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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)
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Most hormone dependent cancers become resistant to treatment after one to three years and resume growth despite hormone therapy. Previously considered "hormone-refractory prostate cancer" or "androgen-independent prostate cancer", the term castration-resistant has replaced "hormone refractory" because while they are no longer responsive to castration treatment (reduction of available androgen/testosterone/DHT by chemical or surgical means), these cancers still show reliance upon hormones for androgen receptor activation.
The cancer chemotherapic docetaxel has been used as treatment for CRPC with a median survival benefit of 2 to 3 months. A second-line chemotherapy treatment is cabazitaxel. A combination of bevacizumab, docetaxel, thalidomide and prednisone appears effective in the treatment of CRPC.
The immunotherapy treatment with sipuleucel-T in CRPC increases survival by 4 months. The second line hormonal therapy abiraterone increases survival by 4.6 months when compared to placebo. Enzalutamide is another second line hormonal agent with a 5-month survival advantage over placebo. Both abiraterone and enzalutamide are currently being tested in clinical trials in those with CRPC who have not previously received chemotherapy.
Only a subset of people respond to androgen signaling blocking drugs and certain cells with characteristics resembling stem cells remain unaffected. Therefore, the desire to improve outcome of people with CRPC has resulted in the claims of increasing doses further or combination therapy with synergistic androgen signaling blocking agents. But even these combination will not affect stem-like cells that do not exhibit androgen signaling. It is possible that for further advances, a combination of androgen signaling blocking agent with stem-like cell directed differentiation therapy drug would prove ideal.
Superficial tumors (those not entering the muscle layer) can be "shaved off" using an electrocautery device attached to a cystoscope, which in that case is called a resectoscope. The procedure is called transurethral resection of bladder tumor—TURBT—and serves primarily for pathological staging. In case of non-muscle invasive bladder cancer the TURBT is in itself the treatment, but in case of muscle invasive cancer, the procedure is insufficient for final treatment.
Immunotherapy by intravesicular delivery of Bacillus Calmette–Guérin (BCG) is also used to treat and prevent the recurrence of superficial tumors. BCG is a vaccine against tuberculosis that is prepared from attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans. BCG immunotherapy is effective in up to 2/3 of the cases at this stage, and in randomized trials has been shown to be superior to standard chemotherapy. The mechanism by which BCG prevents recurrence is unknown, but the presence of bacteria in the bladder may trigger a localized immune reaction which clears residual cancer cells.
Patients whose tumors recurred after treatment with BCG are more difficult to treat. Many physicians recommend cystectomy for these patients. This recommendation is in accordance with the official guidelines of the European Association of Urologists (EAU) and the American Urological Association (AUA) However, many patients refuse to undergo this life changing operation, and prefer to try novel conservative treatment options before opting to this last radical resort. Device assisted chemotherapy is one such group of novel technologies used to treat superficial bladder cancer. These technologies use different mechanisms to facilitate the absorption and action of a chemotherapy drug instilled directly into the bladder. Another technology - electromotive drug administration (EMDA) – uses an electric current to enhance drug absorption after surgical removal of the tumor. Another technology, thermotherapy, uses radio-frequency energy to directly heat the bladder wall, which together with chemotherapy shows a synergistic effect, enhancing each other's capacity to kill tumor cells. This technology was studied by different investigators.
Palliative care is medical care which focuses on treatment of symptoms of serious illness, like cancer, and improving quality of life. One of the goals of treatment in palliative care is symptom control rather than a cure of the underlying cancer. Pain is common in metastatic prostate cancer, and cancer pain related to bone metastases can be treated with bisphosphonates, medications such as opioids, and palliative radiation therapy to known metastases. Spinal cord compression can occur with metastases to the spine and can be treated with steroids, surgery, or radiation therapy. Other symptoms that can be addressed through palliative care include fatigue, delirium, lymphedema in the scrotum or penis, nausea, vomiting, and weight loss.
In order to address the problem of micrometastatic disease which in itself has implications on longtime survival, new treatment options are dearly needed. Micrometastatic dissemination is often not treatable with only major surgery and the concept of neoadjuvant chemotherapy has evolved. In this patients first receive chemotherapy in 3 or 4 cycles, and after that proceed to major surgery. In a number of meta-analyses of randomised prospective trials worldwide, the results have shown survival benefits between 5–8% with this therapy, in a follow up time of 5 years.
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.
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.
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.
The goals of the treatment for bone metastases include pain control, prevention and treatment of fractures, maintenance of patient function, and local tumor control. Treatment options are determined by multiple factors, including performance status, life expectancy, impact on quality of life, and overall status of clinical disease.
Pain management
The World Health Organization's pain ladder was designed for the management of cancer-associated pain, and mainly involves various strength of opioids. Mild pain or breakthrough pain may be treated with nonsteroidal anti-inflammatory drugs.
Other treatments include bisphosphonates, corticosteroids, radiotherapy, and radionucleotides.
Percutaneous osteoplasty involves the use of bone cement to reduce pain and improve mobility. In palliative therapy, the main options are external radiation and radiopharmaceuticals. High-intensity focused ultrasound (HIFU) has CE approval for palliative care for bone metastasis, though treatments are still in investigatory phases as more information is needed to study effectiveness in order to obtain full approval in countries such as the USA.
Thermal ablation techniques are increasingly being used in the palliative treatment of painful metastatic bone disease. Although the majority of patients experience complete or partial relief of pain following external radiation therapy, the effect is not immediate and has been shown in some studies to be transient in more than half of patients. For patients who are not eligible or do not respond to traditional therapies ( i.e. radiation therapy, chemotherapy, palliative surgery, bisphosphonates or analgesic medications), thermal ablation techniques have been explored as alternatives for pain reduction. Several multi-center clinical trials studying the efficacy of radiofrequency ablation in the treatment of moderate to severe pain in patients with metastatic bone disease have shown significant decreases in patient reported pain after treatment. These studies are limited, however, to patients with one or two metastatic sites; pain from multiple tumors can be difficult to localize for directed therapy. More recently, cryoablation has also been explored as a potentially effective alternative as the area of destruction created by this technique can be monitored more effectively by CT than radiofrequency ablation, a potential advantage when treating tumors adjacent to critical structures.
Monthly injections of radium-223 chloride (as Xofigo, formerly called Alpharadin) have
been approved by the FDA in May 2013 for castration-resistant prostate cancer (CRPC) with bone metastases.
A Cochrane review of calcitonin for the treatment of metastatic bone pain indicated no benefit in reduction of bone pain, complications, or quality of life.
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.
Treatment options vary and depend on the type and stage of cancer. Common treatments include surgery, chemotherapy, radiation therapy, amputation, and immunotherapy. A combination of therapies may be used. Knowledge and treatment of cancer have increased significantly in the past three decades. Survival rates have also increased due to the increase prevalence of canine cancer treatment centers and breakthroughs in targeted drug development. Canine cancer treatment has become an accepted clinical practice and access to treatment for owners has widely expanded recently. Cancer-targeting drugs most commonly function to inhibit excessive cell proliferation by attacking the replicating cells. However, there is still a prevalent pharmacy gap in veterinary oncology.
There is one canine tumor vaccine approved by the USDA, for preventing canine melanoma. The Oncept vaccine activates T-cell responses and antibodies against tumor-specific tyrosinase proteins. There is limited information about canine tumor antigens, which is the reason for the lack of tumor-specific vaccines and immunotherapy treatment plans for dogs.
Success of treatment depends on the form and extent of the cancer and the aggressiveness of the therapy. Early detection offers the best chance for successful treatment. The heterogeneity of tumors makes drug development increasingly complex, especially as new causes are discovered. No cure for cancer in canines exist.
Some dog owners opt for no treatment of the cancer at all, in which case palliative care, including pain relief, may be offered. Regardless of how treatment proceeds following a diagnosis, the quality of life of the pet is an important consideration. In cases where the cancer is not curable, there are still many things which can be done to alleviate the dog's pain. Good nutrition and care from the dog's owner can greatly enhance quality of life.
HGPIN in isolation does not require treatment. In prostate biopsies it is not predictive of prostate cancer in one year if the prostate was well-sampled, i.e. if there were 8 or more cores.
The exact timing of repeat biopsies remains an area of controversy, as the time required for, and probability of HGPIN transformations to prostate cancer are not well understood.
The 5α-reductase inhibitors finasteride and dutasteride may also be used in men with BPH. These medications inhibit the 5α-reductase enzyme, which, in turn, inhibits production of DHT, a hormone responsible for enlarging the prostate. Effects may take longer to appear than alpha blockers, but they persist for many years. When used together with alpha blockers, no benefit was reported in short-term trials, but in a longer term study (3–4 years) there was a greater reduction in BPH progression to acute urinary retention and surgery than with either agent alone, especially in patients were more severe symptoms and larger prostates. Other trials have confirmed reductions in symptoms, within 6 months in one trial, an effect that was maintained after withdrawal of the alpha blocker. Side effects include decreased libido and ejaculatory or erectile dysfunction. The 5α-reductase inhibitors are contraindicated in pregnant women because of their teratogenicity due to interference with fetal testosterone metabolism, and as a precaution, pregnant women should not handle crushed or broken tablets.
Selective α-blockers are the most common choice for initial therapy. They include alfuzosin, doxazosin, silodosin, tamsulosin, and terazosin. They have a small to moderate benefit. All five are equally effective but have slightly different side effect profiles. Alpha blockers relax smooth muscle in the prostate and the bladder neck, thus decreasing the blockage of urine flow. Common side effects of alpha blockers include orthostatic hypotension (a head rush or dizzy spell when standing up or stretching), ejaculation changes, erectile dysfunction, headaches, nasal congestion, and weakness.
Tamsulosin and silodosin are selective α1 receptor blockers that preferentially bind to the α1A receptor in the prostate instead of the α1B receptor in the blood vessels. Less-selective α1 receptor blockers such as terazosin and doxazosin may lower blood pressure. The older, less selective α1-adrenergic blocker prazosin is not a first line choice for either high blood pressure or prostatic hyperplasia; it is a choice for patients who present with both problems at the same time. The older, broadly non-selective alpha blocker medications such as phenoxybenzamine are not recommended for control of BPH. Non-selective alpha blockers such as terazosin and doxazosin may also require slow dose adjustments as they can lower blood pressure and cause syncope (fainting) if the response to the medication is too strong.
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.
Prognosis can range considerably for patients, depending where on the scale they have been staged. Generally speaking, the earlier the cancer is diagnosed, the better the prognosis. The overall 5-year survival rate for all stages of penile cancer is about 50%.
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.
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").
Tamoxifen, a selective estrogen receptor modulator (SERM) with antiestrogenic actions in breast tissue and estrogenic actions in bone, has been found to be highly effective in preventing and reversing bicalutamide-induced gynecomastia in men. Moreover, in contrast to analogues (which also alleviate bicalutamide-induced gynecomastia), tamoxifen poses minimal risk of accelerated bone loss and osteoporosis. For reasons that are unclear, anastrozole, an aromatase inhibitor (or an inhibitor of estrogen biosynthesis), has been found to be much less effective in comparison to tamoxifen for treating bicalutamide-induced gynecomastia. A systematic review of -induced gynecomastia and breast tenderness concluded that tamoxifen (10–20 mg/day) and radiotherapy could effectively manage the side effect without relevant adverse effects, though with tamoxifen showing superior effectiveness. Surgical breast reduction may also be employed to correct bicalutamide-induced gynecomastia.
Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. Survival rates are lower in cases with visceral metastatic disease, ranging from 6 to 9 months. Survival rates are higher when the cancer is more limited to lymph nodes, pleura, or peritoneal metastasis, which ranges from 14 to 16 months. Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.
Combination of bicalutamide with medical (i.e., a analogue) or surgical castration modifies the side effect profile of bicalutamide. Some of its side effects, including breast pain/tenderness and gynecomastia, are far less likely to occur when the drug is combined with a analogue, while certain other side effects, including hot flashes, depression, fatigue, and sexual dysfunction, occur much more frequently in combination with a analogue. It is thought that this is due to the suppression of estrogen levels (in addition to androgen levels) by analogues, as estrogen may compensate for various negative central effects of androgen deprivation. If bicalutamide is combined with a analogue or surgical castration, the elevation of androgen and estrogen levels in men caused by bicalutamide will be prevented and the side effects of excessive estrogens, namely gynecomastia, will be reduced. However, due to the loss of estrogen, bone loss will accelerate and the risk of osteoporosis developing with long-term therapy will increase.
Although metastasis is widely accepted to be the result of the tumor cells migration, there is a hypothesis saying that some metastases are the result of inflammatory processes by abnormal immune cells. The existence of metastatic cancers in the absence of primary tumors also suggests that metastasis is not always caused by malignant cells that leave primary tumors.
In urologic pathology, high-grade prostatic intraepithelial neoplasia, abbreviated HGPIN, is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer).
It may be referred to simply as prostatic intraepithelial neoplasia (abbreviated as PIN). It is considered to be a pre-malignancy, or carcinoma in situ, of the prostatic glands.
Over the past two decades, CT guided radiofrequency ablation has emerged as a less invasive alternative to surgical resection in the care of benign bone tumors, most notably osteoid osteomas. In this technique, which can be performed under conscious sedation, a RF probe is introduced into the tumor nidus through a cannulated needle under CT guidance and heat is applied locally to destroy tumor cells. Since the procedure was first introduced for the treatment of osteoid osteomas in the early 1990s, it has been shown in numerous studies to be less invasive and expensive, to result in less bone destruction and to have equivalent safety and efficacy to surgical techniques, with 66 to 96% of patients reporting freedom from symptoms. While initial success rates with RFA are high, symptom recurrence after RFA treatment has been reported, with some studies demonstrating a recurrence rate similar to that of surgical treatment.
Thermal ablation techniques are also increasingly being used in the palliative treatment of painful metastatic bone disease. Currently, external beam radiation therapy is the standard of care for patients with localized bone pain due to metastatic disease. Although the majority of patients experience complete or partial relief of pain following radiation therapy, the effect is not immediate and has been shown in some studies to be transient in more than half of patients. For patients who are not eligible or do not respond to traditional therapies ( i.e. radiation therapy, chemotherapy, palliative surgery, bisphosphonates or analgesic medications), thermal ablation techniques have been explored as alternatives for pain reduction. Several multi-center clinical trials studying the efficacy of RFA in the treatment of moderate to severe pain in patients with metastatic bone disease have shown significant decreases in patient reported pain after treatment. These studies are limited however to patients with one or two metastatic sites; pain from multiple tumors can be difficult to localize for directed therapy. More recently, cryoablation has also been explored as a potentially effective alternative as the area of destruction created by this technique can be monitored more effectively by CT than RFA, a potential advantage when treating tumors adjacent to critical structures.
Ocular oncology is the branch of medicine dealing with tumors relating to the eye and its adnexa.
Ocular oncology takes into consideration that the primary requirement for patients is preservation of life by removal of the tumor, along with best efforts directed at preservation of useful vision, followed by cosmetic appearance. The treatment of ocular tumors is generally a multi-specialty effort, requiring coordination between the ophthalmologist, medical oncologist, radiation specialist, head & neck surgeon/ENT surgeon, pediatrician/internal medicine/hospitalist and a multidisciplinary team of support staff and nurses.
Identifying and treatment the underlying malignancy constitutes an uptime approach. Topical 5-fluorouracil may occasionally be help, as may oral retinoids, topical steroids, vitamin A acid, urea, salicylic acid, podophyllotoxin, and cryodestruction employing liquid.