IP Chemotherapy Research Articles

Intraoperative Normothermic Intraperitoneal Chemotherapy Following Optimal Cytoreduction in Advanced Ca Ovary: A Feasibility Study

Introduction: Extrapolating the results from the studies using HIPEC, EPIC and normothermic intraperitoneal chemotherapy, we proposed that normothermic chemotherapy instilled after optimal cytoreduction will improve survival in patients who underwent optimal cytoreduction. We undertook this feasibility study with the aim of studying the effectiveness of intraoperative normothermic intraperitoneal chemotherapy in patients with advanced-stage epithelial carcinoma ovary. Methods: This was a single institutional feasibility study. The primary objective was progression-free survival (PFS) following the instillation of normothermic chemotherapy following optimal cytoreduction in cases of advanced ovarian cancer after neoadjuvant chemotherapy. The secondary objective was to study tolerability and toxicity. The study received institutional ethical committee clearance. Results: A total of 24 patients were included in the pilot study over two years. The short-term analysis was made by comparing 45 patients who underwent interval cytoreductive surgery (ICS) with CC 0 and 1 during the same period. The most common side effect was prolonged post-operative ileus which was seen in six patients. The median PFS among patients who received IP chemotherapy was significantly better in comparison to patients who received ICS alone (34.0 vs. 13.0 months, p=0.018). Conclusion: Uniform state-of-the-art management of advanced epithelial ovarian cancer may not be accessible to all due to global resource limitations. Although the evidence is weak due to the small sample size and short follow-up of patients, the findings are encouraging. This feasibility study has provided substantial evidence to work further with this approach in our institute and plan an randomised controlled trial to gain more evidence.

Oncological outcomes of intraperitoneal chemotherapy in advanced ovarian cancer: BRCA mutation role

IntroductionThe knowledge of BRCA status offers a chance to evaluate the role of the intraperitoneal route in patients selected by biomolecular profiles after primary cytoreduction surgery in advanced ovarian cancer. Materials and methodsWe performed a retrospective, multicenter study to assess oncological outcomes depending on adjuvant treatment (intraperitoneal [IP] vs intravenous [IV]) and BRCA status (BRCA1/2 mutated vs. BRCA wild type [WT]). The primary endpoint was to determine progression-free survival. The secondary objectives were overall survival and toxicity. ResultsA total of 288 women from eight centers were included: 177 in the IP arm and 111 in the IV arm, grouped into four arms according to BRCA1/2 status. Significantly better PFS was observed in BRCA1/2-mutated patients with IP chemotherapy (HR: 0.35; 95% CI, 0.16–0.75, p = 0.007), which was not present in BRCA1/2-mutated patients with IV chemotherapy (HR: 0.65; 95% CI, 0.37–1.12, p = 0.14). Significantly better OS was also observed in IP chemotherapy (HR: 0.17; 95% CI, 0.06–043, p < 0.0001), but was not present in IV chemotherapy in relation with BRCA mutation (HR: 0.52; 95% CI, 0.22–1.27, p = 0.15). For BRCA WT patients, worse survival was observed regardless of the adjuvant route used. The IP route was more toxic compared to the IV route, but toxicity was equivalent at the long-term follow-up. ConclusionThis retrospective study suggests that BRCA status can help to offer an individualized, systematic treatment after optimal primary surgery for advanced ovarian cancer, but is limited by the small sample size. Prospective trials are essential to confirm these results.

Disease Distribution at Presentation Impacts Benefit of IP Chemotherapy Among Patients with Advanced-Stage Ovarian Cancer.

Ovarian cancer with miliary disease spread is an aggressive phenotype lacking targeted management strategies. We sought to determine whether adjuvant intravenous/intraperitoneal (IV/IP) chemotherapy is beneficial in this disease setting. Patient/tumor characteristics and survival data of patients with stage IIIC epithelial ovarian cancer who underwent optimal primary debulking surgery from 01/2010 to 11/2014 were abstracted from records. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables. The Kaplan-Meier method was used to estimate survival curves, and outcomes were compared using log-rank tests. Factors significant on univariate analysis were combined into multivariate logistic regression survival models. Among 90 patients with miliary disease spread, 41 (46%) received IV/IP chemotherapy and 49 (54%) received IV chemotherapy. IV/IP chemotherapy, compared with IV chemotherapy, resulted in improved progression-free survival (PFS; 23.0 versus 12.0 months; p = 0.0002) and overall survival (OS; 52 versus 36 months; p = 0.002) in patients with miliary disease. Among 78 patients with nonmiliary disease spread, 23 (29%) underwent IV/IP chemotherapy and 55 (71%) underwent IV chemotherapy. There was no PFS or OS benefit associated with IV/IP chemotherapy over IV chemotherapy in these patients. On multivariate analysis, IV/IP chemotherapy was associated with improved PFS (HR, 0.28; 95% CI 0.15-0.53) and OS (HR, 0.33; 95% CI 0.18-0.61) in patients with miliary disease compared with those with nonmiliary disease (PFS [HR, 1.53; 95% CI 0.74-3.19]; OS [HR, 1.47; 95% CI 0.70-3.09]). Adjuvant IV/IP chemotherapy was associated with oncologic benefit in miliary disease spread. This survival benefit was not observed in nonmiliary disease.

CRS + HIPEC in stage IIIc epithelial ovarian cancer and comparison of oncological outcome only with CRS and IV chemotherapy and CRS + IP chemotherapy.

e18054 Background: Our study aims to describe role of CRS &amp; HIPEC in stage IIIC epithelial ovarian malignancy &amp; compare the oncological outcome (DFS &amp; OS) of extensive CRS+ HIPEC in comparison with CRS &amp; IV chemotherapy &amp; CRS + IP chemotherapy. Methods: Patients diagnosed of stage IIIc EOC underwent extensive CRS + HIPEC. All data prospectively entered in the HIPEC registry was analysed. Outcome of CRS &amp; IV group (n = 50), CRS + IP group (n = 60) operated around same period was compared with the CRS &amp; HIPEC group. Results: Out of 135 patients, upfront, interval and secondary cytoreduction plus HIPEC was done in 29.6%, 44.4% &amp; 25.9% &amp; mean PCI was 14.1, 9.6 &amp; 13.0 respectively. Multi-visceral resection, diaphragmatic resection &amp; bowel resection was required in 12.7%, 50% &amp; 41.8% respectively. Overall G3- G5 morbidity was seen in 25.4% with major being electrolyte imbalance 16.3%, hematological 12.7% &amp; surgical 11.8%. Mean ICU &amp; hospital stay 1.5 &amp; 11 days respectively. Overall 30 day mortality was 4.5%. With a median follow up of 42 months DFS was 30, 33 &amp; 16 months and OS was 70%, 67% &amp; 51% at 4 year for upfront, interval and the recurrent settings respectively. Detailed description presented in Table. Most of the recurrences in CRS &amp; IV group were in peritoneum whereas the other two groups had lesser peritoneal &amp; systemic recurrence. Conclusions: Optimal cytoreduction &amp; some form of IP therapy is needed to improve outcomes. CRS+ HIPEC is feasible in all groups of ovarian cancer with acceptable morbidity &amp; mortality. However the role of single HIPEC in comparison to 6 cycles of IP chemotherapy needs to be evaluated with a well-designed multi-institutional randomised study. [Table: see text]

Adherence and adverse events of intraperitoneal chemotherapy in optimally debulked ovarian cancer patients: Real-life study.

Intraperitoneal with intravenous chemotherapy (IP/IV) is the recommended option for patients with stage III cancer with optimally debulked (<1 cm residual) disease based on randomized controlled trials and showing important improvements in overall survival and progression free survival. However, its application has not been largely adopted due to its difficult administration that requires a trained nurse staff. The aim of this work was to study the completion and the toxicity of an IP outpatient chemotherapy regimen in optimally debulked stage III ovarian cancer patients. A single-center, retrospective observational study in women with stage III ovarian cancer following optimal cytoreductive surgery (<1 cm) followed by IP/IV chemotherapy from 2009 to 2017. The IP/IV regimen was as it follows: IV paclitaxel 175 mg/m2 in 3 h, day 1; IP cisplatin (100 mg/m2-until December 2013-or 75 mg/m2), day 2; IP paclitaxel 60 mg/m2, day 8, each 21 days for six cycles. A total of 60 patients received IP/IV regimen. Of these, 41 patients (68.3%) completed the six IP chemotherapy cycles and 51 (84.9%) completed four or more cycles. Most of the adverse events reported were non-hematological and G1-2. There was no difference neither in adherence nor in the frequency of adverse events between both cisplatin groups. Despite a high rate of adverse events, IP chemotherapy can be delivered with a high completion rate and manageable toxicity to patients with optimally debulked ovarian cancer.

Intraperitoneal chemotherapy following neoadjuvant chemotherapy and optimal interval tumor reductive surgery for advanced ovarian cancer

ObjectivesIntraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and interval tumor reductive surgery (TRS) for advanced ovarian cancer is feasible, however, the impact on disease outcomes remains unclear. We compare outcomes of patients treated with IP chemotherapy versus intravenous (IV) chemotherapy following NACT and interval TRS. MethodsIn this retrospective review, patients with advanced ovarian cancer were included if they received NACT followed by optimal interval TRS between 1/2004 and 4/2017. Patients were excluded if they had an ECOG PS >1, received >6 cycles of NACT or postoperative chemotherapy, and/or received bevacizumab during primary therapy. Primary outcomes were progression free survival (PFS) and overall survival (OS). ResultsThere were 134 patients included in this study, 37 (28%) received IP and 97 (72%) received IV chemotherapy postoperatively. Patients in the IV group were older (median 66.3 vs 59.7 years, p = 0.0039) though there were no differences in BMI, race, BRCA status, stage, or histology. Median PFS was 3 months longer in the IP group (14.5 versus 11.5 months, p = 0.028) however there was no significant difference in OS. On univariate analysis, increasing number of NACT cycles (HR 1.914, 95% CI 1.024–3.497) and residual disease at completion of TRS (HR 1.541, 95% CI 1.042–2.248) were associated with decreased PFS; IP chemotherapy was associated with increased PFS (HR 0.633, 95% CI 0.414–0.944). These associations remained on multivariate analysis. Toxicity was comparable between the groups. ConclusionsIP after NACT and optimal interval TRS was associated with in improved PFS compared to IV chemotherapy without significant differences in toxicity.

Preliminary study of S-1 maintenance therapy in extensive stage small-cell lung cancer.

e20080 Background: 4-6 cycles platinum and etoposide (EP) or platinum and irinotecan (IP) chemotherapy is the mainstay treatment for the extensive-stage small-cell lung cancer (SCLC); but the role of maintenance treatment is not fully understood. This study compared the efficacy and toxicities of 4-6 cycles EP or IP chemotherapy treatment followed by S-1 maintenance treatment or placebo control. Methods: In this phase 2, open-label, three-center preliminary study, patients who reached complete response (CR), partial response (PR) or stable disease (SD) after 4-6 cycles of EP or IP therapy were randomly assigned (1:1) with a minimization procedure. One group received oral S-1 25mg/mg2 twice a day as maintenance treatment until disease progression or unacceptable toxic effects. The other group was received placebo and routine follow-up. The primary end point of this study was progression-free survival (PFS) and the secondary end points were response rates, toxicities and overall survival (OS). This trial was registered with ClinicalTrials.gov, number NCT03769935. Results: A total of 89 patients were enrolled, of whom 45 received S-1 maintenance therapy and 44 received placebo. The median PFS was 6.35 months in the S-1 group, as compared with 5.98 months in the placebo group (hazard ratio for progression in the S-1 group, 1.057; 95% confidence interval [CI], 0.656-1.707; P = 0.820). The median OS was 10.82 months in the S-1 group, as compared with 10.09 months in the placebo group (hazard ratio for death in the S-1 group, 0.860; 95% CI, 0.374-1.617; P = 0.905). Tumor regression rate influenced patients’ survival. The PFS was 7.2 months and 5.3 months (p = 0.015), and OS was 12.9 months and 10.9 months (p = 0.042) in patients with CR or PR compared to in patients with SD after induction chemotherapy respectively. The adverse events were mild to moderate skin rash and acne, diarrhea, alopecia, dry skin and fatigue; which were mainly induced by induction chemotherapy and S-1 administration. Conclusions: S-1 maintenance treatment for extensive-stage SCLC had acceptable toxicities; however, there was no significant difference in PFS or OS statistically. Further research with novel agents in the maintenance setting is warranted. Clinical trial information: NCT03769935.

Hyperthermic IP chemotherapy in ovarian cancer cost effective

Hyperthermic IP chemotherapy in ovarian cancer cost effective

A 3D CFD model of the interstitial fluid pressure and drug distribution in heterogeneous tumor nodules during intraperitoneal chemotherapy

Although intraperitoneal chemotherapy (IPC) has evolved into an established treatment modality for patients with peritoneal metastasis (PM), drug penetration into tumor nodules remains limited. Drug transport during IPC is a complex process that depends on a large number of different parameters (e.g. drug, dose, tumor size, tumor pressure, tumor vascularization). Mathematical modeling allows for a better understanding of the processes that underlie drug transport and the relative importance of the parameters influencing it. In this work, we expanded our previously developed 3D Computational Fluid Dynamics (CFD) model of the drug mass transport in idealized tumor nodules during IP chemotherapy to include realistic tumor geometries and spatially varying vascular properties. DCE-MRI imaging made it possible to distinguish between tumorous tissues, healthy surrounding tissues and necrotic zones based on differences in the vascular properties. We found that the resulting interstitial pressure profiles within tumors were highly dependent on the irregular geometries and different zones. The tumor-specific cisplatin penetration depths ranged from 0.32 mm to 0.50 mm. In this work, we found that the positive relationship between tumor size and IFP does not longer hold in the presence of zones with different vascular properties, while we did observe a positive relationship between the percentage of viable tumor tissue and the maximal IFP. Our findings highlight the importance of incorporating both the irregular tumor geometries and different vascular zones in CFD models of IPC.

Novel Surgical Strategies in the Treatment of Gynecological Malignancies.

The main advancement in the surgical treatment of early cervical cancer has been a de-escalation in the radical surgical approach of early stage disease. Similarly, sentinel lymph node detection with cervical tracer injection can be performed alone in microscopic tumors (stage IA) while additional lymphadenectomy is still performed in macroscopic tumors (IB1 and IIA). Parametrial resection has been progressively reduced in tumors less than 2cm, and simple procedures, conservative (trachelectomy) or not (simple hysterectomy), are currently being evaluated in several phase III trials. Since the preliminary results of the LACC (locally advanced cervical cancer) trial, the value of minimally invasive surgery as the standard approach for the treatment of early stage cervical cancer has been questioned and patients should be aware when discussing the approach for radical hysterectomy. While awaiting the results of ongoing clinical trials comparing radiological and surgical staging in locally advanced cervical cancer patients, surgical staging with paraaortic lymphadenectomy remains the standard of care before definitive chemoradiotherapy in patients with negative aortic PET/TDM. Patients undergoing salvage surgeries for isolated pelvic recurrences of cervical cancer benefit from advanced reconstructive techniques as DIEP flaps and continent reconstructive urinary techniques. In selected patients, a minimally invasive approach can be considered. Surgery is the mainstay of the treatment of endometrial cancer. The major evolution in surgical strategy has occurred in lymph node staging. The standard surgical staging includes pelvic and paraaortic lymph node dissection to the level of the left renal vein. Sentinel lymph node dissection has been validated as a less morbid alternative of systematic lymphadenectomy, indicated in patients with low and intermediate risk of lymph node involvement. In advanced ovarian cancer, complete cytoreduction is the main objective of surgery. To achieve this goal, upper abdominal complex procedures have been developed. Best survival rates are obtained with primary debulking surgery. Exploratory laparoscopy may be performed before cytoreduction to evaluate resectability and thus avoid unnecessary laparotomy. Although systematic pelvic and paraaortic lymphadenectomy is being questioned in patients with advanced ovarian cancer and clinically negative lymph nodes undergoing complete primary debulking surgery, this procedure is still recommended. While waiting publication of the GOG 252 trial, IP chemotherapy after complete CRS is under debate. HIPEC after interval debulking surgery in patients undergoing complete cytoreduction is an intriguing new option. Patients within the first recurrence of ovarian cancer, with score AGO-positive, benefit from a second complete cytoreductive surgery followed by chemotherapy. Ovarian cancer survival rates are higher in specialized high-volume centers, and thus cases should be centralized and quality indicators used.

Evaluation of the efficacy and toxicity profile associated with intraperitoneal chemotherapy use in older women

ObjectiveIntraperitoneal (IP) chemotherapy (CT) for treatment of epithelial ovarian cancer (EOC) has been shown to provide a substantial OS advantage. This study aims to compare the toxicity and benefits of IP CT in patients ≥70 with those <70. MethodsWe performed a single institution retrospective review of patients diagnosed with Stage IIA-IIIC EOC from 2000 to 2013 who received IP CT. Clinicopathologic characteristics were extracted, and survival was calculated. Results133 patients were included with 100 pts. <70years old and 33 pts. ≥70years old. Clinical trial enrollment was similar despite age. In trial enrolled patients, older patients received statistically fewer cycles of therapy (6.4 vs 5.8, p=0.002) but had similar dose delays (0.9 vs 0.7, p=0.72), and modifications (0.9 vs 0.36, p=0.11). Median PFS (27 vs 31months) and OS (71 and 62months) were not statistically different. Grade 3/4 neutropenia was significantly worse in the older patients (82% vs 100%, p=0.04). Neuropathy grade ≥2 and other non-hematologic toxicities were not different between age groups. ConclusionsDespite completing fewer cycles of IP CT, older EOC patients had comparable survival to younger patients. The population of older patients receiving IP CT in this study were on clinical trial and likely to be heartier than the general older population. IP CT appears well tolerated and effective among select older patients and is likely under-utilized outside of clinical trials.

Stage IV colorectal cancer: An NCDB analysis of the surgical treatment of peritoneal carcinomatosis versus liver metastases.

e15067 Background: Traditionally, peritoneal carcinomatosis (PC) secondary to colorectal cancer (CRC) was perceived as a terminal disease, for which the only palliation was offered. With the emergence of new surgical approaches such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), surgical intervention in select patients with ‘curative’ intent was made possible. In this study, we compared the outcomes of the surgical intervention on stage IV CRC patients with isolated liver metastases (LM) to those with PC only. Methods: The National Cancer Database (NCDB) for CRC was analyzed excluding patients with PMP. Patients with isolated LM or with PC were identified, then divided into 2 treatment groups per the current treatment of each scenario: LM patients treated with surgery±chemotherapy (LM group), and PC patients treated with surgery+chemo±HIPEC (PC group). Results: 21,829 patients were identified; 18,932 fell in the LM group, and 2,897 in the PC group. Mean age in the LM and PC groups was 62.94±13.54 vs. 59.59±13.73. No significant difference was noted in the 30-day readmission rates (6.0% vs. 6.6%; p = 0.103). LM group had higher rates of 30- and 90-day mortality (4.3% vs. 0.3% and 8.6% vs. 1.8%, respectively; p &lt; 0.0001), but a slightly shorter hospitalization (7.70±8.64 vs. 7.92±7.07; p = 0.024) Median overall survival was not different between the groups (27.3 vs. 25.36 months; p = 0.214). Conclusions: Surgery with systemic and IP chemotherapy can be a viable treatment option in stage IV CRC patients with PC with comparable short-term and survival outcomes to the widely accepted liver resection in patients with isolated LM.

Safety and efficacy outcomes for patients ages 65 and older treated with dose-dense chemotherapy for epithelial ovarian cancer.

e17058 Background: Dose-dense chemotherapy is increasingly more utilized in the adjuvant treatment of patients (pts) with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC), as compared to the conventional q3 week chemotherapy regimen. The safety and tolerability of the dose-dense regimen in pts ≥65 yrs old has not been well studied. We performed a retrospective analysis of pts with stage II-IV EOC treated at our institution with either regimen. Methods: We identified pts with stage II-IV EOC treated at Northwell Health from 2010-2015 who received adjuvant chemotherapy with the dose-dense (carboplatin q3 weeks/weekly paclitaxel) or the conventional (carboplatin and paclitaxel q3 weeks) regimen. Pts who received IP chemotherapy were excluded. Demographics, adverse events (AEs), dose delays/reductions and efficacy outcomes were evaluated. Results: 38 pts received conventional chemotherapy (median age 68 yrs) and 29 pts received dose-dense chemotherapy (median age 61 yrs). There were no differences in the frequency of grade ≥3 hematologic toxicities b/w the two arms. There were no differences in delayed or missed doses between the two arms but a higher proportion of dose reductions in the dose-dense arm ( P= 0.0472). Among pts treated in the dose-dense arm, 87.5% of women &lt; 65 yrs old had at least one grade ≥3 AE when compared to 38.5% of women ≥ 65 yrs old ( P= 0.0161). There were no differences in dose delays, dose reductions, or missed doses when compared by age in the dose-dense arm. In the dose-dense arm, stage III-IV pts &lt; 65 yrs old had a median time to progression (TTP) of 13.0 mo (95% CI, 6.7-13.8) and a median overall survival (OS) of 48.3 months (95% CI, 11.5-48.3). Pts ≥ 65 yrs old had a median TTP of 10.9 mo (95% CI, 8.7-12.7) and median OS of 35.9 mo (95% CI, 30.8-not reached). There was no difference in TTP ( P= 0.2154) or OS ( P= 0.9260) between the two cohorts. Conclusions: Our institutional experience of administering dose-dense adjuvant chemotherapy to women with EOC suggests that this regimen is likely safe in women ≥ 65 yrs old, with similar efficacy outcomes and should be considered for this population. Further study with larger sample sizes and in prospective trials is warranted.

Adjuvant intraperitoneal chemotherapy for the treatment of gastric cancer at risk for peritoneal carcinomatosis: A systematic review.

The peritoneal surface is a frequent site of recurrence following surgery for gastric cancer. A systematic review and random effect analysis was undertaken to analyze current literature regarding the role of adjuvant intraperitoneal chemotherapy in gastric cancer. While pooled analysis supports the use of adjuvant IP chemotherapy in resectable gastric cancer, maximal benefit occured with intra-operative delivery, and possibly the use of MMC. J. Surg. Oncol. 2017;115:192-201. © 2016 Wiley Periodicals, Inc.

Intraperitoneal chemotherapy after interval debulking surgery for advanced-stage ovarian cancer: Feasibility and outcomes at a comprehensive cancer center

ObjectivesIntraperitoneal (IP)-based chemotherapy following primary debulking surgery (PDS), although associated with substantial toxicity, is supported by a strong evidence base. We sought to determine feasibility and outcomes of IP chemotherapy after interval debulking surgery (IDS) among patients deemed ineligible for PDS. MethodsWe identified all patients with high-grade, stage III/IV ovarian cancer treated at our institution with neoadjuvant chemotherapy (NACT) followed by IDS and postoperative chemotherapy from 1/2008–5/2013. IP and intravenous (IV) regimens were defined; demographic and clinical data were analyzed using appropriate statistics. ResultsOf 128 evaluable patients, 118 (92%) achieved ≤1cm residual disease at IDS and 74 (58%) achieved a complete gross resection (CGR). An IP port was placed in 54/128 patients (42%), with 89% port utilization. Forty-eight (38%) of 128 patients received IP chemotherapy, 17 (13%) weekly IV paclitaxel/q3week carboplatin, and 63 (49%) q3week IV carboplatin/paclitaxel. Patients completed a median of 3 IP cycles (range, 2–6), with 3 (5.5%) of 54 ports removed due to complications. Overall survival (OS) for patients with a CGR treated with IP and weekly IV chemotherapy was 53.2months (range, 24.7-NE), and 44.2months (range, 30.2-NE) with any visible residual disease (p<0.001). Median OS was 53.2months (range, 44.5-NE) for IP-, not reached for weekly IV-, and 34.2months (range, 27.5–49.8) for q3week IV-treated patients (p=0.1). ConclusionsPatients administered IP after IDS had a high rate of successful port utilization, with few regimen switches. Oncologic outcomes were optimal in patients with a CGR at IDS, regardless of chemotherapy used.

Abstract 4753: Ovarian cancer stem cell marker ALDH1A2 is a candidate biomarker for patient selection for intraperitoneal chemotherapy

Abstract Objective. To evaluate ovarian cancer stem cells as predictors of survival we analyzed associations of cancer stem cell markers ALDH1, CD117 and CD133 with survival outcomes among patients with high grade serous ovarian cancer (HGS OvCa). Methods. Data from HGS OvCa patients who were surgically staged prior to treatment with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Multivariate Cox proportional-hazards regression tested associations of tumor mRNA expression of 5 cancer stem cell markers with progression free survival (PFS) and overall survival (OS). Expression was analyzed as a continuous variable by restricted mean survival (RMS) analysis. Mean PFS or OS were compared between IP and IV groups by permutation testing stratified by expression. P-values were two-tailed. Results. Increased tumor ALDH1A2 expression was associated with decreased OS among patients treated with IP chemotherapy, HR 2.36 (1.16-4.80), p = 0.017. IP treated patients with upper 20th percentile ALDH1A2 expression had decreased OS compared to bottom 20th percentile expression (30.4 versus 51.1 months, -20.7 months difference, p = 0.017). RMS curves for PFS and OS of IP versus IV treated patients crossed at high ALDH1A2 expression, indicating that IP treated patients had decreased survival compared to IV-only treated patients. Patients with upper 20th percentile ALDH1A2 expression treated with IP versus IV-only chemotherapy had no difference in mean PFS (21.3 versus 21.6 months, -0.3 months difference, p = 0.67) and decreased OS (30.4 versus 35.3 months, -4.9 months difference, p &amp;lt; 0.0001). Upper 10th percentile ALDH1A2 expression was associated with decreased PFS (19.5 versus 22.0 months, -2.5 months, p = 0.005) and OS (27.1 versus 35.2 months, -8.1 months, p &amp;lt; 0.0001) comparing IP versus IV groups. Increased CD133 expression was associated with increased PFS among IV-only patients, HR 0.85 (0.74-0.97), p = 0.016. CD117 and the ALDH1 genes ALDH1A1/3 were not associated with survival. Conclusions. High primary tumor ALDH1A2 expression was independently associated with significantly decreased OS among patients treated with IP chemotherapy. High ALDH1A2 was associated with lack of benefit or decreased survival among patients treated with IP compared to IV-only adjuvant chemotherapy. Citation Format: Brandon-Luke L. Seagle, Monica Dandapani, Chen Hui Luo, Claire Hoppenot, Robert Samuelson, Kevin H. Eng, Kunle Odunsi, Shohreh Shahabi. Ovarian cancer stem cell marker ALDH1A2 is a candidate biomarker for patient selection for intraperitoneal chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4753.

Abstract 4754: Overexpression of TSH and ERBB2 (HER2) receptors is associated with sharply decreased survival in high grade serous ovarian cancer

Abstract Objective. To test if hormone or growth factor receptor expression is associated with survival among patients with high grade serous ovarian cancer (HGS OvCa) we analyzed tumor mRNA expression microarray and clinical data from The Cancer Genome Atlas (TCGA). Methods. HGS OvCa patients were surgically staged prior to treatment with IP (n = 90) or IV-only (n = 398) chemotherapy. Multivariate Cox proportional-hazards regression tested associations of expression of 9 hormone or growth factor receptors with progression free survival (PFS) and overall survival (OS). Hazard ratios are hazard per each one standard deviation increase in gene expression. Expression was analyzed as a continuous variable by restricted mean survival analysis. Mean PFS or OS were compared between IP and IV groups by permutation testing stratified by expression. P-values were two-tailed. Results. Expression of ESR1, PGR, FSHR, LHCGR, MET, and EGFR were not associated with PFS or OS. TSHR expression was associated with decreased OS (HR 1.22 (1.06-1.41), p = 0.005) and PFS (HR 1.18 (1.05-1.33), p = 0.006) among IV-only treated patients. ERBB2 expression was associated with decreased OS (HR 1.48 (1.05-2.10), p = 0.027) among patients who received IP chemotherapy. Using multigene (ESR2, PGR, TSHR, and ERBB2) analysis, among the IP group, ERBB2 (HR 1.76 (1.11-2.79), p = 0.015) and ESR2 (HR 0.28 (0.08-0.93), p = 0.037) were associated with OS. Only TSHR expression was associated with decreased OS (HR 1.22 (1.06-1.41), p = 0.005) and decreased PFS (HR 1.18 (1.05-1.33), p = 0.007) on multigene analysis of IV-only treated patients. OS and PFS decreased steeply at high expression of TSHR and ERBB2. Among patients with upper 10th percentile TSHR expression, no significant difference in mean OS or PFS was observed between patients treated with IP versus IV-only chemotherapy. Patients with lower TSHR expression (&amp;lt; 90% percentile) experienced a mean 13.7-month increased OS and 16.4-month increased PFS associated with IP chemotherapy (p &amp;lt; 0.0001). Conclusions. Among HGS OvCa patients treated with IV-only chemotherapy, increased tumor TSHR expression was associated with decreased OS and PFS. High TSHR expression characterized patients who did not benefit from IP chemotherapy. Citation Format: Brandon-Luke L. Seagle, Monica Dandapani, Chen Hui Luo, Claire Hoppenot, Robert Samuelson, Kevin H. Eng, Kunle Odunsi, Shohreh Shahabi. Overexpression of TSH and ERBB2 (HER2) receptors is associated with sharply decreased survival in high grade serous ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4754.

A phase III trial of bevacizumab with IV versus IP chemotherapy for ovarian, fallopian tube, and peritoneal carcinoma: An NRG Oncology Study

A phase III trial of bevacizumab with IV versus IP chemotherapy for ovarian, fallopian tube, and peritoneal carcinoma: An NRG Oncology Study

Patient-reported outcomes in GOG 252: NRG Oncology Study of IV vs IP chemotherapy for ovarian, fallopian, or peritoneal carcinoma

Patient-reported outcomes in GOG 252: NRG Oncology Study of IV vs IP chemotherapy for ovarian, fallopian, or peritoneal carcinoma

Complications associated with 9–10 Fr venous access port use in adjuvant intraperitoneal chemotherapy after a cytoreductive surgery in ovarian cancer patients

PurposeTo determine the complication rate associated with using a single-lumen intravenous access port with a silicone catheter of 9–10Fr size in the intraperitoneal treatment, including hyperthermic intraperitoneal chemotherapy, in ovarian cancer. Patients/methodsWe reviewed 27 patients who had subcutaneous venous access ports placed for the administration of IP chemotherapy. With four patients, the catheter was implanted during a hyperthermic intraperitoneal chemotherapy-related laparotomy using the closed technique. Each case was categorized as to the number of cycles of IP therapy received. ResultsSeven catheter-related complications were noted. These were divided into two categories: six malfunctions (24%) and one infection (4%). Overall, of the patients who had IP catheters placed and received IP chemotherapy, 13 (54.2%) were able to complete the six regimens. Among the four (14.8%) patients who had the catheters planted directly following the HIPEC, one experienced a catheter leak, one an infection and one concluded the treatment successfully; one is still being treated. ConclusionsA subcutaneous single-lumen intravenous access port with a silicone catheter of a large size (9–10Fr) is related to a lower rate of catheter-related complications than previously reported open-ended Tenckhoff catheter treatment. An additional advantage is the possibility of removing the catheter as an office procedure under local anesthesia. Intraperitoneal chemotherapy following a HIPEC procedure may cause increased occurrence of catheter-related complications. As of 2010 we have been using silicone subcutaneous catheters in our center.