|
1
|
Simonsen M, Mendoza López RV, Maistro S, Ikeoka LT, Pereira GFDL, Lugão AB, Sadalla JC, Katayama MLH, Folgueira MAAK. Peritoneal chemotherapy delivery systems for ovarian cancer treatment: systematic review of animal models. Front Oncol 2025; 14:1487376. [PMID: 39845320 PMCID: PMC11750819 DOI: 10.3389/fonc.2024.1487376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 12/06/2024] [Indexed: 01/24/2025] Open
Abstract
Introduction Intraperitoneal chemotherapy for ovarian cancer treatment has controversial benefits as most methodologies are associated with significant morbidity. We carried out a systematic review to compare tumor response, measured by tumor weight and volume, between intraperitoneal chemotherapy delivered via drug delivery systems (DDSs) and free intraperitoneal chemotherapy in animal models of ovarian cancer. The secondary aim was to assess the toxicity of DDS-delivered chemotherapy, based on changes in animal body weight. Methods Based on PRISMA and SYRCLE guidelines, we identified 38 studies for review, of which 20, were used in the meta-analysis. We evaluated outcome, through tumor volume and tumor weight and, toxicity, through animal weight. Analysis was based on drugs employed and treatment duration. Results Most studies were performed on mice. Ovarian cancer cell lines most commonly used to induce xenografts were SKOV3 (19 studies) and A2780 (6 studies). Intraperitoneal device, also known as drug delivery systems (DDS), consisted in nanoparticles, hydrogels, lipid polymer and others. The most commonly used drugs were paclitaxel and cisplatin. Most studies used as the control treatment the same chemotherapy applied free intraperitoneally and tumor response/animal weight were evaluated weekly. There was a small benefit in overall tumor reduction in animals treated with intraperitoneal chemotherapy applied through the slow release device compared with animals treated with intraperitoneal free chemotherapy, as evaluated through tumor weight - results in standardized mean difference. (-1.06; 95% CI: -1.34, -0.78) and tumor volume (-3.72; 95% CI: -4.47, -2.97), a benefit that was seen in most weekly evaluations and for most chemotherapy drugs, such as carboplatin (tumor weight: -5.60; 95% CI: -7.83, -3.37), paclitaxel (tumor weight: -1.18; 95% CI: -1.52, -0.83), and cisplatin (tumor volume: -2.85; 95% CI: -3.66, -2.04) carboplatin (tumor volume: -12.71; 95% CI: -17.35, -8.07); cisplatin (tumor volume: -7.76; 95% CI: -9.88, -5.65); paclitaxel (tumor volume: -2.85; 95% CI: -3.66, -2.04). Regarding animal weight, there was no weight reduction in animals treated with intraperitoneal chemotherapy applied through the slow-release device compared with animals treated with intraperitoneal free chemotherapy. However, significant heterogeneity was observed in some comparisons. Conclusion slow-release devices are overall safe and effective in animal models of ovarian cancer. It was not possible to evaluate which one is the most promising device to treat ovarian cancer, because many different types were used to apply chemotherapy intraperitoneally. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42021224573.
Collapse
Affiliation(s)
- Marcelo Simonsen
- Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (HCFMUSP), Sao Paulo, SP, Brazil
- Gynecology and Obstetrics Department, Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE), São Paulo, SP, Brazil
| | - Rossana Verónica Mendoza López
- Departamento de Radiologia e Oncologia, Comprehensive Center for Precision Oncology (C2PO), Centro de Investigação Translacional em Oncologia (CTO), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (HCFMUSP), Sao Paulo, SP, Brazil
| | - Simone Maistro
- Departamento de Radiologia e Oncologia, Comprehensive Center for Precision Oncology (C2PO), Centro de Investigação Translacional em Oncologia (CTO), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (HCFMUSP), Sao Paulo, SP, Brazil
| | - Lucas Takeshi Ikeoka
- Faculdade de Medicina, Undergraduate program, Universidade de Sao Paulo (FMUSP), Sao Paulo, SP, Brazil
| | - Glaucia Fernanda de Lima Pereira
- Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (HCFMUSP), Sao Paulo, SP, Brazil
| | - Ademar Benévolo Lugão
- Nuclear and Energy Research Institute, IPEN-Comissão Nacional de Energia Nuclear (CNEN)/SP—University of São Paulo, São Paulo, SP, Brazil
| | - José Carlos Sadalla
- Departamento de Ginecologia e Obstetrícia, Instituto do Câncer do Estado de Sao Paulo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, SP, Brazil
| | - Maria Lúcia Hirata Katayama
- Departamento de Radiologia e Oncologia, Comprehensive Center for Precision Oncology (C2PO), Centro de Investigação Translacional em Oncologia (CTO), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (HCFMUSP), Sao Paulo, SP, Brazil
| | - Maria Aparecida Azevedo Koike Folgueira
- Departamento de Radiologia e Oncologia, Comprehensive Center for Precision Oncology (C2PO), Centro de Investigação Translacional em Oncologia (CTO), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (HCFMUSP), Sao Paulo, SP, Brazil
| |
Collapse
|
|
2
|
Pazir Y, Esmeray A, Caglar U, Erbin A, Ozgor F, Sarilar O, Akbulut F. Comparison of hyperthermic intravesical chemotherapy and Bacillus Calmette-Guerin therapy in high-risk non-muscle invasive bladder cancer: a matched-pair analysis. Int Urol Nephrol 2024; 56:957-963. [PMID: 37880493 DOI: 10.1007/s11255-023-03849-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 10/06/2023] [Indexed: 10/27/2023]
Abstract
PURPOSE To compare adjuvant hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C and standard Bacillus Calmette-Guerin (BCG) therapy in terms of oncological outcomes and adverse events in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS The data of patients with high-risk papillary NMIBC treated with adjuvant intravesical BCG instillations or HIVEC in our institution between June 2017 and August 2022 were analyzed retrospectively. Twenty-four patients who received HIVEC were matched 1:1 with patients receiving BCG therapy based on tumor characteristics (tumor stage and grade), age, gender, smoking status, and the number of tumors (single or multiple). HIVEC and standard BCG treatments were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and adverse events. RESULTS Forty-eight patients (24 in the BCG group and 24 in the HIVEC group) were included in the study. The median follow-up times of the BCG and HIVEC groups were 32 [interquartile range (IQR): 28.0-47.8] and 28 (IQR: 16.7-41.8) months, respectively (p = 0.11). There was no significant difference between the groups in terms of the 24-month RFS (BCG 83% vs HIVEC 88%, p = 0.64) and the 24-month PFS (BCG 100% vs HIVEC 94%, p = 0.61). Regarding the safety profile, at least one adverse event occurred in 13 (54%) of the patients in the BCG group and 12 (50.0%) of those in the HIVEC group (p = 0.77). CONCLUSION This study demonstrated that HIVEC with mitomycin C has a similar oncological efficacy and safety profile to standard BCG therapy in high-risk NMIBC.
Collapse
Affiliation(s)
- Yasar Pazir
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey.
| | - Abdullah Esmeray
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Ufuk Caglar
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Akif Erbin
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Faruk Ozgor
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Omer Sarilar
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Fatih Akbulut
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| |
Collapse
|
|
3
|
Shaker EH, Soliman AM, Hussein AF, Fayek ES, Elrawas MM. Evaluating the Efficacy and Safety of a Single-Dose Tranexamic Acid in Reducing Blood Loss During Cytoreductive Surgery Followed by Hyperthermic Intraperitoneal Chemotherapy: A Randomized Comparative Pilot Study. Anesth Pain Med 2023; 13:e136578. [PMID: 38024001 PMCID: PMC10664172 DOI: 10.5812/aapm-136578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/31/2023] [Accepted: 06/08/2023] [Indexed: 12/01/2023] Open
Abstract
Background Hyperthermic intraperitoneal chemotherapy (HIPEC), following cytoreductive surgery (CRS), is a lengthy procedure, usually associated with considerable bleeding due to the extensive nature of surgery. Various techniques have been used to decrease blood transfusion requirements. Objectives This study aimed to evaluate the possible advantage of a single dose of tranexamic acid (TA) in such surgeries. Methods In this randomized comparative pilot study, 60 patients scheduled to undergo CRS followed by HIPEC were randomly assigned to 2 equal groups: group 1 (TA group) that received 10 mg/kg of TA in 100 mL of 0.9% NaCl over 20 minutes after the induction of anesthesia and before surgical incision, and group 2 (control group) that received a placebo of 100 mL of 0.9% NaCl during the same time interval. The primary endpoint was the blood loss volume. The secondary endpoints were the number of patients requiring transfusion and the occurrence of any postoperative thrombotic events 30 days after surgery. Serum creatinine levels were measured before the operation and on postoperative days 1, 3, and 5. Intraoperative and first 24 hours urine outputs were also recorded. The levels of hemoglobin (Hb) were measured before the operation, immediately after the operation, and 5 days postoperatively. Results Compared to the control group, the TA group exhibited lower intraoperative blood loss, as well as lower blood loss on postoperative day 1 and in total blood loss (P = 0.006, 0.035, and 0.001, respectively). However, the blood loss on the remaining postoperative days was comparable between both groups. Intraoperative blood transfusion requirements were lower in the TA group (P = 0.032) than in the control group. The total number of units of blood and plasma transfused was also lower in the TA group both intra and postoperatively (0.007, 0.40, and 0.032, 0.008, respectively) than in the control group. Hemoglobin levels, serum creatinine levels, and urine outputs during the first 24 hours postoperatively were comparable between the 2 groups. The thromboembolic events within 30 days were also comparable between the 2 groups. Conclusions Administering a single dose of TA between the induction of anesthesia and the surgical incision may reduce blood loss and transfusion rates in CRS followed by HIPEC without causing significant adverse effects. It is a promising approach in surgeries where massive blood loss is expected shortly after anesthesia induction. This can minimize the drawbacks of repeated blood transfusions during and after the operation without causing significant adverse effects. Besides reducing the need for repeated blood transfusions, it would also reduce the costs of blood/blood products and the risks of transfusion.
Collapse
Affiliation(s)
- Ehab Hanafy Shaker
- Department of Anesthesia, Intensive Care and Pain Management, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Ahmed Mohamed Soliman
- Department of Anesthesia, Intensive Care and Pain Management, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Ahmed Fahmy Hussein
- Department of Anesthesia, Intensive Care and Pain Management, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Ehab Samy Fayek
- Department of Surgical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Mai Mohamed Elrawas
- Department of Anesthesia, Intensive Care and Pain Management, National Cancer Institute, Cairo University, Cairo, Egypt
| |
Collapse
|
|
4
|
Karadayi K, Karabacak U. Is complete mesocolic excision or total mesorectal excision necessary during cytoreductive surgery in ovarian peritoneal carcinomatosis with colonic involvement? Acta Chir Belg 2023; 123:124-131. [PMID: 34253150 DOI: 10.1080/00015458.2021.1955193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Cytoreductive surgery (CRS) and intraperitoneal chemotherapy are effective in the treatment of ovarian peritoneal carcinomatosis (OPC). Colon resection is often required to achieve maximal cytoreduction during CRS. The success of complete mesocolic excision (CME) and total mesorectal excision (TME) in the surgical treatment of primary colorectal tumors is well-known. Our study aimed to investigate the factors affecting mesocolic lymph node metastasis (MLNM) and the contribution of CME/TME techniques to maximal cytoreduction in patients diagnosed with ovarian peritoneal carcinomatosis (OPC) with colon metastasis. PATIENTS AND METHODS Between 2004-2020, 30 patients who underwent colorectal resection with CME/TME techniques due to OPC-related colon metastasis were retrospectively analyzed. RESULTS The median age of patients was 61 (33-86). Six (20%) patients underwent total colectomy, 7 (23%) subtotal colectomy, 6 (20%) right hemicolectomy, 4 (13%) left hemicolectomy, and 7 (23%) rectosigmoid resection. Histopathological diagnosis was high-grade serous carcinoma in 29 (97%) patients, and malignant mixed Mullerian tumor in 1 (3%) patient. MLNM was detected in 17 (56%) of 30 patients. There was a significant relationship between MLNM and pelvic and para-aortic lymph node metastasis (PALNM) (p = 0.009) and lymphovascular invasion in primary ovarian tumors (p = 0.017). There was no significant relationship between MLNM and depth of colonic invasion (p = 0.463), histological grade (p = 0.711), and primary/secondary surgery (p = 0.638). MLNM was seen in 8 (47%) of 17 patients with only serosal invasion. CONCLUSION A high rate of MLNM can be seen in OPC-induced colon metastasis regardless of the degree of colon wall invasion. In patients with PALNM, the frequency of MLNM increases. We believe that if colon resection is to be performed in OPC, a colectomy should be performed by CME/TME principles to achieve maximal cytoreduction.
Collapse
Affiliation(s)
- Kursat Karadayi
- Department of Surgical Oncology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Ufuk Karabacak
- Department of Surgical Oncology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| |
Collapse
|
|
5
|
Panoskaltsis T, Papadimitriou C, Pallas N, Karamveri C, Kyziridis D, Hristakis C, Kiriakopoulos V, Kalakonas A, Vaikos D, Tzavara C, Tentes AA. Prognostic Value of En-Block Radical Bowel Resection in Advanced Ovarian Cancer Surgery With HIPEC. Cancer Control 2023; 30:10732748231165878. [PMID: 36958947 PMCID: PMC10041633 DOI: 10.1177/10732748231165878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2023] Open
Abstract
PURPOSE To identify prognostic factors of survival and recurrence in advanced ovarian cancer patients undergoing radical surgery and HIPEC. METHODS In a single Department of Surgical Oncology, Peritoneal Surface Malignancy Program, and over a 16-year period, from a total of 274 epithelial ovarian cancer patients, retrospectively, we identified 152 patients undergoing complete (CC-0) or near-complete (CC-1) cytoreduction, including at least one colonic resection, and HIPEC. RESULTS Mean age of patients was 58.8 years and CC-0 was possible in 72.4%. Rates of in-hospital mortality and major morbidity were 2.6% and 15.7%. Only 122 (80.3%) patients completed Adjuvant Systemic Chemotherapy (ASCH). Rates of metastatic Total Lymph Nodes (TLN), Para-Aortic and Pelvic Lymph Nodes (PAPLN) and Large Bowel Lymph Nodes (LBLN) were 58.7%, 58.5%, and 51.3%, respectively. Median, 5- and 10-year survival rates were 39 months, 43%, and 36.2%, respectively. The recurrence rate was 35.5%. On univariate analysis, CC-1, high Peritoneal Cancer Index (PCI), in-hospital morbidity, and no adjuvant chemotherapy were adverse factors for survival and recurrence. On multivariate analysis, negative survival indicators were the advanced age of patients, extensive peritoneal dissemination, low total number of TLN and no systemic PAPLN. Metastatic LBLN and segmental resection of the small bowel (SIR) were associated with a high risk for recurrence. CONCLUSION CC-O is feasible in most advanced ovarian cancer patients and HIPEC may confer a survival benefit. Radical bowel resection, with its entire mesocolon, may be necessary, as its lymph nodes often harbor metastases influencing disease recurrence and survival. The role of metastatic bowel lymph nodes has to be taken into account when assessing the impact of systemic lymphadenectomy in this group of patients.
Collapse
Affiliation(s)
- T Panoskaltsis
- Gynaecological Oncology Unit, 2nd Academic Department of Obstetrics and Gynaecology, Aretaieion Hospital, 68989The National and Kapodistrian University of Athens, Athens, Greece
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, 376520Metropolitan Hospital, Athens, Greece
| | - C Papadimitriou
- Oncology Unit, 2nd Department of Surgery Aretaieion Hospital, 68989The National and Kapodistrian University of Athens, Athens, Greece
| | - N Pallas
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, 376520Metropolitan Hospital, Athens, Greece
| | - C Karamveri
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, 376520Metropolitan Hospital, Athens, Greece
| | - D Kyziridis
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, Euromedica Kyanous Stavros, Thessaloniki, Greece
| | - C Hristakis
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, Euromedica Kyanous Stavros, Thessaloniki, Greece
| | - V Kiriakopoulos
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, 376520Metropolitan Hospital, Athens, Greece
| | - A Kalakonas
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, Euromedica Kyanous Stavros, Thessaloniki, Greece
| | - D Vaikos
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, Euromedica Kyanous Stavros, Thessaloniki, Greece
| | - C Tzavara
- Department of Hygiene, Epidemiology and Medical Statistics, Centre for Health Services Research, School of Medicine, 68989The National and Kapodistrian University of Athens, Athens, Greece
| | - A A Tentes
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, 376520Metropolitan Hospital, Athens, Greece
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, Euromedica Kyanous Stavros, Thessaloniki, Greece
| |
Collapse
|
|
6
|
Menzies AV, Usher EC, Hsu FC, Levine EA, Lentz SS, Kelly MG. HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients. Gynecol Oncol 2022; 167:234-238. [PMID: 36085091 DOI: 10.1016/j.ygyno.2022.08.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/19/2022] [Accepted: 08/22/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To evaluate toxicity, quality of life and PFS in patients with advanced ovarian cancer who underwent neoadjuvant chemotherapy (NAC) followed by CRS and HIPEC with carboplatin. METHODS Patients with stage IIIC or IVA epithelial ovarian cancer, who were not candidates for primary CRS, were enrolled in this phase two trial. Patients received 3-6 cycles of NAC with an IV carboplatin doublet followed by CRS with HIPEC (carboplatin 800 mg/m2 for 90 min). They were followed for at least 12 months to assess for adverse events, quality of life (QOL) and disease progression. QOL was measured using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaires prior to CRS and post-operatively at 6 weeks, 3 months, and 6 months after CRS. RESULTS Twenty patients were enrolled. HIPEC was completed successfully in all twenty patients, and there was no peri-operative mortality. Twelve (70.6%) patients experienced a grade 3 or 4 toxicity; most commonly anemia (59%), thrombocytopenia (29%), and hypokalemia (24%). There was no significant change between the pre-operative and postoperative 6 weeks, 3 month, and 6 month FACT-O, NTX, and AD scores. Nine (45%) patients have experienced disease recurrence to date. The median progression free survival in this cohort is 11.2 months (2.5-23.7 months). CONCLUSION The addition of HIPEC with carboplatin to interval CRS was well tolerated in patient population. Myelosuppression was the most common adverse event. CRS with HIPEC did not adversely impact these patients' QOL indices. The efficacy of this regimen should be further evaluated in a larger clinical trial.
Collapse
Affiliation(s)
- Anya V Menzies
- Department of Obstetrics and Gynecology, Atrium Health Wake Forest Baptist, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America.
| | - Erik C Usher
- Department of Obstetrics and Gynecology, Atrium Health Wake Forest Baptist, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| | - Fang-Chi Hsu
- Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| | - Edward A Levine
- Department of Surgical Oncology, Atrium Health Wake Forest Baptist, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| | - Samuel S Lentz
- Department of Obstetrics and Gynecology, Atrium Health Wake Forest Baptist, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| | - Michael G Kelly
- Department of Obstetrics and Gynecology, Atrium Health Wake Forest Baptist, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America
| |
Collapse
|
|
7
|
Sugarbaker PH. Optimizing regional chemotherapy for epithelial ovarian cancer. J Obstet Gynaecol Res 2022; 48:1306-1317. [PMID: 35343033 DOI: 10.1111/jog.15224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 01/19/2022] [Accepted: 03/03/2022] [Indexed: 11/27/2022]
Abstract
AIM The response with intravenous chemotherapy using cisplatin and paclitaxel in patients with advanced ovarian cancer is often substantial. However, this regression of the malignancy is not durable, and a majority of patients succumb to this disease process. It is possible that alternative types of chemotherapy and alternative routes of chemotherapy administration can improve the results of treatment and perhaps, reduce the morbidity and mortality that patients experience. METHODS Regional chemotherapy treatments previously presented in the ovarian cancer literature were reviewed and critically analyzed. New methods for chemotherapy delivery for both advanced primary and recurrent ovarian cancer were reviewed. This included hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) long-term. RESULTS An important addition to perioperative chemotherapy delivery is the simultaneous use of heat with intraperitoneal drug delivery after a complete cytoreductive surgery. Drugs to be considered for HIPEC are cisplatin, gemcitabine, and melphalan. For EPIC, chemotherapy agents to consider include paclitaxel, pemetrexed, gemcitabine, and liposomal doxorubicin. For NIPEC, paclitaxel is the drug of choice usually combined with a systemic agent as bidirectional chemotherapy. Also, pemetrexed, gemcitabine, and liposomal doxorubicin are drugs to be considered for NIPEC in phase I/II trials. CONCLUSIONS Innovative regimens of regional chemotherapy may improve the outcome of patients with advanced ovarian cancer. These chemotherapy treatments must be integrated with complete cytoreductive surgery and the availability of peritoneal access for repeated delivery of chemotherapy solutions.
Collapse
Affiliation(s)
- Paul H Sugarbaker
- Washington Cancer Institute, Program in Peritoneal Surface Malignancy, Washington, District of Columbia, USA
| |
Collapse
|
|
8
|
Paquette B, Kalbacher E, Mercier F, Lakkis Z, Doussot A, Turco C, Caputo E, Pili-Floury S, Royer B, Mansi L, Delroeux D, Demarchi M, Pivot X, Chauffert B, Clement E, Heyd B. Cytoreductive Surgery and Intraperitoneal Chemotherapy in Advanced Serous Epithelial Ovarian Cancer: A 14-Year French Retrospective Single-Center Study of 124 Patients. Ann Surg Oncol 2022; 29:3322-3334. [PMID: 34994906 DOI: 10.1245/s10434-021-11211-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 11/30/2021] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Ovarian cancer (OC) is the most lethal gynecological cancer. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy appears to increase survival, and normothermic intraperitoneal chemotherapy (IPC) could improve overall survival (OS). Furthermore, intraperitoneal epinephrine could decrease the toxicity of chemotherapy by decreasing the systemic absorption of chemotherapy. The goal of this study was to assess the effects of CRS and IPC with intraperitoneal epinephrine, as first-line therapy, on the survival of patients with serous epithelial OC (EOC) with peritoneal metastases. METHODS A prospective monocentric database was retrospectively searched for all patients with advanced serous EOC treated by interval or consolidative CRS plus IPC with intraperitoneal epinephrine after neoadjuvant chemotherapy. OS and disease-free survival (DFS), postoperative complications, and prognostic factors were analyzed. RESULTS From January 2003 to December 2017, 124 patients with serous EOC were treated with interval (n = 58) or consolidative (n = 66) complete CRS plus IPC with intraperitoneal epinephrine. The median follow-up was 77.8 months, the median OS was 60.8 months, and the median DFS was 21.2 months. In our multivariate analysis, a higher Peritoneal Cancer Index (PCI) and positive lymph node status resulted in worse OS, while higher World Health Organization score, higher PCI score, and positive lymph node status were risk factors for worse DFS. Grade 3 or higher surgical morbidity occurred in 27.42% of cases; only 3.2% had grade 3 renal toxicity and mortality was 0.8%. CONCLUSION CRS and IPC with intraperitoneal epinephrine in stage III EOC offer good OS and DFS with acceptable morbidity and mortality rates.
Collapse
Affiliation(s)
- Brice Paquette
- Department of Surgery, University Hospital, Besançon, France.
| | - Elsa Kalbacher
- Department of Oncology, University Hospital, Besançon, France
| | | | - Zaher Lakkis
- Department of Surgery, University Hospital, Besançon, France
| | | | - Célia Turco
- Department of Surgery, University Hospital, Besançon, France
| | - Edda Caputo
- Dracénie Hospital Center, Draguignan, France
| | | | - Bernard Royer
- Medical Biology Laboratory, University Hospital, Besançon, France
| | - Laura Mansi
- Department of Oncology, University Hospital, Besançon, France
| | | | - Martin Demarchi
- Institut de Cancérologie Strasbourg Europe, Strasbourg, France
| | - Xavier Pivot
- Institut de Cancérologie Strasbourg Europe, Strasbourg, France
| | - Bruno Chauffert
- Department of Oncology, University Hospital, Amiens Cedex 1, France
| | - Elise Clement
- Department of Surgery, University Hospital, Besançon, France
| | - Bruno Heyd
- Department of Surgery, University Hospital, Besançon, France
| |
Collapse
|
|
9
|
Novel Perspectives in Pseudomyxoma Peritonei Treatment. Cancers (Basel) 2021; 13:cancers13235965. [PMID: 34885075 PMCID: PMC8656832 DOI: 10.3390/cancers13235965] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/11/2021] [Accepted: 11/23/2021] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Pseudomyxoma Peritonei (PMP) represents a rare entity which greatly benefits from Cytoreductive Surgery (CRS) associated with Hyperthermic Intraperitoneal Chemotherapy (HIPEC). In fact, CRS-HIPEC represents the treatment with potential chances of cure and long-term disease control of patients affected by PMP. This therapeutic strategy should be performed in referral centers, where a consolidated know-how of this locoregional treatment and a multidisciplinary approach are available. CRS-HIPEC provides excellent results for PMP patients in terms of postoperative outcome, overall and disease-free survival, and quality of life. However, in patients with an extensive or recurrent disease, few therapeutic opportunities are available. This review is focused on the most recent clinical evidence and provides a better understanding of the molecular prognostic factors and potential therapeutic targets in this rare malignancy. Abstract Pseudomyxoma Peritonei (PMP) is an anatomo-clinical condition characterized by the implantation of neoplastic cells on peritoneal surfaces with the production of a large amount of mucin. The rarity of the disease precludes the evaluation of treatment strategies within randomized controlled trials. Cytoreductive Surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) has proven to be the only therapeutic option with potential chances of cure and long-term disease control. The present review discusses the epidemiology, pathogenesis, clinical presentation and treatment of PMP, focusing on the molecular factors involved in tumor progression and mucin production that could be used, in the upcoming future, to improve patient selection for surgery and to expand the therapeutic armamentarium.
Collapse
|
|
10
|
Hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer. Biomed J 2021; 45:821-827. [PMID: 34656802 PMCID: PMC9661499 DOI: 10.1016/j.bj.2021.10.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 08/04/2021] [Accepted: 10/05/2021] [Indexed: 01/17/2023] Open
Abstract
Background To investigate outcomes and morbidity of patients undergoing secondary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer. Materials and methods Between April 2014 and January 2019, a total of 51 recurrent ovarian cancer patients receiving secondary CRS and HIPEC were retrospectively reviewed. Results Among the 51 patients, median peritoneal cancer index score was 13 (range 3–34), and completeness of cytoreduction (CC) score of 0/1 was achieved in 41 patients (78.8%). Regimen of HIPEC included cisplatin and paclitaxel in 39 (75%) cases. The median follow-up duration of survivors was 20.2 months. Sixteen (30.8%) patients remained free of recurrence after HIPEC. The median progression-free survival (PFS) and overall survival (OS) were 11.8 months and 34.5 months respectively. Multivariate analysis showed previous chemotherapy <2 lines (HR 0.24, 0.11–0.52; p = 0.001), chemotherapy-free interval ≥6 months (HR 0.19, 0.09–0.37; p < 0.001) and CA125 < 35 U/mL before HIPEC (HR 0.133, 0.021–0.0832; p = 0.031) were good prognostic factors for PFS. CC0/1 was not significant in multivariate analysis. The most common grade 3/4 toxicity was anemia (17.3%), pleural effusion (11.5%) and renal insufficiency (5.7%). Patients with age ≥50, peritoneal carcinomatosis index (PCI) ≥ 11, operation time ≥10 h and diaphragm surgery had significantly higher incidence of pleural effusion. Conclusions The current study showed adding HIPEC to secondary CRS might prolong PFS especially in patients with previous chemotherapy <2 lines, chemotherapy-free interval ≥6 months and CA125 < 35 U/mL before HIPEC.
Collapse
|
|
11
|
Raj H, Keerthi MSS, Palaniappan R, Prakash U, Dhanushkodi M, Ganesan TS. Phase 2 non-randomised trial of secondary cytoreduction and hyperthermic intraperitoneal chemotherapy in recurrent platinum-sensitive ovarian cancer. Ecancermedicalscience 2021; 15:1260. [PMID: 34567245 PMCID: PMC8426017 DOI: 10.3332/ecancer.2021.1260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Indexed: 11/07/2022] Open
Abstract
Background The role of secondary cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) is not clearly defined in recurrent platinum-sensitive ovarian cancer (PSOC). There is a paucity of studies on secondary cytoreduction with HIPEC in PSOC from developing countries like India. This study was done to assess the feasibility and safety of secondary cytoreduction and HIPEC in recurrent PSOC. Methods This was a prospective, non-randomised, open-label, phase 2 trial of secondary cytoreduction and HIPEC (Cisplatin 75 mg/m2 43°C over 60 minutes) in patients with recurrent platinum-sensitive epithelial carcinoma of ovary/fallopian tube/peritoneum done in a tertiary cancer centre from February 2016 to August 2019. The primary outcome was to assess the overall survival (OS) and the secondary outcomes were to assess the progression-free survival (PFS) and toxicity. Results Twenty-seven patients were screened and among them, 15 patients were included in this analysis with a median follow-up of 25 months. The mean cancer antigen (CA) 125 at the time of recurrence was 149 U/mL (range: 10–2,030 U/mL) and the median platinum-free interval was 21 months. The perioperative chemotherapy used was paclitaxel + carboplatin 53.3% (8/15), liposomal doxorubicin + carboplatin 40% (6/15) and none 6.5% (1/15). The median Peritoneal Carcinomatosis Index score was 8 (range: 3–25). The Clavien Dindo score was I, II and III in 6.7%, 26.7% and 13.3% patients, respectively. Recurrence was radiological and biochemical in 60% (9/15) and 7% (1/15), respectively. The most common site of recurrence was intra-abdominal (peritoneal). The median PFS and OS were 15 months (range: 0–34) and 26 months (range: 23–29), respectively. The grade 3 or 4 toxicity was 40%. Conclusion Secondary cytoreduction with HIPEC is feasible and safe in recurrent PSOC. Conclusive evidence that secondary cytoreduction with HIPEC is essential awaits the results from ongoing randomised controlled trials.
Collapse
Affiliation(s)
- Hemanth Raj
- Department of Surgical Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamil Nadu, India.,Hemanth Raj and Marri Sri Santosh Keerthi contributed equally
| | - Marri Sri Santosh Keerthi
- Department of Surgical Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamil Nadu, India.,Hemanth Raj and Marri Sri Santosh Keerthi contributed equally
| | - Ravisankar Palaniappan
- Department of Surgical Oncology, Sri Venkateshwaraa Medical College Hospital and Research Centre, Puducherry 605102, India
| | - Ujwala Prakash
- Department of Surgical Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamil Nadu, India
| | - Manikandan Dhanushkodi
- Department of Medical Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamil Nadu, India.,https://orcid.org/0000-0002-8192-3856
| | - Trivadi S Ganesan
- Department of Medical Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamil Nadu, India
| |
Collapse
|
|
12
|
Burg L, Timmermans M, van der Aa M, Boll D, Rovers K, de Hingh I, van Altena A. Incidence and predictors of peritoneal metastases of gynecological origin: a population-based study in the Netherlands. J Gynecol Oncol 2021; 31:e58. [PMID: 32808491 PMCID: PMC7440978 DOI: 10.3802/jgo.2020.31.e58] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 03/19/2020] [Accepted: 03/22/2020] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE Peritoneal metastases (PM) are a challenge in gynecological cancers, but its appearance has never been described in a population-based study. Therefore, we describe the incidence of PM and identify predictors that increase the probability of peritoneal spread. METHODS All ovarian, endometrial and cervical cancer patients diagnosed in the Netherlands between 1989 and 2015 were identified from the Netherlands Cancer Registry and stratified for PM. Crude and age-adjusted incidence over time was calculated. Independent predictors for PM were identified using uni- and multivariable analyses. RESULTS The 94,981 patients were diagnosed with ovarian, endometrial or cervical cancer and respectively 61%, 2% and 1% presented with PM. Predictors for PM in ovarian cancer were: age between 50 and 74 years (odds ratio [OR]=1.19; 95% confidence interval [CI]=1.08-1.32), other distant metastases (OR=1.25; 95% CI=1.10-1.41), poor differentiation grade (OR=2.00; 95% CI=1.73-2.32) and serous histology. Predictors in endometrial cancer were lymph node metastases (OR=2.32; 95% CI=1.65-3.26), other distant metastases (OR=1.38; 95% CI=1.08-1.77), high-grade tumors (OR=1.95; 95% CI=1.38-2.76) and clear cell (OR=1.49; 95% CI=1.04-2.13) or serous histology (OR=2.71; 95% CI=2.15-3.42). In cervical cancer, the risk is higher in adenocarcinoma than in squamous cell carcinoma (OR=4.92; 95% CI=3.11-7.79). CONCLUSION PM are frequently seen in patients with ovarian cancer. In endometrial and cervical cancer PM are rare. Histological subtype was the strongest predictive factor for PM in all 3 cancers. Better understanding of predictive factors for PM and thus the biological behavior is of paramount importance.
Collapse
Affiliation(s)
- Lara Burg
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Maite Timmermans
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands.,Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, The Netherlands.,GROW, School for Oncology and Developmental Biology, Maastricht, The Netherlands
| | - Maaike van der Aa
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Dorry Boll
- Department of Obstetrics and Gynecology, Catharina Hospital, Eindhoven, The Netherlands
| | - Koen Rovers
- Department of Surgical Oncology, Catharina Cancer Hospital, Eindhoven, The Netherlands
| | - Ignace de Hingh
- Department of Surgical Oncology, Catharina Cancer Hospital, Eindhoven, The Netherlands
| | - Anne van Altena
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
| |
Collapse
|
|
13
|
Marrelli D, Petrioli R, Cassetti D, D'Ignazio A, Marsili S, Mazzei MA, Lazzi S, Roviello F. A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer. Surg Oncol 2021; 37:101523. [PMID: 33545658 DOI: 10.1016/j.suronc.2021.101523] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 11/24/2020] [Accepted: 01/25/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Few prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31). MATERIALS AND METHODS Between 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC. RESULTS A complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26-45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29-76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19-27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors. CONCLUSIONS A novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.
Collapse
Affiliation(s)
- Daniele Marrelli
- Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy.
| | - Roberto Petrioli
- Department of Oncology, Unit of Medical Oncology, Azienda Ospedaliera Universitaria Senese, Italy
| | - Dario Cassetti
- Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy
| | - Alessia D'Ignazio
- Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy
| | - Stefania Marsili
- Department of Oncology, Unit of Medical Oncology, Azienda Ospedaliera Universitaria Senese, Italy
| | - Maria Antonietta Mazzei
- Department of Medicine, Surgery and Neuroscience, Unit of Diagnostic Imaging, University of Siena, Italy
| | - Stefano Lazzi
- Department of Medical Biotechnologies, Unit of Pathology, University of Siena, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy
| |
Collapse
|
|
14
|
Charo LM, Jou J, Binder P, Hohmann SF, Saenz C, McHale M, Eskander RN, Plaxe S. Current status of hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in the United States. Gynecol Oncol 2020; 159:681-686. [PMID: 32977989 DOI: 10.1016/j.ygyno.2020.09.022] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 09/13/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVES 1.) To compare frequency of HIPEC use in ovarian cancer treatment before and after publication of the phase III study by van Driel et al. in January 2018. 2.) To compare associated rates of hospital-based outcomes, including length of stay, intensive care unit (ICU) admission, complications, and costs in ovarian cancer surgery with or without HIPEC. METHODS We queried Vizient's administrative claims database of 550 US hospitals for ovarian cancer surgeries from January 2016-January 2020 using ICD-10 diagnosis and procedure codes. Sodium thiosulfate administration was used to identify HIPEC cases according to the published protocol. Student t-tests and relative risk (RR) were used to compare continuous variables and contingency tables, respectively. RESULTS 152 ovarian cancer patients had HIPEC at 39 hospitals, and 20,014 ovarian cancer patients had surgery without HIPEC at 256 hospitals. Following the trial publication, 97% of HIPEC cases occurred. During the index admission, HIPEC patients had longer median length of stay (8.4 vs. 5.7 days, p < 0.001) and higher percentage of ICU admissions (63.1% vs. 11.0%, p < 0.001) and complication rates (RR = 1.87, p = 0.002). Index admission direct costs ($21,825 vs. $12,038, p < 0.001) and direct cost index (observed/expected costs) (1.87 vs. 1.11, p < 0.001) were also greater in the HIPEC patients. No inpatient deaths or 30-day readmissions were identified after HIPEC. CONCLUSIONS Use of HIPEC for ovarian cancer increased in the US after publication of a phase III clinical trial in a high-impact journal, though the absolute number of cases remains modest. Incorporation of HIPEC was associated with increased cost, hospital length of stay, ICU admission, and hospital-acquired complication rates. Further studies are needed in order to evaluate long-term outcomes, including morbidity and survival.
Collapse
Affiliation(s)
- Lindsey M Charo
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, Reproductive Sciences, University of California San Diego, Moores Cancer Center, La Jolla, CA 92093, USA.
| | - Jessica Jou
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, Reproductive Sciences, University of California San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
| | - Pratibha Binder
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, Reproductive Sciences, University of California San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
| | | | - Cheryl Saenz
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, Reproductive Sciences, University of California San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
| | - Michael McHale
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, Reproductive Sciences, University of California San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
| | - Ramez N Eskander
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, Reproductive Sciences, University of California San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
| | - Steven Plaxe
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, Reproductive Sciences, University of California San Diego, Moores Cancer Center, La Jolla, CA 92093, USA
| |
Collapse
|
|
15
|
Wang S, Zhang Q, Chen L, Liu G, Liu PF. Thromboelastography-guided blood transfusion during cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a prospective randomised controlled trial. BMJ Open 2020; 10:e042741. [PMID: 33184089 PMCID: PMC7662436 DOI: 10.1136/bmjopen-2020-042741] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 09/02/2020] [Accepted: 09/25/2020] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a well-established treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high incidence of complications. Moreover, relative studies have indicated that traditional laboratory testing is insufficient to demonstrate the overall haemostatic physiology of CRS/HIPEC. Thromboelastography (TEG), administered by monitoring dynamic changes in haemostasis, has been shown to contribute to reducing transfusion requirements and improving survival. However, there is no evidence to verify whether TEG can be applied to guide transfusion strategies during CRS/HIPEC. Therefore, we aim to investigate whether TEG-guided blood product transfusion (TEG-BT) therapy is superior to traditional blood product transfusion (T-BT) therapy for guiding perioperative blood transfusion treatment and improving the prognosis of patients undergoing CRS/HIPEC. METHODS AND ANALYSIS The TEG-BT versus T-BT study is a single-centre, randomised, blinded outcome assessment clinical trial of 162 patients with PC, aged 18-64 years and undergoing CRS/HIPEC. Participants will be randomly allocated to receive TEG-BT or T-BT. The primary outcome will be the evaluation of perioperative blood transfusion, which refers to the total amount of blood transfusion given from the time patients enter the operating room up to 72 hours postoperatively. The secondary outcomes will include the transfusion volume during surgery, total amount of intraoperative infusion, amount of blood lost during the operation, total blood transfusion between 0 and 72 hours after surgery, lowest haemoglobin level within 72 hours after surgery, intensive care unit duration, overall length of stay, total cost of hospitalisation and adverse events. Data will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION The study protocol has been approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University (Approval Number: sjtkyll-lx-2020-3). The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER Chinese Clinical Trial Registry (ChiCTR2000028835).
Collapse
Affiliation(s)
- Shaoheng Wang
- Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Qing Zhang
- Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Linfeng Chen
- Department of Blood Transfusion, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Gang Liu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Peng Fei Liu
- Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
16
|
Wang S, Liu P, Gao T, Guan L, Li T. The impact of ultrasound-guided bilateral rectus sheath block in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy - a retrospective study. BMC Anesthesiol 2020; 20:197. [PMID: 32781985 PMCID: PMC7418388 DOI: 10.1186/s12871-020-01099-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 07/15/2020] [Indexed: 11/23/2022] Open
Abstract
Background Rectus sheath block (RSB) is known to attenuate postoperative pain and reduce perioperative opioid consumption. Thus, a retrospective study was performed to examine the effects of bilateral rectus sheath block (BRSB) in cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods A total of 178 patients undergoing CRS/HIPEC at our hospital were included. Patient information and anaesthesia-related indicators were collected from the electronic medical record (EMR) system. All subjects were divided into the following two groups: the G group (general anaesthesia) and the GR group (RSB combined with general anaesthesia). Patients in the GR group received 0.375% ropivacaine for BRSB before surgery. The primary outcomes included the total amount of remifentanil and rocuronium, the total consumption of dezocine after surgery, the visual analogue scale (VAS) score and the patient-controlled intravenous analgesia (PCIA) input dose at 1 h (T6), 6 h (T7), 12 h (T8), 24 h (T9) and 48 h (T10) after surgery. Other outcomes were also recorded, such as patient demographic data, the intraoperative heart rate (HR) and mean arterial pressure (MAP), and postoperative complications. Results Compared with the G group, the GR group showed a shorter time to tracheal extubation (P < 0.05), a decreased total amount of remifentanil and rocuronium (P < 0.05), and a reduced VAS score, PCIA input dose and number of PCIA boluses at 1 h, 6 h and 12 h after surgery (P < 0.05). However, at 24 h and 48 h after surgery, there were no differences in the VAS score of pain at rest or during motion between the two groups (P > 0.05). Moreover, the incidence of hypertension, emergence agitation, delayed recovery, hypercapnia, and nausea and vomiting was lower in the GR group than in the G group (P < 0.05). There were no differences in the changes in MAP and HR during the surgery between the two groups (P > 0.05). No complications associated with nerve block occurred. Conclusion BRSB could provide short-term postoperative analgesia, reduce perioperative opioid consumption and reduce the incidence of postoperative complications. It is an effective and safe procedure in CRS/HIPEC.
Collapse
Affiliation(s)
- Shaoheng Wang
- Department of Anesthesiology, Beijing Shijitan Hospital Capital Medical University, Beijing, 10038, China
| | - Pengfei Liu
- Department of Anesthesiology, Beijing Shijitan Hospital Capital Medical University, Beijing, 10038, China
| | - Teng Gao
- Department of Anesthesiology, Beijing Shijitan Hospital Capital Medical University, Beijing, 10038, China
| | - Lei Guan
- Department of Anesthesiology, Beijing Shijitan Hospital Capital Medical University, Beijing, 10038, China
| | - Tianzuo Li
- Department of Anesthesiology, Beijing Shijitan Hospital Capital Medical University, Beijing, 10038, China.
| |
Collapse
|
|
17
|
Lei Z, Wang Y, Wang J, Wang K, Tian J, Zhao Y, Chen L, Wang J, Luo J, Jia M, Tang H, He Q, Liao Q, Yang X, Guan T, Wang L, Cui S. Evaluation of Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Stage III Epithelial Ovarian Cancer. JAMA Netw Open 2020; 3:e2013940. [PMID: 32840622 PMCID: PMC7448829 DOI: 10.1001/jamanetworkopen.2020.13940] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
IMPORTANCE Interval cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising oncologic outcomes for patients with advanced ovarian cancer, but a large-scale, multicenter study to evaluate the efficacy of HIPEC combined with primary cytoreductive surgery (PCS) has yet to be conducted. OBJECTIVE To compare survival outcomes between PCS with HIPEC vs PCS alone for patients with stage III epithelial ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted from January 2010 to May 2017 at 5 high-volume institutions in China. A total of 584 patients with stage III primary epithelial ovarian cancer were treated with either PCS alone or PCS with HIPEC. The median (interquartile range) follow-up period was 42.2 (33.3-51.0) months. Data analysis was conducted from August to December 2019. EXPOSURES PCS with HIPEC vs PCS alone. MAIN OUTCOMES AND MEASURES Primary outcomes were median survival time and 3-year overall survival. The inverse probability of treatment weighting (IPTW) method, based on propensity score, was used to control for confounding factors. RESULTS From a total of 789 patients with stage III epithelial ovarian cancer, 584 patients (74.0%; mean [SD] age, 55.0 [10.5] years) were ultimately included for IPTW in this study. Of the 584 patients, 425 (72.8%) underwent PCS with HIPEC and 159 (27.2%) underwent PCS alone. After IPTW adjustment, the median survival time was 49.8 (95% CI, 45.2-60.2) months for patients undergoing PCS with HIPEC and 34.0 (95% CI, 28.9-41.5) months for patients undergoing PCS alone, and the 3-year overall survival rate was 60.3% (95% CI, 55.3%-65.0%) for patients undergoing PCS with HIPEC and 49.5% (95% CI, 41.0%-57.4%) for patients undergoing PCS alone (weighted hazard ratio, 0.64; 95% CI, 0.50-0.82; P < .001). Further stratified into complete and incomplete surgery subgroups, patients in the PCS with HIPEC group had significantly better survival than those in the PCS group, except for the 3-year overall survival rate in the incomplete subgroup. Among those who underwent complete surgical procedures and comparing those who received PCS with HIPEC vs those who received PCS alone, the median survival time was 53.9 (95% CI, 46.6-63.7) months vs 42.3 (95% CI, 31.1-59.3) months (P = .02), and the 3-year overall survival rate was 65.9% (95% CI, 60.1%-71.2%) vs 55.4% (95% CI, 44.7%-64.8%) (P = .04); meanwhile, among patients who underwent incomplete surgical procedures and comparing those who received PCS with HIPEC vs those who received PCS alone, the median survival time was 29.2 (95% CI, 22.3-45.5) months vs 19.9 (95% CI, 11.6-39.1) months (P = .03), and the 3-year OS rate was 44.3% (95% CI, 34.6%-53.4%) vs 36.7% (95% CI, 23.4%-50.1%) (P = .19). The treatment was well tolerated in both groups. CONCLUSIONS AND RELEVANCE In this study, the PCS with HIPEC treatment approach was associated with better long-term survival. When complete PCS is possible, this approach could be a valuable therapy for patients with stage III epithelial ovarian cancer.
Collapse
Affiliation(s)
- Ziying Lei
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Yue Wang
- Henan Provincial People’s Hospital, Zhengzhou, China
| | - Jiahong Wang
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Ke Wang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin, China
| | - Jun Tian
- Huaihe Hospital of Henan University, Kaifeng, China
| | - Ying Zhao
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Lipai Chen
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Jin Wang
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Jiali Luo
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Manman Jia
- Affiliated Tumor Hospital of Zhengzhou University, Tumor Hospital of Henan Province, Henan, China
| | - Hongsheng Tang
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Qingjun He
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Quanxing Liao
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Xiansheng Yang
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Tianpei Guan
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Li Wang
- Affiliated Tumor Hospital of Zhengzhou University, Tumor Hospital of Henan Province, Henan, China
| | - Shuzhong Cui
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| |
Collapse
|
|
18
|
Tan WP, Chang A, Brousell SC, Grimberg DC, Fantony JJ, Longo TA, Etienne W, Spasojevic I, Maccarini P, Inman BA. Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study. Int J Hyperthermia 2020; 37:854-860. [PMID: 32664768 DOI: 10.1080/02656736.2020.1780328] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
BACKGROUND Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity. OBJECTIVE To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS). METHODS Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry. RESULTS The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose. CONCLUSIONS Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.
Collapse
Affiliation(s)
- Wei Phin Tan
- Division of Urology, Duke University Medical Center, Durham, NC, USA.,Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
| | - Andrew Chang
- Division of Urology, Duke University Medical Center, Durham, NC, USA
| | - Steven C Brousell
- Division of Urology, Duke University Medical Center, Durham, NC, USA
| | | | - Joseph J Fantony
- Division of Urology, Duke University Medical Center, Durham, NC, USA
| | - Thomas A Longo
- Division of Urology, Duke University Medical Center, Durham, NC, USA
| | - Wiguins Etienne
- Division of Urology, Duke University Medical Center, Durham, NC, USA
| | - Ivan Spasojevic
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
| | - Paolo Maccarini
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Brant A Inman
- Division of Urology, Duke University Medical Center, Durham, NC, USA.,Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
| |
Collapse
|
|
19
|
Vining CC, Izquierdo F, Eng OS, Turaga KK. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Technical considerations and the learning curve. J Surg Oncol 2020; 122:85-95. [DOI: 10.1002/jso.25939] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 04/05/2020] [Indexed: 12/26/2022]
Affiliation(s)
| | | | - Oliver S. Eng
- Department of SurgeryUniversity of Chicago Chicago Illinois
| | | |
Collapse
|
|
20
|
Rettenmaier MA, Micha JP, Bohart R, Goldstein BH. A retrospective study comparing the efficacy of dose-dense chemotherapy, intraperitoneal chemotherapy and dose-dense chemotherapy with hyperthermic intraperitoneal chemotherapy in the treatment of advanced stage ovarian carcinoma. Eur J Obstet Gynecol Reprod Biol 2019; 244:101-105. [PMID: 31778904 DOI: 10.1016/j.ejogrb.2019.10.047] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/25/2019] [Accepted: 10/29/2019] [Indexed: 11/18/2022]
Abstract
OBJECTIVES Hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP) and dose-dense (DD) chemotherapy have been employed with varying success in the treatment of advanced stage ovarian carcinoma. Despite the clinical benefits associated with these specific forms of chemotherapy administration, they have not been comparatively analyzed, vis-à-vis their efficacy. STUDY DESIGN Advanced stage ovarian cancer patients who were treated with platinum/taxane chemotherapy via a DD regimen (n = 100), IP approach (n = 81) or a DD regimen in conjunction with HIPEC (n = 64) were retrospectively evaluated. The clinical variables of interest were patient age, body mass index, surgery and pathology data, chemotherapy regimen, inclusion of maintenance therapy, and progression free/overall survival. RESULTS Progression free survival (PFS) was significantly more pronounced in the HIPEC (34.9 months) and IP (34.0 months) patients, compared to the DD group (27.6 months) (P = 0.005). A cox-proportional hazards regression model indicated that there was a decreased risk of disease progression accorded to the patients who were treated with IP chemo or HIPEC and DD chemotherapy (HR, 0.43; 95 % CI: 0.21-0.88; P = 0.022) and the subjects who underwent optimal cytoreductive surgery (HR, 2.42; 95 % CI: 1.22-4.80; P = 0.011). Positive BRCA status (HR, 0.434; 95 % CI: 1.59-3.44; P = 0.001) and number of chemotherapy regimens (HR, 1.36; 95 % CI: 1.159-1.61; P = 0.001) were significantly correlated with improved OS although we did not discern a survival benefit associated with any of the chemotherapy treatments (P = 0.136). CONCLUSION We observed PFS advantages conferred to the ovarian cancer patients treated with HIPEC and IP chemotherapy compared to DD chemotherapy. However, an overall survival advantage related to the chemotherapy regimens was not borne out, possibly due to the retrospective nature of the study or differing time periods wherein the specific patient cohorts underwent treatment.
Collapse
Affiliation(s)
- Mark A Rettenmaier
- Southern California Gynecologic Oncology, 1010 West La Veta, Orange, CA 92868, United States
| | - John P Micha
- Gynecologic Oncology Associates Partners, 361 Hospital Road, Suite #422, Newport Beach, CA 92663, United States
| | - Randy Bohart
- Oso Home Care, 17175 Gillette Avenue, Irvine, CA 92614, United States
| | - Bram H Goldstein
- Women's Cancer Research Foundation, Newport Beach, CA 92663, United States.
| |
Collapse
|
|
21
|
De Clercq K, Xie F, De Wever O, Descamps B, Hoorens A, Vermeulen A, Ceelen W, Vervaet C. Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer. Sci Rep 2019; 9:14881. [PMID: 31619730 PMCID: PMC6795903 DOI: 10.1038/s41598-019-51419-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 09/25/2019] [Indexed: 01/12/2023] Open
Abstract
Patients with advanced ovarian cancer develop recurrence despite initial treatment response to standard treatment of surgery and intravenous/intraperitoneal (IP) chemotherapy, partly due to a limited peritoneal exposure time of chemotherapeutics. Paclitaxel-loaded genipin-crosslinked gelatin microspheres (PTX-GP-MS) are evaluated for the treatment of microscopic peritoneal carcinomatosis and prevention of recurrent disease. The highest drug load (39.2 µg PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTXnano-GP-MS) instead of ethanolic PTX solution (PTXEtOH-GP-MS). PTX release from PTX-GP-MS was prolonged. PTXnano-GP-MS displayed a more controlled release compared to a biphasic release from PTXEtOH-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTXEtOH-GP-MS, D = 7.5 mg PTX/kg; PTXnano-GP-MS D = 7.5 and 35 mg PTX/kg), IP nanoparticular albumin-bound PTX (D = 35 mg PTX/kg) and controls (0.9% NaCl, blank GP-MS) was evaluated in a microscopic peritoneal carcinomatosis xenograft mouse model. PTXnano-GP-MS showed superior anticancer efficacy with significant increased survival time, decreased peritoneal carcinomatosis index score and ascites incidence. However, prolonged PTX release over 14 days from PTXnano-GP-MS caused drug-related toxicity in 27% of high-dosed PTXnano-GP-MS-treated mice. Dose simulations for PTXnano-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5-15 mg PTX/kg. Low-dosed PTXnano-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer.
Collapse
Affiliation(s)
- Kaat De Clercq
- Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Feifan Xie
- Laboratory for Medical Biochemistry and Clinical Analysis, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
| | - Olivier De Wever
- Laboratory of Experimental Cancer Research, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Benedicte Descamps
- Infinity (IBiTech-MEDISIP), Department of Electronics and Information Systems, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium
| | - Anne Hoorens
- Department of Pathology, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium
| | - An Vermeulen
- Department of Gastro-intestinal Surgery, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium
| | - Wim Ceelen
- Department of Gastro-intestinal Surgery, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Chris Vervaet
- Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
| |
Collapse
|
|
22
|
Abstract
Non-muscle-invasive bladder cancer (NMIBC), the most prevalent type of bladder cancer, accounts for ~75% of bladder cancer diagnoses. This disease has a 50% risk of recurrence and 20% risk of progression within 5 years, despite the use of intravesical adjuvant treatments (such as BCG or mitomycin C) that are recommended by clinical guidelines. Intravesical device-assisted therapies, such as radiofrequency-induced thermochemotherapeutic effect (RITE), conductive hyperthermic chemotherapy, and electromotive drug administration (EMDA), have shown promising efficacy. These device-assisted treatments are an attractive alternative to BCG, as issues with supply have been a problem in some countries. RITE might be an effective treatment option for some patients who have experienced BCG failure and are not candidates for radical cystectomy. Data from trials using EMDA suggest that it is effective in high-risk disease but requires further validation, and results of randomized trials are eagerly awaited for conductive hyperthermic chemotherapy. Considerable heterogeneity in patient cohorts, treatment sessions, use of maintenance regimens, and single-arm study design makes it difficult to draw solid conclusions, although randomized controlled trials have been reported for RITE and EMDA.
Collapse
|
|
23
|
Model-based analysis of treatment effects of paclitaxel microspheres in a microscopic peritoneal carcinomatosis model in mice. Pharm Res 2019; 36:127. [DOI: 10.1007/s11095-019-2660-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 06/16/2019] [Indexed: 01/23/2023]
|
|
24
|
Abstract
Epithelial ovarian cancer classically presents with vague persistent gastrointestinal, urologic, or nonacute abdominal/pelvic symptoms (bloating, early satiety, discomfort). Ultimately, a pelvic examination or imaging identifies an adnexal mass typically with accompanied advanced peritoneal dissemination. Management involves aggressive cytoreductive surgery in combination with platinum and taxane chemotherapy. Over the last 20 years, optimal resection and mode and timing of chemotherapy have evolved. The authors review the initial diagnosis and management and present the available data and recommendations to guide the decision tree of when to use neoadjuvant, intraperitoneal, HIPEC, dose-dense, and maintenance chemotherapy in the front-line treatment of epithelial ovarian cancer.
Collapse
Affiliation(s)
- Brian Orr
- Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA 15213, USA
| | - Robert P Edwards
- Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA 15213, USA.
| |
Collapse
|
|
25
|
Variation in Clinical Application of Hyperthermic Intraperitoneal Chemotherapy: A Review. Cancers (Basel) 2019; 11:cancers11010078. [PMID: 30641919 PMCID: PMC6357036 DOI: 10.3390/cancers11010078] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/02/2019] [Accepted: 01/07/2019] [Indexed: 12/24/2022] Open
Abstract
Peritoneal metastasis (PM) originating from gastrointestinal and gynecological malignancies are associated with a poor prognosis and rapid disease progression. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment option with curative intent. Hyperthermia enhances the cytotoxicity of chemotherapeutic drugs, thereby killing microscopic tumors and reducing the risk of tumor recurrence. Eight parameters potentially have an impact on the efficacy of HIPEC: the type of drug, drug concentrations, carrier solution, volume of the perfusate, temperature of the perfusate, duration of the treatment, the technique of delivery, and patient selection. In this review, a literature search was performed on PubMed, and a total of 564 articles were screened of which 168 articles were included. Although HIPEC is a successful treatment, there is no standardized method for delivering HIPEC: the choice of parameters is presently largely determined by institutional preferences. We discuss the current choice of the parameters and hypothesize about improvements toward uniform standardization. Quantifying the effect of each parameter separately is necessary to determine the optimal way to perform HIPEC procedures. In vivo, in vitro, in silico, and other experimental studies should shed light on the role of each of the eight parameters.
Collapse
|
|
26
|
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an evolving strategy in the locoregional management of peritoneal surface malignancies, and the role of laparoscopy is expanding. Staging laparoscopy is routinely used to obtain tissue for diagnosis and assess extent of tumor burden. Laparoscopic CRS and HIPEC with curative intent is safe and effective in patients with a low disease burden. In patients with refractory malignant ascites, complete resolution of ascites and improvement in quality of life have been demonstrated with palliative laparoscopic HIPEC. Laparoscopic CRS and HIPEC has an expanding role in the treatment of peritoneal surface disease.
Collapse
|
|
27
|
Implications of Stoma Formation as Part of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. World J Surg 2018; 42:2036-2042. [PMID: 29302727 DOI: 10.1007/s00268-017-4450-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Formation of protective stoma as part of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) may be an effective tool in reducing anastomotic leak incidence. Our aim was to evaluate the incidence and implications of stoma formation during CRS-HIPEC and to examine whether a creation of protective stoma reduces the postoperative morbidity. METHODS A cohort retrospective analysis of all CRS-HIPEC procedures performed between 2004 and 2016 was conducted. Predicting factors for stoma formation were assessed by comparing all patients who underwent stoma formation to those who did not; both groups were then restricted to cases with ≥2 bowel anastomoses and compared in terms of perioperative outcomes in order to determine whether protective stoma confers a morbidity benefit. RESULTS One hundred and ninety-nine CRS-HIPEC procedures were performed on 186 patients. Thirty-four patients (17%) underwent stoma formation, 24 of them as protective stoma. Formation of a stoma was correlated with higher peritoneal carcinomatosis index score (13.6 ± 8 vs. 9.5 ± 7.7, p = 0.007), larger number of organs resected (p < 0.001), greater number of anastomoses (p < 0.001), prolonged operative time (8.1 ± 2.7 vs. 6.6 ± 2.2 h, p = 0.002), and prolonged hospital stay (12 vs. 8.5 days, p = 0.001). In procedures requiring ≥2 anastomoses, formation of protective stoma reduced the anastomotic leak rate (6 vs. 37%, p = 0.025), the morbidity rate (6 vs. 41%, p = 0.017), and reoperation rate (0 vs. 28%, p = 0.03). Overall, 15 patients (44%) underwent stoma reversal, 3 of whom had a complication treated non-operatively. CONCLUSIONS Protective stoma should be considered in extensive CRS-HIPEC procedures requiring two or more bowel anastomoses in order to reduce the postoperative morbidity rate.
Collapse
|
|
28
|
Paris I, Cianci S, Vizzielli G, Fagotti A, Ferrandina G, Gueli Alletti S, Costantini B, Cosentino F, Capoluongo E, Pasqualoni M, Scambia G. Upfront HIPEC and bevacizumab-containing adjuvant chemotherapy in advanced epithelial ovarian cancer. Int J Hyperthermia 2018; 35:370-374. [PMID: 30300042 DOI: 10.1080/02656736.2018.1503346] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Abstract
INTRODUCTION In advanced epithelial ovarian cancer patients, the standard of care is primary debulking surgery, followed by first-line chemotherapy often with bevacizumab addiction. In this context, some experiences have shown that a comprehensive treatment approach to surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) could improve the prognosis. OBJECTIVE This is a study aimed to explore the feasibility of primary debulking surgery and HIPEC upfront followed by first-line therapy with bevacizumab. STUDY DESIGN Phase II monocentric, open label, non-randomised and single-arm study. Forty patients affected by advanced ovarian cancer submitted to primary debulking surgery with HIPEC were enrolled in the study. After surgery, all patients underwent systemic chemotherapy with bevacizumab addiction. RESULTS Complete cytoreduction (RT = 0) was achieved in all cases. Treatment-related early complications were observed in 23 patients and in 15 cases were G1-G2. Major complications were reported in 8 patients. No postoperative death was recorded. Subsequent chemotherapy was administered in all cases. Median time between surgery and first cycle of chemotherapy was 42 days (range 30-76). Concomitant bevacizumab was administered in 34 patients (85%). Maintenance with bevacizumab was feasible in 33 patients (82.5%) and its withdrawal was necessary for 1 patient (2.5%) due to G3 hypertension. CONCLUSION Our data suggest that HIPEC can be safely introduced in the upfront therapy of advanced ovarian cancer.
Collapse
Affiliation(s)
- Ida Paris
- a Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome , Italy
| | - Stefano Cianci
- a Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome , Italy
| | - Giuseppe Vizzielli
- a Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome , Italy
| | - Anna Fagotti
- b Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita' Cattolica , Rome , Italy
| | - Gabriella Ferrandina
- b Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita' Cattolica , Rome , Italy
| | - Salvatore Gueli Alletti
- a Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome , Italy
| | - Barbara Costantini
- a Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome , Italy
| | - Francesco Cosentino
- a Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome , Italy
| | - Ettore Capoluongo
- c Department of Clinical Chemistry , Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita' Cattolica , Rome , Italy
| | - Mariangela Pasqualoni
- a Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome , Italy
| | - Giovanni Scambia
- b Department of Women's and Children's Health , Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita' Cattolica , Rome , Italy
| |
Collapse
|
|
29
|
Miailhe G, Arfi A, Mirshahi M, Eveno C, Pocard M, Touboul C. A new animal model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing mice in the treatment of peritoneal carcinomatosis of ovarian origin. J Visc Surg 2018; 155:183-189. [PMID: 29108718 DOI: 10.1016/j.jviscsurg.2017.10.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
AIM OF THE STUDY We set out to develop and evaluate the morbidity of a non-invasive hyperthermic intraperitoneal chemotherapy (HIPEC) procedure in mice. HIPEC has been shown to improve overall survival in treating ovarian cancer with peritoneal carcinomatosis. However, related complications, toxicity and the lack of randomized trials limits its widespread use. To improve the surgical technique, there is a need for animal models that allow teams to work on large groups without burdensome logistics. MATERIALS AND METHODS To develop the model, we first determined optimal HIPEC conditions in 20 Black Six mice without carcinomatosis. To evaluate HIPEC morbidity, peritoneal carcinomatosis cells of ovarian origin were injected into the peritoneum of 10 pathogen-free Nude mice. The mice underwent HIPEC 21 days later under general anesthesia. An inflow catheter was introduced into the left hypochondria and an outflow catheter was introduced into the left iliac fossa. Bath infusion was oxaliplatin (920mg/m2) at 43°C for 12minutes. The mice were monitored and sacrificed two weeks after the procedure. RESULTS No deaths were observed during the procedure and infusion was well tolerated throughout the HIPEC. One mouse died the day after the procedure. No major dehydration, hemoperitoneum or evisceration was observed. CONCLUSION This mouse model of closed abdomen HIPEC has limited morbidity and could be a useful model to study HIPEC regimens and its effects on peritoneal carcinomatosis.
Collapse
Affiliation(s)
- G Miailhe
- Service de gynécologie obstétrique, hôpital intercommunal de Créteil, université Paris Est, Paris XII, 40, avenue de Verdun, 94000 Créteil, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - A Arfi
- Service de gynécologie obstétrique, hôpital intercommunal de Créteil, université Paris Est, Paris XII, 40, avenue de Verdun, 94000 Créteil, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - M Mirshahi
- UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - C Eveno
- Service de chirurgie digestive et cancérologique, hôpital Lariboisière Fernand-Widal, université Paris VII, 49, boulevard de la chapelle, 75010 Paris, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - M Pocard
- Service de chirurgie digestive et cancérologique, hôpital Lariboisière Fernand-Widal, université Paris VII, 49, boulevard de la chapelle, 75010 Paris, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - C Touboul
- Service de gynécologie obstétrique, hôpital intercommunal de Créteil, université Paris Est, Paris XII, 40, avenue de Verdun, 94000 Créteil, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France.
| |
Collapse
|
|
30
|
Diagnostic value of contrast-enhanced CT combined with 18-FDG PET in patients selected for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Abdom Radiol (NY) 2018; 43:1094-1100. [PMID: 28770289 DOI: 10.1007/s00261-017-1276-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
PURPOSE Aim of the study is to assess the reliability and correlation with surgical peritoneal cancer index (PCI) of combined PET/CT and ceCT scans (PET/ceCT) performed in a session in patients with peritoneal carcinomatosis candidates for cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS We retrospectively analyzed data collected from 27 patients with different types of peritoneal carcinomatosis candidates to CS + HIPEC who underwent FDG PET/ceCT in a single session. Two nuclear medicine physicians and two radiologists independently and blindly evaluated PET/CT and ceCT imaging, respectively. In the case of discordance, the consensus was reached by a discussion between the specialists. Moreover, the combined images were evaluated by all the specialists in consensus. The PCIs obtained from surgical look, PET/CT, ceCT, and PET/ceCT were compared with each other. The coefficients of correlation (r) were calculated. The study was conducted after approval of local ethics committee. RESULTS Surgical PCI was available in 21 patients. The coefficient of correlation between PCI of PET/CT and surgery was 0.528, while it resulted higher between PET/ceCT and surgery (r = 0.878), very similar to ceCT and surgery (r = 0.876). The r coefficient between surgical PCI and PET/CT was higher in patients with a non-mucinous cancer (n = 12) than the counterpart (0.601 vs. 0.303) and the addition of ceCT significantly increases the correlation (r = 0.863), which is anyway similar to ceCT alone (r = 0.856). CONCLUSIONS PET/ceCT as single examination is more accurate than PET/CT but not than ceCT alone for the definition of PCI in a selected group of patients candidates to CS + HIPEC.
Collapse
|
|
31
|
Kerbage Y, Canlorbe G, Estevez JP, Grabarz A, Mordon S, Uzan C, Collinet P, Azaïs H. [Microscopic peritoneal metastases of epithelial ovarian cancers. Clinical relevance, diagnostic and therapeutic tools]. ACTA ACUST UNITED AC 2018; 46:497-502. [PMID: 29656069 DOI: 10.1016/j.gofs.2018.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Indexed: 10/17/2022]
Abstract
Understanding the biology and progression mechanisms of peritoneal metastases in ovarian epithelial cancers (EOC) is important because peritoneal carcinomatosis is present or will occur during surveillance of a majority of patients. Despite the clinical remission achieved after complete macroscopic cytoreductive surgery and platinum-based chemotherapy, 60% of patients will develop peritoneal recurrence. This suggests that microscopic lesions, which are not eradicated by surgery may be present and may participate in the mechanisms leading to peritoneal recurrence. This paper discusses current available data on microscopic peritoneal metastases, their diagnosis and their treatment. We reviewed all publications dealing with microscopic peritoneal metastases of EOC between 1980 and 2017. The most recent and most relevant publications dealing with the treatment modalities of these metastases were selected. Peritoneal and epiploic microscopic localizations would occur in 1.2 to 15.1% of cases at early-stage and are not treated during conventional surgery. They could represent a potential therapeutic target. Local treatments (intraperitoneal chemotherapy, photodynamic therapy, fluorescence-guided surgery) seem to be necessary in addition to surgery and chemotherapy and may help reduce the risk of peritoneal recurrence. The place of these treatments in the management of EOC remains to be defined by subsequent researches.
Collapse
Affiliation(s)
- Y Kerbage
- Service de chirurgie gynécologique, CHU de Lille, 59000 Lille, France; Inserm, U1189, ONCO-THAI, thérapies laser assistées par l'imagerie, 59000 Lille, France
| | - G Canlorbe
- Service de chirurgie et oncologie gynécologique et mammaire, hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, Pitié-Salpêtrière, AP-HP, 47/83, boulevard de l'Hôpital, 75013 Paris, France
| | - J P Estevez
- Service de chirurgie gynécologique, CHU de Lille, 59000 Lille, France
| | - A Grabarz
- Service de chirurgie gynécologique, CHU de Lille, 59000 Lille, France; Inserm, U1189, ONCO-THAI, thérapies laser assistées par l'imagerie, 59000 Lille, France
| | - S Mordon
- Inserm, U1189, ONCO-THAI, thérapies laser assistées par l'imagerie, 59000 Lille, France
| | - C Uzan
- Service de chirurgie et oncologie gynécologique et mammaire, hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, Pitié-Salpêtrière, AP-HP, 47/83, boulevard de l'Hôpital, 75013 Paris, France
| | - P Collinet
- Service de chirurgie gynécologique, CHU de Lille, 59000 Lille, France; Inserm, U1189, ONCO-THAI, thérapies laser assistées par l'imagerie, 59000 Lille, France
| | - H Azaïs
- Inserm, U1189, ONCO-THAI, thérapies laser assistées par l'imagerie, 59000 Lille, France; Service de chirurgie et oncologie gynécologique et mammaire, hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, Pitié-Salpêtrière, AP-HP, 47/83, boulevard de l'Hôpital, 75013 Paris, France.
| |
Collapse
|
|
32
|
Cavaliere D, Cirocchi R, Coccolini F, Fagotti A, Fambrini M, Federici O, Lorusso D, Vaira M, Ceresoli M, Delrio P, Garofalo A, Pignata S, Scollo P, Trojano V, Amadori A, Ansaloni L, Cariti G, De Cian F, De Iaco P, De Simone M, Deraco M, Donini A, Fiorentini G, Frigerio L, Greggi S, Macrì A, Pasqual EM, Roviello F, Sammartino P, Sassaroli C, Scambia G, Staudacher C, Vici P, Vizza E, Valle M. 1st Evidence-based Italian consensus conference on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinosis from ovarian cancer. TUMORI JOURNAL 2017; 103:525-536. [PMID: 28430350 DOI: 10.5301/tj.5000623] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2017] [Indexed: 12/11/2022]
Abstract
Ovarian cancer (OC) remains relatively rare, although it is among the top 4 causes of cancer death for women younger than 50. The aggressive nature of the disease and its often late diagnosis with peritoneal involvement have an impact on prognosis. The current scientific literature presents ambiguous or uncertain indications for management of peritoneal carcinosis (PC) from OC, both owing to the lack of sufficient scientific data and their heterogeneity or lack of consistency. Therefore, the Italian Society of Surgical Oncology (SICO), the Italian Society of Obstetrics and Gynaecology, the Italian Association of Hospital Obstetricians and Gynaecologists, and the Italian Association of Medical Oncology conducted a multidisciplinary consensus conference (CC) on management of advanced OC presenting with PC during the SICO annual meeting in Naples, Italy, on September 10-11, 2015. An expert committee developed questions on diagnosis and staging work-up, indications, and procedural aspects for peritonectomy, systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy for PC from OC. These questions were provided to 6 invited speakers who answered with an evidence-based report. Each report was submitted to a jury panel, representative of Italian experts in the fields of surgical oncology, gynecology, and medical oncology. The jury panel revised the reports before and after the open discussion during the CC. This article is the final document containing the clinical evidence reports and statements, revised and approved by all the authors before submission.
Collapse
Affiliation(s)
- Davide Cavaliere
- General Surgery and Surgical Oncology, Morgagni-Pierantoni Hospital, Forlì - Italy
| | - Roberto Cirocchi
- General and Oncological Surgery, University of Perugia, Terni - Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Papa Giovanni XXIII Hospital, Bergamo - Italy
| | - Anna Fagotti
- Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome - Italy
| | - Massimiliano Fambrini
- Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence - Italy
| | - Orietta Federici
- Department of Digestive Surgery, Regina Elena National Cancer Institute, IRCCS-IFO, Rome - Italy
| | - Domenica Lorusso
- Gynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Milan - Italy
| | - Marco Vaira
- Surgical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo (Turin) - Italy
| | - Marco Ceresoli
- General, Emergency and Trauma Surgery Department, Papa Giovanni XXIII Hospital, Bergamo - Italy
| | - Paolo Delrio
- Abdominal Oncology Department, Fondazione Giovanni Pascale, IRCCS, Naples - Italy
| | - Alfredo Garofalo
- Department of Digestive Surgery, Regina Elena National Cancer Institute, IRCCS-IFO, Rome - Italy
| | - Sandro Pignata
- Department of Gynecologic and Urologic Oncology, Fondazione Giovanni Pascale, IRCCS, Naples - Italy
| | - Paolo Scollo
- Division of Gynecology and Obstetrics, Maternal and Child Department, Cannizzaro Hospital, Catania - Italy
| | - Vito Trojano
- Division of Gynaecologic Oncology, Istituto Tumori Giovanni Paolo II, IRCCS, Bari - Italy
| | - Andrea Amadori
- Department of Maternity and Childhood, Morgagni-Pierantoni Hospital, Forlì - Italy
| | - Luca Ansaloni
- General, Emergency and Trauma Surgery Department, Papa Giovanni XXIII Hospital, Bergamo - Italy
| | - Giuseppe Cariti
- Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence - Italy
| | - Franco De Cian
- Department of Surgical Science and Integrated Diagnostics, IRCCS AOU San Martino-IST, Genoa - Italy
| | - Pierandrea De Iaco
- Department of Obstetrics and Gynecology, St. Orsola Hospital, University of Bologna, Bologna - Italy
| | - Michele De Simone
- Surgical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo (Turin) - Italy
| | - Marcello Deraco
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Milan - Italy
| | - Annibale Donini
- General and Emergency Surgery, Santa Maria della Misericordia Hospital, University of Perugia, Perugia - Italy
| | | | - Luigi Frigerio
- Division of Gynecology and Obstetrics, Papa Giovanni XXIII Hospital, Bergamo - Italy
| | - Stefano Greggi
- Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence - Italy
| | - Antonio Macrì
- Department of Human Pathology, University of Messina, Messina - Italy
| | | | - Franco Roviello
- Department of Medical, Surgical and Neuroscience, University of Siena, Siena - Italy
| | - Paolo Sammartino
- Department of Surgery Pietro Valdoni, Sapienza University of Rome, Rome - Italy
| | - Cinzia Sassaroli
- Abdominal Oncology Department, Fondazione Giovanni Pascale, IRCCS, Naples - Italy
| | - Giovanni Scambia
- Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome - Italy
| | - Carlo Staudacher
- Department of Surgery, San Raffaele Scientific Institute, Milan - Italy
| | - Patrizia Vici
- Division of Medical Oncology B, Regina Elena National Cancer Institute, IRCCS-IFO, Rome - Italy
| | - Enrico Vizza
- Gynecology Oncology Unit, Department of Oncological Surgery, Regina Elena National Cancer Institute, IRCCS-IFO, Rome - Italy
| | - Mario Valle
- Department of Digestive Surgery, Regina Elena National Cancer Institute, IRCCS-IFO, Rome - Italy
| |
Collapse
|
|
33
|
Almerie MQ, Gossedge G, Wright KE, Jayne DG. Treatment of peritoneal carcinomatosis with photodynamic therapy: Systematic review of current evidence. Photodiagnosis Photodyn Ther 2017; 20:276-286. [PMID: 29111390 DOI: 10.1016/j.pdpdt.2017.10.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 10/11/2017] [Accepted: 10/26/2017] [Indexed: 11/28/2022]
Abstract
BACKGROUND Peritoneal carcinomatosis results when tumour cells implant and grow within the peritoneal cavity. Treatment and prognosis vary based on the primary cancer. Although therapy with intention-to-cure is offered to selective patients using cytoreductive surgery with chemotherapy, the prognosis remains poor for most of the patients. Photodynamic therapy (PDT) is a cancer-therapeutic modality where a photosensitiser is administered to patients and exerts a cytotoxic effect on cancer cells when excited by light of a specific wavelength. It has potential application in the treatment of peritoneal carcinomatosis. METHODS We systematically reviewed the evidence of using PDT to treat peritoneal carcinomatosis in both animals and humans (Medline/EMBASE searched in June 2017). RESULTS Three human and 25 animal studies were included. Phase I and II human trials using first-generation photosensitisers showed that applying PDT after surgical debulking in patients with peritoneal carcinomatosis is feasible with some clinical benefits. The low tumour-selectivity of the photosensitisers led to significant toxicities mainly capillary leak syndrome and bowel perforation. In animal studies, PDT improved survival by 15-300%, compared to control groups. PDT led to higher tumour necrosis values (categorical values 0-4 [4=highest]: PDT 3.4±1.0 vs. control 0.4±0.6, p<0.05) and reduced tumour size (residual tumour size is 10% of untreated controls, p<0.001). CONCLUSION PDT has potential in treating peritoneal carcinomatosis, but is limited by its narrow therapeutic window and possible serious side effects. Recent improvement in tumour-selectivity and light delivery systems is promising, but further development is needed before PDT can be routinely applied for peritoneal carcinomatosis.
Collapse
Affiliation(s)
- Muhammad Qutayba Almerie
- Section of Translational Anaesthesia and Surgical Sciences, Leeds Institute of Biomedical & Clinical Sciences (LIBACS), St James's University Hospital, Leeds LS9 7TF, UK.
| | - Gemma Gossedge
- Section of Translational Anaesthesia and Surgical Sciences, Leeds Institute of Biomedical & Clinical Sciences (LIBACS), St James's University Hospital, Leeds LS9 7TF, UK.
| | - Kathleen E Wright
- Section of Translational Anaesthesia and Surgical Sciences, Leeds Institute of Biomedical & Clinical Sciences (LIBACS), St James's University Hospital, Leeds LS9 7TF, UK.
| | - David G Jayne
- Section of Translational Anaesthesia and Surgical Sciences, Leeds Institute of Biomedical & Clinical Sciences (LIBACS), St James's University Hospital, Leeds LS9 7TF, UK.
| |
Collapse
|
|
34
|
Pavlov MJ, Ceranic MS, Latincic SM, Sabljak PV, Kecmanovic DM, Sugarbaker PH. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial and recurrent ovarian carcinoma: a single center experience. Int J Hyperthermia 2017; 34:564-569. [PMID: 28877609 DOI: 10.1080/02656736.2017.1371341] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND With standard treatment of epithelial ovarian cancer (EOC), prognosis is very poor. The aim of this study is to show early and late results in patients who underwent cytoreductive surgery and intraperitoneal chemotherapy. PATIENTS AND METHODS This was a retrospective single centre study. All patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) or modified early postoperative intraperitoneal chemotherapy (EPIC) were included in the study. RESULTS In the period 1995-2014, 116 patients were treated, 55 with primary EOC and 61 with recurrent EOC. The mean age was 59 years (26-74). Statistically, median survival time was significantly longer in the group with primary advanced cancer of the ovary (41.3 months) compared to relapsed ovarian cancer (27.3 months). Survival for the primary EOC was 65 and 24% at 3 and 5 years, respectively. Survival for recurrent EOC was 33 and 16% at 3 and 5 years, respectively. Mortality was 1/116 (0.8%). Morbidity was 11/116 (9.5%). Peritoneal cancer index (PCI) was ≤20 in 59 (51%) patients and statistically, their average survival was significantly longer than in the group of 57 (49%) patients with PCI >20 (p = 0.014). CONCLUSIONS In advanced or recurrent EOC, a curative therapeutic approach was pursued that combined optimal cytoreductive surgery and intraperitoneal chemotherapy. PCI and timing of the intervention (primary or recurrent) were the strongest independent prognostic factors.
Collapse
Affiliation(s)
- Maja J Pavlov
- a School of Medicine , University of Belgrade , Belgrade , Serbia.,b Department for Colorectal and Pelvic Surgery , First Surgical Clinic, Clinical Center of Serbia , Belgrade , Serbia
| | - Miljan S Ceranic
- a School of Medicine , University of Belgrade , Belgrade , Serbia.,b Department for Colorectal and Pelvic Surgery , First Surgical Clinic, Clinical Center of Serbia , Belgrade , Serbia
| | - Stojan M Latincic
- b Department for Colorectal and Pelvic Surgery , First Surgical Clinic, Clinical Center of Serbia , Belgrade , Serbia
| | - Predrag V Sabljak
- a School of Medicine , University of Belgrade , Belgrade , Serbia.,c Department for Esophagogastric Surgery , First Surgical Clinic, Clinical Center of Serbia , Belgrade , Serbia
| | - Dragutin M Kecmanovic
- a School of Medicine , University of Belgrade , Belgrade , Serbia.,b Department for Colorectal and Pelvic Surgery , First Surgical Clinic, Clinical Center of Serbia , Belgrade , Serbia
| | - Paul H Sugarbaker
- d Center for Gastrointestinal Malignancies, MedStar Washington Cancer Institute, MedStar Washington Hospital Center , Washington , DC , USA
| |
Collapse
|
|
35
|
|
|
36
|
Wong EY, Tan GH, Chia CS, Kumar M, Soo KC, Teo MC. Morbidity and mortality of elderly patients following cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Asia Pac J Clin Oncol 2017; 14:e193-e202. [PMID: 28695617 DOI: 10.1111/ajco.12723] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Accepted: 05/15/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Evelyn Y.T. Wong
- Division of Surgical Oncology; National Cancer Center Singapore; Singapore Republic of Singapore
| | - Grace H.C. Tan
- Division of Surgical Oncology; National Cancer Center Singapore; Singapore Republic of Singapore
| | - Claramae S.L. Chia
- Division of Surgical Oncology; National Cancer Center Singapore; Singapore Republic of Singapore
| | - Mrinal Kumar
- Division of Surgical Oncology; National Cancer Center Singapore; Singapore Republic of Singapore
| | - Khee Chee Soo
- Division of Surgical Oncology; National Cancer Center Singapore; Singapore Republic of Singapore
| | - Melissa C.C. Teo
- Division of Surgical Oncology; National Cancer Center Singapore; Singapore Republic of Singapore
| |
Collapse
|
|
37
|
Arjona-Sanchez A, Rufián-Peña S. Progress in the management of primary and recurrent ovarian carcinomatosis with peritonectomy procedure and HIPEC in a high volume centre. Int J Hyperthermia 2017; 33:554-561. [DOI: 10.1080/02656736.2017.1278631] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Alvaro Arjona-Sanchez
- Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sofia, Cordoba, Spain
- CIBERehd, IMIBIC, University Hospital Reina Sofia, Cordoba, Spain
| | - Sebastian Rufián-Peña
- Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sofia, Cordoba, Spain
- CIBERehd, IMIBIC, University Hospital Reina Sofia, Cordoba, Spain
| |
Collapse
|
|
38
|
Ni X, Wu P, Wu J, Ji M, Tian B, Jiang Z, Sun Y, Xing X, Jiang J, Wu C. Hyperthermic intraperitoneal perfusion chemotherapy and response evaluation in patients with gastric cancer and malignant ascites. Oncol Lett 2017; 14:1691-1696. [PMID: 28789396 DOI: 10.3892/ol.2017.6342] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 03/03/2017] [Indexed: 12/11/2022] Open
Abstract
The present study describes the use of bidirectional chemotherapy in the treatment of patients with gastric cancer and peritoneal carcinomatosis (PC), using newly developed response criteria for the treatment of malignant ascites. In addition, the association between effusion response and survival was analyzed. Between June 2010 and May 2014, patients affected by malignant ascites secondary to unresectable PC of gastric origin were treated with a combination of systemic and loco-regional chemotherapy. Cisplatin (75 mg/m2) at an inflow temperature of 43°C was infused intraperitoneally, and docetaxel (75 mg/m2) was infused simultaneously via a peripheral vein, on day 1 every 3 weeks. The primary endpoint was overall survival rate, and the secondary endpoint was efficacy against malignant ascites using new response criteria. In total, 41 patients were enrolled, the majority of whom received 6 cycles of intraperitoneal chemotherapy in combination with hyperthermia. The majority of patients exhibited clinical regression of ascites and relief of associated symptoms. Malignant ascites disappeared [complete response (CR)] or decreased by 50% [partial response (PR)] in 73.2% of patients. No mortalities associated with the procedures occurred. The median survival time was 8.6 months, and the 1-year survival rate was 24.4%. As these new response criteria for the treatment of malignant ascites were found to be feasible, bidirectional chemotherapy may be the preferred strategy for the treatment of gastric cancer with PC. The CR, PR and non-PR groups showed significant differences in overall survival, indicating that decreased effusion was associated with improved patient survival.
Collapse
Affiliation(s)
- Xuefeng Ni
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Ping Wu
- Department of Pharmacology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Jun Wu
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Mei Ji
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Bo Tian
- Department of Pathology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Zhenxing Jiang
- Department of Radiology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Yue Sun
- Department of Ultrasonography, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Xiaoxiao Xing
- Department of Ultrasonography, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Jingting Jiang
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Changping Wu
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| |
Collapse
|
|
39
|
Huang Y, Alzahrani NA, Chua TC, Liauw W, Morris DL. Repeat cytoreductive surgery with or without perioperative intraperitoneal chemotherapy for peritoneal surface malignancy. Am J Surg 2017; 213:1024-1030. [PMID: 27839689 DOI: 10.1016/j.amjsurg.2016.09.046] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 09/25/2016] [Accepted: 09/29/2016] [Indexed: 01/27/2023]
Abstract
BACKGROUND A significant proportion of patients with peritoneal surface malignancy (PSM) experienced recurrence after initial cytoreductive surgery (CRS). Thus the aims of this study were to determine short-term outcomes and long-term survivals associated with repeat CRS. METHODS This was a retrospective study of prospectively collected data of consecutive patients with PSM who underwent CRS by one surgical team at St George Hospital in Sydney, Australia between Jan 1996 and May 2016. RESULTS There was no significant difference in hospital mortality (p=0.343) and major morbidity rate (p=0.454). Patients who underwent repeat surgery had a significantly higher 5-year overall survival (OS) rate (p<0.001) and a longer median disease free interval (DFS) (p<0.001). Repeat CRS was also found to be a significant prognostic factor for OS (p<0.001) and DFS (p<0.001). CONCLUSIONS Repeat CRS with or without perioperative intraperitoneal chemotherapy could provide long-term survival benefits to patients with PSM with acceptable mortality and morbidity rates. SUMMARY 1. Repeat CRS with or without PIC provides long-term survival benefits to patients with PSM. 2. Repeat CRS with or without PIC is feasible and can be performed without acceptable mortality and morbidity rates.
Collapse
Affiliation(s)
- Yeqian Huang
- Department of Surgery, University of New South Wales, St George Hospital, New South Wales, Australia
| | - Nayef A Alzahrani
- Department of Surgery, University of New South Wales, St George Hospital, New South Wales, Australia; College of Medicine, Imam Muhammad ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Terence C Chua
- Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Winston Liauw
- Department of Medical Oncology, University of New South Wales, St George Hospital, Sydney, New South Wales, Australia
| | - David L Morris
- Department of Surgery, University of New South Wales, St George Hospital, New South Wales, Australia.
| |
Collapse
|
|
40
|
Kapoor S, Bassily-Marcus A, Alba Yunen R, Tabrizian P, Semoin S, Blankush J, Labow D, Oropello J, Manasia A, Kohli-Seth R. Critical care management and intensive care unit outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. World J Crit Care Med 2017; 6:116-123. [PMID: 28529913 PMCID: PMC5415851 DOI: 10.5492/wjccm.v6.i2.116] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 12/14/2016] [Accepted: 01/14/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To study the early postoperative intensive care unit (ICU) management and complications in the first 2 wk of patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).
METHODS Our study is a retrospective, observational study performed at Icahn School of Medicine at Mount Sinai, quaternary care hospital in New York City. All adult patients who underwent CRS and HIPEC between January 1, 2007 and December 31, 2012 and admitted to ICU postoperatively were studied. Fifty-one patients came to the ICU postoperatively out of 170 who underwent CRS and HIPEC therapy during the study period. Data analysis was performed using descriptive statistics.
RESULTS Of the 170 patients who underwent CRS and HIPEC therapy, 51 (30%) came to the ICU postoperatively. Mean ICU length of stay was 4 d (range 1-60 d) and mean APACHE II score was 15 (range 7-23). Thirty-one/fifty-one (62%) patients developed postoperative complications. Aggressive intraoperative and postoperative fluid resuscitation is required in most patients. Hypovolemia was seen in all patients and median amount of fluids required in the first 48 h was 6 L (range 1-14 L). Thirteen patients (25%) developed postoperative hypotension with seven requiring vasopressor support. The major cause of sepsis was intraabdominal, with 8 (15%) developing anastomotic leaks and 5 (10%) developing intraabdominal abscess. The median survival was 14 mo with 30 d mortality of 4% (2/51) and 90 d mortality of 16% (8/51). One year survival was 56.4% (28/51). Preoperative medical co morbidities, extent of surgical debulking, intraoperative blood losses, amount of intra op blood products required and total operative time are the factors to be considered while deciding ICU vs non ICU admission.
CONCLUSION Overall, ICU outcomes of this study population are excellent. Triage of these patients should consider preoperative and intraoperative factors. Intensivists should be vigilant to aggressive postop fluid resuscitation, pain control and early detection and management of surgical complications.
Collapse
|
|
41
|
Di Giorgio A, De Iaco P, De Simone M, Garofalo A, Scambia G, Pinna AD, Verdecchia GM, Ansaloni L, Macrì A, Cappellini P, Ceriani V, Giorda G, Biacchi D, Vaira M, Valle M, Sammartino P. Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases. Ann Surg Oncol 2017; 24:914-922. [PMID: 27896512 PMCID: PMC5339330 DOI: 10.1245/s10434-016-5686-1] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Indexed: 12/15/2022]
Abstract
PURPOSE The aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease. METHODS In a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC. RESULTS The 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors. CONCLUSIONS This selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.
Collapse
Affiliation(s)
- Angelo Di Giorgio
- Department of Surgery 'P. Valdoni', Sapienza University of Rome, Rome, Italy
| | - Pierandrea De Iaco
- General Surgery and Gynecologic Oncology Unit, Sant'Orsola Hospital, Bologna, Italy
| | | | - Alfredo Garofalo
- Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy
| | - Giovanni Scambia
- Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy
| | | | | | - Luca Ansaloni
- General Surgery Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Antonio Macrì
- Department of Human Pathology, University of Messina, Messina, Italy
| | - Paolo Cappellini
- General Surgery Unit, San Giovanni di Dio Hospital, Florence, Italy
| | - Valerio Ceriani
- General Surgery UnitPoliclinico Polispecialistico Multimedica, Sesto San Giovanni, Italy
| | - Giorgio Giorda
- Department of Gynecological Oncology, CRO National Cancer Institute, Aviano, Italy
| | - Daniele Biacchi
- Department of Surgery 'P. Valdoni', Sapienza University of Rome, Rome, Italy
| | - Marco Vaira
- Unit of Surgical Oncology, Candiolo Cancer Institute, Turin, Italy
| | - Mario Valle
- Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy
| | - Paolo Sammartino
- Department of Surgery 'P. Valdoni', Sapienza University of Rome, Rome, Italy.
| |
Collapse
|
|
42
|
Flessner MF. Pharmacokinetic problems in peritoneal drug administration: an update after 20 years. Pleura Peritoneum 2016; 1:183-191. [PMID: 30911622 DOI: 10.1515/pp-2016-0022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 11/29/2016] [Indexed: 12/14/2022] Open
Abstract
Intraperitoneal chemotherapy has demonstrated significant pharmacologic and clinical advantage over traditional intravenous administration for cancers that are restricted to the peritoneal cavity. The combination of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard technique used to fight ovarian and gastrointestinal cancers in many centers. However, challenges remain for HIPEC to contact the entire peritoneal surface, penetrate the tumor tissue, and transport to the lymphatics and other metastatic sites. New innovations in delivery technique, such as heated aerosol, and in delivery molecules, such as microparticles, nanoparticles, nanogels, and tumor-penetrating peptides are being tested in animal models and will likely soon be in human trials. Improvements in overall care, such as the recent clinical trial of an oral agent for maintenance therapy in ovarian carcinoma, will continue in this field for the next 20 years.
Collapse
|
|
43
|
Rancoule C, Guy JB, Vallard A, Ben Mrad M, Rehailia A, Magné N. [50th anniversary of cisplatin]. Bull Cancer 2016; 104:167-176. [PMID: 27989629 DOI: 10.1016/j.bulcan.2016.11.011] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/06/2016] [Accepted: 11/12/2016] [Indexed: 01/08/2023]
Abstract
We have just celebrated the 50th anniversary of cisplatin cytotoxic potential discovery. It is time to take stock… and it seems mainly positive. This drug, that revolutionized the treatment of many cancer types, continues to be the most widely prescribed chemotherapy. Despite significant toxicities, resistance mechanisms associated with treatment failures, and unresolved questions about its mechanism of action, the use of this cytotoxic agent remains unwavering. The interest concerning this "old" invincible drug has not yet abated. Indeed many research axes are in the news. New platinum salts agents are tested, new cisplatin formulations are developed to target tumor cells more efficiently, and new combinations are established to increase the cytotoxic potency of cisplatin or overcome the resistance mechanisms.
Collapse
Affiliation(s)
- Chloé Rancoule
- Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez, France; CNRS UMR 5822, laboratoire de radiobiologie cellulaire et moléculaire de Lyon Sud, 165, chemin du Grand-Revoyet, BP 12, 69921 Oullins cedex, France
| | - Jean-Baptiste Guy
- Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez, France; CNRS UMR 5822, laboratoire de radiobiologie cellulaire et moléculaire de Lyon Sud, 165, chemin du Grand-Revoyet, BP 12, 69921 Oullins cedex, France
| | - Alexis Vallard
- Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez, France
| | - Majed Ben Mrad
- Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez, France
| | - Amel Rehailia
- Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez, France
| | - Nicolas Magné
- Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez, France; CNRS UMR 5822, laboratoire de radiobiologie cellulaire et moléculaire de Lyon Sud, 165, chemin du Grand-Revoyet, BP 12, 69921 Oullins cedex, France.
| |
Collapse
|
|
44
|
López-López V, Cascales-Campos P, Schneider M, Gil J, Gil E, Gomez-Hidalgo NR, Parrilla P. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients. A systematic literature review. Surg Oncol 2016; 25:378-384. [DOI: 10.1016/j.suronc.2016.09.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 08/30/2016] [Accepted: 09/05/2016] [Indexed: 02/07/2023]
|
|
45
|
Rajeev R, Turaga KK. Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery in the Management of Peritoneal Carcinomatosis. Cancer Control 2016; 23:36-46. [PMID: 27009455 DOI: 10.1177/107327481602300107] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Malignant peritoneal disease can lead to significant debility due to bowel obstructions, ascites, and cancer cachexia. Moreover, inadequate imaging techniques can lead to the suboptimal detection of disease, and the poor vascularity of tumors can lead to a poor response to systemic chemotherapy. However, combination cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising novel treatment for patients with this disease. METHODS The medical literature focusing on diagnostic updates and the management of peritoneal disease was reviewed. The application principles of HIPEC for use in peritoneal disease were also summarized. RESULTS Improvements in imaging and the application of laparoscopic techniques have significantly increased the rate of diagnosis of early peritoneal disease with consequently less morbid cytoreductive procedures. Appropriate patient selection based on prognostic scores along with complete cytoreduction can identify a cohort of patients likely to derive durable benefit from this combination treatment. CONCLUSIONS Advances in diagnostic and therapeutic techniques, including surgical cytoreductive techniques, have demonstrated significant survival gains in patients with peritoneal disease. Although HIPEC can be used for the management of various types of histologies, further development of high-level evidence is necessary to advance the field.
Collapse
Affiliation(s)
| | - Kiran K Turaga
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
| |
Collapse
|
|
46
|
Cistaro A, Cucinotta M, Cassalia L, Priola A, Priola S, Pappalardo M, Coppolino P, De Simone M, Quartuccio N. 18 F-FDG PET/CT, cytoreductive surgery and intraperitoneal chemohyperthermia for the therapeutic management in peritoneal carcinomatosis: A pilot study. Rev Esp Med Nucl Imagen Mol 2016. [DOI: 10.1016/j.remnie.2016.01.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
|
|
47
|
Cistaro A, Cucinotta M, Cassalia L, Priola A, Priola S, Pappalardo M, Coppolino P, De Simone M, Quartuccio N. (18)F-FDG PET/CT, cytoreductive surgery and intraperitoneal chemohyperthermia for the therapeutic management in peritoneal carcinomatosis: A pilot study. Rev Esp Med Nucl Imagen Mol 2016; 35:232-237. [PMID: 26907833 DOI: 10.1016/j.remn.2016.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 12/30/2015] [Accepted: 01/03/2016] [Indexed: 02/07/2023]
Abstract
AIM Peritoneal carcinomatosis is a common evolution of neoplasms and the terminal stage of disease. A new therapeutic technique, based on the total surgical removal of peritoneal lesions (peritonectomy procedure - PP) combined with the intraperitoneal chemohyperthermia (IPCH), has been developed. Proper patient selection is mandatory for optimizing the results of treatment. The aim of this study was to investigate the role of [(18)F]fluoro-2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography ((18)F-FDG PET/CT) in patients with peritoneal carcinosis selected to undergo PP and IPCH. Furthermore, we aimed to identify characteristic patterns of abdominal(18)F-FDG uptake and to correlate these patterns with available anatomic findings after surgery. METHODS Patients with either histologically confirmed peritoneal carcinosis or suspected upon clinical follow-up and/or imaging findings were prospectively submitted to pre-surgery (18)F-FDG PET/CT scan. Only those patients without evidence of extra-peritoneal metastases at PET/CT scan were treated with PP and IPCH. RESULTS 11 patients with peritoneal carcinomatosis (5 colorectal, 4 ovarian, 1 pancreatic) and 1 unknown primitive cancer, were eligible for the study. In all cases PET/CT scan showed multiple peritoneal implants. In 6 out of 11 cases (54%) metastases were evidenced by (18)F-FDG PET/CT: 2 cases with liver metastases; 1 case with bone metastases; 3 patients with lymph-node lesions. Two distinct imaging patterns, with focal or diffuse increased (18)F-FDG uptake, were recognized. CONCLUSIONS PP+IPCH of patients selected by (18)F-FDG PET/CT seems to be safe and feasible. PET/CT scan appears as a reliable tool for the detection, characterization of peritoneal implants with potential impact in the therapeutic management of these patients.
Collapse
Affiliation(s)
- A Cistaro
- Positron Emission Tomography Centre IRMET S.p.A., Affidea, Turin, Italy; PET Pediatric AIMN InterGroup, Italy; Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy.
| | - M Cucinotta
- Nuclear Medicine Unit Department of Biomedical Sciences and of Mophologic and Functional Images, University of Messina, Italy
| | - L Cassalia
- Nuclear Medicine Unit Department of Biomedical Sciences and of Mophologic and Functional Images, University of Messina, Italy
| | - A Priola
- Department of Diagnostic Imaging, San Luigi Gonzaga Hospital, University of Torino, Orbassano, Torino, Italy
| | - S Priola
- Department of Diagnostic Imaging, San Luigi Gonzaga Hospital, University of Torino, Orbassano, Torino, Italy
| | - M Pappalardo
- Department of Plastic and Reconstructive Surgery, E-DA Hospital, Kaohsiung, Taiwan
| | - P Coppolino
- Nuclear Medicine Unit Department of Biomedical Sciences and of Mophologic and Functional Images, University of Messina, Italy
| | - M De Simone
- Candiolo Cancer Institute - FPO, IRCCS, Unit of Surgical Oncology, Turin, Italy
| | - N Quartuccio
- Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, United Kingdom
| |
Collapse
|
|
48
|
Cascales-Campos P, López-López V, Gil J, Arévalo-Pérez J, Nieto A, Barceló F, Gil E, Parrilla P. Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference? Surg Oncol 2016; 25:164-70. [PMID: 27566018 DOI: 10.1016/j.suronc.2016.05.010] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Revised: 04/26/2016] [Accepted: 05/19/2016] [Indexed: 12/15/2022]
Abstract
OBJETIVE To compare the results of the administration of HIPEC with Paclitaxel or Cisplatin after cytoreduction in patients with stage IIIC-IV ovarian cancer, especially focused on disease-free survival. PATIENTS We retrospectively analyzed a consecutive series of patients operated after being diagnosed with stage III-C/IV serous epithelial ovarian carcinoma. Patients included in the study were treated between January 2008 and March 2015. After cytoreduction, Paclitaxel (doses of 60 mg/m(2)O or Cisplatin (doses of 75 mg/m(2)) were used. RESULTS A total of 111 patients were included. Median age was 61 years. In 60 of them (54%) Paclitaxel was used during HIPEC treatment and 51 patients (46%) were treated with Cisplatin. PCI was similar between groups (PCI = 11 in both cases). Median follow up was 34 months (12-96 months). The median disease free survival in Paclitaxel Group was 27 months and 33 months in Cisplatin Group (p = 0.551). In patients treated with Paclitaxel disease free survival rates at 1, 2, and 3 years were 79%, 60% and 46%. In patients treated with Cisplatin disease free survival at 1, 2, and 3 years were 64%, 50% and 40% respectively. After a multivariate analysis, incomplete cytoreduction (HR: 6.54, 95% CI 2.98-10.17, p < 0.01) and PCI >11 (HR: 2.15, 95% CI 1.42-6.68, p < 0.05) were identified as independent factors associated with a reduced disease-free survival. Cystotatic used was not relevant regarding disease free survival analysis. CONCLUSION HIPEC with paclitaxel or cisplatin after cytoreduction in patients with ovarian cancer IIIC-IV has not shown different results in disease-free survival outcomes.
Collapse
Affiliation(s)
- P Cascales-Campos
- Unidad De Cirugía De La Carcinomatosis Peritoneal, Departamento De Cirugía General, Spain; Peritoneal Carcinomatosis Unit, Department of Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain.
| | - V López-López
- Unidad De Cirugía De La Carcinomatosis Peritoneal, Departamento De Cirugía General, Spain; Peritoneal Carcinomatosis Unit, Department of Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - J Gil
- Unidad De Cirugía De La Carcinomatosis Peritoneal, Departamento De Cirugía General, Spain; Peritoneal Carcinomatosis Unit, Department of Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - J Arévalo-Pérez
- Radiology Department, Memorial Sloan-Kettering Cancer Center, USA; Peritoneal Carcinomatosis Unit, Department of Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - A Nieto
- Unidad De Ginecología Oncológica, Servicio De Ginecología y Obstetricia, Spain; Peritoneal Carcinomatosis Unit, Department of Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - F Barceló
- Unidad De Ginecología Oncológica, Servicio De Ginecología y Obstetricia, Spain; Peritoneal Carcinomatosis Unit, Department of Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - E Gil
- Unidad De Cirugía De La Carcinomatosis Peritoneal, Departamento De Cirugía General, Spain; Peritoneal Carcinomatosis Unit, Department of Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - P Parrilla
- Unidad De Cirugía De La Carcinomatosis Peritoneal, Departamento De Cirugía General, Spain; Peritoneal Carcinomatosis Unit, Department of Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| |
Collapse
|
|
49
|
Polom K, Roviello G, Generali D, Marano L, Petrioli R, Marsili S, Caputo E, Marrelli D, Roviello F. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for treatment of ovarian cancer. Int J Hyperthermia 2016; 32:298-310. [PMID: 26984715 DOI: 10.3109/02656736.2016.1149233] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery and maximal regional chemotherapy, has been applied to treat ovarian cancer resulting in long-term survival rates in selected patients. However, the status of HIPEC in ovarian cancer remains an experimental procedure, given the many variables among the data and trials reviewed, to enable us to derive strong conclusions about its role from this overview. In this review we discuss treatment with HIPEC in patients with ovarian cancer and future prospective of its use in clinical setting. HIPEC is an effective tool in the treatment of selected patients with peritoneal carcinomatosis from ovarian cancer. Unfortunately, due to the lack of randomised trials, the evidence of HIPEC is very limited. Future randomised studies are awaited to define the role and clinical impact of HIPEC in ovarian cancer.
Collapse
Affiliation(s)
- Karol Polom
- a Unit of General and Minimally Invasive Surgery, Surgery and Neuroscience , University of Sienna , Sienna
| | - Giandomenico Roviello
- b Section of Pharmacology and University Centre, DIFF - Drug Innovation Forward Future, Department of Molecular and Translational Medicine , University of Brescia , Brescia
- c Unit of Molecular Therapy and Pharmacogenomics , AO Azienda Istituti Ospitalieri di Cremona , Cremona
| | - Daniele Generali
- c Unit of Molecular Therapy and Pharmacogenomics , AO Azienda Istituti Ospitalieri di Cremona , Cremona
- d Department of Medical, Surgery and Health Sciences , University of Trieste , Trieste
| | - Luigi Marano
- e General, Minimally Invasive, and Robotic Surgery, Department of Surgery , 'San Matteo degli Infermi' Hospital , Spoleto
| | | | | | - Edda Caputo
- a Unit of General and Minimally Invasive Surgery, Surgery and Neuroscience , University of Sienna , Sienna
| | - Daniele Marrelli
- g Department of Medical, Surgical and Neurosciences , Section of Advanced Surgical Oncology, University of Sienna , Sienna , Italy
| | - Franco Roviello
- a Unit of General and Minimally Invasive Surgery, Surgery and Neuroscience , University of Sienna , Sienna
| |
Collapse
|
|
50
|
Heated IntraPEritoneal Chemotherapy (HIPEC) for Patients With Recurrent Ovarian Cancer: A Systematic Literature Review. Int J Gynecol Cancer 2016; 26:661-70. [DOI: 10.1097/igc.0000000000000664] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BackgroundDespite advances in surgical oncology, most patients with primary ovarian cancer develop a recurrence that is associated with a poor prognosis. The aim of this review was to establish the impact of Heated IntraPEritoneal Chemotherapy (HIPEC) in the overall survival of patients with recurrent ovarian cancer.MethodsA search of PubMed/MEDLINE databases was performed in February 2015 using the terms “recurrent ovarian cancer,” “cytoreductive surgery/cytoreduction,” and “heated/hyperthermic intraperitoneal chemotherapy.” Only English articles with available abstracts assessing the impact of HIPEC in patients with recurrent ovarian cancer were examined. The primary outcome measure was overall survival, whereas secondary outcomes included disease-free survival and HIPEC-related morbidity.ResultsSixteen studies with 1168 patients were analyzed. Most studies were Level IV, with 4 studies graded as Level III and 1 Level II. Cisplatin was the main chemotherapeutic agent used, but variations were observed in the actual technique, temperature of perfusate, and duration of treatment. In patients undergoing cytoreductive surgery and HIPEC, the overall survival ranged between 26.7 and 35 months, with disease-free survival varying between 8.5 and 48 months. Heated IntraPEritoneal Chemotherapy seems to confer survival benefits to patients with recurrent disease, with a randomized controlled study reporting that the overall survival is doubled when cytoreductive surgery is compared with cytoreductive surgery and chemotherapy (13. 4 vs 26.7 months). Heated IntraPEritoneal Chemotherapy–related morbidity ranged between 13.6% and 100%, but it was mainly minor and not significantly different from that experienced by patients who only underwent cytoreduction.ConclusionsCytoreductive surgery and HIPEC seem to be associated with promising results in patients with recurrent ovarian cancer. Large international prospective studies are required to further quantify the true efficacy of HIPEC and identify the optimal treatment protocol for a maximum survival benefit.
Collapse
|