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Induction chemotherapy is the treatment adapted for shrinking the tonsil tumor. It is given prior to other treatments, hence, the term induction. After the therapy is completed, the patient is asked to rest and is evaluated over a period of time. Then the patient is given chemo-radiation therapy (a combination of chemotherapy and radiation) to completely destroy the tumor cells.
Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.
Simple surgical excision is considered curative. Rare recurrences have been reported.
Radiotherapy is commonly used to treat Merkel-cell cancers. The radiotherapy fields used are usually very large so as to cover sufficient areas of skin. This is necessary because of MCC's aggressive local and regional metastatic behavior.
Adjuvant radiotherapy has been shown to be effective in reducing the rates of recurrence and in increasing the survival of patients with MCC. Patients who present with no distant metastases and a negative sentinel lymph node biopsy have a very good prognosis when treated with both surgery and radiotherapy (approximately 90% survival rate at five years).
Metastatic MCC may respond to treatment with chemotherapy and/or radiation, but current multimodal therapies are usually not curative. Intensive treatment can be effective in shrinking the tumor and improving operability when tumors are too large to be removed or located in a place where removal would be difficult or dangerous, or in palliation of signs and symptoms caused by metastatic tumors.
Complete radical surgical resection is the treatment of choice for EMECL, and in most cases, results in long-term survival or cure.
Surgery is usually the first treatment that a patient undergoes for Merkel-cell cancer. Lesions usually appear purple-red in color, and there is little else to distinguish this variant of skin cancer from other types. Its identity usually comes as a surprise after surgery and pathologic examination.
As with surgery for most other forms of cancer, it is normal for the surgeon to remove a border of healthy tissue surrounding the tumor. While it has been thought that leaving this margin may not be as critical as it is in the surgical resection of melanoma, studies also reveal that local recurrences are fairly common in MCC near the site of the surgery.
Local or regional lymph nodes are usually removed if the lesion is more than 1 cm in diameter, due to a high risk that they will contain cancer cells (micrometastasis) that could develop into a new tumor or spread further. Sometimes, however, the doctor will first perform a sentinel lymph node biopsy. In this procedure, the doctor injects a dye or radioactive substance near the tumor. This material flows into adjacent lymph nodes, which are identified, removed, and checked for cancer cells, indicating the sites where cancer is most likely to spread (the "sentinel" nodes). This procedure has been demonstrated to be an important prognostic indicator. Results help dictate the use of appropriate adjuvant therapies. Usually, however, surgery alone is insufficient to control Merkel-cell carcinoma.
Treatment consists of surgical excision (the extent of which ranges from tumor excision to limb amputation, depending on the tumor) and in almost all cases radiation. Radiation eliminates the need for limb amputation and there is level I evidence to show that it leads to equivalent rates of survival (Rosenberg et al. NCI Canada). Radiation may be delivered either pre-op or post-op depending on surgeon and multidisciplinary tumor board's recommendations. Radiation can be omitted for low grade, Stage I excised tumors with >1 cm margin (NCCN). Chemotherapy remains controversial in MFH.
The usual site of metastatic disease is the lungs, and metastases should be resected if possible. Unresectable or inoperable lung metastasis may be treated with stereotactic body radiation therapy (SBRT) with excellent local control. However, neither surgery nor SBRT will prevent emergence of additional metastasis elsewhere in the lung. Therefore, role of chemotherapy needs to be further explored to address systemic metastasis.
Various chemotherapy agents, including temozolomide, dacarbazine (also termed DTIC), immunotherapy (with interleukin-2 (IL-2) or interferon (IFN)), as well as local perfusion, are used by different centers. The overall success in metastatic melanoma is quite limited.
IL-2 (Proleukin) was the first new therapy approved (1990 Europe, 1992 USA) for the treatment of metastatic melanoma in 20 years. Studies have demonstrated that IL-2 offers the possibility of a complete and long-lasting remission in this disease, although only in a small percentage of patients. Intralesional IL-2 for in-transit metastases has a high complete response rate ranging from 40 to 100%.
By 2005 a number of new agents and novel approaches were under evaluation and showed promise.
In 2009 Clinical trial participation was considered the standard of care for metastatic melanoma.
Therapies for metastatic melanoma include biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.
Ongoing research is looking at treatment by adoptive cell transfer. For this purpose, application of prestimulated or modified T cells or dendritic cells is possible.
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 primary treatment is surgical. FIGO-cancer staging is done at the time of surgery which consists of peritoneal cytology, total hysterectomy, bilateral salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and omentectomy. The tumor is aggressive and spreads quickly into the myometrium and the lymphatic system. Thus even in presumed early stages, lymphadenectomy and omentectomy should be included in the surgical approach. If the tumor has spread surgery is cytoreductive followed by radiation therapy and/or chemotherapy.
In a study to determine if adjuvant therapy should be used in patients with stage I UPSC who had undergone surgery, no increased survival was seen when radiation therapy was added versus observation, while the postsurgical treatment with chemotherapy may be beneficial but more data are needed.
A study of the usefulness of platinum-based chemotherapy as an adjuvant after surgery of stage I patients showed that patients with stage 1A who had no residual disease in the hysterectomy specimen had no recurrence regardless if chemotherapy was used or not, however, patients with stage 1A disease with residual disease in the hysterectomy specimen had no recurrence with platinum-based therapy, but those who had no such chemotherapy showed recurrence in 43%. Similarly, patients with stage 1B disease with chemotherapy had no recurrence, while those without chemotherapy had a high degree (77%) of recurrence.
Specific treatment depends on the location, type, and stage of the tumour. Treatment may involve surgery, radiotherapy, or chemotherapy, alone or in combination. This is a specialised area which requires the coordinated expertise of ear, nose and throat (ENT) surgeons (Otorhinolaryngologists) and Oncologists. A severely affected patient may require a laryngectomy, the complete or partial removal of the vocal cords.
Confirmation of the clinical diagnosis is done with a skin biopsy. This is usually followed up with a wider excision of the scar or tumor. Depending on the stage, a sentinel lymph node biopsy is done, as well, although controversy exists around trial evidence for this procedure. Treatment of advanced malignant melanoma is performed from a multidisciplinary approach.
Treatment depends upon the site and the extent of the disease. Clear cell sarcoma is usually treated with surgery in the first place in order to remove the tumor. The surgical procedure is then followed by radiation and sometimes chemotherapy. Few cases of clear cell sarcoma respond to chemotherapy. Several types of targeted therapy that may be of benefit to clear cell sarcoma patients are currently under investigation.
Aggressive surgical removal of the tumor and any enlarged sublumbar lymph nodes is essential for treatment of the tumor and associated hypercalcaemia. There is a high recurrence rate, although removal of lymph nodes with metastasis may improve survival time. Radiation therapy and chemotherapy may be helpful in treatment. Severe hypercalcaemia is treated with aggressive IV fluid therapy using sodium chloride and medications such as loop diuretics (increased kidney excretion of calcium) and aminobisphosphonates (decreased calcium release from bones). A poorer prognosis is associated with large tumor size (greater than 10 cm), hypercalcaemia, and distante metastasis. Early, incidental diagnosis of small anal sac masses may lead to a better prognosis with surgery alone (ongoing study).
Treatment of invasive carcinoma of no special type (NST) depends on the size of the mass (size of the tumor measured in its longest direction):
- <4 cm mass: surgery to remove the main tumor mass and to sample the lymph nodes in the axilla. The stage of the tumor is ascertained after this first surgery. Adjuvant therapy (i.e., treatment after surgery) may include a combination of chemotherapy, radiotherapy, hormonal therapy (e.g., tamoxifen) and/or targeted therapy (e.g., trastuzumab). More surgery is occasionally needed to complete the removal of the initial tumor or to remove recurrences.
- 4 cm or larger mass: modified (a less aggressive form of radical mastectomy) radical mastectomy (because any malignant mass in excess of 4 cm in size exceeds the criteria for a lumpectomy) along with sampling of the lymph nodes in the axilla.
The treatment options offered to an individual patient are determined by the form, stage and location of the cancer, and also by the age, history of prior disease and general health of the patient. Not all patients are treated the same way.
Treatment and survival is determined, to a great extent, by whether or not a cancer remains localized or spreads to other locations in the body. If the cancer metastasizes to other tissues or organs it usually dramatically increases a patient's likelihood of death. Some cancers—such as some forms of leukemia, a cancer of the blood, or malignancies in the brain—can kill without spreading at all.
Once a cancer has metastasized it may still be treated with radiosurgery, chemotherapy, radiation therapy, biological therapy, hormone therapy, surgery, or a combination of these interventions ("multimodal therapy"). The choice of treatment depends on a large number of factors, including the type of primary cancer, the size and location of the metastases, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP it is often still possible to treat the disease even when the primary tumor cannot be located.
Current treatments are rarely able to cure metastatic cancer though some tumors, such as testicular cancer and thyroid cancer, are usually curable.
Palliative care, care aimed at improving the quality of life of people with major illness, has been recommended as part of management programs for metastasis.
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").
Staging and treatment are generally handled by an oncologist familiar with gynecologic cancer. Surgery is a mainstay of therapy depending on anatomical staging and is usually reserved for cancers that have not spread beyond the vulva. Surgery may involve a wide local excision, radical partial vulvectomy, or radical complete vulvectomy with removal of vulvar tissue, inguinal and femoral lymph nodes. In cases of early vulvar cancer, the surgery may be less extensive and consist of wide excision or a simple vulvectomy. Surgery is significantly more extensive when the cancer has spread to nearby organs such as the urethra, vagina, or rectum. Complications of surgery include wound infection, sexual dysfunction, edema and thrombosis, as well as lymphedema secondary to dissected lymph nodes.
Sentinel lymph node (SLN) dissection is the identification of the main lymph node(s) draining the tumor, with the aim of removing as few nodes as possible, decreasing the risk of adverse effects. Location of the sentinel node(s) may require the use of technetium(99m)-labeled nano-colloid, or a combination of technetium and 1% isosulfan blue dye, wherein the combination may reduce the number of women with "'missed"' groin node metastases compared with technetium only.
Radiation therapy may be used in more advanced vulvar cancer cases when disease has spread to the lymph nodes and/or pelvis. It may be performed before or after surgery. Chemotherapy is not usually used as primary treatment but may be used in advanced cases with spread to the bones, liver or lungs. It may also be given at a lower dose together with radiation therapy.
Women with vulvar cancer should have routine follow-up and exams with their oncologist, often every 3 months for the first 2–3 years after treatment. They should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising. Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival and is associated with its own side effects and financial costs.
First-line chemotherapy regimens for advanced or metastatic TCC consists of gemcitabine and cisplatin) (GC) or a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC).
Taxanes or vinflunine have been used as second-line therapy (after progression on a platinum containing chemotherapy).
Immunotherapy such as pembrolizumab is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC.
In May 2016 FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of cisplatin-based chemotherapy. The confirmatory trial (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of overall survival.
CUP is a term that refers to many different cancers. For that reason, treatment depends on where the cancer is found, the microscopic appearance of the cancer cells, the biochemical characterization of the cells, and the patient’s age and overall physical condition. In women, who present with axillary lymph node involvement, treatment is offered along the lines of breast cancer. In patients, who have neck lymph node involvement, then treatment is offered along the lines of head and neck cancer. If inguinal lymph nodes are involved, then treatment may be offered along the lines of genitourinary cancer.
If the site of origin is unknown or undiscovered, then the histology of the tumor (e.g., adenocarcinoma, squamous cell or mesenchymal) can usually be identified, and a probable origin may be assumed. When this is possible, then treatment is based on the type of cell and probable origin. Based on histological subtype, combination chemotherapy may be selected. A combination of carboplatin and paclitaxel is often used. Advances techniques such as FISH and tissue of origin testing may also be employed. Germ cell tumors often carry abnormality of chromosome 12, which if identified, directs treatment for metastatic germ cell tumors.
No method is standard for all forms of CUP, but chemotherapy, radiation therapy, hormone therapy, and surgery may be used alone or in combination to treat patients who have CUP. Even when the cancer is unlikely to be cured, treatment may help the patient live longer or improve the patient’s quality of life. Radiation may be used to shrink a variety of local tumors. However, the potential side effects of the treatment must be considered along with the potential benefits.
In CUP to secondary neck nodes, surgery followed by external beam radiotherapy is sufficient.
For CUP with an unfavorable prognosis, treatment with taxanes may provide a slight survival benefit. The uncertainties and ambiguity inherent in a CUP diagnosis may cause additional stress for the patient.
Transitional cell carcinoma (TCC) can be very difficult to treat. Treatment for localized stage TCC is surgical resection of the tumor, but recurrence is common. Some patients are given mitomycin into the bladder either as a one-off dose in the immediate post-operative period (within 24 hrs) or a few weeks after the surgery as a six dose regimen.
Localized/early TCC can also be treated with infusions of BCG into the bladder. These are given weekly for either 6 weeks (induction course) or 3 weeks (maintenance/booster dose). Side effects include a small chance of developing systemic tuberculosis or the patient becoming sensitized to the BCG causing severe intolerance and a possible reduction in bladder volume due to scarring.
In patients with evidence of early muscular invasion, radical curative surgery in the form of a cysto-prostatectomy usually with lymph node sampling can also be performed. In such patients, a bowel loop is often used to create either a "neo-bladder" or an "ileal conduit" which act as a place for the storage of urine before it is evacuated from the body either via the urethra or a urostomy respectively.
Nasopharyngeal carcinoma can be treated by surgery, by chemotherapy, or by radiotherapy. The expression of EBV latent proteins within undifferentiated nasopharyngeal carcinoma can be potentially exploited for immune-based therapies.
MASC is currently treated as a low-grade (i.e. Grade 1) carcinoma with an overall favorable prognosis. These cases are treated by complete surgical excision. However, the tumor does have the potential to recur locally and/or spread beyond surgically dissectible margins as well as metastasize to regional lymph nodes and distant tissues, particularly in tumors with histological features indicating a high cell growth rate potential. One study found lymph node metastasis in 5 of 34 MASC patients at initial surgery for the disease; these cases, when evidencing no further spread of disease, may be treated with radiation therapy. The treatment of cases with disease spreading beyond regional lymph nodes has been variable, ranging from simple excision to radical resections accompanied by adjuvant radiotherapy and/or chemotherapy, depending on the location of disease. Mean disease-free survival for MASC patients has been reported to be 92 months in one study.
The tyrosine kinase activity of NTRK3 as well as the ETV6-NTRK3 protein is inhibited by certain tyrosine kinase inhibitory drugs such as Entrectinib and LOXO-101; this offers a potential medical intervention method using these drugs to treat aggressive MASC disease. Indeed, one patient with extensive head and neck MASC disease obtained an 89% fall in tumor size when treated with entrectinib. This suppression lasted only 7 months due to the tumor's acquirement of a mutation in the "ETV6-NTRK3" gene. The newly mutated gene encoded an entrectinib-reisistant "ETV6-NTRK3" protein. Treatment of aggressive forms of MASC with NTRK3-inhibiting tyrosine kinase inhibiting drugs, perhaps with switching to another type of tyrosine kinase inhibitor drug if the tumor acquires resistance to the initial drug, is under study.STARTRK-2
There are several treatment options for penile cancer, depending on staging. They include surgery, radiation therapy, chemotherapy, and biological therapy. The most common treatment is one of five types of surgery:
- Wide local excision—the tumor and some surrounding healthy tissue are removed
- Microsurgery—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible
- Laser surgery—laser light is used to burn or cut away cancerous cells
- Circumcision—cancerous foreskin is removed
- Amputation (penectomy)—a partial or total removal of the penis, and possibly the associated lymph nodes.
Radiation therapy is usually used adjuvantly with surgery to reduce the risk of recurrence. With earlier stages of penile cancer, a combination of topical chemotherapy and less invasive surgery may be used. More advanced stages of penile cancer usually require a combination of surgery, radiation and chemotherapy.
In addition to all the above, treatment of the underlying disease like brucellosis, is important to limit disease recurrence.
Treatment of rhabdomyosarcoma is a multidisciplinary practice involving the use of surgery, chemotherapy, radiation, and possibly immunotherapy. Surgery is generally the first step in a combined therapeutic approach. Resectability varies depending on tumor site, and RMS often presents in sites that don't allow for full surgical resection without significant morbidity and loss of function. Less than 20% of RMS tumors are fully resected with negative margins. Fortunately, rhabdomyosarcomas are highly chemosensitive, with approximately 80% of cases responding to chemotherapy. In fact, multi-agent chemotherapy is indicated for all patients with rhabdomyosarcoma. Before the use of adjuvant and neoadjuvant therapy involving chemotherapeutic agents, treatment solely by surgical means had a survival rate of <20%. Modern survival rates with adjuvant therapy are approximately 60–70%.
There are two main methods of chemotherapy treatment for RMS. There is the VAC regimen, consisting of vincristin, actinomyocin D, and cyclophosphamide, and the IVA regimen, consisting of ifosfamide, vincristin, and actinomyocin D. These drugs are administered in 9–15 cycles depending on the staging of the disease and other therapies used. Other drug and therapy combinations may also show additional benefit. Addition of doxorubicin and cisplatin to the VAC regimen was shown to increase survival rates of patients with alveolar-type, early-stage RMS in IRS study III, and this same addition improved survival rates and doubled bladder salvage rates in patients with stage III RMS of the bladder.
Radiation therapy, which kill cancer cells with focused doses of radiation, is often indicated in the treatment of rhabdomyosarcoma, and the exclusion of this treatment from disease management has been shown to increase recurrence rates. Radiation therapy is used when resecting the entirety of the tumor would involve disfigurement or loss of important organs (eye, bladder, etc.). Generally, in any case where a lack of complete resection is suspected, radiation therapy is indicated. Administration is usually following 6–12 weeks of chemotherapy if tumor cells are still present. The exception to this schedule is the presence of parameningeal tumors that have invaded the brain, spinal cord, or skull. In these cases radiation treatment is started immediately. In some cases, special radiation treatment may be required. Brachytherapy, or the placement of small, radioactive “seeds” directly inside the tumor or cancer site, is often indicated in children with tumors of sensitive areas such as the testicles, bladder, or vagina. This reduces scattering and the degree of late toxicity following dosing. Radiation therapy is more often indicated in higher stage classifications.
Immunotherapy is a more recent treatment modality that is still in development. This method involves recruiting and training the patient's immune system to target the cancer cells. This can be accomplished through administering small molecules designed to pull immune cells towards the tumors, taking immune cells pulled from the patient and training to attack tumors through presentation with tumor antigen, or other experimental methods. A specific example here would be presenting some of the patient's dendritic cells, which direct the immune system to foreign cells, with the PAX3-FKHR fusion protein in order to focus the patient's immune system to the malignant RMS cells. All cancers, including rhabdomyosarcoma, could potentially benefit from this new, immune-based approach.