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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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Cancer screening uses medical tests to detect disease in large groups of people who have no symptoms. For individuals with high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person options to respond to it in a way that prolongs life. This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%). High risk people are those age 55–74 who have smoked equivalent amount of a pack of cigarettes daily for 30 years including time within the past 15 years.
CT screening is associated with a high rate of falsely positive tests which may result in unneeded treatment. For each true positive scan there are about 19 falsely positives scans. Other concerns include radiation exposure and the cost of testing along with follow up. Research has not found two other available tests—sputum cytology or chest radiograph (CXR) screening tests—to have any benefit.
The United States Preventive Services Task Force (USPSTF) recommends yearly screening using low-dose computed tomography in those who have a total smoking history of 30 pack-years and are between 55 and 80 years old until a person has not been smoking for more than 15 years. Screening should not be done in those with other health problems that would make treatment of lung cancer if found not an option. The English National Health Service was in 2014 re-examining the evidence for screening.
Antibodies may be used to determine the expression of protein markers on the surface of cancer cells. Often the expression of these antigens is similar to the tissue that the cancer grew from, so immunohistochemical testing sometimes helps to identify the source of the cancer. Individual tests often do not provide definitive answers, but sometimes patterns may be observed, suggesting a particular site of origin (e.g. lung, colon, etc.). Immunohistochemical testing suggests a single source of cancer origin in about one in four cases of CUP. However, there is a lack of definitive research data showing that treatment guided by information from immunohistochemical testing improves outcomes or long-term prognosis.
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.
While cancer is generally considered a disease of old age, children can also develop cancer. In contrast to adults, carcinomas are exceptionally rare in children..
The two biggest risk factors for ovarian carcinoma are age and family history.
Carcinomas can be definitively diagnosed through biopsy, including fine-needle aspiration (FNA), core biopsy, or subtotal removal of single node. Microscopic examination by a pathologist is then necessary to identify molecular, cellular, or tissue architectural characteristics of epithelial cells.
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.
The presence of HPV within the tumour has been realised to be an important factor for predicting survival since the 1990s. Tumor HPV status is strongly associated with positive therapeutic response and survival compared with HPV-negative cancer, independent of the treatment modality chosen and even after adjustment for stage. While HPV+OPC patients have a number of favourable demographic features compared to HPV-OPC patients, such differences account for only about ten per cent of the survival difference seen between the two groups. Response rates of over 80% are reported in HPV+ cancer and three-year progression free survival has been reported as 75–82% and 45–57%, respectively, for HPV+ and HPV- cancer, and improving over increasing time. It is likely that HPV+OPC is inherently less maligant than HPV-OPC, since patients treated by surgery alone have a better survival after adjustment for stage. In one study, less than 50% of patients with HPV-OPC were still alive after five years, compared to more than 70% with HPV+OPC and an equivalent stage and disease burden.
In RTOG clinical trial 0129, in which all patients with advanced disease received radiation and chemotherapy, a retrospective analysis (recursive-partitioning analysis, or RPA) at three years identified three risk groups for survival (low, intermediate, and high) based on HPV status, smoking, T stage and N stage ("see" Ang et al., Fig. 2). HPV status was the major determinant of survival, followed by smoking history and stage. 64% were HPV+ and all were in the low and intermediate risk group, with all non-smoking HPV+ patients in the low risk group. 82% of the HPV+ patients were alive at three years compared to 57% of the HPV- patients, a 58% reduction in the risk of death. Locoregional failure is also lower in HPV+, being 14% compared to 35% for HPV-. HPV positivity confers a 50–60% lower risk of disease progression and death, but the use of tobacco is an independently negative prognostic factor. A pooled analysis of HPV+OPC and HPV-OPC patients with disease progression in RTOG trials 0129 and 0522 showed that although less HPV+OPC experienced disease progression (23 v. 40%), the median time to disease progression following treatment was similar (8 months). The majority (65%) of recurrences in both groups occurred within the first year after treatment and were locoregional. HPV+ did not reduce the rate of metastases (about 45% of patients experiencing progression), which are predominantly to the lungs (70%), although some studies have reported a lower rate. with 3-year distant recurrence rates of about 10% for patients treated with primary radiation or chemoradiation. Even if recurrence or metastases occur, HPV positivity still confers an advantage.
By contrast tobacco usage is an independently negative prognostic factor, with decreased response to therapy, increased disease recurrence rates and decreased survival. The negative effects of smoking, increases with amount smoked, particularly
if greater than 10 pack-years. For patients such as those treated on RTOG 0129 with primary chemoradiation, detailed nomograms have been derived from that dataset combined with RTOG 0522, enabling prediction of outcome based on a large number of variables. For instance, a 71 year old married non-smoking high school graduate with a performance status (PS) of 0, and no weight loss or anaemia and a T3N1 HPV+OPC would expect to have a progression-free survival of 92% at 2 years and 88% at 5 years. A 60 year old unmarried nonsmoking high school graduate with a PS of 1, weight loss and anaemia and a T4N2 HPV+OPC would expect to have a survival of 70% at two years and 48% at five years. Less detailed information is available for those treated primarily with surgery, for whom less patients are available, as well as low rates of recurrence (7–10%), but features that have traditionally been useful in predicting prognosis in other head and neck cancers, appear to be less useful in HPV+OPC. These patients are frequently stratified into three risk groups:
- Low risk: No adverse pathological features
- Intermediate risk: T3–T4 primary, perineural or lymphovascular invasion, N2 (AJCC 7)
- High risk: Positive margins, ECE
HPV+OPC patients are less likely to develop other cancers, compared to other head and neck cancer patients. A possible explanation for the favourable impact of HPV+ is "the lower probability of occurrence of 11q13 gene amplification, which is considered to be a factor underlying faster and more frequent recurrence of the disease" Presence of TP53 mutations, a marker for HPV- OPC, is associated with worse prognosis. High grade of p16 staining is thought to be better than HPV PCR analysis in predicting radiotherapy response.
In some situations HPV+OPC may present with cervical lymph nodes but no evident disease of a primary tumour (T0 N1-3) and is therefore classed as Squamous Cell Carcinoma of Unknown Primary Origin. The lack of any such evidence of a primary tumour occurs in 2-4% of patients presenting with metastatic cancer in the cervical nodes. The incidence of HPV positivity is increasing at a similar rate to that seen in OPC. In such situations, resection of the lingual and palatine tonsils, together with neck dissection may be diagnostic and constitute sufficient intervention, since recurrence rates are low.
Diagnosis is made by the doctor on the basis of a medical history, physical examination, and special investigations which may include a chest x-ray, CT or MRI scans, and tissue biopsy. The examination of the larynx requires some expertise, which may require specialist referral.
The physical exam includes a systematic examination of the whole patient to assess general health and to look for signs of associated conditions and metastatic disease. The neck and supraclavicular fossa are palpated to feel for cervical adenopathy, other masses, and laryngeal crepitus. The oral cavity and oropharynx are examined under direct vision. The larynx may be examined by indirect laryngoscopy using a small angled mirror with a long handle (akin to a dentist's mirror) and a strong light. Indirect laryngoscopy can be highly effective, but requires skill and practice for consistent results. For this reason, many specialist clinics now use fibre-optic nasal endoscopy where a thin and flexible endoscope, inserted through the nostril, is used to clearly visualise the entire pharynx and larynx. Nasal endoscopy is a quick and easy procedure performed in clinic. Local anaesthetic spray may be used.
If there is a suspicion of cancer, biopsy is performed, usually under general anaesthetic. This provides histological proof of cancer type and grade. If the lesion appears to be small and well localised, the surgeon may undertake excision biopsy, where an attempt is made to completely remove the tumour at the time of first biopsy. In this situation, the pathologist will not only be able to confirm the diagnosis, but can also comment on the completeness of excision, i.e., whether the tumour has been completely removed. A full endoscopic examination of the larynx, trachea, and esophagus is often performed at the time of biopsy.
For small glottic tumours further imaging may be unnecessary. In most cases, tumour staging is completed by scanning the head and neck region to assess the local extent of the tumour and any pathologically enlarged cervical lymph nodes.
The final management plan will depend on the site, stage (tumour size, nodal spread, distant metastasis), and histological type. The overall health and wishes of the patient must also be taken into account. A prognostic multigene classifier has been shown to be potentially useful for the distinction of laryngeal cancer of low or high risk of recurrence and might influence the treatment choice in future.
The long-term use of supplemental vitamin A, vitamin C, vitamin D or vitamin E does not reduce the risk of lung cancer. Some studies suggest that people who eat diets with a higher proportion of vegetables and fruit tend to have a lower risk, but this may be due to confounding—with the lower risk actually due to the association of a high fruit/vegetables diet with less smoking. Several rigorous studies have not demonstrated a clear association between diet and lung cancer risk, although meta-analysis that accounts for smoking status may show benefit from a healthy diet.
In the detection of bone metastases, skeletal scintigraphy (bone scan) is very sensitive and is recommended as the first imaging study in asymptomatic individuals with suspected breast-cancer metastases. X-ray radiography is recommended if there is abnormal radionuclide uptake from the bone scan and in assessing the risk of pathological fractures, and is recommended as the initial imaging study in patients with bone pain. MRI or the combination PET-CT may be considered for cases of abnormal radionuclide uptake on bone scan, when radiography does not give an acceptably clear result.
Some drugs are particularly effective against cancers which fit certain requirements. For example, Herceptin is very effective in patients who are Her2 positive, but much less effective in patients who are Her2 negative. Once the primary tumor is removed, biopsy of the current state of the cancer through traditional tissue typing is not possible anymore. Often tissue sections of the primary tumor, removed years prior, are used to do the typing. Further characterisation of CTC may help determining the current tumor phenotype. FISH assays has been performed on CTC to as well as determination of IGF-1R, Her2, Bcl-2, [ERG (gene)|ERG], PTEN, AR status using immunofluorescence. Single cell level qPCR can also be performed with the CTCs isolated from blood.
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.
For surface epithelial-stromal tumors, the most common sites of metastasis are the pleural cavity (33%), the liver (26%), and the lungs (3%).
Because this is a rare tumor, not many family physicians or oncologists are familiar with this disease. DSRCT in young patients can be mistaken for other abdominal tumors including rhabdomyosarcoma, neuroblastoma, and mesenteric carcinoid. In older patients DSRCT can resemble lymphoma, peritoneal mesothelioma, and peritoneal carcinomatosis. In males DSRCT may be mistaken for germ cell or testicular cancer while in females DSRCT can be mistaken for Ovarian cancer. DSRCT shares characteristics with other small-round blue cell cancers including Ewing's sarcoma, acute leukemia, small cell mesothelioma, neuroblastoma, primitive neuroectodermal tumor, rhabdomyosarcoma, and Wilms' tumor.
Definitive diagnosis of Merkel cell carcinoma (MCC) requires examination of biopsy tissue. An ideal biopsy specimen is either a punch biopsy or a full-thickness incisional biopsy of the skin including full-thickness dermis and subcutaneous fat. In addition to standard examination under light microscopy, immunohistochemistry (IHC) is also generally required to differentiate MCC from other morphologically similar tumors such as small cell lung cancer, the small cell variant of melanoma, various cutaneous leukemic/lymphoid neoplasms, and Ewing's sarcoma. Similarly, most experts recommend longitudinal imaging of the chest, typically a CT scan, to rule out that the possibility that the skin lesion is a cutaneous metastasis of an underlying small cell carcinoma of the lung.
DSRCT is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center.
There is no standard protocol for the disease; however, recent journals and studies have reported that some patients respond to high-dose (P6 Protocol) chemotherapy, maintenance chemotherapy, debulking operation, cytoreductive surgery, and radiation therapy. Other treatment options include: hematopoietic stem cell transplantation, intensity-modulated radiation Therapy, radiofrequency ablation, stereotactic body radiation therapy, intraperitoneal hyperthermic chemoperfusion, and clinical trials.
Metastasis is a complex and interconnected multi-step process. Each step in the process is a potential target for therapies to prevent or reduce metastasis. Those steps which have a good clinical window are the best targets for therapy. Each event in metastasis is highly regulated and requires a synergistic activation of different ECM proteins, growth factors and so on. Although the occasional patient with metastatic breast cancer benefits from surgical resection of an isolated metastasis and most patients receive radiotherapy (often for palliation alone) during the course of their disease, the treatment of metastatic breast carcinoma typically involves the use of systemic therapy.
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.
All in all, small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low.
In "limited-stage" disease, median survival with treatment is 14–20 months, and about 20% of patients with limited-stage small-cell lung carcinoma live 5 years or longer. Because of its predisposition for early metastasis, the prognosis of SCLC is poor, with only 10% to 15% of patients surviving 3 years.
The prognosis is far more grim in "extensive-stage" small-cell lung carcinoma; with treatment, median survival is 8–13 months; only 1–5% of patients with extensive-stage small-cell lung carcinoma treated with chemotherapy live 5 years or longer.
Giant-cell lung cancers have long been considered to be exceptionally aggressive malignancies that grow very rapidly and have a very poor prognosis.
Many small series have suggested that the prognosis of lung tumors with giant cells is worse than that of most other forms of non-small-cell lung cancer (NSCLC), including squamous cell carcinoma, and spindle cell carcinoma.
The overall five-year survival rate in GCCL varies between studies but is generally considered to be very low. The (US) Armed Forces Institute of Pathology has reported a figure of 10%, and in a study examining over 150,000 lung cancer cases, a figure of 11.8% was given. However, in the latter report the 11.8% figure was based on data that included spindle cell carcinoma, a variant which is generally considered to have a less dismal prognosis than GCCL. Therefore, the likely survival of "pure" GCCL is probably lower than the stated figure.
In the large 1995 database review by Travis and colleagues, giant-cell carcinoma has the third-worst prognosis among 18 histological forms of lung cancer. (Only small-cell carcinoma and large-cell carcinoma had shorter average survival.)
Most GCCL have already grown and invaded locally and/or regionally, and/or have already metastasized distantly, and are inoperable, at the time of diagnosis.
Prostate cancer screening is an attempt to find unsuspected cancers. Initial screens may lead to more invasive follow-up tests such as a biopsy. Options include the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. Such screening is controversial and, in some people, may lead to unnecessary disruption and possibly harmful consequences. Routine screening with either a DRE or PSA is not supported by the evidence as there is no mortality benefit from screening.
The United States Preventive Services Task Force (USPSTF) recommends against the PSA test for prostate cancer screening in healthy men regardless of age. They concluded that the potential benefit of testing does not outweigh the expected harms. The Centers for Disease Control and Prevention shared that conclusion. The American Society of Clinical Oncology and the American College of Physicians discourages screening for those who are expected to live less than ten to fifteen years, while in those with a greater life expectancy a decision should be made by the person in question based on the potential risks and benefits. In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment." American Urological Association (AUA 2013) guidelines call for weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a ten-year period against the known harms associated with diagnostic tests and treatment. The AUA recommends screening decisions in those 55 to 69 be based on shared decision making, and that if screening is performed it should occur no more often than every two years.
In those who are being regularly screened, 5-alpha-reductase inhibitor (finasteride and dutasteride) reduce the overall risk of being diagnosed with prostate cancer; however, there is insufficient data to determine if they have an effect on the risk of death and may increase the chance of more serious cases.
For more general information, see ovarian cancer.
For advanced cancer of this histology, the US National Cancer Institute recommends a method of chemotherapy that combines intravenous (IV) and intraperitoneal (IP) administration. Preferred chemotherapeutic agents include a platinum drug with a taxane.
MCACL has a much more favorable prognosis than most other forms of adenocarcinoma and most other NSCLC's. Cases have been documented of continued growth of these lesions over a period of 10 years without symptoms or metastasis. The overall mortality rate appears to be somewhere in the vicinity of 18% to 27%, depending on the criteria that are used to define this entity.