30.01.2014

Neoadjuvant therapy for ovarian cancer

Given the association between achievement of a pathologic complete response (pCR) and superior long-term outcomes in triple-negative breast cancer (TNBC), should the standard neoadjuvant regimen for TNBC be updated to reflect results from trials that report higher pCR rates with acceptable toxicity, or should any revision await demonstration of improvements in recurrence-free or overall survival? This journal is a member of and subscribes to the principles of the Committee on Publication Ethics. Doing that will cause an invisible character to be written to the f1_notes field by frmnotesack.asp!! Primary debulking surgery by a gynecologic oncologist remains the standard of care in advanced ovarian cancer. The importance of cytoreductive surgery in the treatment of advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] stage III and IV) was first suggested as early as 1934 by Meigs.[1] But this procedure was long disputed until, in the 1970s, Aure et al[2] and Griffiths et al[3] showed that the amount of residual tumor following primary surgery was an important prognostic factor in advanced ovarian carcinoma.
Conclusion-Although evidence from retrospective studies suggests that neoadjuvant chemotherapy followed by interval debulking surgery is a valid alternative in a selected group of patients with stage III or IV ovarian carcinoma, this needs to beconfirmed in a prospective randomized trial. The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article. Colorectal Surgeons Sydney provide specialist colorectal surgery & bowel cancer screening including colonoscopy. The Australian NHMRC guidelines advise that radiotherapy be given for all large rectal cancers that are extending into the muscle wall of the rectum (T3,T4) or that have evidence of lymph node spread on MRI or ultrasound (N1). Once a diagnosis of rectal cancer is made, the size and spread of your cancer can be estimated by doing a number of scans.
Rectal ultrasound involves insertion of a small ultrasound probe about the size of a finger into the rectum to acquire real-time images of the tumour. MRI with contrast injection (gadolinium) will determine the size of the cancer as well as whether or not it has spread to nearby lymph nodes. The only reliable test to determine the spread (staging) of rectal cancer is by examining the specimen under the microscope (histopathological examination), after your surgery. Radiotherapy delivered before surgery (pre-operatively) is preferable to radiotherapy delivered after surgery, as it causes fewer side effects.
A small dose of radiotherapy (25Gy) can be given quickly over 5 days (short-course radiotherapy), or can be given as a large dose of radiotherapy (50Gy) delivered slowly over 5 weeks (long course radiotherapy). Post-operative radiotherapy is occasionally indicated when pre-operative radiotherapy was not given, and microscopic examination of the tumour after it has been removed shows advanced disease. In order to post comments, please make sure JavaScript and Cookies are enabled, and reload the page.
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Unfortunately, no prospective randomized controlled trials have investigated the role of primary cytoreductive surgery in advanced ovarian carcinoma. Therefore, the EORTCGCG, in cooperation with the National Cancer Institute of Canada, launched a prospective randomized trial to compare primary debulking surgery with neoadjuvant chemotherapy (Figure 3). In this situation, even with good surgery there is a 5-10% risk of local recurrence of the cancer in the first 5 years after surgery. A CT scan will be performed to determine the size of the rectal cancer and to determine if there are any obvious features to suggest spread (metastasis) to glands (lymph nodes) or elsewhere (liver, lung or bones). It is useful for early tumours which have not yet spread into the muscle of the rectum (called “T1” or “T2” rectal tumours).
If the cancer has spread to local lymph nodes, a positive MRI result will be accurate in only 70% of cases (false negative report will occur in 30% of cases)[4].
This gives exact accurate information about the spread of the tumour locally and to lymph nodes. Currently the evidence suggests that short course and long course radiotherapy are equivalent in efficacy with regard to preventing local recurrence,[6-8], however for lower and larger tumours long-course radiotherapy may have the advantage resulting in fewer permanent stomas[8].
Best results are achieved when surgery is performed 6-8 weeks following the completion of radiotherapy to allow the swelling and inflammation to settle.[9-10] A small dose of chemotherapy with also be given with the radiotherapy prior to surgery as it improves the action of radiotherapy (chemo sensitiser). The complications of receiving radiotherapy after surgery include poor rectal function, faecal incontinence, and injury to small bowel. In retrospective analyses, neoadjuvant chemotherapy followed by interval debulking surgery does not seem to worsen prognosis compared to primary debulking surgery followed by chemotherapy. To be eligible, patients must have biopsy- proven stage IIIC or IV epithelial ovarian cancer or peritoneal or fallopian tube carcinoma (with the biopsy taken at laparoscopy or laparotomy, or image-guided).
If the cancer has not spread to lymph nodes, it will tell you this with an accuracy of 95% (false positive report will occur in 5% of cases). This is a lengthy procedure and results will usually not be available for at least 5 days following your surgery.
These complications need to be discussed with your colorectal surgeon and radiation oncologist.


A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R-03. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. Long term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter sparing surgery for rectal cancer: the Lyon R90-01 randomised trial.
However, we will have to wait for the results of future randomized trials to know whether neoadjuvant chemotherapy followed by interval debulking surgery is as good as primary debulking surgery in stage IIIC and IV patients. During the same time period, several institutions started using neoadjuvant chemotherapy in patients with advanced ovarian cancer (without a primary attempt at debulking) followed by an interval debulking surgery. The study is expected to close in the summer of 2006, with a target accrual of 704 patients.Laparoscopy to Select Patients for Neoadjuvant ChemotherapyNelson et al[53] proposed computed tomographic (CT) criteria to predict operability in patients with suspected ovarian masses. The only definitive way of determining the extent of spread of your tumour is by examination under a microscope (histopathological examination) of the tumour after surgery. Interval debulking is defined as an operation performed after a short course of induction chemotherapy.
We will try to define the current role of primary or neoadjuvant chemotherapy followed by interval debulking surgery in the primary management of advanced ovarian cancer.
Tumor localization on the spleen or tumors larger than 2 cm on the diaphragm, liver surface, mesentery, or gall bladder on CT were regarded as inoperable.
Based on the randomized European Organization for Research and Treatment of Cancer–Gynecological Cancer Group (EORTC-GCG) trial, interval debulking by an experienced surgeon improves survival in some patients who did not undergo optimal primary debulking surgery. Definitions Agreement about the terminology for surgical procedures is essential for a clear understanding. However, 6 out of 18 patients (33%) judged to be inoperable based on these criteria were optimally debulked. Based on Gynecologic Oncology Group (GOG) 152 data, interval debulking surgery does not seem to be indicated in patients who underwent primarily a maximal surgical effort by a gynecologic oncologist.
Griffiths CT, Fuller AF: Intensive surgical and chemotherapeutic management of advanced ovarian cancer.
Open laparoscopy is probably the most valuable tool for evaluating the operability primarily or at the time of interval debulking surgery. Interval cytoreductive surgery: an operation performed in patients after a short course of induction chemotherapy- usually two or three cycles of chemotherapy-to remove as much primary and metastatic disease as possible, in order to facilitate response to subsequent chemotherapy and to improve survival.
Secondary cytoreductive surgery: an operation performed in patients who have either persistent disease at the completion of a planned course of chemotherapy or who subsequently experienced clinical relapse. Berek JS, Trope C, Vergote I: Surgery during chemotherapy and at relapse of ovarian cancer. Consecutively, the different layers of the abdominal wall are opened (ie, a mini-laparotomy), and a blunt trocar is introduced under direct vision.
Between 1995 and 2002, we performed an open laparoscopy in 173 patients to establish the diagnosis of stage III or IV ovarian carcinoma and found that open laparoscopy was the best technique to evaluate the operability. This procedure also provides the opportunity to perform biopsies and to exclude other primary tumors metastatic to the pelvis (eg, intestinal tumors, pancreatic tumors, and so forth).[58] The possible development of port site metastases might prevent some surgeons from performing laparoscopy. We explored this issue further and completely excised all port sites at the time of primary debulking surgery or interval debulking surgery in the last 71 cases.
The total number of port site metastases (clinically detected or diagnosed at microscopic examination of the excised port site) in the whole series of 173 patients was 30 (17%). Goldie JH, Coldman AJ: Mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. It should be noted that, in this series, all port site metastases disappeared during the neoadjuvant chemotherapy or were excised at the time of surgery.
None of the patients developed a subsequent recurrence in the port sites during follow- up, and none of the patients had a port site metastasis at the time of death. Smith JP, Day TG: Review of ovarian cancer at the University of Texas Systems Cancer Center, MD Anderson Hospital and Tumor Institute.
Therefore, we believe that port site metastases in advanced ovarian cancer are frequent but not of prognostic significance.Conclusion-Open laparoscopy is an important tool in the evaluation of the operability of patients with ovarian cancer. To date, this technique has produced no proven detrimental effects on the prognosis of these patients.


Bertelsen K, Jakobsen A, Andersen JE, et al: A randomized study of cyclophosphamide and cisplatinum with or without doxorubicin in advanced ovarian carcinoma. Marsoni S: Randomized comparison of cisplatin with cyclophosphamide cisplatin and with cyclophosphamide doxorubicin cisplatin in advanced ovarian cancer.
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Neijt JP, ten Bokkel Huinink WW, van der Burg ME, et al: Randomized trial comparing two combination chemotherapy regimens (CHAP-5 v CP) in advanced ovarian carcinoma. Hacker NF, Berek JS, Lagasse LD, et al: Primary cytoreductive surgery for epithelial ovarian cancer.
Eisenkop SM, Spirtos NM: What are the current surgical objectives, strategies, and technical capabilities of gynecologic oncologists treating advanced epithelial ovarian cancer?
Burghardt E, Girardi F, Lahousen M, et al: Patterns of pelvic and paraaortic lymph-node involvement in ovarian cancer. Friedlander ML, Hedley DW, Swanson C, et al: Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer. Berchuck A, Iversen ES, Lancaster JM, et al: Prediction of optimal versus suboptimal cytoreduction of advanced-stage serous ovarian cancer with the use of microarrays. Kehoe S, Powell J, Wilson S, et al: The influence of the operating surgeons specialization on patient survival in ovarian carcinoma.
Farias-Eisner R, Teng F, Oliveira M, et al: The influence of tumor grade, distribution, and extent of carcinomatosis in minimal residual stage III epithelial ovarian cancer after optimal primary cytoreductive surgery.
Naik R, Nordin A, Cross PA, et al: Optimal cytoreductive surgery is an independent prognostic indicator in stage IV epithelial ovarian cancer with hepatic metastases. Zang RY, Zhang ZY, Cai SM, et al: Cytoreductive surgery for stage IV epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. Lawton FG, Redman CW, Luesley DM, et al: Neoadjuvant (cytoreductive) chemotherapy combined with intervention debulking surgery in advanced, unresected epithelial ovarian cancer. Jacob JH, Gershenson DM, Morris M, et al: Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer. Lim JT, Green JA: Neoadjuvant carboplatin and ifosfamide chemotherapy for inoperable FIGO stage III and IV ovarian carcinoma.
Shimizu Y, Hasumi K: Treatment of stage III and IV ovarian cancer: Is neoadjuvant chemotherapy effective? Onnis A, Marchetti M, Padovan P, et al: Neoadjuvant chemotherapy in advanced ovarian cancer. Surwit E, Childers J, Atlas I, et al: Neoadjuvant chemotherapy for advanced ovarian cancer. Kuhn W, Rutke S, Spathe K, et al: Neoadjuvant chemotherapy followed by tumor debulking prolongs survival for patients with poor prognosis in International Federation of Gynecology and Obstetrics stage IIIC ovarian carcinoma. Recchia F, De Filippis S, Rosselli M, et al: Primary chemotherapy in stage IV ovarian cancer.
Kayikcioglu F, Kose MF, Boran N, et al: Neoadjuvant chemotherapy or primary surgery in advanced epithelial ovarian carcinoma.
Ushijima K, Ota S, Komai K, et al: Clinical assessment of neoadjuvant chemotherapy and interval cytoreductive surgery for unresectable advanced ovarian cancer.
Fanfani F, Ferrandina G, Corrado G, et al: Impact of interval debulking surgery on clinical outcome in primary unresectable FIGO stage IIIC ovarian cancer patients.
Morice P, Dubernard G, Rey A, et al: Results of interval debulking surgery compared with primary debulking surgery in advanced stage ovarian cancer. Mazzeo F, Berliere M, Kerger J, et al: Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable, advanced-stage ovarian cancer. Nelson BE, Rosenfield AT, Schwartz PE: Preoperative abdominopelvic computed tomographic prediction of optimal cytoreduction in epithelial ovarian carcinoma. Bristow RE, Duska LR, Lambrou NC, et al: A model for predicting surgical outcome in patients with advanced ovarian carcinoma using computed tomography. Tate S, Hirai Y, Takeshima N, et al: CA125 regression during neoadjuvant chemotherapy as an independent prognostic factor for survival in patients with advanced ovarian serous adenocarcinoma. Gryspeerdt S, Clabout L, Van Hoe L, et al: Intraperitoneal contrast material combined with CT for detection of peritoneal metastases of ovarian cancer.



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