International Collaboration Studies Teratoma with Malignant Transformation's 'Dismal' Outcomes

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Optimal chemotherapy remains unclear for metastatic teratoma with malignant transformation.
Optimal chemotherapy remains unclear for metastatic teratoma with malignant transformation.

ORLANDO—Optimal chemotherapy remains unclear for patients with metastatic teratoma with malignant transformation (TMT), and only histology and stage predict overall survival, according to authors of the largest study ever reported for this rare malignancy study (Abstract 375) presented during the 2015 Genitourinary Cancers Symposium.1

TMT is rare and linked to chemoresistance; it occurs most frequently among patients with germ cell tumor (GCT).

“For the first time to our knowledge, analyses were sufficiently powered to recognize independent predictors of overall survival,” reported study coauthor Andrea Necchi, MD, of the Fondazione IRCCS Istituto Nazionale Tumori in Milan, Italy.

“These factors were: primary tumor site, the number of prior chemotherapy regimens, and transformed histology,” with rhabdomyosarcomas having the best prognosis and PNETs having the worst prognosis.

While stage of disease is a crucial predictor of survival, uncertainties persist regarding optimal chemotherapy, Dr. Necchi reported. “GCT regimens may have a role both given up-front and at the occurrence of relapse.”

In order to better assess predictive clinical factors and treatment outcomes, the study authors developed an international collaboration involving five referral centers worldwide.

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Between April 2014 and January 2015, they identified a total of 320 patients; median patient age was 28 years (range: 8 to 76), and primary tumor sites were gonadal (89.7% of patients), mediastinal (5% of patients), and extragonadal (5.3% of patients), Dr. Necchi reported. Of the 320 patients, 130 (40.6%) patients were simultaneously diagnosed with both GCT and TMT, and 25 patients (8%) had metastatic TMT tumors in the liver, bone or brain at time of diagnosis.

At a median follow-up of 2.1 years, 35.2% of patients administered GCT chemotherapy regimens had died, compared to 57.1% of those administered TMT chemotherapy and 27.2% of patients who were treated with surgery only, Dr. Necchi reported.

Multivariate analysis identified primary tumor site identified three prognostic factors that were significantly associated with overall survival: primary tumor site (hazard ratios=0.47 for gonadal primary tumors and 2.06 for mediastinal; P=0.002), the number of chemotherapy regimens preceding TMT diagnosis (0-1 vs ≥2; HR=2.64; P<0.001), and histology (rhabdomyosarcoma HR=0.18; P=0.004), Dr. Necchi reported.

The findings should be interpreted very cautiously, said Darren R. Feldman, MD, of Memorial Sloan Kettering Cancer Center in New York, NY.

“Can we really conclude that outcome varies by TMT histology? Well, yes and no,” he cautioned. “Rhabdomyosarcomas do better, but the other (histology outcome) curves overlap with little discriminatory power. “

Surgery “remains the mainstay of therapy” for TMT, Dr. Feldman emphasized.  “No conclusions can be made about benefit or lack of benefit of TMT chemotherapy.”

Reference

  1. Giannatempo P, Pond GR, Sonpavde G, et al. Treatment and clinical outcomes of patients with teratoma with somatic-type malignant transformation (TMT): An international collaboration. 2015 Genitourinary Cancers Symposium. Abstract 375.

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