Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
The majority of cases of cholangiocarcinoma present as inoperable (unresectable) disease in which case patients are generally treated with palliative chemotherapy, with or without radiotherapy. Chemotherapy has been shown in a randomized controlled trial to improve quality of life and extend survival in patients with inoperable cholangiocarcinoma. There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin, gemcitabine as a single agent, or gemcitabine plus cisplatin, irinotecan, or capecitabine. A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in patients with advanced cholangiocarcinoma.
If the tumor can be removed surgically, patients may receive adjuvant chemotherapy or radiation therapy after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally ), adjuvant therapy is of uncertain benefit. Both positive and negative results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors. The role of combined chemoradiotherapy in this setting is unclear. However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.
Partial surgical resection is the optimal treatment for hepatocellular carcinoma (HCC) when patients have sufficient hepatic function reserve. Increased risk of complications such as liver failure can occur with resection of cirrhotic (i.e. less-than-optimally functional) livers. 5-year survival rates after resection have massively improved over the last few decades and can now exceed 50%. However, recurrence rates after resection can exceed 70%, whether due to spread of the initial tumor or formation of new tumors . Liver transplantation can also be considered in cases of HCC where this form of treatment can be tolerated and the tumor fits specific criteria (such as the Milan criteria). In general, patients who are being considered for liver transplantation have multiple hepatic lesions, severe underlying liver dysfunction, or both. Less than 30-40% of individuals with HCC are eligible for surgery and transplant because the cancer is often detected at a late stage. Also, HCC can progress during the waiting time for liver transplants, which can prevent transplant due to the strict criteria.
Percutaneous ablation is the only non-surgical treatment that can offer cure. There are many forms of percutaneous ablation, which consist of either injecting chemicals into the liver (ethanol or acetic acid) or producing extremes of temperature using radio frequency ablation, microwaves, lasers or cryotherapy. Of these, radio frequency ablation has one of the best reputations in HCC, but the limitations include inability to treat tumors close to other organs and blood vessels due to heat generation and the heat sink effect, respectively. In addition, long-term of outcomes of percutaneous ablation procedures for HCC have not been well studied. In general, surgery is the preferred treatment modality when possible.
Systemic chemotherapeutics are not routinely used in HCC, although local chemotherapy may be used in a procedure known as transarterial chemoembolization. In this procedure, cytotoxic drugs such as doxorubicin or cisplatin with lipiodol are administered and the arteries supplying the liver are blocked by gelatin sponge or other particles. Because most systemic drugs have no efficacy in the treatment of HCC, research into the molecular pathways involved in the production of liver cancer produced sorafenib, a targeted therapy drug that prevents cell proliferation and blood cell growth. Sorafenib obtained FDA approval for the treatment of advanced hepatocellular carcinoma in November 2007. This drug provides a survival benefit for advanced HCC.
Radiotherapy is not often used in HCC because the liver is not tolerant to radiation. Although with modern technology it is possible to provide well-targeted radiation to the tumor, minimizing the dose to the rest of the liver. Dual treatments of radiotherapy plus chemoembolization, local chemotherapy, systemic chemotherapy or targeted therapy drugs may show benefit over radiotherapy alone.
Resection is an option in cholangiocarcinoma, but less than 30% of cases of cholangiocarcinoma are resectable at diagnosis. After surgery, recurrence rates are up to 60%. Liver transplant may be used where partial resection is not an option, and adjuvant chemoradiation may benefit some cases.
60% of cholangiocarcinomas form in the perihilar region and photodynamic therapy can be used to improve quality of life and survival time in these unresectable cases. Photodynamic therapy is a novel treatment that utilitizes light activated molecules to treat the tumor. The compounds are activated in the tumor region by laser light, which causes the release of toxic reactive oxygen species, killing tumor cells.
Systemic chemotherapies such as gemcitabine and cisplatin are sometimes used in inoperable cases of cholangiocarcinoma.
Radio frequency ablation, transarterial chemoembolization and internal radiotherapy (brachytherapy) all show promise in the treatment of cholangiocarcinoma.
Radiotherapy may be used in the adjuvant setting or for palliative treatment of cholangiocarcinoma.
After surgery, adjuvant chemotherapy with gemcitabine or 5-FU can be offered if the person is sufficiently fit, after a recovery period of one to two months. In people not suitable for curative surgery, chemotherapy may be used to extend life or improve its quality. Before surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases that are considered to be "borderline resectable" (see Staging) in order to reduce the cancer to a level where surgery could be beneficial. In other cases neoadjuvant therapy remains controversial, because it delays surgery.
Gemcitabine was approved by the United States Food and Drug Administration (FDA) in 1997, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in people with advanced pancreatic cancer. This was the first chemotherapy drug approved by the FDA primarily for a nonsurvival clinical trial endpoint. Chemotherapy using gemcitabine alone was the standard for about a decade, as a number of trials testing it in combination with other drugs failed to demonstrate significantly better outcomes. However, the combination of gemcitabine with erlotinib was found to increase survival modestly, and erlotinib was licensed by the FDA for use in pancreatic cancer in 2005.
The FOLFIRINOX chemotherapy regimen using four drugs was found more effective than gemcitabine, but with substantial side effects, and is thus only suitable for people with good performance status. This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine in pancreas cancer. By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine were regarded as good choices for those able to tolerate the side-effects, and gemcitabine remained an effective option for those who were not. A head-to-head trial between the two new options is awaited, and trials investigating other variations continue. However, the changes of the last few years have only increased survival times by a few months. Clinical trials are often conducted for novel adjuvant therapies.
The role of radiotherapy as an auxiliary (adjuvant) treatment after potentially curative surgery has been controversial since the 1980s. The European Society for Medical Oncology recommends that adjuvant radiotherapy should only be used for people enrolled in clinical trials. However, there is a continuing tendency for clinicians in the US to be more ready to use adjuvant radiotherapy than those in Europe. Many clinical trials have tested a variety of treatment combinations since the 1980s, but have failed to settle the matter conclusively.
Radiotherapy may form part of treatment to attempt to shrink a tumor to a resectable state, but its use on unresectable tumors remains controversial as there are conflicting results from clinical trials. The preliminary results of one trial, presented in 2013, "markedly reduced enthusiasm" for its use on locally advanced tumors.
In general, treatment for PanNET encompasses the same array of options as other neuroendocrine tumors, as discussed in that main article. However, there are some specific differences, which are discussed here.
In functioning PanNETs, octreotide is usually recommended prior to biopsy or surgery but is generally avoided in insulinomas to avoid profound hypoglycemia.
PanNETs in MEN1 are often multiple, and thus require different treatment and surveillance strategies.
Some PanNETs are more responsive to chemotherapy than are gastroenteric carcinoid tumors. Several agents have shown activity. In well differentiated PanNETs, chemotherapy is generally reserved for when there are no other treatment options. Combinations of several medicines have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU) and capecitabine with temozolomide. Although marginally effective in well-differentiated PETs, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancers (PDNECs), particularly if the PDNEC has an extremely high Ki-67 score of over 50%.
Several targeted therapy agents have been approved in PanNETs by the FDA based on improved progression-free survival (PFS):
- everolimus (Afinitor) is labeled for treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The safety and effectiveness of everolimus in carcinoid tumors have not been established.
- sunitinib (Sutent) is labeled for treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Sutent also has approval from the European Commission for the treatment of 'unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults'. A phase III study of sunitinib treatment in well differentiated pNET that had worsened within the past 12 months (either advanced or metastatic disease) showed that sunitinib treatment improved progression-free survival (11.4 months vs. 5.5 months), overall survival, and the objective response rate (9.3% vs. 0.0%) when compared with placebo.
a) Surgical resection is mainstay of treatment, whenever possible. If tumor is completely removed, post-operative radiation therapy is typically not needed since acinic cell is considered a low-grade histology. Post-operative radiation therapy for acinic cell carcinoma is used if: 1) margins are positive, 2) incomplete resection, 3) tumor invades beyond gland, 4) positive lymph nodes.
b) Neutron beam radiation
c) Conventional radiation
d) Chemotherapy
These lesions rarely require surgery unless they are symptomatic or the diagnosis is in question. Since these lesions do not have malignant potential, long-term observation is unnecessary. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy.
In secretory tumors, somatostatin analogs given subcutaneously or intramuscularly alleviate symptoms by blocking hormone release. A consensus review has reported on the use of somatostatin analogs for GEP-NETs.
These medications may also anatomically stabilize or shrink tumors, as suggested by the PROMID study (Placebo-controlled prospective randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumors): at least in this subset of NETs, average tumor stabilization was 14.3 months compared to 6 months for placebo.
The CLARINET study (a randomized, double-blind, placebo-controlled study on the antiproliferative effects of lanreotide in patients with enteropancreatic neuroendocrine tumors) further demonstrated the antiproliferative potential of lanreotide, a somatostatin analog and recently approved FDA treatment for GEP-NETS. In this study, lanreotide showed a statistically significant improvement in progression-free survival, meeting its primary endpoint. The disease in sixty five percent of patients treated with lanreotide in the study had not progressed or caused death at 96 weeks, the same was true of 33% of patients on placebo. This represented a 53% reduction in risk of disease progression or death with lanreotide based on a hazard ratio of .47.
Lanreotide is the first and only FDA approved antitumor therapy demonstrating a statistically significant progression-free survival benefit in a combined population of patients with GEP-NETS.
Other medications that block particular secretory effects can sometimes relieve symptoms.
Even if the tumor has advanced and metastasized, making curative surgery infeasible, surgery often has a role in neuroendocrine cancers for palliation of symptoms and possibly increased lifespan.
Cholecystectomy is recommended if there is a consideration of long-term treatment with somatostatin analogs.
ACC can be treated with a Whipple procedure or (depending on the location within the pancreas) with left partial resection of pancreas.
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.
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.
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 role of external beam radiotherapy (EBRT) in thyroid cancer remains controversial and there is no level I evidence to recommend its use in the setting of differentiated thyroid cancers such as papillary and follicular carcinomas. Anaplastic thyroid carcinomas, however, are histologically distinct from differentiated thyroid cancers and due to the highly aggressive nature of ATC aggressive postoperative radiation and chemotherapy are typically recommended.
The National Comprehensive Cancer Network Clinical Practice Guidelines currently recommend that postoperative radiation and chemotherapy be strongly considered. No published randomised controlled trials have examined the addition of EBRT to standard treatment, namely surgery. Radioactive iodine is typically ineffective in the management of ATC as it is not an iodine-avid cancer.
Imbalances in age, sex, completeness of surgical excision, histological type and stage, between patients receiving and not receiving EBRT, confound retrospective studies. Variability also exists between treatment and non-treatment groups in the use of radio-iodine and post-treatment thyroid stimulating hormone (TSH) suppression and treatment techniques between and within retrospective studies.
Some recent studies have indicated that EBRT may be promising, though the number of patients studies has been small.
Clinical trials for investigational treatments are often considered by healthcare professionals and patients as first-line treatment.
Complete radical surgical resection is the treatment of choice for EMECL, and in most cases, results in long-term survival or cure.
In the absence of extracervical or unresectable disease, surgical excision should be followed by adjuvant radiotherapy. In the 18–24% of patients whose tumour seems both confined to the neck and grossly resectable, complete surgical resection followed by adjuvant radiotherapy and chemotherapy could yield a 75–80% survival at 2 years.
There are a number of clinical trials for anaplastic thyroid carcinoma underway or being planned.
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.
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").
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.
Many treatment options for cancer exist. The primary ones include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and palliative care. Which treatments are used depends on the type, location and grade of the cancer as well as the patient's health and preferences. The treatment intent may or may not be curative.
Laser therapy uses high-intensity light to treat cancer by shrinking or destroying tumors or precancerous growths. Lasers are most commonly used to treat superficial cancers that are on the surface of the body or the lining of internal organs. It is used to treat basal cell skin cancer and the very early stages of others like cervical, penile, vaginal, vulvar, and non-small cell lung cancer. It is often combined with other treatments, such as surgery, chemotherapy, or radiation therapy. Laser-induced interstitial thermotherapy (LITT), or interstitial laser photocoagulation, uses lasers to treat some cancers using hyperthermia, which uses heat to shrink tumors by damaging or killing cancer cells. Laser are more precise than surgery and cause less damage, pain, bleeding, swelling, and scarring. A disadvantage is surgeons must have specialized training. It may be more expensive than other treatments.
Renal medullary carcinoma is extremely rare and it is not currently possible to predict those individuals with sickle cell trait who will eventually develop this cancer. It is hoped that early detection could result in better outcomes but screening is not feasible.
When BAC recurs after surgery, the recurrences are local in about three-quarters of cases, a rate higher than other forms of NSCLC, which tends to recur distantly.