Germ cell tumors (GCTs) are neoplasms that are derived from germ cells, which are the sex cells (eggs and sperm). The majority of GCT arise from gonads (more commonly from the testes than ovaries) and account for 95% of testicular cancers.

PMGCTs are derived from abnormal migration of primitive germ cells during a very early stage of development, and account for 1% to 3% of all GCTs (around 200 cases in the US per year).

These tumors most commonly arise in males between the ages of 20 and 35, and often cause symptoms such as chest pain and cough at the time of diagnosis.

Mediastinal GCTs are categorized as seminomas and non-seminomas (NSGCT) based on their appearance under the microscope.

The non-seminomas include teratoma, yolk sac tumors, choriocarcinoma, embryonal cell carcinoma, and mixed tumors in decreasing frequency. 2 out of 3 cases of mediastinal GCT are non-seminomas as compared to testicular tumors, where most are seminomas.

Non-seminoma mediastinal GCTs have a poorer prognosis as compared to the same tumor type arising in the testes or retroperitoneum, and compared with mediastinal seminoma. The 5-year survival rate of mediastinal GCT was 80% to 85% for seminomas, and 40% to 45% for non-seminomas.

Prognostic groups are used more commonly than staging for extragonadal germ cell tumors. A non-seminoma primary mediastinal germ cell tumor is in the poor prognosis group.

Different subtypes of NSGCT produce substances known as tumor markers, which can be measured by a blood test. The levels of these markers have implications for prognosis, and also provide a means for monitoring the effectiveness of treatment. These include alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH).

Treatment for a primary mediastinal GCT should be done at a tertiary care hospital, where the staff is experienced in the administration of chemotherapy and its potential complications.

Seminomas are usually treated with cisplatin-based chemotherapy, or if localized, with radiotherapy. Surgery is usually not necessary.

For non-seminomas, the treatment is chemotherapy followed by surgery to remove any remaining resectable mass. This is ideally performed a few months after the completion of chemotherapy to allow for maximum shrinkage of any residual mass. Radiation therapy is usually not used for NSGCTs, as they tend to be resistant to radiation.

The 3 month long chemotherapy regimen consists of VIP (Etoposide, Ifosfamide and Cisplatin) given in combination for five consecutive days as an inpatient, every 3 weeks (a cycle), four times. This is administered through a mediport, which requires a minor surgical procedure. The first week home after the chemotherapy is difficult with regard to fatigue, infection risk and other symptoms, but the second week is much better. Patients are frequently given a drug called Pegfilgrastim (Neulasta) the day after treatment to help the body restore normal blood counts.

If the first line chemotherapy does not adequately treat the tumor, either due to progression of the tumor or inadequate reduction of tumor markers (referred to as platinum resistance), the only other option to potentially achieve a cure is high dose chemotherapy (HDCT) followed by an autologous (using the patient’s own stem cells) bone marrow transplant, repeated either twice or three times depending on the regimen (Indiana University and Memorial Sloan Kettering).

This process starts with injections of a medicine to increase the number of stem cells, and placement of a large central IV line. Subsequently, the patient undergoes leukopheresis (plasma pheresis), where blood is extracted through the catheter and filtered through an apheresis machine (cell separator), removing the stem cells. The stem cells are then frozen and stored to be used when its time for the bone marrow transplant.

The patient is admitted to the bone marrow transplant unit, and then receives three consecutive days of high dose Carboplatin and Etoposide. This hopefully treats the tumor, but also completely depletes the bone marrow. A couple days after the chemotherapy is done, the patient is given back their stem cells. The process of restoring the bone marrow takes about a week. In the meantime the patient is given medicine to fend off infection during this process, and given red blood cell and platelet transfusions as necessary, to maintain adequate oxygen delivery and to prevent bleeding complications.

Unfortunately, the prognosis of a non-seminoma primary mediastinal germ cell tumor that is platinum resistant with very high levels of AFP or HCG is poor, with HDCT success of only 25-30%.

If this treatment is unsuccessful, the disease is incurable, and the patient is considered terminal. The remaining options include several different regimens of palliative chemotherapy, which is treatment to alleviate symptoms, improve quality of life, and to prolong survival, or enrollment in a clinical trial.

Radiation therapy is usually not used for NSGCTs, as they tend to be resistant to radiation.

However some recent studies have shown some benefit in dual modality treatment involving a regimen that includes chemotherapy as well as radiotherapy localized to any remaining diseased area. There is evidence to suggest that this can result in greater survival rate of primary malignant mediastinal non-seminomatous germ cell tumor patients. It has also shown evidence of potential reduction in local disease recurrence.

For more information about radiotherapy treatment research for Primary Mediastinal Germ Cell Cancer patients:

• “Role of radiotherapy in treating patients with primary malignant mediastinal non-seminomatous germ cell tumor”

• “Primary mediastinal germ cell tumors: Survival outcomes and prognostic factors”

• “Chemoradiotherapy is an alternative choice for patients with primary mediastinal seminoma”

Seminomas are usually treated with cisplatin-based chemotherapy, or if localized, with radiotherapy. Surgery is usually not necessary.

For non-seminomas, the treatment is chemotherapy followed by surgery to remove any remaining resectable mass. This is ideally performed a few months after the completion of chemotherapy to allow for maximum shrinkage of any residual mass.

Clinical trials are research studies overseen by the National Cancer Institute, which provide opportunities for patients to receive experimental treatments which are not part of the standard treatment options.

https://www.cancer.gov/about-cancer/treatment/clinical-trials/disease/extragonadal-germ-cell-tumors/treatment

They are commonly available at your nearest cancer center, although some may require a greater amount of travel. The treatment may turn out to help significantly or at least prolong survival, and at the very least, still contributes to the goal of finding new treatment options, and a greater chance for a cure.

Many of these trials use targeted therapies, which are pharmaceuticals developed to specifically target a cancer mutation. These treatments have been used with good success in breast, lung and several other more common cancers. It may be useful to do genetic testing on the tumor before deciding which trial to enroll in, but this is very expensive, and for GCTs is not usually covered by insurance.

Immunotherapy, which uses drugs that modulate the immune system to treat the cancer, is another area of investigation in clinical trials.