Franka Menge, Eva Hartmann, Monika Mathew, Bernd Kasper, Peter Hohenberger

The impact of operative techniques to the onset of peritoneal tumor dissemination in patients with uterine leiomyosarcomas Franka Menge, Eva Hartmann, Monika Mathew, Bernd Kasper, Peter Hohenberger Div. of Surgical Oncology & Thoracic Surgery Interdisciplinary Sarcoma Center Faculty of Medicine Mannheim University of Heidelberg, Germany

Disclosures • No disclosures

Introductory remarks • Uterine sarcomas are rare, but highly malignant tumors • Approximately 8-10% of all uterine cancers • Mostly diagnosed incidentally, postresectional • < 2% of all hysterectomy specimens for uterine leiomyoma • Historically, confusion in understanding of pathological subtypes • Different pathologies often combined in clinical reviews

Introductory remarks - 2 Main histologic subtypes: Leiomyosarcoma (LMS) 67 % Endometrial stromal sarcoma (ESS) 17-25 % Undifferentiated sarcomas (UES, AJSP2008) 8-17 % Carcinosarcoma (former malignant Mullerian mixed tumor)

Surgical problems of treatment • Sarcoma is not recognized preoperatively • Historical and ‚modern‘ operative techniques: • ‚Hooking‘ and myoma drill of the tumor • Intraabdominal morcellation • Consequence: intraoperative tumor cell spillage • Inoculation of the abdominal cavity Morice, Eur J Gynaecol Oncol 2003 Einstein, Int J Gynaecol Cancer 2008 Perri, Int J Gynaecol Cancer 2009Seidman, PLOS One 2012

Courtesy: Storz Co.

Typical procedure for laparoscopic myoma removal from the uterus Courtesy: Storz Co.

What if this leiomyoma is later diagnosed as a leiomyosarcoma ? Typical procedure for laparoscopic myoma removal from the uterus Courtesy: Storz Co.

Case report: Patient: 43 yr Signs and symptoms: abdominal pain, dysuria Preoperative diagnosis: rapidly growing uterine leiomyoma Therapy: abdominal hysterectomy and salpingectomy with intraabdominal morcellation (10/Dec/2012) Histological diagnosis: uterine leiomyosarcoma FIGO IB (no grading) Course of disease: 10/Dec/12: operation and first diagnosis 30/Jan/13: CT scan: multiple intraabdominal mets. 06/Feb/13: treatment start with doxorubicin (trial) result: PD 2nd line therapy: gemcitabine/docetaxel, result: PD 3rd line therapy with pazopanib

Case #29, 43yr: this was later diagnosed as a leiomyosarcoma ! 2 month follow up preoperative

Trocar positioning Courtesy: Storz Co.

Location of mets. as a consequence of trocar positioning 2 month follow up preoperative

Methods We tried to identify the impact of intrabdominal fragmentation or damage to the uterus on the occurrence and the time interval of peritoneal metastases of uterine LMS. All female patients presenting with advanced sarcoma of uterine origin 2004 – 2013, negative selection, typically M1 or locoregionally recurrent Retrospectively evaluated EORTC example of GIST study 62024

Quality of Surgery for Primary Gastro-Intestinal Stromal Tumors in Patients Undergoing Adjuvant Imatinib Treatment. Experience of the EORTC STBSG 62024 Study P. Hohenberger1, S. Bonvalot2, F. van Coevorden3, P. Rutkowski4, E. Stoeckle5, C. Olungu6, M. vanGlabbeke6, A. Gronchi7, P. Casali7 CTOS 2011: Mannheim University Medical Center1; Institute Gustave Roussy, Paris2; NKI/van Leuuvenhoek Ziekenhuis3; Maria Sklodowska Cancer Center Warsaw4; Bergonie, Bordeaux5; EORTC Brussels6; Istituto Nazionale dei Tumori, Milano7

Data to be reported : • Reason for surgery, n = 926 • Circumstances of resection and technique(emergency, open vs. laparoscopically) • Extent of resection • Concordance of preop. and intraop. findings • Completeness of resection

Adopted for uterine sarcoma • The data of primary surgery were reviewed. • Revision of all source data documents : - operation records - pathology report - letter of discharge - Data from 39 (46) patients could be reviewed

Endpoint of the analysis retrospective comparison of the cum survival time without peritoneal recurrence of uterine LMS in patients with or without intraabdominal tumor fragmentation or damage.

The impact of tumor morcellation on the prognosis of patients with uterine leiomyosarcoma Results 1

Clinical parameters of all patients with peritoneal metastatic spread :

The impact of tumor morcellation on the prognosis of patients with uterine leiomyosarcoma Results 2

22/39 (58%) pts. had developed peritoneal metastases (13 LMS, 4 ESS, 5 other histologies) LMS : only two patients had M1PER at initial surgery. LMS n=11, sarcoma had not being recognized at surgery. 6/11 women had a documented intrabd. morcellation or injured uterus due to the use of an myoma drill Time to diagnosis of the peritoneal metastases: 18,3 months (range, 2-39 mos.) 5/11 pts. without tumor damagetime to detection of peritoneal spread: 33,6 months(range, 14-51 mos.), p = 0.0804 The impact of tumor morcellation on the prognosis of patients with uterine leiomyosarcoma Results 3

The impact of tumor morcellation on the prognosis of patients with uterine leiomyosarcoma Results 4 Cumulative peritoneal recurrence-free survival time Cumulative Disease -free Survival p=0.0804 add 3 recent pts p=0.0677

The impact of tumor morcellation on the prognosis of patients with uterine leiomyosarcoma Results 5 Characteristics of patients with no tumor recurrence:

Limitations of the study Patient selection criteria ! Referral to tertiary center for metastatic disease Atypical history, unclear histology, unclear relationship to previous abdominal surgery Limited follow-up

Conclusions • Intraoperative mechanical damage such as morcellation and use of a myoma drill in unrecognized uterine leiomyosarcoma seems to have a (statistical) significant impact to the onset of intraperitoneal recurrence of the disease.

Conclusions How to influence surgical data in cancer: • Preoperative diagnosis of uterine sarcoma and separation from benign leiomyoma is required. • Due to the lack of adequate preoperative diagnostics, surgery often performed as non-oncologic intended procedure • Abandonment of techniques with tumor cell spillage is a must as soon as there is any hint for malignancy.

Conclusions How to influence surgical data in cancer: • A specimen extraction bag could be the easiest aid to avoid devastating tumor progression. • Influencing surgery (technique + indication) impacts the disease at the early stage • Very much cost-effectivein comparison tochemotherapy for M1PER

Franka Menge, Eva Hartmann, Monika Mathew, Bernd Kasper, Peter Hohenberger