Targeted therapies in the treatment of germ cell tumors: The need for new approaches against “orphan” tumors

Cochrane Review: abstract - Chemotherapy for malignant germ cell ovarian cancer [Cochrane Database Syst Rev. 2011] - PubMed result

AUTHORS' CONCLUSIONS:
We found only low quality evidence on the use of chemotherapy in malignant germ cell tumours of the ovaries. Therefore we are unable to reach definite conclusions about the relative benefits and harms of chemotherapy use in this disease regardless of disease stage. Due to the benefit of chemotherapy in germ cell cancer of the testis, a trial of chemotherapy versus best supportive care is unlikely to be feasible. Despite this, good quality randomised studies are warranted in this disease to define the role of chemotherapy (type of chemotherapy, duration of treatment, benefit, short and long term toxicities). Given the rarity of this disease, we feel a trans-global approach would be essential in order to perform such trials.

alternate source including professional commentary (gynecologic oncology) link

Review Multidisciplinary management of malignant ovarian germ cell tumours

Abstract

Objectives

Malignant ovarian germ cell tumours (MOGCT) are rare cancers of young women. Limited prospective trials exist from which evidence-based management can be developed. This review summarizes the available literature concerning MOGT in order to provide the clinician with information relevant to their multidisciplinary management.

Research Highlights

►Ovarian germ cell tumours are highly curable.
►Treatment options are limited for recurrent and residual tumours. ►Long term results suggest no significant impact on fertility and menstrual function.

Abstract:

Ovarian teratoma is a type of germ cell tumour. Germ cell tumours are cancers that begin in egg cells in women or sperm cells in men. There are two main types of ovarian teratoma

* Mature teratoma, which is benign
* Immature teratoma, which is cancerous

Background: The most common type of ovarian germ cell tumor is the teratoma. Thyroid tissue, both benign and malignant, may be a component of an ovarian teratoma. Here we review this topic and illustrate major features by presenting multimodal management of a patient with BRAF-positive disseminated follicular thyroid cancer arising in an ovarian teratoma.

Conclusions: Aggressive multimodal management appears to be the most promising approach for malignant thyroid tissue arising in ovarian teratomas.

PARP inhibition: targeting the Achilles' heel of DNA repair..PARP inhibition: targeting the Achilles' heel of DNA repair to treat germline and sporadic ovarian cancers

abstract: Clinical syndromes associated with ovarian neoplasms: a comprehensive review

Radiographics. 2010 Jul-Aug;30(4):903-19.

Functional ovarian neoplasms have unique clinical manifestations related to hormone overproduction and may give rise to a broad spectrum of clinical syndromes.

Sex cord-stromal tumors, the most common functional ovarian neoplasms, are associated with either hyperestrogenism (as in granulosa cell tumor and thecoma) or hyperandrogenism (as in Sertoli-Leydig cell tumor and Leydig cell tumor). Other, less common ovarian neoplasms that may have endocrine or nonendocrine syndromic manifestations include germ cell tumors associated with the excessive production of human chorionic gonadotropin (eg, choriocarcinoma, dysgerminoma), monodermal teratomas (eg, carcinoid tumor, struma ovarii) associated with carcinoid syndrome and hyperthyroidism, and primary epithelial ovarian cancers associated with paraneoplastic syndromes.

The application of diagnostic algorithms based on patient demographic information, clinical manifestations, laboratory findings, and cross-sectional imaging features may help identify ovarian neoplasms in complex clinical settings.

Management of rare ovarian cancers: The experience of the French website «Observatory for rare malignant tumours of the ovaries» by the GINECO group

Background

Non-epithelial ovarian cancers are rare; their natural history is poorly understood and prognostic factors remain unclear. A French website (www.ovaire-rare.org) was developed to collect clinical cases and tumour samples in order to better define prognostic factors and develop specific trials. We report the results of the first 100 patients with germ cell (GCT) and sex cord-stromal (SCT) tumours.

 Conclusions

This online observatory allows assessing medical practice for GCT and SCT in France. Histological discrepancies between diagnosis and second opinion confirm the need for systematic review before treatment. Extension to other rare gynaecologic malignancies is on-going.

summary: Targeted therapies for rare gynaecological cancers : The Lancet Oncology

"Some gynaecological cancers are uncommon, such as sex cord-stromal tumours, malignant germ-cell tumours, vulvar carcinoma, melanoma of the female genital tract, clear-cell carcinoma of the ovary and endometrium, neuroendocrine tumours of the cervix, and gestational trophoblastic neoplasia. All these cancers have different clinicopathological characteristics, suggesting different molecular biological pathogeneses. Despite aggressive treatment, some cancers recur or respond poorly to therapy. Comprehensive knowledge of the molecular biology of each cancer might help with development of novel treatments that maximise efficacy and minimise toxic effects. Targeted therapy is a new treatment strategy that has been investigated in various tumours in clinical and laboratory settings. Since these cancers are rare and large clinical trials are difficult to do, molecular biological techniques might allow rapid proof-of-principle experiments in few patients. Novel targeted agents either alone or in combination with other treatments offer promising therapeutic options."

free full text: Non-epithelial ovarian cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up

Note: the papers from ESMO (ovarian cancer) requires registration/access is free 1) Classification of germ cell ovarian tumors 2) Classification of sex cord stromal ovarian tumors "This set of recommendations applies to invasive epithelial ovarian carcinoma; the management of tumors of low malignant potential (‘borderline’) is not covered here."

Targeted therapies for rare gynaecological cancers : The Lancet Oncology

The Lancet Oncology, Early Online Publication, 1 April 2010

Targeted therapies for rare gynaecological cancers

Summary

Some gynaecological cancers are uncommon, such as sex cord-stromal tumours, malignant germ-cell tumours, vulvar carcinoma, melanoma of the female genital tract, clear-cell carcinoma of the ovary and endometrium, neuroendocrine tumours of the cervix, and gestational trophoblastic neoplasia.

All these cancers have different clinicopathological characteristics, suggesting different molecular biological pathogeneses. Despite aggressive treatment, some cancers recur or respond poorly to therapy. Comprehensive knowledge of the molecular biology of each cancer might help with development of novel treatments that maximise efficacy and minimise toxic effects. Targeted therapy is a new treatment strategy that has been investigated in various tumours in clinical and laboratory settings.

Since these cancers are rare and large clinical trials are difficult to do, molecular biological techniques might allow rapid proof-of-principle experiments in few patients. Novel targeted agents either alone or in combination with other treatments offer promising therapeutic options.