metastasectomy in recurrent cervical cancer. Data of 139 consecutive cervical cancer patients, who underwent primary external-beam radiotherapy with concomitant chemotherapy, followed by magnetic resonance image-guided adaptive brachytherapy between 2015 and 2019, was analyzed. Oncologic outcomes of recurrence patterns, defined according to the European Society for Radiotherapy and Oncology (ESTRO) and the American Society for Radiation Oncology (ASTRO) consensus, was assessed according to the type of recurrence therapy. Of 54 patients (38.8%) with metachronous disease recurrence, 21 (38.8%) classified as metastatic and 22 (40.7%) as oligometastatic. Oligometastatic recurrence was associated with improved progression-free survival after recurrence (PFS2; hazard ratio [HR]=2.95; 95% confidence interval [CI]=1.23-7.08; p=0.015) and disease-specific survival after recurrence (HR=3.28; 95% CI=1.40-7.70; p=0.006) irrespective of the type of recurrence therapy. An exploratory subgroup analysis of oligometastatic patients undergoing surgical resection ± adjuvant therapy (n=12) suggested reduced risk of second disease recurrence (odds ratio=0.15; 95% CI=0.02-0.92; p=0.020) and improved PFS2 (HR=0.24; 95% CI=0.06-0.99; p=0.048) as compared to palliative systemic treatment (n=7). A relevant number of recurrences qualifies as oligometastatic according to the ESTRO-ASTRO consensus, which associate with improved prognosis irrespective of the type of recurrence therapy. Patients experiencing oligometastatic recurrence should be carefully evaluated for potentially curative treatment approaches.

Toward 3D-TRUS image-guided interstitial brachytherapy for cervical cancer

To qualitatively and quantitatively analyze needle visibility in combined intracavitary and interstitial cervical cancer brachytherapy on 3D transrectal ultrasound (TRUS) in comparison to gold standard MRI. Image acquisition was done with a customized TRUS stepper unit and software (Medcom, Germany; Elekta, Sweden; ACMIT, Austria) followed by an MRI on the same day with the applicator in place. Qualitative assessment was done with following scoring system: 0 = no visibility 1 (= poor), 2 (= fair), 3 (= excellent) discrimination, quantitative assessment was done by measuring the distance between each needle and the tandem two centimeters (cm) above the ring and comparing to the respective measurement on MRI. Twenty-nine implants and a total of 188 needles (132 straight, 35 oblique, 21 free-hand) were available. Overall, 79% were visible (87% straight, 51% oblique, 76% free-hand). Mean visibility score was 1.4 ± 0.5 for all visible needles. Distance of the visible needles to tandem was mean ± standard deviation (SD) 21.3 millimeters (mm) ± 6.5 mm on MRI and 21.0 mm ± 6.4 mm on TRUS, respectively. Difference between MRI and TRUS was max 14 mm, mean ± SD -0.3 mm ± 2.6 mm. 11% differed more than 3 mm. Straight needles were better detectable than oblique needles (87% vs. 51%). Detectability was impaired by insufficient rotation of the TRUS probe, poor image quality or anatomic variation. As needles show a rather indistinct signal on TRUS, online detection with a standardized imaging protocol in combination with tracking should be investigated, aiming at the development of real time image guidance and online treatment planning.

Diffusion weighted imaging for gross tumor volume delineation in primary radiochemotherapy and image guided adaptive brachytherapy for cervical cancer

Accurate gross tumor volume (GTV) delineation is critical for successful radiochemotherapy and image-guided adaptive brachytherapy (BT) in cervical cancer. This study investigated whether diffusion-weighted imaging (DWI) improves GTV delineation accuracy compared to T2-weighted (T2w) MRI alone, across different physician experience levels. Twenty-seven patients with locally advanced cervical carcinoma undergoing primary radiochemotherapy were analyzed. Six physicians (three experts, three residents) delineated GTVs at three time points: diagnosis (init), pre-brachytherapy (preBT), and pre-brachytherapy with applicator in situ (BT). Segmentations were performed using T2w images alone and T2w plus DWI (b=800smm DWI guidance significantly improved inter-observer agreement among experts at init (conformity index: 0.62→ 0.70, p<0.05) and BT (0.33→ 0.39, p<0.05) time points. For residents, DWI guidance enhanced agreement with expert consensus, particularly during BT, with significant improvements in Dice coefficient (median increase 9%, p<0.05) and reduced Hausdorff distance (median decrease 1.3 mm, p<0.05). Tumor volume correlation between preBT and BT time points improved with DWI guidance for both groups. Incorporating DWI into the segmentation workflow reduces inter-observer variability for both expert and resident radiation oncologists. DWI guidance particularly benefits less experienced physicians, enabling them to achieve contours closer to expert consensus standards through additional functional information.

Cardiac metastasis in uterine cervical cancer

Abstract Purpose Cardiac metastasis from cervical cancer is rare and only scarcely documented. We aim to present a new case and systematically summarize the available literature. Materials and methods PubMed, Scopus, Web of Science, Central, and ClinicalTrials.gov were systematically searched following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. Results were screened via title, abstract, and full text. Additionally, the reference lists of all papers chosen for the review were screened. Results Eighty-one papers were identified, describing 86 cases in total. Cardiac metastasis occurred at all stages of cervical cancer and in all age groups. Median time from initial diagnosis to diagnosis of cardiac metastasis was 12 months. Patients mainly complained of dyspnea and chest pain, 60.8% had pathologic ECG (electrocardiographic) findings. The cardiac mass was most frequently detected by transthoracic echography. The most common tumor histology was squamous cell carcinoma. Chemotherapy and surgical interventions were the main treatment modalities. Median survival after diagnosis of cardiac metastasis was 3 months. Conclusion This largest review on cardiac metastases from cervical cancer confirmed the heart as a very infrequent site of metastasis. There are &lt; 100 cases described in the literature, with very poor prognosis and undefined clinical management.