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Pure mediastinal seminomas are curable in the large majority of patients, even when metastatic at the time of diagnosis. These tumors are highly sensitive to radiation therapy and to combination chemotherapy. However, the cardiotoxicity of mediastinal radiation is substantial and the standard treatment of mediastinal seminomas is with chemotherapy using bleomycin, etoposide and cisplatin for either three or four 21-day treatment cycles depending on the location of any metastatic disease.
Patients with small tumors (usually asymptomatic) that appear resectable usually undergo thoracotomy and attempted complete resection followed by chemotherapy.
The treatment for mediastinal nonseminomatous germ cell tumors should follow guidelines for poor-prognosis testicular cancer. Initial treatment with four courses of bleomycin, etoposide, and cisplatin, followed by surgical resection of any residual disease, is considered standard therapy.
Most treatments involve some combination of surgery and chemotherapy. Treatment with cisplatin, etoposide, and bleomycin has been described.
Before modern chemotherapy, this type of neoplasm was highly lethal, but the prognosis has significantly improved since.
When endodermal sinus tumors are treated promptly with surgery and chemotherapy, fatal outcomes are exceedingly rare.
GCNIS is generally treated by radiation therapy and/or orchiectomy. Chemotherapy used for metastatic germ cell tumours may also eradicate GCNIS.
Unlike classical seminoma, spermatocytic seminomas rarely metastasise, so radical orchidectomy alone is sufficient treatment, and retroperitoneal lymph node dissection and adjuvant chemotherapy or radiotherapy are generally not required.
Germinomas, like several other types of germ cell tumor, are sensitive to both chemotherapy and radiotherapy. For this reason, treatment with these methods can offer excellent chances of longterm survival, even cure.
Although chemotherapy can shrink germinomas, it is not generally recommended alone unless there are contraindications to radiation. In a study in the early 1990s, carboplatinum, etoposide and bleomycin were given to 45 germinoma patients, and about half the patients relapsed. Most of these relapsed patients were then recovered with radiation or additional chemotherapy.
Women with benign germ cell tumors such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or oophorectomy. In general, all patients with malignant germ cell tumors will have the same staging surgery that is done for epithelial ovarian cancer. If the patient is in her reproductive years, an alternative is unilateral salpingoophorectomy, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This isn't an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging including salpingoophorectomy on both sides as well as hysterectomy.
Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin).
Around 50% of the AT/RTs will transiently respond, but chemotherapy by itself is rarely curative. No standard treatment for AT/RT is known. Various chemotherapeutic agents have been used against AT/RTs, which are also used against other CNS tumors including cisplatinum, carboplatinum, cyclophosphamide, vincristine, and etoposide. Some chemotherapy regimens are listed below:
- CCG clinical trial CCG-9921 was activated in 1993 and published its results in 2005. The proposed treatments did not have different outcomes and were not an improvement on prior treatments. Geyer published a review of chemotherapy on 299 infants with CNS tumors that evaluated response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors. Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.
- Sarcoma protocols. There has been at least one report in the literature of malignant rhabdoid tumors of the CNS being treated in as a high-grade intracranial sarcoma. These three cases were treated with surgery, chemotherapy, radiotherapy and triple intrathecal chemotherapy similar to the Intergroup Rhabdomyosarcoma Study III guidelines.
- Intrathecal protocols. One of the difficulties with brain and spinal tumors is that the blood brain barrier needs to be crossed so that the drug can get to the tumor. One mechanism to deliver the drug is through a device called an Ommaya reservoir. This is a device which shares some characteristics with a shunt in which a tube a surgically placed in the fluid surrounding the brain and a bulb shaped reservoir attached to the tubing is placed under the skin of the scalp. When the child is to receive intrathecal chemotherapy, the drug is administered into this bulb reservoir. At other times intrathecal chemotherapeutic agents are delivered through a lumbar puncture (spinal tap). A current Pediatric Brain Tumor Consortium Protocol uses intrathecal mafosfamide, a pre-activated cyclophosphamide derivative, in addition to other modalities to try to effect this tumor.
- High dose chemotherapy with stem cell rescue. This therapy uses chemotherapy at doses high enough to completely suppress the bone marrow. Prior to instituting this therapy, the child has a central line placed and stem cells are gathered. After therapy these cells are given back to the child to regrow the bone marrow. Stem cell rescue or autologous bone marrow transplantation, was initially thought to be of benefit to a wide group of patients, but has declined over the history of chemotherapy protocols.
The Stehlin Foundation currently offers DSRCT patients the opportunity to send samples of their tumors free of charge for testing. Research scientists are growing the samples on nude mice and testing various chemical agents to find which are most effective against the individual's tumor.
Patients with advanced DSRCT may qualify to participate in clinical trials that are researching new drugs to treat the disease.
The traditional practice for childhood brain tumors has been to use chemotherapy and to defer radiation therapy until a child is older than three years. This strategy is based upon observations that children under three have significant long-term complications as a result of brain irradiation. However, the long-term outcomes of AT/RT are so poor that some protocols call for upfront radiation therapy, often in spite of young age.
The dose and volume of radiation had not been standardized, but radiation does appear to improve survival. The use of radiation has been limited in children younger than three because of the risk of severe neurocognitive deficits. Protocols using conformal, local radiation in the young child are used to try to cure this tumor.
External beam (conformal) radiation uses several beams that intersect at the tumor location; the normal brain tissue receives less radiation and cognitive function is thereby less affected.
Proton beam radiation was only offered at Massachusetts General Hospital in Boston and at Loma Linda, California, as of 2002. Since 2003, three or four more proton therapy centers have opened in the United States. St. Jude Children's Research Hospital is in the process of building one at their Memphis, Tennessee, location. Some centers have since opened in Europe. (Germany, Switzerland, and France).
A wide variety of chemotherapies options exist for used in advanced (metastatic) NSCLC. These agents include both traditional chemotherapies like cisplatin which indiscriminately target all rapidly dividing cells as well as newer targeted agents which are more tailored to specific genetic aberrations found within a patient's tumor. At present there are two genetic markers which are routinely profiled in NSCLC tumors to guide further treatment decision making: mutations within EGFR and Anaplastic Lymphoma Kinase. There are also a number of additional genetic markers which are known to be mutated within NSCLC and may impact treatment in the future, including BRAF (gene), HER2/neu and KRAS.
Thermal ablations i.e. radiofrequency ablation, cryoablation, microwave ablation are appropriate for palliative treatment of tumor-related symptoms or recurrences within treatment fields. Patients with severe pulmonary fibrosis and severe emphysema with a life expectancy <1 year should be considered poor candidates for this treatment.
NSCLCs are usually "not" very sensitive to chemotherapy and/or radiation, so surgery remains the treatment of choice if patients are diagnosed at an early stage. If patients have small, but inoperable tumors, they may undergo highly targeted, high intensity radiation therapy. New methods of giving radiation treatment allow doctors to be more accurate in treating lung cancers. This means less radiation affects nearby healthy tissues. New methods include Cyberknife and stereotactic body radiation therapy(SBRT). Certain patients deemed to be higher risk may also receive adjuvant (ancillary) chemotherapy after initial surgery or radiation therapy. There are a number of possible chemotherapy agents which can be selected however most will involve the platinum-based chemotherapy drug called cisplatin.
Other treatments include percutaneous ablation and chemoembolization. The most widely used ablation techniques for lung cancer are radiofrequency ablation, cryoablation, and microwave ablation. Ablation may be an option for patients whose tumors are near the outer edge of the lungs. Nodules less than 1 cm from the trachea, main bronchi, oesophagus and central vessels should be excluded from RFA given high risk of complications and frequent incomplete ablation. Additionally, lesions greater than 5 cm should be excluded and lesions 3 to 5 cm should be considered with caution given high risk of recurrence. As a minimally invasive procedure, it can be a safer alternative for patients who are poor candidates for surgery due to co-morbidities or limited lung function. A study comparing thermal ablation to sublobar resection as treatment for early stage NSCLC in older patients found no difference in overall survival of the patients. It is possible that RFA followed by radiation therapy has a survival benefit due to synergysm of the two mechanisms of cell destruction.
The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.
A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.
Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell tumors diagnosed between 1975 and 1989, 5-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, even though the unit treated more men with the worst prognosis.
Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers
In ES-SCLC, combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases, which, in small-cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.
Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, however.
If complete response to chemotherapy occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.
The treatment of choice in any patient with BAC is complete surgical resection, typically via lobectomy or pneumonectomy, with concurrent ipsilateral lymphadenectomy.
Non-mucinous BACs are highly associated with classical EGFR mutations, and thus are often responsive to targeted chemotherapy with erlotinib and gefitinib. K-ras mutations are rare in nm-BAC.
Mucinous BAC, in contrast, is much more highly associated with K-ras mutations and wild-type EGFR, and are thus usually insensitive to the EGFR tyrosine kinase inhibitors. In fact, there is some evidence that suggests that the administration of EGFR-pathway inhibitors to patients with K-ras mutated BACs may even be harmful.
Spermatocytic seminomas are not considered a subtype of seminoma and unlike other germ cell tumours do not arise from intratubular germ cell neoplasia.
The prognosis for DSRCT remains poor. Prognosis depends upon the stage of the cancer. Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.
There is no known organ or area of origin. DSRCT can metastasize through lymph nodes or the blood stream. Sites of metastasis include the spleen, diaphragm, liver, large and small intestine, lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain.
A multi-modality approach of high-dose chemotherapy, aggressive surgical resection, radiation, and stem cell rescue improves survival for some patients. Reports have indicated that patients will initially respond to first line chemotherapy and treatment but that relapse is common.
Some patients in remission or with inoperable tumor seem to benefit from long term low dose chemotherapy, turning DSRCT into a chronic disease.
While chemotherapy, radiation therapy, curettage and liquid nitrogen have been effective in some cases of ameloblastoma, surgical resection or enucleation remains the most definitive treatment for this condition. In a detailed study of 345 patients, chemotherapy and radiation therapy seemed to be contraindicated for the treatment of ameloblastomas. Thus, surgery is the most common treatment of this tumor. Because of the invasive nature of the growth, excision of normal tissue near the tumor margin is often required. Some have likened the disease to basal cell carcinoma (a skin cancer) in its tendency to spread to adjacent bony and sometimes soft tissues without metastasizing. While rarely not a cancer that actually invades adjacent tissues, ameloblastoma is suspected to spread to adjacent areas of the jaw bone via marrow space. Thus, wide surgical margins that are clear of disease are required for a good prognosis. This is very much like surgical treatment of cancer. Often, treatment requires excision of entire portions of the jaw.
Radiation is ineffective in many cases of ameloblastoma. There have also been reports of sarcoma being induced as the result of using radiation to treat ameloblastoma. Chemotherapy is also often ineffective. However, there is some controversy regarding this and some indication that some ameloblastomas might be more responsive to radiation that previously thought.
In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide, cisplatinum, doxorubicin, etoposide, vincristine and/or paclitaxel) is administered together with concurrent chest radiotherapy (RT).
Chest RT has been shown to improve survival in LS-SCLC.
Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. However, relapse rate remains high, and median survival is only 18 to 24 months.
Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s. However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").
Intratesticular masses that appear suspicious on an ultrasound should be treated with an inguinal orchiectomy. The pathology of the removed testicle and spermatic cord indicate the presence of the seminoma and assist in the staging. Tumors with both seminoma and nonseminoma elements or that occur with the presence of AFP should be treated as nonseminomas. Abdominal CT or MRI scans as well as chest imaging are done to detect for metastasis. The analysis of tumor markers also helps in staging.
The preferred treatment for most forms of stage 1 seminoma is active surveillance. Stage 1 seminoma is characterized by the absence of clinical evidence of metastasis. Active surveillance consists of periodic history and physical examinations, tumor marker analysis, and radiographic imaging. Around 85-95% of these cases will require no further treatment. Modern radiotherapy techniques as well as one or two cycles of single-agent carboplatin have been shown to reduce the risk of relapse, but carry the potential of causing delayed side effects. Regardless of treatment strategy, stage 1 seminoma has nearly a 100% cure rate.
Stage 2 seminoma is indicated by the presence of retroperitoneal metastasis. Cases require radiotherapy or, in advanced cases, combination chemotherapy. Large residual masses found after chemotherapy may require surgical resection. Second-line treatment is the same as for nonseminomas.
Stage 3 seminoma is characterized by the presence of metastasis outside the retroperitoneum—the lungs in "good risk" cases or elsewhere in "intermediate risk" cases. This is treated with combination chemotherapy. Second-line treatment follows nonseminoma protocols.
Prophylactic mastectomy to reduce the risk of breast cancer is an option.
This cancer is typically aggressive, presents at an advanced stage when the cancer has already metastasized, and is resistant to chemotherapy. It therefore poses a significant management challenge. Current treatment options include surgical resection and chemotherapy with a variety of agents, including (but not limited to) ifosfamide, etoposide, carboplatin, and topotecan. A recent study looked at the use of methotrexate, vinblastine, doxorubicin, and cisplatin in 3 patients and saw a partial response and longer survival than historical reports. Carboplatin, gemcitibine, and paclitaxel provided a complete response in a patient with advanced disease. The role of radiation is unclear; some tumors have shown a response to radiation. Due to the apparent propensity for the tumor to spread to the central nervous system, it has been suggested that prophylactic craniospinal irradiation should be considered.
Dysgerminomas, like other seminomatous germ cell tumors, are very sensitive to both chemotherapy and radiotherapy. For this reason, with treatment patients' chances of long-term survival, even cure, is excellent.
Because of its rarity, there have been no randomized clinical trials of treatment of GCCL, and all information available derives from small retrospective institutional series or multicenter metadata.
For malignant teratomas, usually, surgery is followed by chemotherapy.
Teratomas that are in surgically inaccessible locations, or are very complex, or are likely to be malignant (due to late discovery and/or treatment) sometimes are treated first with chemotherapy.
The treatment of choice is complete surgical removal ("i.e.," complete resection). Teratomas are normally well-encapsulated and non-invasive of surrounding tissues, hence they are relatively easy to resect from surrounding tissues. Exceptions include teratomas in the brain, and very large, complex teratomas that have pushed into and become interlaced with adjacent muscles and other structures.
Prevention of recurrence does not require "en bloc" resection of surrounding tissues.