Gastrectomy after response to intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology

450 Background: Patients with peritoneal metastasis have significantly poor prognosis. We have performed pretherapeutic staging laparoscopy (SL) to diagnose peritoneal metastasis for patients with large type 3, type 4 or serosa-invasive gastric cancer. When peritoneal metastasis disappears by chemotherapy for patients with positive peritoneal cytology (CY1) or peritoneal dissemination (P1), we perform the conversion surgery (CS). Methods: We retrospectively analyzed clinical outcomes of 134 patients with advanced gastric cancer who underwent SL between 2005 from 2016. We examined safety and usefulness of CS for patients with CY1 or P1. Results: CY0P0, CY1P0 and P1 were found in 67, 28 and 39 patients, respectively. The median survival time (MST) of patients with CY0P0, CY1P0 and P1 were 39, 21 and 11 months (CY0P0 vs CY1P0; p = 0.029, CY0P0 vs P1; p<0.001, CY1P0 vs P1; p<0.001). In patients with CY1P0, 20 of 26 patients who received chemotherapy underwent the second look SL, and 14 patients (54%) underwent CS (R0) as peritoneal cytology turned negative. These regimens of chemotherapy were S-1/CDDP (n = 9), Docetaxel/CDDP/S-1 (n = 2), SOX (n = 2) and S-1/Docetaxel (n = 1) and the median number of treatment courses was5courses. The MSTs of patients with or without CS were 40 months and 11 months (p<0.001). Then, there was no difference in overall survival between patients with CS and patients with CY0P0 at the first SL (p = 0.866). All patients with P1received chemotherapy, and 11 of these patients underwent the second look SL. As peritoneal metastasis of 7 patients (18%) disappeared by chemotherapy, they underwent CS (R0). The MSTs of patients with or without CS were 31 months and 9 months (p = 0.026). Regarding complications after CS, surgical-site infection and interstitial pneumonia each occurred in one patient (grade II), and intestinal obstruction (grade IIIa) occurred in one patient. There was no mortality. Conclusions: This study suggests that CS is probably safe and may contribute to improve the survival rate of patients with peritoneal metastasis. Moreover, we developed the NSOX regimen, comprised of a combination nab-paclitaxel, S-1 and oxaliplatin, and have performed a phase I/II trial using the NSOX regimen (UMIN000030909).

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Retrospective comparison of S-1 plus cisplatin versus S-1 monotherapy for the treatment of advanced gastric cancer patients with positive peritoneal cytology but without gross peritoneal metastasis

International Journal of Clinical Oncology ◽

10.1007/s10147-017-1164-4 ◽

2017 ◽

Vol 22 (6) ◽

pp. 1060-1068 ◽

Cited By ~ 5

Author(s):

Izuma Nakayama ◽

Keisho Chin ◽

Tomohiro Matsushima ◽

Daisuke Takahari ◽

Mariko Ogura ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Peritoneal Metastasis ◽

Peritoneal Cytology ◽

Retrospective Comparison ◽

Positive Peritoneal Cytology ◽

Gastric Cancer Patients

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The role of staging laparoscopy in type 4 gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.35 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 35-35

Author(s):

Norihiko Sugisawa ◽

Etsuro Bando ◽

Yuichiro Miki ◽

Rie Makuuchi ◽

Hironobu Goto ◽

...

Keyword(s):

Gastric Cancer ◽

Peritoneal Metastasis ◽

Invasive Procedure ◽

Staging Laparoscopy ◽

Peritoneal Cytology ◽

Clinical Imaging ◽

Surgical Interventions ◽

Peritoneal Lavage Cytology ◽

Positive Peritoneal Cytology

35 Background: In type 4 gastric cancer, the incidence of peritoneal metastasis which was unexpectedly found during surgery was as high as 40 percent. It is very difficult to detect peritoneal metastasis in clinical imaging such as computed tomography or ultrasound before operation. Staging laparoscopy (SL) is considered to be an only minimal invasive procedure to detect peritoneal metastasis. However, the significance of SL had not yet been fully elucidated. The aim of this study is to assess the role of SL in type 4 gastric cancer. Methods: From September 2002 to March 2012, a total of 169 patients with type 4 gastric cancer who were diagnosed as not having distant metastasis in clinical imaging were enrolled in this study. SL was performed for 56 patients, and the other 113 patients underwent open laparotomy (OL) without SL. We retrospectively examined the incidence of peritoneal metastasis and positive peritoneal cytology and treatment courses in patients who underwent SL and OL. Results: In 56 patients undergoing SL, 23 (41%) had peritoneal metastasis and 40 (71%) had positive peritoneal cytology. Similarly, 54 (48%) had peritoneal metastasis and 86 (76%) had positive peritoneal cytology in 113 patients undergoing OL. There were no significant differences of the incidence of peritoneal metastasis and positive peritoneal cytology between the two groups. Subsequent treatments after SL or OL were diverse depends on patients condition and participating clinical trials, however, 17 (32%) in SL group and 13 (12%) in OL group were treated without surgical interventions. There was no morbidity and mortality in both SL group and OL group. In SL group, open surgery was performed soon afterword in 39 patients. Among them, 2 patients was failed to detect peritoneal metastasis by SL. Therefore the accuracy of detecting peritoneal metastasis in SL was 23/25 (92%). Conclusions: In type 4 gastric cancer, the incidence of peritoneal metastasis was around 40% and positive peritoneal lavage cytology was around 70% in both SL and OL. As SL is less invasive than OL, SL appears to be a useful way to detect peritoneal seeding and establish treatment strategy in patients with type 4 gastric cancer.

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A phase II study of induction chemotherapy with docetaxcel, cisplatin, and S-1 (DCS) for gastric cancer with peritoneal metastasis (KUGC06): Early results.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15574 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15574-e15574

Author(s):

Hiroshi Okabe ◽

Hiroaki Hata ◽

Shugo Ueda ◽

Hisahiro Hosogi ◽

Shuichi Ota ◽

...

Keyword(s):

Gastric Cancer ◽

Induction Chemotherapy ◽

Phase Ii ◽

Peritoneal Metastasis ◽

Phase Ii Study ◽

R0 Resection ◽

Peritoneal Cytology ◽

Resection Rate ◽

Early Results ◽

Positive Peritoneal Cytology

e15574 Background: Although the prognosis of gastric cancer with peritoneal metastasis is extremely poor, we previously showed the significant efficacy of S-1 plus cisplatin for limited peritoneal dissemination, and favorable outcome following curative resection. We conducted a phase II study to evaluate the safety and efficacy of induction chemotherapy with docetaxel, cisplatin, and S-1 (DCS) triplet regimen for patients (pts) with gastric cancer with peritoneal metastasis. Methods: The key eligibility criteria were gastric cancer with peritoneal metastasis or positive peritoneal cytology, without any other distant metastases, age between 20 and 75 years old, PS 0 or 1, capable of oral administration, and adequate hematologic, hepatic, and renal function. Pts received three 28-day cycles of DCS (cisplatin of 60 mg/m2, docetaxel of 40mg/m2 on day 1, and S-1 of 80 mg/m2 from day 1 to 14). Following evaluation for resectability, pts received D2 gastrectomy if R0 was possible. Primary endpoint was R0 resection rate. Secondary endpoints were clinical response of peritoneal metastasis, overall response, pathological response, adverse events, progression free survival, and overall survival. Sample size was determined to have 80% power for detecting 20% improvement of R0 resection rate over 45% baseline at one-sided alpha of 0.1. Results: Between June 2011 and April 2015, 30 pts were enrolled. All pts started DCS and were included in the analysis. Three cycles of DCS (80%) were completed in 24 pts (80%). The most frequent grade 3/4 toxicity was neutropenia (60%). Complete response of peritoneal metastasis was observed in 16 pts (53%), 21 pts underwent surgery, and 14 pts achieved R0 resection (47%; 95%CI, 28-66%). When the extent of peritoneal metastasis was classified as P0CY1, P1, P2, and P3 according to the Japanese classification, R0 resection rate for each group was 63%, 60%, 46%, or 0%, respectively. Conclusions: Induction chemotherapy with DCS is safe, and could achieve R0 resection in some patients with limited peritoneal metastasis or positive peritoneal cytology. However, the efficacy seems to be similar to the conventional S-1 plus cisplatin. Clinical trial information: UMIN000004932.

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Phase II study of intraperitoneal paclitaxel plus S-1/paclitaxel for gastric cancer with positive peritoneal cytology: CY-PHOENIX trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.96 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 96-96 ◽

Cited By ~ 4

Author(s):

Masaki Aizawa ◽

Hironori Ishigami ◽

Hiroshi Yabusaki ◽

Atsushi Nashimoto ◽

Haruhiko Imamoto ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Peritoneal Cavity ◽

Peritoneal Metastasis ◽

Phase Ii Study ◽

Peritoneal Cytology ◽

Positive Peritoneal Cytology ◽

Grade 3 ◽

Gastric Cancer Patients

96 Background: The presence of free cancer cells in the peritoneal cavity has been known as a poor prognostic factor in gastric cancer patients. Intraperitoneal (IP) paclitaxel (PTX) provides powerful local effects in the peritoneal cavity, and we previously reported the efficacy and safety of a regimen combining IP PTX with S-1/PTX in gastric cancer patients with peritoneal metastasis. This multicenter phase II study was conducted to evaluate the efficacy of IP PTX plus S-1/PTX for gastric cancer with positive peritoneal cytology. Methods: Eligibility criteria included pathologically confirmed gastric adenocarcinoma, intraperitoneal free cancer cells confirmed by peritoneal washing cytology, and no evidence of overt distant metastasis including macroscopic peritoneal metastasis. Patients were administered IP PTX 20 mg/m2, intravenous PTX 50 mg/m2 on days 1 and 8, and S-1 80 mg/m2/day on days 1-14, q3 weeks. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Thirty eight patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 12.5 (range 2-35). The 1-year OS rate was 84.2% (95 % confidence interval, 68.2-92.6%). Of 3 patients with target lesions, partial response and stable disease were obtained in 2 and 1 patient(s), respectively. The peritoneal cytology findings converted from positive to negative in 36 (94.7 %) patients. The incidences of grade 3/4 hematological and non-hematological toxicities were 45 % and 26 %, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), leukopenia (7%) and anemia (8%). Regarding adverse events related to IP port, 2 patients developed swelling around the port site. Conclusions: IP PTX with S-1/PTX was suggested to be a promising option for gastric cancer with positive peritoneal cytology through the clearance of cancer cells in the peritoneal cavity. Clinical trial information: UMIN000002850.

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The Importance of Extensive Intraoperative Peritoneal Lavage as a Promising Method in Patients with Gastric Cancer Showing Positive Peritoneal Cytology Without Overt Peritoneal Metastasis and Other Therapeutic Approaches

Journal of Investigative Surgery ◽

10.1080/08941939.2016.1247930 ◽

2016 ◽

Vol 30 (5) ◽

pp. 318-324 ◽

Cited By ~ 1

Author(s):

Enver Ilhan ◽

Ali Alemdar ◽

Orhan Ureyen ◽

Koray Bas

Keyword(s):

Gastric Cancer ◽

Peritoneal Metastasis ◽

Peritoneal Lavage ◽

Promising Method ◽

Peritoneal Cytology ◽

Therapeutic Approaches ◽

Positive Peritoneal Cytology

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Intraperitoneal Chemotherapy as Adjuvant or Perioperative Chemotherapy for Patients with Type 4 Scirrhous Gastric Cancer: PHOENIX-GC2 Trial

Journal of Clinical Medicine ◽

10.3390/jcm10235666 ◽

2021 ◽

Vol 10 (23) ◽

pp. 5666

Author(s):

Hironori Ishigami ◽

Yasushi Tsuji ◽

Hisashi Shinohara ◽

Yasuhiro Kodera ◽

Mitsuro Kanda ◽

...

Keyword(s):

Gastric Cancer ◽

Peritoneal Metastasis ◽

Systemic Chemotherapy ◽

Disease Free Survival ◽

Phase Iii ◽

Peritoneal Cytology ◽

Scirrhous Gastric Cancer ◽

Peritoneal Lavage Cytology ◽

Lavage Cytology ◽

Gastric Cancer Patients

The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.

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Systemic Chemotherapy Including Ramucirumab in Combination With Pressurized Intra-Peritoneal Aerosol Chemotherapy Is a Safe Treatment Option for Peritoneal Metastasis of Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.610572 ◽

2021 ◽

Vol 10 ◽

Author(s):

Linda Feldbrügge ◽

Felix Gronau ◽

Andreas Brandl ◽

Timo Alexander Auer ◽

Alan Oeff ◽

...

Keyword(s):

Gastric Cancer ◽

Systemic Therapy ◽

Peritoneal Metastasis ◽

Systemic Chemotherapy ◽

Postoperative Morbidity ◽

Laparoscopic Technique ◽

Complication Rates ◽

The Mean ◽

Safe Treatment Option ◽

Length Of Interval

BackgroundPressurized intraperitoneal aerosol chemotherapy (PIPAC) is a laparoscopic technique for local chemotherapy. It has been used for treatment of peritoneal metastasis of gastric cancer (PM GC) in combination with systemic therapy. VEGFR2 antagonist ramucirumab is a second-line therapy for GC, and has been suspected to cause wound healing disorders.MethodsThis is a retrospective single center cohort study of patients with PM GC, who received PIPAC treatment in combination with systemic chemotherapy with and without ramucirumab. Data on patients’ characteristics and their perioperative courses were collected and complication rates were compared with regard to preoperative use of ramucirumab and time between last dose of systemic therapy and PIPAC treatment.ResultsFifty patients underwent 90 PIPAC treatments for PM GC in 3 years. Overall postoperative morbidity was 11% with 6% severe complications. The mean interval between systemic therapy and PIPAC was 20 days. Neither the length of interval nor the use of ramucirumab had an effect on complication rates.ConclusionOur study suggests that addition of ramucirumab to pre-PIPAC systemic therapy, irrespective of the length of the treatment-free interval before PIPAC, does not increase the risk of postoperative complications and is therefore a safe option for treatment of PM GC.

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