Local Control of Perineal Rhabdomyosarcoma: Are Current Recommendations Adequate?

Rhabdomyosarcoma (RMS) is a rare malignancy that can develop in nearly any soft-tissue of the body. Location of the primary tumor affects treatment strategy and prognosis, and RMS of the perineal areas can be especially difficult to treat successfully. RMS is treated systemically with chemotherapy. Local control options include surgical excision, radiation treatment, or a combination of the 2. Treating RMS with radiation treatment can be challenging due to the absence of standardized dosage protocols, along with the presence of conflicting recommendations in the literature. Each case of perineal RMS may benefit from a more individualized treatment plan.

The differences between gonadal and extra-gonadal malignant teratomas in both genders and the effects of chemotherapy.

BACKGROUND: A tumor comprising of different types of tissues (such as hair, muscle, bone, etc.) is known as a teratoma. It is a type of germ cell (cells that make sperm or eggs) tumor. When these germ cells have rapid cancerous growth, then such a teratoma is called a malignant teratoma. We have studied the differences between gonadal and extra-gonadal malignant teratomas and the effects of chemotherapy in both genders. METHODS: The samples of 3799 male and 1832 female patients with malignant teratoma samples, between the ages of 1 and 85+ years, were selected from the years 1973 to 2014. Trends in incidence, estimated prevalence, incidence rates, and frequency were calculated in gonadal and extra-gonadal tumors with age adjustment. The five-year observed, expected, and relative survival rates were analyzed to study the prognosis. RESULTS: The gonadal took over a majority percentage of malignant teratomas compared with the extra-gonadal (90% vs. 10% in male; 83% vs. 17% in female). For the male, the total of the gonadal and the extra-gonadal were all significantly decreased from 1973 to 2014 (p < 0.05). For the female, there were no significant trends. As for prevalence, incidence, and frequency, there were two separate peaks of malignant teratomas. One peak was at under 1 year old, which was composed of the extra-gonadal tumor; the other peak was at 20-24 for male and 10-34 for female, which was composed of the gonadal tumor. This separation of the gonadal and extra-gonadal showed a significant difference (p < 0.05). As for the prognosis, the extra-gonadal tumor showed significantly lower survival rates than the gonadal (p < 0.05). In the short term, the survival rate of the chemotherapy group was higher than the supportive care group. However, in the long term, the survival rate of the chemotherapy group was lower than the supportive care group. CONCLUSION: The gonadal and extra-gonadal malignant teratomas show lots of differences. Chemotherapy might not help improve survival rates.

The therapeutic potential of blocking the activin signalling pathway.

Members of the transforming growth factor ß (TGF-ß) family regulate fundamental physiological process, such as cell growth, differentiation and apoptosis. As a result, defects in this pathway have been linked to uncontrolled proliferation and cancer progression. Here we explore the signal transduction mechanism of TGF-ß focusing on therapeutic intervention in human diseases. Like TGF-ß, another member of the TGF-ß superfamily, activin has been proven to play an important role in maintenance of tissue homeostasis and dysregulation leads to disease. Several studies showed elevated levels of activin are responsible for the development of gonadal tumours and a cachexia-like weight loss syndrome. Discussing the recent advances in approaches developed to antagonise the activin pathway and the encouraging results obtained in animal models, this review presents a therapeutic rationale for targeting the activin pathway in conditions such as cachexia, neuromuscular and/or musculoskeletal disorders.

Paclitaxel plus ifosfamide and cisplatin in second-line treatment of germ cell tumors: a phase II study.

The aim of this study was to determine efficacy and toxicity of TIP combination (paclitaxel, ifosfamid, cisplatin) as first salvage treatment in patients with relapsed germ cell tumours (GCTs). Excellent results were achieved from TIP combination with a dose 250 mg/m(2) of paclitaxel [5]. Our hypothesis was that comparable efficacy with less toxicity could be achieved even with a lower dose of 175 mg/m(2) paclitaxel in TIP. In 17 consecutive patients with failed standard 1st line treatment, we used four to six courses of paclitaxel 175 mg/m(2) on day 1 and ifosfamide 1,200 mg/m(2) plus cisplatin 20 mg/m(2), both on day 1 through 5, every 3 weeks. Eleven patients achieved favorable response (65%; 95% confidence interval, 42 to 87%) with 7 complete responses (41%). Estimated 2-year disease free survival is 47% (95% CI, 23-71%). Treatment combination was well tolerated and myelosupression was major toxicity. Granulocytopenia Gr3-4 was observed in 8% and febrile neutropenia in 7% of the courses. No case of severe neurotoxicity or treatment-related death was observed. In our study, TIP combination had good toxicity profile. The results however, did not show expected treatment efficacy and we raise the idea of paclitaxel dosage relevance in TIP.

Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study.

BACKGROUND: To investigate the efficacy and toxicity of the combination of gemcitabine and oxaliplatin (GEMOX) in patients with relapsed or cisplatin-refractory non-seminomatous germ cell tumors (NSGCT). PATIENTS AND METHODS: Twenty-nine patients with relapsed or cisplatin-refractory NSGCT were treated with gemcitabine 1000 mg/m2 on days 1 and 8 followed by oxaliplatin 130 mg/m2 on day 1 every 3 weeks for a maximum of six cycles. Twenty-four patients (83%) were considered refractory and five (17%) absolutely refractory to cisplatin. RESULTS: Twenty-eight patients were assessable for response. Overall, nine patients (32%) achieved a favourable response (complete response, four; partial response, five). One of the complete responders relapsed after 7 months and went into disease-free status lasting for 11+ months after resection of lung metastases. The rest of the complete responders are continuously disease-free at 14+, 19+ and 28+ months with the study regimen plus or minus surgery. One of the complete responders had absolutely cisplatin-refractory disease and another one presented with a late relapse. Toxicity was primarily hematological and generally manageable: 62% of patients experienced grade 3/4 neutropenia, 10% neutropenic fever and 41% grade 3/4 thrombocytopenia. Non-hematological toxicity consisted mainly of nausea/vomiting. Three patients (10%) developed grade 3 neurotoxicity and discontinued treatment. CONCLUSIONS: The combination of GEMOX is an active, moderately toxic and easily administered regimen in patients with relapsed or cisplatin-refractory NSGCT. The 14% long-term disease-free status accomplished in this heavily pretreated patient population is quite encouraging.