Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial.

OBJECTIVE: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. METHODS: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%. RESULTS: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). CONCLUSION: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.

Safety of radiotherapy for hemodialysis patients with cancer.

BACKGROUND: The number of hemodialysis (HD) patients is increasing worldwide, and they are at a higher risk of cancer than the general population. Because HD patients are more likely to have inflammation, radiotherapy (RT)-induced adverse effects (AEs) are theoretically expected to be worse for HD patients. Since only a few reports have been published on this subject, we aimed to evaluate the tolerability of RT in HD patients. METHODS: We retrospectively analyzed AEs related to RT for HD patients. Our study included patients from three institutions treated between January 2007 and July 2017. The patient eligibility criteria were (i) receipt of maintenance HD 2-3 times per week for end-stage renal disease prior to the start of RT and (ii) pathologically confirmed malignancies. The endpoints were acute and late non-hematologic AEs. RESULTS: The study included 56 patients. The most common histology was head and neck cancer (23%), followed by lung cancer (14%) and prostate cancer (11%). The median radiation dose was 60 (range, 12-93.8) Gy at an equivalent dose in 2-Gy fractions (EQD2). The RT completion rate was 96%. Patients had a median follow-up period after RT of 9.1 (range 0.5-98.1) months. Grade 3 or worse acute and late AEs were noted in 6 (11%) and 3 (7%) patients, respectively. In the acute phase, 2 patients had grade 5 AEs, both of which were infections. CONCLUSION: Our results suggest that RT for HD patients is clinically tolerable. However, some patients can experience severe infections related to treatment.

A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer.

OBJECTIVE: To develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. METHODS: A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. RESULTS: The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). CONCLUSIONS: We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field.

Distribution patterns of metastatic pelvic lymph nodes assessed by CT/MRI in patients with uterine cervical cancer.

BACKGROUND: To investigate the three-dimensional (3D) distribution patterns of clinically metastatic (positive) lymph nodes on pretreatment computed tomography (CT)/magnetic resonance imaging (MRI) images of patients with locally advanced cervical cancer. METHODS: We enrolled 114 patients with uterine cervical cancer with positive nodes by CT/MRI (≥10 mm in the shortest diameter). Pretreatment CT/MRI data were collected at 6 institutions. The FIGO stage was IB1 in 2 patients (2%), IB2 in 6 (5%), IIA in 3 (3%), IIB in 49 (43%), IIIB in 50 (44%), and IVA in 4 (4%) patients. The median cervical tumor diameter assessed by T2-weighted MRI was 55 mm (range, 10-87 mm). The anatomical distribution of the positive nodes was evaluated on CT/MRI images by two radiation oncologists and one diagnostic radiologist. RESULTS: In these patients, 273 enlarged nodes were assessed as positive. The incidence of positive nodes was 104/114 (91%) for the obturator region, 31/114 (27%) for the external iliac region, 16/114 (14%) for the internal iliac region, 22/114 (19%) for the common iliac region, and 6/114 (5%) for the presacral region. The external iliac region was subdivided into four sub-regions: lateral, intermediate, medial, and caudal. The obturator region was subdivided into two sub-regions: cranial and caudal. The majority of patients had positive nodes in the cranial obturator and/or the medial external iliac region (111/114). In contrast, few had positive nodes in the lateral external iliac, caudal external iliac, caudal obturator, internal iliac and presacral regions. All cases with positive nodes in those low-risk regions also had positive nodes in other pelvic nodal regions concomitantly. The incidence of positive nodes in the low-risk regions/sub-regions was significantly related to FIGO stage (p=0.017) and number of positive nodes (p<0.001). CONCLUSIONS: We demonstrated the 3D distribution patterns of clinical metastatic pelvic lymph nodes on pretreatment CT/MRI images of patients with locally advanced cervical cancer. These findings might contribute to future individualization of the clinical target volume of the pelvic nodes in patients with cervical cancer.