Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial.

BACKGROUND: Intraperitoneal chemotherapy has been shown to be effective at reducing mortality for patients with advanced epithelial ovarian cancer but is not widely used in practice. METHODS: We performed the Intraperitoneal Therapy for Ovarian Cancer with Carboplatin (iPocc) trial as an open-label, international, multi-institutional, randomized phase 2/3 clinical trial in women with newly diagnosed epithelial ovarian cancer who underwent laparotomy or laparoscopy. All patients received intravenous paclitaxel (80 mg/m2 on days 1, 8, and 15 of a 21-day cycle). In addition, patients in the control group received intravenous carboplatin (dose-dense intravenous paclitaxel plus intravenous carboplatin [dd-TCiv]), whereas patients in the experimental group received dose-dense intravenous paclitaxel plus intraperitoneal carboplatin (dd-TCip). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response, treatment completion rate, and incidence of adverse events (AEs). RESULTS: Among 655 patients randomized to treatment, median (95% confidence interval [CI]) PFS was 20.7 (18.1 to 22.8) months for dd-TCiv (n=328) and 23.5 (20.5 to 26.9) months for dd-TCip (n=327; hazard ratio, 0.83; 95% CI, 0.69 to 0.99; P=0.04). The PFS benefit with dd-TCip was consistent in patients with different baseline characteristics, stage, size of residual tumor, age, and performance status. The treatment completion rates were 68.3 and 59.9% in the dd-TCiv and dd-TCip groups, respectively. The incidence of intraperitoneal catheter-related AEs in the dd-TCip group was 10.1%; there were no such AEs in the dd-TCiv group. CONCLUSIONS: In the first-line treatment of advanced epithelial ovarian cancer, intraperitoneal carboplatin resulted in a modest prolongation of PFS when given with dose-dense weekly paclitaxel regardless of residual tumor size, with no impact on noncatheter-related toxicities. (Funded by the Japan Agency for Medical Research and Development, and others; Japan Registry of Clinical Trials number, jRCTs031180141.)

Impact of pre-brachytherapy magnetic resonance imaging on dose-volume histogram of locally advanced cervical cancer patients treated with radiotherapy including high-dose-rate brachytherapy.

PURPOSE: This study investigated the suitability of brachytherapy technique selection based on pre-brachytherapy magnetic resonance imaging (MRI) findings in cervical cancer by evaluating dose-volume histogram parameters. MATERIAL AND METHODS: We retrospectively evaluated data from 61 patients with cervical cancer who underwent pre-brachytherapy MRI within 7 days before their first high-dose-rate brachytherapy treatment, selected according to pre-brachytherapy MRI findings. Combined intracavitary brachytherapy with interstitial techniques (IC/ISBT) or interstitial brachytherapy (ISBT) were favored treatments for poor-responding tumors after concurrent chemoradiotherapy, asymmetrical tumors, bulky parametrial extensions, bulky primary disease, and extensive paravaginal or distal vaginal involvement. Intracavitary brachytherapy (ICBT) was the preferred treatment for small tumors without extensive involvement of the vagina and parametrium. RESULTS: The median tumor size was 58 mm on pre-treatment MRI and 38 mm on pre-brachytherapy MRI. On pre-brachytherapy MRI, 13 patients had a tumor with severe vaginal invasion, 15 patients presented with an asymmetrical bulky tumor, and 4 patients had bulky residual tumors. IC/ISBT or ISBT were administered to 26 patients (43%). Median equivalent dose in 2 Gy fractions of clinical target volume D90 was 70.8 Gy for all patients. Median clinical target volume D90 in each brachytherapy session exceeded the prescribed dose in both patients treated with ICBT and IC/ISBT or ISBT. Median equivalent dose in 2 Gy fractions of D2cc to the bladder, sigmoid colon, and rectum was 69.5, 52.0, and 58.4 Gy, respectively. All cases remained within the doses recommended for organs at risk. CONCLUSIONS: Pre-brachytherapy MRI may be helpful in selecting suitable candidates for each type of brachytherapy and deliver the recommended doses to the tumor and organs at risk, particularly in cases with large tumors, poor response to concurrent chemoradiotherapy, asymmetrical tumors, severe vaginal invasion, extensive parametrial invasion, and/or corpus invasion.

High prevalence of intrapelvic parasitic arteries in patients with placenta accreta spectrum: A case-control study using unenhanced magnetic resonance angiography.

PURPOSE: To compare the prevalence of enlarged ovarian and intrapelvic parasitic arteries to the gravid uterus between cases of placenta accreta spectrum (PAS) and those with normal placentation using unenhanced magnetic resonance (MR) angiography. METHODS: Unenhanced time-of-flight MR angiography was performed in 12 consecutive women with PAS (mean age, 34 years; range, 23-42 years) and 24 women with normal placentation (mean age, 31 years; range, 24-42 years) in their third trimester and reviewed by two independent observers. The consensus reading served as the reference standard. Findings of pelvic arteriography performed at cesarean hysterectomy were reviewed in all cases of PAS. The prevalence of enlarged ovarian and intrapelvic parasitic arteries was compared using Fisher's exact test. The interobserver agreement was assessed with Kappa statistics. RESULTS: The prevalence of enlarged ovarian arteries was not significantly different between cases of PAS and normal placentation (17% [4/24 pelvic sides] vs. 4% [2/48 pelvic sides], P = .091). The prevalence of intrapelvic parasitic arteries was significantly higher in cases of PAS than in those with normal placentation (67% [16/24 pelvic sides] vs. 0% [0/48 pelvic sides], P < .0001). On a patient-by-patient basis, the intrapelvic parasitic artery was frequently present in women with PAS (92% [11/12 patients]). The Kappa values were 0.915 and 0.852 for detecting enlarged ovarian and intrapelvic parasitic arteries, respectively, indicating excellent interobserver agreement. CONCLUSIONS: The development of intrapelvic parasitic arteries was an anomalous phenomenon observed on unenhanced MR angiography in the majority of women with PAS but was not observed in those with normal placentation.

Four cases of Mayer-Rokitansky-Küster-Hauser syndrome treated via non-surgical vaginal reconstruction using uterine cervical dilators.

Vaginal creation is the standard treatment for Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Although non-surgical method is recommended as a first-line treatment in the American College of Obstetricians and Gynecologists guidelines for gynecological practice, it is not commonly performed in Japan. At our hospital, vaginal dilation using uterine cervical dilators (Hegar's dilator) is performed for patients with MRKH syndrome. We report four cases successfully treated with vaginal dilation. After the examination, patients were instructed to practice daily self-dilation at home. The initiation size was No. 13 with 10.5-mm diameter. After the vaginal cavity was dilated to a depth of 6 cm, the size of dilators was gradually increased until No. 30 with 25-mm diameter in a tip and 28-mm diameter in a trunk. The duration required to achieve the outcome was 5-22 months. All cases were successfully treated without any severe complication.

Increased Soluble CD155 in the Serum of Cancer Patients.

Emerging evidence suggests that DNAM-1 (CD226) play an important role in the recognition of tumor cells and their lysis by cytotoxic T lymphocytes (CTL) and NK cells. Although the DNAM-1 ligand CD155 is ubiquitously expressed in various tissues, many human tumors significantly upregulate the expression of CD155; DNAM-1 on CTL and NK cells may be involved in tumor immunity. However, unlike those in mice, human tissues also express soluble isoforms of CD155 (sCD155) that lack the transmembrane region. Here, we show that sCD155 levels were significantly higher in the sera of 262 patients with lung, gastrointestinal, breast, and gynecologic cancers than in sera from healthy donors. In addition, the sCD155 levels were significantly higher in patients with early stage (stages 1 and 2) gastric cancer than in healthy donors, and were significantly higher in patients with advanced stage (stages 3 and 4) disease than in patients in those with early stage disease and healthy donors. Moreover, the sCD155 levels were significantly decreased after surgical resection of cancers. Thus, sCD155 level in serum may be potentially useful as a biomarker for cancer development and progression.

Can MRI predict local control rate of uterine cervical cancer immediately after radiation therapy?

PURPOSE: To evaluate the utility of measuring the volumes of areas of high signal intensity on T(2)-weighted magnetic resonance (MR) images immediately after irradiation for predicting the local control rate of uterine cervical cancer. MATERIALS AND METHODS: From our departmental database, we identified 109 patients with cervical cancer who underwent MR imaging before irradiation and just before or just after completion of radiation therapy from 1994 to 2007. We included 46 of the 109 patients in this study, 5 patients with local recurrence and 41 patients who were free of disease for more than 2 years. Fifteen received radiation therapy alone, and 28 patients received concurrent chemoradiation therapy. We measured the volumes of areas of high signal intensity involving the uterine cervix on T(2)-weighted MR images before radiation therapy and just before or just after its completion. We measured the 3 orthogonal diameters to calculate the volume as an ellipsoid and evaluated proportional tumor volume and the rate of reduction. We analyzed statistics with Student's t-test. RESULTS: In patients with local recurrence, the mean volume of the areas of high signal intensity on T(2)-weighted MR images just before completion of irradiation therapy or just after was 19.70 cm(3), which was significantly larger than that in patients without recurrence (1.77 cm(3), P<0.05). The proportional tumor volume was also significantly larger (P<0.05). CONCLUSIONS: Although areas of high signal intensity on T(2)-weighted MR images include acute radiation change, their volume and the proportional tumor volume after irradiation can be useful clues in predicting the local control rate of uterine cervical cancer.