Adjuvant Intraperitoneal Chemotherapy Research Articles

Predictive nomogram of the risk of peritoneal relapse following radical gastric cancer surgery

Background: Peritoneal relapse (PR) is the most common pattern of gastric cancer (GC) recurrence after radical treatment. Currently, a variety of adjuvant intraperitoneal chemotherapy methods are being tested for their efficacy in reducing the level of PR. The investigation of prospective predictors of metachronous peritoneal metastases enables us to develop a predictive nomogram of peritoneal relapse risk of GC after radical surgery, which is crucial in surgical oncology today. Such a nomogram will allow clinicians to easily and quickly identify a group of patients who require adjuvant intraperitoneal chemotherapy.

ПРЕДИКТИВНА НОМОГРАМА РИЗИКУ ІНТРАПЕРИТОНЕАЛЬНОГО РЕЦИДИВУ ПІСЛЯ РАДИКАЛЬНОЇ ХІРУРГІЇ РАКУ ШЛУНКА

Background and objectives. Peritoneal relapse (PR) is the most common pattern of gastric cancer (GC) recurrence after radical treatment. Currently, a variety of adjuvant intraperitoneal chemotherapy methods are being tested for their efficacy in reducing the level of PR. Methods. The radical treatment results of 226 patients with localized and locally-advanced GC have been analyzed. In order to select a group of patients with indications for adjuvant intraperitoneal therapy, a study of independent predictive factors and the development of a predictive PR nomogram for gastric cancer was completed. Results. As a result of the analysis of about three dozen potential factors in mono- and multivariate analysis, the impact on PR risk was confirmed by 4 independent predictive factors, namely: serosal invasion and its size (HR 9.36, p <0.001), morphological type according to Lauren (HR 5.3, p <0.001), index of regional lymph node involvement (HR 2.23, p = 0.015) and localization of the tumor in the stomach (HR 3.98, p <0,001). Conclusions. A predictive PR risk nomogram of gastric cancer after radical surgical treatment has been developed based on the identified independent factors, and it is of great clinical importance as a tool for segregating patients who require adjuvant intraperitoneal chemotherapy.

A genomically stable molecular type of gastric cancer as a predictor of peritoneal relapse after radical surgical treatment

Peritoneal metastases are commonly associated with gastric cancer (GC) recurrence after radical treatment. Thus, patients at a high risk of peritoneal relapse require adjuvant intraperitoneal chemotherapy during the initial treatment. Along with clinical and morphological predictors of peritoneal relapse, another approach in surgical oncology is proving to be promising today. It refers to the prediction of the risk of developing metachronous peritoneal metastases in various molecular types of GC.
 Objective — to study the risk of peritoneal relapse in patients with the genomically stable type of GC in comparison to its other molecular types.
 Materials and methods. 37 patients with GC were enrolled into the study and evaluated after the radical treatment. 19 (51.4 %) patients formed a subgroup with peritoneal relapse and 18 patients (48.6 %) were included into a subgroup without metachronous carcinomatosis in the long term. All patients underwent immunohistochemical study for the E‑cadherin (CDH1 gene) expression in a gastric tumor. The genomically stable molecular type was identified on the basis of the aberrant E‑cadherin (CDH1‑mutated) tumor phenotype detection.
 Results. There was a statistically significant difference (p = 0.022, χ2 = 5.22) in the degree of aberrant E‑cadherin expression in subgroups of patients with and without peritoneal relapse — 68.4 and 33.3 %, respectively. Hence, it was noted that the genomically stable molecular type had a significant influence on the risk of peritoneal recurrence: the 2‑year peritoneal relapse‑free survival of GC patients with E‑cadherin of aberrant type was 31.6 %, and in GC patients with wild‑type E‑cadherin expression — 71.4 % (p = 0.022). The 2‑year overall survival of GC patients with aberrant type E‑cadherin expression was 36.8 %, whereas in GC patients with E‑cadherin of the wild type — 77.8 % (p = 0.003).
 Conclusions. The study found that the genomically stable molecular type of GC may serve as a predictive factor associated with an increased probability of peritoneal relapse, as well as a prognostic factor due to its negative impact on patient prognosis. The genomically stable molecular type of GC may be used as a tool for forming a cohort of patients with indications for adjuvant intraperitoneal therapy.

The Role of expedited adjuvant intraperitoneal chemotherapy in locally advanced colorectal cancer - a systematic review

Introduction: Locally advanced colorectal cancer (LACRC), defined as T4 N0-2 M0 tumours, frequently metastasizes intraperitoneally. Peritoneal metastases occur in 41% of T4 tumours, and augur significant morbidity and mortality. Adjuvant intraperitoneal chemotherapy targets micro-metastatic deposits from the primary tumour which may progress to peritoneal carcinomatosis. We systematically reviewed the effect of intraperitoneal chemotherapy delivered within a month of cytoreductive surgery on outcomes in LACRC.

Feasibility of neoadjuvant and adjuvant intraperitoneal chemotherapy in patients with advanced epithelial ovarian cancer: A single-center experience.

Intraperitoneal (IP) chemotherapy is believed to prolong the survival of patients with advanced ovarian cancer after primary debulking surgery. However, there is little knowledge about IP chemotherapy in the setting of neoadjuvant chemotherapy, and there are contradictory conclusions about adjuvant IP chemotherapy. Here, we evaluated the feasibility of neoadjuvant and adjuvant IP chemotherapy in patients with advanced epithelial ovarian cancer (AEOC).We retrospectively reviewed the data of 114 patients with AEOC who received neoadjuvant chemotherapy followed by laparoscopic conservative interval debulking surgery (NACT + LIDS) in our institution from January 1, 2009 to December 31, 2017.The median overall survival (OS) was 56 months and the median disease-free interval (DFI) was 14 months for the entire study population. Neoadjuvant IP chemotherapy cycles were crucial for the treatment of no gross residual (R0) disease (hazard ratio [HR] = 0.446, 95% confidence interval [CI] = 0.245–0.811), which was independently associated with OS of the entire study population (HR = 9.589, 95% CI = 3.911–23.507). In addition, residual disease and body mass index (BMI) were the prognostic factors for DFI (HR = 6.022, 95% CI = 3.632–9.986; HR = 1.085, 95% CI = 1.012–1.163). However, adjuvant IP cycles along with BMI were the determining factors for DFI in the R0 group (HR = 0.703, 95% CI = 0.525–0.941; HR = 1.130, 95% CI = 1.025–1.247), and were associated with OS in the R0 group (HR = 0.488, 95% CI = 0.289–0.824). The OS and DFI Kaplan-Meier curves stratified by adjuvant IP chemothearpy cycles within the R0 group were statistically significant (P = .024 and P = .033, respectively).Our results showed improvement in patients with AEOC in terms of survival, thus suggesting the feasibility of neoadjuvant and adjuvant IP chemotherapy.

Clinical benefit and tolerability of adjuvant intraperitoneal chemotherapy in patients who have or have not received neoadjuvant chemotherapy for advanced ovarian cancer.

BACKGROUNDAdjuvant chemotherapy using intraperitoneal (IP) treatment has demonstrated survival benefit over intravenous (IV) therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian cancer. Neoadjuvant chemotherapy followed by interim surgery and adjuvant chemotherapy has similar outcome in survival as compared to upfront surgery followed by adjuvant IV chemotherapy. IP chemotherapy has not been widely adopted in clinical practice for a number of reasons. Whether IP chemotherapy delivered in the patients who received neoadjuvant chemotherapy can be well tolerated or confers any clinical benefit has not been well studied.AIMTo evaluate the experience of adjuvant IP chemotherapy in the community cancer clinic setting, and the clinical benefit and tolerability of incorporating IP chemotherapy in patients who received neoadjuvant treatment.METHODSWe retrospectively evaluated toxicities and outcomes of patients with stage III and IV ovarian cancer diagnosed at our institution between 07/2007 and 07/2015 who received intraperitoneal chemotherapy after cytoreductive surgery (group 1) or after neoadjuvant chemotherapy followed by interim surgery (group 2).RESULTSThirty eight patients were treated with IP chemotherapy, median age was 54 years old (range 38.6 to 71 years). In group 1 (n = 25), 12 (48%) of the patients completed 4 or more cycle of IP treatment after upfront debulking surgery; while in group 2 (n = 13), 8 (61.5%) of the patients completed all 3 cycles of the assigned IP chemotherapy after receiving neoadjuvant IV chemotherapy followed by surgery, and 2 (15.4%) more patients tolerated more than 3 cycles. In those patients who did not get planned IP chemotherapy, most of them were treated with substitutional IV chemotherapy, and the completion rate for 6 cycles of IV + IP was 92%. Abdominal pain, (64% in group 1 and 38% in group 2), vomiting, (36% in group 1 and 30.8% in group 2), dehydration (16% in group 1 and 15.4% in group 2), and hypomagnesemia (12% in group 1 and 15.4% in group 2) were the most common adverse effects in all patients, while patients who have received neoadjuvant chemotherapy were more likely to get hypokalemia, fatigue and renal insufficiency. Progression free survival (PFS) was 26.5 mo (95% CI 14.9, 38.0) in group 1 and 27.6 mo (95% CI 13.1, 42.1) in group 2. The overall survival was 100.2 mo (95% CI 67.9, 132.5) for group 1 and 68.2 mo (95% CI 32.2, 104.0) for group 2. For the entire cohort, PFS was 26.5 mo (95% CI 15.9, 37.0) and OS was 78.8 mo (95% CI 52.3, 105.4).CONCLUSIONThe use of IP/IV chemotherapy can be safely administrated in the community cancer clinic setting. The use of IP/IV chemotherapy in patients who have received neoadjuvant chemotherapy followed by surgery is feasible and tolerable. Despite various modification of the IP regimen, incorporation of IP chemotherapy in the adjuvant setting appears to be associated with improved PFS and overall survival.

Intraperitoneal perfusion chemotherapy and whole abdominal hyperthermia using external radiofrequency following radical D2 resection for treatment of advanced gastric cancer

Background: The peritoneum is the most frequent site of disease recurrence in gastric cancer, and the prognosis remains poor. This study assessed the role of adjuvant intraperitoneal (IP) chemotherapy with whole abdominal hyperthermia using external radiofrequency in gastric cancer patients after D2 dissection.Methods: Patients with gastric cancer who underwent gastrectomy with D2 regional lymph node dissection were enrolled in the study. Patients received IP chemotherapy with whole abdominal hyperthermia. Preheated normal saline containing 75 mg/m2 of cisplatin was delivered into the abdominal cavity through a Tenckhoff catheter at McBurney’s point. Regional hyperthermia was performed using two sets of orthogonal radiofrequency waves immediately after all saline was irrigated into the abdominal cavity. For each patient, recurrent or metastatic sites and adverse events were evaluated.Results: A total of 22 patients were finally included. All patients tolerated hyperthermia well. Only two patients experienced grade 1 superficial thermal injury. The most frequent grade 3/4 adverse events were myelosuppression, nausea/vomiting, trichomadesis and liver dysfunction. We also found IP chemotherapy with whole abdominal hyperthermia could reduce the total recurrent/metastatic rate, especially peritoneal metastasis (4.5%).Conclusions: This hypothesis-generating study indicated that IP chemotherapy with whole abdominal hyperthermia might be feasible for gastric cancer patients after D2 resection.

Does Neoadjuvant Chemotherapy Impact Prognosis in Advanced-Stage Epithelial Ovarian Cancer Optimally Debulked at Surgery?

Neoadjuvant chemotherapy (NAC) has been shown to be noninferior to primary surgery in advanced stage ovarian cancer. We examined the impact of the neoadjuvant approach in patients with optimal residuals (<1 cm). Retrospective review of optimally debulked stage 3/4 ovarian cancer was performed. Chi-square tests were used to detect significant associations between categorical variables. A Cox regression model was built to predict patients' overall survival, adjusting for age, tumour grade, histology, use of adjuvant intraperitoneal chemotherapy, residual status, and primary treatment modality. One hundred one patients were reviewed. Median age was 60.5 (range 39-85). NAC was used in 34 patients. Serous histology was documented in 60 of 101 patients (59%). Microscopic residuals were achieved in 70 patients (69%). There was no significant association between primary treatment modality and microscopic residuals status. With a median follow-up time of 33 months, progression was observed in 53% of patients, with a median progression-free survival of 19.4 months. The use of NAC was an independent adverse prognostic factor (hazard ratio 5.79; 95% CI 2.15-15.55, P = 0.001) for overall survival. Macroscopic residual was an independent adverse prognostic factor (hazard ratio 10.76; 95% CI 2.98-38.89, P < 0.001). The overall Kaplan-Meier median survival estimate was 54.5 months (95% CI 50.64-58.36) in the primary surgery group compared with 41.43 months (95% CI 35.58-47.29) in those given NAC (P = 0.002) CONCLUSION: Primary surgery should be the preferred approach in patients with an initial high likelihood of being optimally cytoreduced.

Patients with BRCA mutations have superior outcomes after intraperitoneal chemotherapy in optimally resected high grade ovarian cancer

ObjectivesTo compare the outcomes after intraperitoneal (IP) chemotherapy in patients with and without pathogenic BRCA mutations. MethodsPatients with high grade ovarian cancer who were treated with adjuvant IP chemotherapy in the initial setting between 2005 and 2016 were identified. Outcomes were compared between patients with pathogenic mutations in BRCA (BRCA+) and those who tested negative or were unknown (BRCA−). ResultsA total of 100 eligible patients were identified. The median follow-up was 47.0 months (range, 6.6–144.1 months). Of these 100 patients, 77 patients underwent BRCA testing; 25 patients (32%) were BRCA+ (23 germline, 2 somatic). No differences were noted between groups with respect to number of IP cycles, stage, or residual disease after surgery. The median progression-free survival (PFS) was longer in the BRCA+ group; median PFS was not reached in the BRCA+ group compared to 17.3 months in the BRCA− group (HR = 0.38; 95% CI 0.20–0.73, P = 0.003). Median overall survival (OS) was longer in the BRCA+ group at 110.4 months versus 67.1 months (HR = 0.28, 95% CI 0.11–0.73, P = 0.009). ConclusionsPathogenic BRCA mutations are more common than expected in optimally resected ovarian cancer patients selected for IP therapy. IP therapy was associated with a dramatic improvement in PFS and OS in BRCA+ patients compared with BRCA− patients. This improvement is greater than has been reported for BRCA+ patients with IV chemotherapy. The magnitude of this benefit suggests that patients with pathogenic mutations in BRCA may benefit from IP therapy.

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.

Efficacy and safety of adjuvant intraperitoneal chemotherapy in carcinoma ovary: A prospective observational study.

e17069Background: It has been demonstrated in few trials, that intraperitoneal and intravenous (IP/IV) chemotherapy improves survival in advanced stage ovarian cancer. But it has been associated wi...

Clinical benefit and tolerability of adjuvant intraperitoneal chemotherapy in patients who received neoadjuvant treatment for advanced ovarian cancer.

e17054Background: Adjuvant chemotherapy using intraperitoneal (IP) treatment has demonstrated survival benefit over intravenous (IV) therapy alone in patients treated with upfront debulking surgery...

Study of efficacy and safety of modified adjuvant intraperitoneal chemotherapy regimen in carcinoma ovary.

It has been demonstrated in few trials that intraperitoneal and intravenous (IP/IV) chemotherapy improves survival in advanced stage ovarian cancer (OC). However, in view of high treatment-related toxicities, various modifications in treatment schedules have been tried. In this study, response and tolerability of IP paclitaxel on day 8 with IV paclitaxel on day 1 and IV cisplatin day 2 in carcinoma ovary were evaluated. In this prospective observational study, from March 2013 to December 2015, the efficacy and tolerability of adjuvant IP/IV chemotherapy in optimally cytoreduced Stage III epithelial OC (EOC) patients were assessed. Totally, sixty patients were enrolled. The median age of patients was 53 years (32-67 years). Out of a total of 360 IP cycles, 316 cycles (88%) were completed. Forty-five patients (76%) received all the 6 cycles by IP route. Eight out of those 45 patients had one or more adjustment including delay or dose reduction. After median follow-up of 22 months, eight patients (14%) had local or systemic recurrence. Median progression-free survival not reached yet. Catheter block was seen in five cases. Two cases had needle displacement and extravasations of drug around the port chamber. Six patients had Grade 3 abdominal pain and cramp. Grade 3/4 leukopenia was experienced by thirty patients (50%), but febrile neutropenia occurred in only 6 (10%) patients. Renal complication present in 4 (7%) patients. In Indian patients, adjuvant chemotherapy with day 8 I/P paclitaxel in optimally cytoreduced EOC is associated with comparable survival outcomes, less side effects and high treatment completion rate relative to literature published from Western countries.

Should we use the hyperthermic intraperitoneal chemotherapy in the management of ovarian cancer? A literature review

Rationale: Epithelial ovarian cancer (EOC) is a relatively chemosensitive malignancy which begins, and most frequentlydisseminates by intraperitoneal seeding. Intraperitoneal chemotherapy (IP) is a route of drug delivery that allows the directinfusion of the chemotherapeutic agents into the peritoneal cavity. It has been proven to be efficient and with lower systemic sideeffects in comparison to the intravenous (IV) route. The combination between hyperthermia and intraperitoneal chemotherapy(Hyperthermic intraperitoneal chemotherapy) has a synergistic killing effect on the malignant cells and appears to be feasible inthe treatment of EOC. Objective: To review the current literature and discuss the use of HIPEC in the course of the EOC treatment: as first line medicaltreatment, at the time of cytoreductive surgery (CS), postoperative adjuvant IP chemotherapy and HIPEC, and for recurrentdisease focusing on the survival benefit, mortality rates, morbidity, adverse effects and limitations. Method: Medline, Pubmed, and the Cochrane Central Register of Controlled Trials (CENTRAL ) were investigated for Englishlanguage articles about the role of HIPEC in women with primary EOC, of any FIGO stage. The analysis was restricted toretrospective studies, randomized and nonrandomized controlled clinical trials, and gynecological oncology journals. The selectedinformation included data on feasibility, overall survival (OS), quality of life, and comparison with standard IV chemotherapy interms of complications, toxicity and anticancer effects. Conclusion: Hyperthermia of the IP chemotherapy solution increases the cytotoxicity of the drug in the peritoneal cavity andits systemic effects on the tumor peritoneal nodules. Although initial investigators presented encouraging survival outcomeswhen HIPEC was used in recurrent EOC, further studies are necessary in order to incorporate HIPEC as a front-line treatmentof EOC or as an adjuvant therapy. More research is required for defining the possible roles of HIPEC within the spectrum ofother treatments for EOC including repeated normothermic IP chemotherapy, early postoperative IP chemotherapy, and novel andbiological agents.

Subsequent chemotherapy is well tolerated in patients who underwent primary adjuvant intraperitoneal chemotherapy for ovarian, fallopian and primary peritoneal cancers

Objectives: Intraperitoneal (IP) chemotherapy is known to be more toxic than standard intravenous chemotherapy in the upfront setting. Our objective was to determine toxicities of subsequent chemotherapy in a cohort of patients who had previously received IP chemotherapy for advanced stage ovarian, fallopian tube and primary peritoneal cancers.

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.

Intraperitoneal chemotherapy as adjuvant treatment to prevent peritoneal carcinomatosis of colorectal cancer origin: a systematic review

Background:Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is associated with poor outcome. This systematic review evaluates the available evidence about adjuvant (hyperthermic) intraperitoneal chemotherapy ((H)IPEC) to prevent the development of PC.Methods:A systematic search of literature was conducted in August 2013 in PubMed, Embase, and the Cochrane database for studies on (H)IPEC to prevent PC in patients who underwent curative surgery for primary CRC.Results:Seven comparative studies and five cohort studies were selected. Treatment schedules varied between repeated fluoropyrimidine-based IPEC administration in the ambulatory setting to intra-operative (H)IPEC procedures using mitomycin-C or oxaliplatin. The reported rates of major complications related to adjuvant (H)IPEC was low. Four out of five evaluable comparative studies reported a significant difference in the incidence of PC in favour of (H)IPEC. All three comparative studies reporting on survival after intra-operative (H)IPEC showed a significant survival benefit in favour of the experimental arm. Substantial heterogeneity in patient selection, treatment protocols, and treatment effect evaluation among studies was observed.Conclusions:The currently available evidence about adjuvant (H)IPEC in high-risk CRC is limited and subject to bias, but points towards improved oncological outcome and supports further randomised studies.

Does Modality of Adjuvant Chemotherapy After Interval Surgical Debulking Matter in Epithelial Ovarian Cancer?: An Exploratory Analysis

This article aimed to study the role of adjuvant intraperitoneal (IP) chemotherapy after neoadjuvant chemotherapy and optimal interval surgical debulking. All patients with epithelial ovarian cancer treated with neoadjuvant chemotherapy were retrospectively reviewed from 2007 to 2009. Demographics, related diseases, and survival outcome data were abstracted from the medical records. χ statistics were applied to categorical variables. Cox regression was used to model progression-free survival (PFS), adjusting for age, residual status, and use of adjuvant IP chemotherapy. All P values less than 0.05 were considered statistically significant. Sixty-five patients were reviewed. The median age was 63.3 years. The majority had stage III disease with serous histology. Optimal residual (<1 cm) after interval debulking was achieved in 34 (54%) of 63 patients. Sixteen patients chose to receive adjuvant IP chemotherapy. The median follow-up was 26.2 months. Fifty-one patients had progressed, with a median PFS of 17.5 months. Adjuvant IP chemotherapy was not predictive of PFS (hazard ratio, 0.91; 95% confidence interval [CI], 0.24-3.44; P = 0.89). The estimated median overall survival was 37.8 months (95% CI, 29.9-45.7) in the intravenous group versus 48.1 months (95% CI, 37.9-58.3) in the IP-treated patients (P = 0.162). Adjuvant IP chemotherapy was not predictive of survival after neoadjuvant chemotherapy in our small exploratory study. The role of IP chemotherapy in this setting needs to be further studied in a larger prospective patient cohort.

Factors predicting peritoneal recurrence in advanced gastric cancer: implication for adjuvant intraperitoneal chemotherapy

Despite adjuvant chemotherapy, patients with advanced gastric cancer (AGC) often develop recurrence, and the peritoneum is the most common site of recurrence. Therefore, intraperitoneal chemotherapy (IPC) has been proposed as a treatment option. The aim of this study was to select the eligible patients for application of IPC. A total of 805 patients with AGC who underwent curative D2 gastrectomy between May 2003 and December 2009 were included in this study. Risk factors for peritoneal recurrence were analyzed. Recurrence developed in 245 patients (30.4%). The first site of recurrence was the peritoneum in 144 patients (58.8%), and the 5-year peritoneal recurrence-free survival was 79.3%. Depth of tumor invasion ≥T3, extensive lymph node metastasis (N3), Bormann type 4, infiltrative type (Ming's classification), and venous invasion were independent risk factors for peritoneal recurrence. In subgroup analysis with patients who had received adjuvant chemotherapy (n=481), depth of tumor invasion ≥T3, Bormann type 4, infiltrative type (Ming's classification), and venous invasion were independent risk factors for peritoneal recurrence. When a peritoneal recurrence risk index was made with each risk factor assigned 1 point (2 points for T4 stage), peritoneal recurrence rates with 0, 1, 2, 3, 4, or 5 points were 0%, 3.9%, 13.1%, 33.3%, 44.0%, and 72.0%, respectively, in those patients. Patients at higher risk for peritoneal recurrence can be identified from the findings of this study. Further prospective studies are required to evaluate the usefulness of IPC for these patients.

Intraperitoneal chemotherapy in ovarian cancer: a review of tolerance and efficacy.

PurposeTo review the two main approaches of intraperitoneal (IP) chemotherapy delivery in ovarian cancer: postoperative adjuvant IP chemotherapy after cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA literature search was conducted to identify studies that employed postoperative adjuvant IP chemotherapy after CRS or combined CRS and intraoperative HIPEC in patients with ovarian cancer. Data of interest included chemotherapy protocol, morbidity and mortality, and survival data.ResultsThree large randomized controlled trials comprising 707 patients with advanced ovarian cancer who received postoperative adjuvant IP chemotherapy were reviewed. Morbidity rate ranged from 56% to 94% in IP chemotherapy, and mortality rate ranged from 1% to 2%. Median disease-free survival ranged from 24 to 28 months, and overall survival ranged from 49 to 66 months. Planned chemotherapy completion rates ranged from 42% to 71%. Twenty-four nonrandomized studies that reported HIPEC comprised 1167 patients with both advanced and recurrent ovarian cancer. In patients with advanced ovarian cancer, mortality ranged from 0% to 5%, minor morbidity ranged from 16% to 90%, and major morbidity ranged from 0% to 40%. Median disease-free survival ranged from 13 to 56 months, and overall survival ranged from 14 to 64 months. Survival at 5 years ranged from 35% to 70%. In patients with recurrent ovarian cancer, the mortality rate ranged from 0% to 10%, minor morbidity ranged from 7% to 90%, and major morbidity ranged from 0% to 49%. Median disease-free survival ranged from 13 to 24 months and overall survival from 23 to 49 months. Survival at 5 years ranged from 12% to 54%.ConclusionThere is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials.