Wiebke Solass

Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin in colorectal peritoneal metastasis

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an experimental drug delivery method that applies chemotherapy into the abdominal cavity as an aerosol under pressure. We present the first results obtained with PIPAC in colorectal peritoneal metastasis (CPM).

Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: A phase 2 study.

OBJECTIVE Recurrent ovarian, fallopian or peritoneal cancer with peritoneal carcinomatosis (ROCPC) is resistant to systemic chemotherapy. We assessed the safety and activity of laparoscopic pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with this cancer. METHODS In this open-label, single-arm phase 2 study, patients underwent 3 courses q 28-42 days of PIPAC with doxorubicin 1·5 mg/m(2) followed by cisplatin 7·5 mg/m(2). A pressure of 12 mm Hg and a temperature of 37 °C were applied for 30 min/course. The primary endpoint was the proportion of patients who had an objective tumor response (OTR) according to RECIST version 1.1 criteria. Analysis was by intention to treat. Secondary endpoints were tumor regression on histology, PC Index improvement on repeated video-laparoscopy, and quality of life measured with the EORTC QLQ-30 questionnaire. RESULTS Sixty-four patients were enrolled. Laparoscopic non-access rate was 11/64 (17%). 53 patients were eligible for analyses. 33/53 (62%) patients had an OTR - three had a partial response and 30 patients had stable disease. Tumor regression on histology and PC Index improvement were observed in 26/34 (76%) and in 26/34 (76%) patients who underwent all 3 PIPACs. There were no treatment-related deaths. No grade 4 toxicity was observed. Grade 3 toxicities were trocar hernia (n=2), bowel obstruction (n=2), abdominal pain (n=2), hematoma (n=1), intraoperative bleeding (n=1), and cystitis with urosepsis (n=1). EORTC QLQ-30 global physical health scores, nausea/vomiting, appetite loss, diarrhea, and constipation improved during therapy. CONCLUSION PIPAC is well tolerated and active in women with ROCPC and warrants further investigation in these patients.

Activity of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian cancer: Preliminary clinical experience

OBJECTIVE To assess the activity of laparoscopic Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in women with recurrent, platinum-resistant ovarian cancer. METHODS Prospective case series using repeated courses q 28-42 days of PIPAC containing cisplatin 7.5 mg/m(2) and doxorubicin 1.5 mg/m(2) at 12 mmHg and 37°C for 30 min. Objective tumor response was defined as tumor regression on histology and peritoneal carcinomatosis index (PCI) improvement on repeated video-laparoscopy. RESULTS 34 PIPAC procedures were performed in 18 women, in 8 instances combined with cytoreductive surgery (CRS). Eight women had repeated PIPAC and objective tumor response was observed in 6 (complete remission: 1; partial remission: 2; stable disease: 3). Five adverse events WHO grade ≥ 2 were noted, 3 of them after combined CRS. No perioperative mortality occurred. Median follow-up was 192 days (min. 13-max. 639). Cumulative survival after 400 days was 62% and mean actuarial survival time was 442 days. In a multivariable regression analysis with objective tumor response (yes vs. no) as the dependent variable and PIPAC (1 vs.>1), patient age (<75 vs.≥75 years), serum CA-125 (<1000 vs.>1000 U/mL), and the presence of ascites (yes vs. no) as independent variables, PIPAC independently predicted objective tumor response. CONCLUSION PIPAC has activity in women with recurrent, platinum-resistant ovarian cancer and should be investigated in prospective clinical trials.

Quality of life of patients with end-stage peritoneal metastasis treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

BACKGROUND Quality of Life (QoL) plays an important role in patients with peritoneal metastasis and is deteriorating continuously until death. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative palliative treatment of peritoneal metastasis. We present the first QoL results under PIPAC therapy. METHODS Retrospective analysis of QLQ30 questionnaire results during repeated courses of PIPAC applications in palliative patients with pretreated peritoneal metastasis. RESULTS 91 patients (M:F = 40:51, median age 64 (34-77) years) with 158 PIPAC applications were analyzed. 86% patients had previously received systemic chemotherapy. Peritoneal metastasis was advanced (Peritoneal Carcinomatosis Index I = 16 ± 10). At admission, only moderate impairment of functioning (62-83%) and symptom scores (17-47%) was observed. 48 patients received at least 2 PIPAC every 6 weeks. After PIPAC # 1, the global physical score deteriorated slightly (from 82% to 75%), but improved after PIPAC # 2 (up to 89%). Gastrointestinal symptoms (nausea/vomiting, constipation, diarrhoea, anorexia) remained stable under PIPAC therapy. CONCLUSIONS Quality of life was relatively high in this group of patients with advanced, pretreated peritoneal metastasis, explaining their wish for further therapy. Functioning scores and disease-related symptoms were not altered for at least 3 months in the patients able to receive repeated PIPAC. Except for a transient moderate increase of pain scores, PIPAC did not cause therapy-related QoL deterioration, especially no gastrointestinal symptoms.

Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy for recurrent adult granulosa cell tumor: A case report

Background Adult granulosa cell tumor of the ovary (AGCT) is a rare functional sex-cord-stromal ovarian neoplasm characterized by low malignant potential and late relapse. Evidence-based management options for women with recurrent AGCT are limited. Case report We present the case of a 60-year-old woman with the fifth recurrence of AGCT initially diagnosed 19 years ago. After initial surgery in 1996, the patient underwent four additional surgical interventions for recurrent disease in 2005 (abdominal wall), 2009 (abdominal wall), 2010 (paravesical), and 2011 (paravesical). In 2011, she underwent pelvic irradiation with 50.5 Gray. In 2015, another recurrence was diagnosed based on an increase of serum inhibin and a tumor seen on CT scan in the right upper abdomen. The patient underwent cytoreductive surgery (CRS) with complete cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin 50 mg/m2 and doxorubicin 15 mg/m2. No intra- or post-operative complications occurred. Final histology revealed recurrent AGCT with 6 cm in the largest diameter. Subsequently, antihormonal treatment with anastrozole 1.5 mg per day was prescribed. With a follow-up of six months, the patient is well and alive. Conclusion CRS and HIPEC are a reasonable treatment option for selected women with recurrent AGCT limited to the abdomen.

Hyperthermic intraperitoneal chemotherapy for women with granulosa cell tumors of the ovary: a systematic review of the literature

Abstract Background: Adult and juvenile granulosa cell tumors of the ovary are rare functional sex-cord-stromal ovarian neoplasms characterized by low malignant potential and late relapse. Evidence-based management options for primary and recurrent juvenile (JGCT) and adult (AGCT) granulosa cell tumors are limited and treatment options have not been standardized. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may be an option to treat these women effectively. Methods: Systematic literature review using PubMed and the Cochrane Central Register of Controlled Trials. Results: No reports of HIPEC among women with a first diagnosis of AGCT were identified. We identified 5 reports on the safety and therapeutic efficacy of CRS and HIPEC in 19 patients with recurrent AGCT and one patient with JGCT. The pooled rate of complete cytoreduction was 95 % (18/19) with 16 % (3/19) severe morbidity and no procedure-related mortality. The median time of follow-up was 30 (range, 3 to 72) months, during which 6/19 (31 %) patients experienced a recurrence and two patients (10 %) died of the disease. Conclusion: CRS and HIPEC are a safe and potentially effective treatment option for selected women with recurrent AGCT limited to the abdomen.