Diaphragmatic Resection And Gynecological Ovarian Neoplasm

Ovarian Cancer Clinical Trial

— DRAGON  

Official title:

Diaphragmatic Resection And Gynecological Ovarian Neoplasm

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03543462
• Other study ID #: D.R.A.G.O.N. ID. 1963
• Status: Completed
• Phase: Phase 4
• Start date: March 20, 2018
• Est. completion date: January 11, 2020

Study information

• Verified date: May 2020
• Source: Catholic University of the Sacred Heart
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective randomized phase IV study aimed to value the impact of diaphragmatic surgery and the useful of intra-operatory thoracic drain in advanced ovarian cancer.

Considering the fact that the diaphragmatic surgery could contribute with the incidence of post-operatory morbidity. The study is aimed to value the role of thoracic drain in post-operative outcomes as hospital stay, time to chemotherapy, drugs use and eventual interventions.

Description:

Ovarian cancer represents the leading cause of death from gynecologic malignancies. The majority of patients present with advanced-stage disease (III/IV) often involving the upper abdomen. Spread by either direct extension or via peritoneal implantation can result in metastases to the diaphragm, as seen in up to 40% of patients with advanced disease.

Standard treatment of advanced-stage disease includes primary cytoreductive surgery followed by combination platinum-taxane chemotherapy. Optimal cytoreduction to ≤1 cm disease has repeatedly been shown to be associated with improved survival.

Diaphragm involvement was considered one of the most frequent obstacles to achieving optimal cytoreduction. The right diaphragm is more frequently and extensively involved than the left diaphragm; however, bilateral involvement is not uncommon. Various studies have advocated and reported the feasibility of diaphragmatic surgery in achieving optimal cytoreduction.

Sometimes, depending on extent of the disease, the diaphragm involvement could be massive and often the resection of the muscle with access to pleural cavity is necessary. Allegedly, entering the pleural cavity increases the morbidity of the procedure.

Extensive upper abdominal surgery involving diaphragmatic peritonectomy/resection and liver mobilization may both contribute to the development of symptomatic pleural effusions.

The aim of the study is to value the impact of diaphragmatic surgery in post-operative complications using a specific score (DRS). The other aim is to asses a correct management of intra-operatory thoracic drain position after diaphragmatic surgery. All parameter that could influence the post-operative outcomes as (EBL,BMI, OT, SCS) are recorded.

The study was approved by Ethical Committee of Fondazione Policlinico Gemelli Hospital (prot n. 9078/18).

The study is a superiority randomized clinical trial to investigate the role of intra-operative chest tube in the large (> 5 cm) diaphragmatic peritonectomy/resection in the ovarian cancer debulking. Calculation of sample size for the analysis of the primary end-point (major pleural effusion) was based on literature results reporting a rate of moderate/severe early peri-operative pleural effusion between 54% and 23% when a large (> 5 cm) diaphragmatic resection is performed. A sample size of 88 patients was required in order to provide 80% power of detecting a reduction of 60% of moderate/severe pleural effusion in PDS with large diaphragmatic resection when intra-operative chest tube was inserted (overall rate 22%) (two-tailed α =0.05, drop-out 5%).

Sample size is composed by 44 Patients affected by advanced stage ovarian cancer, meeting inclusion criteria, undergo diaphragmatic surgery followed by intra-operatory thoracic drain position and 44 patients with same characteristics undergo to diaphragmatic surgery without intra-operatory thoracic drain position. Both groups are compared in terms of incidence of post-operative complications (especially pleural effusion, pneumothorax, respiratory disease). Secondary endpoints are the evaluation of surgical outcomes and clinical outcomes in terms hospital stay, procedures and radiologic examinations required. All patients are adequately informed and inserted in the study only after having read and signed an informed consent. Diagnostic, clinical and surgical data of each patient are prospectively recorded.

Surgical procedures consist of surgical standard cytoreduction, performed for all cases of advanced stage ovarian cancer disease. The procedures performed depending on disease spread.

The diaphragmatic procedures, depending on the disease infiltration can consists of superficial peritonectomy, deep peritonectomy (until muscular layer) or diaphragmatic resection. Considering the randomization, if required, a thoracic drain tube 24 Fr. is positioned. A post-operative chest X-Ray is performed on all cases.

At the end of the procedure, a schedule is compiled with intraoperative data.

Post-operative examinations are follows:

• Chest X-Ray (2 h post-op)

• Chest X-Ray (day 1)

• Chest X-Ray (if required, depending of clinical indications)

• Thoracic US scan evaluation before discharge

• Thoracic US scan evaluation 10 days after discharge

• Radiological examinations (if required, depending of clinical indications)

All clinical and histologic data will be recorded prospectively using an electronic database.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: January 11, 2020
• Est. primary completion date: November 11, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age > 18 < 80 years

• Patient's informed consent

• American Society of Anesthesiologists: < class III or IV

• No actual pregnancies or pelvic inflammatory disease (P.I.D.)

• BMI < 40

• Macroscopic diaphragmatic disease infiltration (mono lateral)

• Grade IIIA-IV diaphragmatic resection score

• Advanced stage ovarian cancer (stage III-IV)

• Primary diagnosis, interval debulking surgery, recurrent disease

• All histotype included

Exclusion Criteria:

• Actual pregnancies or P.I.D

• BMI > 40

• Pulmonary or thoracic preoperatory disease

• Preoperative pleural effusion

• Residual thoracic disease after surgery

• Residual diaphragmatic disease after surgery

Related Conditions & MeSH terms

• Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Device:
• thoracic Drain Tube 24 Fr.
Positioning of Thoracic Drain after diaphragmatic resection and consequently diaphragmatic repair

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Agostino Gemelli	Roma	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Catholic University of the Sacred Heart

Country where clinical trial is conducted

Italy, 

References & Publications (13)

Aletti GD, Dowdy SC, Podratz KC, Cliby WA. Surgical treatment of diaphragm disease correlates with improved survival in optimally debulked advanced stage ovarian cancer. Gynecol Oncol. 2006 Feb;100(2):283-7. Epub 2005 Sep 22. — View Citation

Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002 Mar 1;20(5):1248-59. — View Citation

Chéreau E, Ballester M, Selle F, Cortez A, Pomel C, Darai E, Rouzier R. Pulmonary morbidity of diaphragmatic surgery for stage III/IV ovarian cancer. BJOG. 2009 Jul;116(8):1062-8. doi: 10.1111/j.1471-0528.2009.02214.x. Epub 2009 May 14. — View Citation

Cliby W, Dowdy S, Feitoza SS, Gostout BS, Podratz KC. Diaphragm resection for ovarian cancer: technique and short-term complications. Gynecol Oncol. 2004 Sep;94(3):655-60. — View Citation

Devolder K, Amant F, Neven P, van Gorp T, Leunen K, Vergote I. Role of diaphragmatic surgery in 69 patients with ovarian carcinoma. Int J Gynecol Cancer. 2008 Mar-Apr;18(2):363-8. doi: 10.1111/j.1525-1438.2007.01006.x. — View Citation

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. — View Citation

Eisenhauer EL, D'Angelica MI, Abu-Rustum NR, Sonoda Y, Jarnagin WR, Barakat RR, Chi DS. Incidence and management of pleural effusions after diaphragm peritonectomy or resection for advanced mullerian cancer. Gynecol Oncol. 2006 Dec;103(3):871-7. Epub 2006 Jul 3. — View Citation

Eisenkop SM, Spirtos NM. What are the current surgical objectives, strategies, and technical capabilities of gynecologic oncologists treating advanced epithelial ovarian cancer? Gynecol Oncol. 2001 Sep;82(3):489-97. — View Citation

Fanfani F, Fagotti A, Gallotta V, Ercoli A, Pacelli F, Costantini B, Vizzielli G, Margariti PA, Garganese G, Scambia G. Upper abdominal surgery in advanced and recurrent ovarian cancer: role of diaphragmatic surgery. Gynecol Oncol. 2010 Mar;116(3):497-501. doi: 10.1016/j.ygyno.2009.11.023. Epub 2009 Dec 11. — View Citation

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17. — View Citation

Tsolakidis D, Amant F, Van Gorp T, Leunen K, Neven P, Vergote I. The role of diaphragmatic surgery during interval debulking after neoadjuvant chemotherapy: an analysis of 74 patients with advanced epithelial ovarian cancer. Int J Gynecol Cancer. 2010 May;20(4):542-51. doi: 10.1111/IGC.0b013e3181d4de23. — View Citation

Winter WE 3rd, Maxwell GL, Tian C, Carlson JW, Ozols RF, Rose PG, Markman M, Armstrong DK, Muggia F, McGuire WP; Gynecologic Oncology Group Study. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Aug 20;25(24):3621-7. — View Citation

Zapardiel I, Peiretti M, Zanagnolo V, Biffi R, Bocciolone L, Landoni F, Aletti G, Colombo N, Maggioni A. Diaphragmatic surgery during primary cytoreduction for advanced ovarian cancer: peritoneal stripping versus diaphragmatic resection. Int J Gynecol Cancer. 2011 Dec;21(9):1698-703. doi: 10.1097/IGC.0b013e31822f65c3. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to start chemotherapy	The time to start chemotherapy is fundamental from oncological point of view. The ideal time to start chemotherapy treatment should exceed 40 days after surgery.; The data measured are; - time between surgery and first chemotherapy cycle	40 Days
Other	Estimated blood loss	The intra operative blood loss is often related to the complexity of procedure and consequently to post-operative complications; The data measured are: - EBL (ml)	1 Day
Other	Operative time	The Operative time is often related to the complexity of procedure and consequently to post-operative complications; The data measured are: - Operative time (minutes)	1 Day
Primary	Measurement of incidence of pleural effusion after diaphragmatic resection and useful of chest drain to prevent pleural effusion and consequent respiratory symptoms as dyspnea.	The diaphragmatic surgery is often related to post-operative complication. The most common complication is pleural effusion. This condition contribute to decrease the clinical outcomes causing increase of hospitalization and necessity medical or surgical treatment.; The main outcome is to asses a correct management of intra-operatory thoracic drain position after diaphragmatic surgery.; The outcomes measured are: - Incidence of post-operatory pleural effusion detected by chest RX measuring pleural fluid collection (cm)	30 days