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
Chemotherapeutic options include:
- Cyclophosphamide plus methotrexate plus fluorouracil (CMF).
- Cyclophosphamide plus doxorubicin plus fluorouracil (CAF).
- Trastuzumab (monoclonal antibody therapy).
Hormonal options include:
- Orchiectomy.
- Gonadotropin hormone releasing hormone agonist (GNRH agonist) with or without total androgen blockage (anti-androgen).
- Tamoxifen for estrogen receptor–positive patients.
- Progesterone.
- Aromatase inhibitors.
In breast cancer survivors, it is recommended to first consider non-hormonal options for menopausal effects, such as bisphosphonates or selective estrogen receptor modulators (SERMs) for osteoporosis, and vaginal estrogen for local symptoms. Observational studies of systemic hormone replacement therapy after breast cancer are generally reassuring. If hormone replacement is necessary after breast cancer, estrogen-only therapy or estrogen therapy with an intrauterine device with progestogen may be safer options than combined systemic therapy.
In breast cancer survivors, non-hormonal birth control methods should be used as first-line options. Progestogen-based methods such as depot medroxyprogesterone acetate, IUD with progestogen or progestogen only pills have a poorly investigated but possible increased risk of cancer recurrence, but may be used if positive effects outweigh this possible risk.
Treatment largely follows patterns that have been set for the management of postmenopausal breast cancer. The initial treatment is surgical and consists of a modified radical mastectomy with axillary dissection or lumpectomy and radiation therapy with similar treatment results as in females. Also, mastectomy with sentinel lymph node biopsy is a treatment option. In males with node-negative tumors, adjuvant therapy is applied under the same considerations as in females with node-negative breast cancer. Similarly, with node-positive tumors, males increase survival using the same adjuvants as affected females, namely both chemotherapy plus tamoxifen and other hormonal therapy. There are no controlled studies in males comparing adjuvant options. In the vast majority of males with breast cancer hormone receptor studies are positive, and those situations are typically treated with hormonal therapy.
Locally recurrent disease is treated with surgical excision or radiation therapy combined with chemotherapy. Distant metastases are treated with hormonal therapy, chemotherapy, or a combination of both. Bones can be affected either by metastasis or weakened from hormonal therapy; bisphosphonates and calcitonin may be used to counterbalance this process and strengthen bones.
There are different opinions on the best treatment of DCIS. Surgical removal, with or without additional radiation therapy or tamoxifen, is the recommended treatment for DCIS by the National Cancer Institute. Surgery may be either a breast-conserving lumpectomy or a mastectomy (complete or partial removal of the affected breast). If a lumpectomy is used it is often combined with radiation therapy. Tamoxifen may be used as hormonal therapy if the cells show estrogen receptor positivity. Chemotherapy is not needed for DCIS since the disease is noninvasive.
While surgery reduces the risk of subsequent cancer, many people never develop cancer even without treatment and there associated side effects. There is no evidence comparing surgery with watchful waiting and some feel watchful waiting may be a reasonable option in certain cases.
Treatment of metastatic breast cancer is currently an active area of research. Several medications are in development or in phase I/II trials. Typically new medications and treatments are first tested in metastatic cancer before trials in primary cancer are attempted.
Another area of research is finding combination treatments which provide higher efficacy with reduced toxicity and side effects.
Experimental medications:
- sorafenib a combined Tyrosine protein kinases inhibitor.
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.
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.
Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a standardized regimen. The term encompasses a variety of drugs, which are divided into broad categories such as alkylating agents and antimetabolites. Traditional chemotherapeutic agents act by killing cells that divide rapidly, a critical property of most cancer cells.
Targeted therapy is a form of chemotherapy that targets specific molecular differences between cancer and normal cells. The first targeted therapies blocked the estrogen receptor molecule, inhibiting the growth of breast cancer. Another common example is the class of Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML). Currently, targeted therapies exist for breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.
The efficacy of chemotherapy depends on the type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in cancer types including breast cancer, colorectal cancer, pancreatic cancer, osteogenic sarcoma, testicular cancer, ovarian cancer and certain lung cancers. Chemotherapy is curative for some cancers, such as some leukemias, ineffective in some brain tumors, and needless in others, such as most non-melanoma skin cancers. The effectiveness of chemotherapy is often limited by its toxicity to other tissues in the body. Even when chemotherapy does not provide a permanent cure, it may be useful to reduce symptoms such as pain or to reduce the size of an inoperable tumor in the hope that surgery will become possible in the future.
Some patients with metastatic breast cancer opt to try alternative therapies such as vitamin therapy, homeopathic treatments, a macrobiotic diet, chiropractic or acupuncture. There is no evidence that any of these therapies are effective; they may be harmful, either because patients pass up effective conventional therapies such as chemotherapy or anti-estrogen therapy in favor of alternative treatments, or because the treatments themselves are harmful (as in the case of apricot-pit therapy—which exposes the patient to cyanide—or in chiropractic, which can be dangerous to patients with cancer metastatic to the spinal bones or spinal cord. A macrobiotic diet is neither effective nor safe as it could hypothetically induce weight loss due to severe dietary restriction. There is limited evidence that acupuncture might relive pain in cancer patients, but data so far is insufficient to recommend its use outside of clinical trials.
There is free peer support and an online platform to interact with others going through various therapies, including Abraxane.
Use of radiation therapy after lumpectomy provides equivalent survival rates to mastectomy, although there is a slightly higher risk of recurrent disease in the same breast in the form of further DCIS or invasive breast cancer. Systematic reviews (including a Cochrane review) indicate that the addition of radiation therapy to lumpectomy reduces recurrence of DCIS or later onset of invasive breast cancer in comparison with breast-conserving surgery alone, without affecting mortality. The Cochrane review did not find any evidence that the radiation therapy had any long-term toxic effects. While the authors caution that longer follow-up will be required before a definitive conclusion can be reached regarding long-term toxicity, they point out that ongoing technical improvements should further restrict radiation exposure in healthy tissues. They do recommend that comprehensive information on potential side effects is given to women who receive this treatment. The addition of radiation therapy to lumpectomy appears to reduce the risk of local recurrence to approximately 12%, of which approximately half will be DCIS and half will be invasive breast cancer; the risk of recurrence is 1% for women undergoing mastectomy.
Standard treatment is surgery with adjuvant chemotherapy and radiotherapy. As a variation, neoadjuvant chemotherapy is very frequently used for triple-negative breast cancers. This allows for a higher rate of breast-conserving surgeries and by evaluating the response to the chemotherapy gives important clues about the individual responsiveness of the particular cancer to chemotherapy.
In addition to chemotherapy, an additive called Didox can be added to aid in the reduction of drug resistance and further treatment efforts. Didox is used to inhibit ribonucleotide reductase M2 (RRM2) which contributes to the cells resistance of the chemotherapy treatment resulting in a large number of relapse (Wilson 2016). RRM2 is upregulated within these specific Triple Negative cancer cells leading to a higher rate of drug resistance and inability to slow or stop the tumor progression which leads to more aggressive forms of triple negative breast cancer that are often fatal (Wilson 2016).
TNBCs are generally very susceptible to chemotherapy. In some cases, however, early complete response does not correlate with overall survival. This makes it particularly complicated to find the optimal chemotherapy. Adding a taxane to the chemotherapy appears to improve outcome substantially.
"BRCA1"-related triple-negative breast cancer appear to be particularly susceptible to chemotherapy including platinum-based agents and taxanes.
Although mutations in single genes were not individually predictive, TNBC tumors bearing mutations in genes involved in the androgen receptor (AR) and FOXA1 pathways were much more sensitive to chemotherapy. Mutations in the AR/FOXA1 pathway provide a novel marker for identifying chemosensitive TNBC patients who may benefit from current standard-of-care chemotherapy regimens. Mutations that lowered the levels of functional BRCA1 or BRCA2 RNA were associated with significantly better survival outcomes. This BRCA deficience signature define a new, highly chemosensitive subtype of TNBC. BRCA-deficient TNBC tumors have a higher rate of clonal mutation burden, defined as more clonal tumors with a higher number of mutations per clone, and are also associated with a higher level of immune activation, which may explain their greater chemosensitivity.
The treatment of cervical cancer varies worldwide, largely due to access to surgeons skilled in radical pelvic surgery, and the emergence of fertility-sparing therapy in developed nations. Because cervical cancers are radiosensitive, radiation may be used in all stages where surgical options do not exist. Surgical intervention may have better outcomes than radiological approaches. In addition, chemotherapy can be used to treat cervical cancer, and has been found to be more effective than radiation alone.
Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina). For stage IA2, the lymph nodes are removed, as well. Alternatives include local surgical procedures such as a loop electrical excision procedure or cone biopsy.
If a cone biopsy does not produce clear margins (findings on biopsy showing that the tumor is surrounded by cancer free tissue, suggesting all of the tumor is removed), one more possible treatment option for women who want to preserve their fertility is a trachelectomy. This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care, as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the woman is under general anesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the woman has given prior consent. Due to the possible risk of cancer spread to the lymph nodes in stage 1b cancers and some stage 1a cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.
A radical trachelectomy can be performed abdominally or vaginally and opinions are conflicting as to which is better. A radical abdominal trachelectomy with lymphadenectomy usually only requires a two- to three-day hospital stay, and most women recover very quickly (about six weeks). Complications are uncommon, although women who are able to conceive after surgery are susceptible to preterm labor and possible late miscarriage. A wait of at least one year is generally recommended before attempting to become pregnant after surgery. Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy. Yet, women are recommended to practice vigilant prevention and follow-up care including Pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.
Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Women treated with surgery who have high-risk features found on pathologic examination are given radiation therapy with or without chemotherapy to reduce the risk of relapse.
Larger early-stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy. When cisplatin is present, it is thought to be the most active single agent in periodic diseases. Such addition of platinum-based chemotherapy to chemoradiation seems not only to improve survival but also reduces risk of recurrence in women with early stage cervical cancer (IA2-IIA).
Advanced-stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On June 15, 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin, for women with late-stage (IVB) cervical cancer treatment. Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects.
For surgery to be curative, the entire cancer must be removed with no cancer found at the margins of the removed tissue on examination under a microscope. This procedure is known as exenteration.
Angiogenesis and EGFR (HER-1) inhibitors are frequently tested in experimental settings and have shown efficacy. Treatment modalities are not sufficiently established for normal use, and it is unclear in which stage they are best used and which patients would profit.
By 2009 A number of new strategies for TNBC were being tested in clinical trials, including the PARP inhibitor BSI 201, NK012.
A novel antibody-drug conjugate known as Glembatumumab vedotin (CDX-011), which targets the protein GPNMB, has also shown encouraging clinical trial results in 2009.
PARP inhibitors had shown some promise in early trials but failed in some later trials.
Nov 2013: An accelerated approval Phase II clinical trial (METRIC) investigating glembatumumab vedotin versus capecitabine has begun, expected to enroll 300 patients with GPNMB-expressing metastatic TNBC.
Three early stage trials reported TNBC results in June 2016, for IMMU-132, Vantictumab, and atezolizumab in combination with the chemotherapy nab-paclitaxel.
Treatment methods include surgery, chemotherapy, radiation therapy and medication.
Since Krukenberg tumors are secondary (metastatic), management might logically be driven by identifying and treating the primary cancer. The optimal treatment of Krukenberg tumors is unclear. The role of surgical resection has not been adequately addressed but if metastasis is limited to the ovaries, surgery may improve survival. The role of chemotherapy and/or radiotherapy is uncertain but may sometimes be beneficial.
Paget's disease of the breast is a type of cancer of the breast. Treatment usually involves a lumpectomy or mastectomy to surgically remove the tumour. Chemotherapy and/or radiotherapy may be necessary, but the specific treatment often depends on the characteristics of the underlying breast cancer.
Invasive cancer or extensive ductal carcinoma "in situ" is primarily treated with modified radical mastectomies. The procedure consists in the removal of the breast, the lining over the chest muscles and a part of the lymph nodes from under the arm. In cases of noninvasive cancers, simple mastectomies are performed in which only the breast with the lining over the chest muscles is removed.
Patients suffering from cancer that has not spread beyond the nipple and the surrounding area are often treated with breast-conserving surgery or lumpectomy. They usually undergo radiation therapy after the actual procedure to prevent recurrence. A breast-conserving surgery consists in the removal of the nipple, areola and the part of the breast that is affected by cancer.
In most cases, adjuvant treatment is part of the treatment schema. This type of treatment is normally given to patients with cancer to prevent a potential recurrence of the disease. Whether adjuvant therapy is needed depends upon the type of cancer and whether the cancer cells have spread to the lymph nodes. In Paget's disease, the most common type of adjuvant therapy is radiation following breast-conservative surgery.
Adjuvant therapy may also consist of anticancer drugs or hormone therapies. Hormonal therapy reduces the production of hormones within the body, or prevents the hormones from stimulating the cancer cells to grow, and it is commonly used in cases of invasive cancer by means of drugs such as tamoxifen and anastrozole.
LCIS may be treated with close clinical follow-up and mammographic screening, tamoxifen or related hormone controlling drugs to reduce the risk of developing cancer, or bilateral prophylactic mastectomy. Some surgeons consider bilateral prophylactic mastectomy to be overly aggressive treatment except for certain high-risk cases.
Vitamin A is associated with a lower risk as are vitamin B12, vitamin C, vitamin E, and beta-Carotene.
In a recent study, about 60% of USCs were found to overexpress the protein HER2/neu—the same one that is overexpressed in some breast cancers. The monoclonal antibody trastuzumab (Herceptin) is currently being tested as a therapy for this subset of USCs.
The antibody trastuzumab (Herceptin), which is used to treat breast cancers that overexpress the HER2/neu protein, has been tried with some success in a phase II trial in women with UPSCs that overexpress HER2/neu.
Several drugs that target molecular pathways in lung cancer are available, especially for the treatment of advanced disease. Erlotinib, gefitinib and afatinib inhibit tyrosine kinase at the epidermal growth factor receptor. Denosumab is a monoclonal antibody directed against receptor activator of nuclear factor kappa-B ligand. It may be useful in the treatment of bone metastases.
The chemotherapy regimen depends on the tumor type. Small-cell lung carcinoma (SCLC), even relatively early stage disease, is treated primarily with chemotherapy and radiation. In SCLC, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used. In advanced non-small cell lung carcinoma (NSCLC), chemotherapy improves survival and is used as first-line treatment, provided the person is well enough for the treatment. Typically, two drugs are used, of which one is often platinum-based (either cisplatin or carboplatin). Other commonly used drugs are gemcitabine, paclitaxel, docetaxel, pemetrexed, etoposide or vinorelbine. Platinum-based drugs and combinations that include platinum therapy may lead to a higher risk of serious adverse effects in people over 70 years old.
Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In NSCLC, samples are taken of nearby lymph nodes during surgery to assist staging. If stage II or III disease is confirmed, adjuvant chemotherapy (including or not including postoperative radiotherapy) improves survival by 4% at five years. The combination of vinorelbine and cisplatin is more effective than older regimens. Adjuvant chemotherapy for people with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit. Chemotherapy before surgery in NSCLC that can be removed surgically may improve outcomes.
Chemotherapy may be combined with palliative care in the treatment of the NSCLC. In advanced cases, appropriate chemotherapy improves average survival over supportive care alone, as well as improving quality of life. With adequate physical fitness maintaining chemotherapy during lung cancer palliation offers 1.5 to 3 months of prolongation of survival, symptomatic relief, and an improvement in quality of life, with better results seen with modern agents. The NSCLC Meta-Analyses Collaborative Group recommends if the recipient wants and can tolerate treatment, then chemotherapy should be considered in advanced NSCLC.
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 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.
Primary treatment for this cancer, regardless of body site, is surgical removal with clean margins. This surgery can prove challenging in the head and neck region due to this tumour's tendency to spread along nerve tracts. Adjuvant or palliative radiotherapy is commonly given following surgery. For advanced major and minor salivary gland tumors that are inoperable, recurrent, or exhibit gross residual disease after surgery, fast neutron therapy is widely regarded as the most effective form of treatment.
Chemotherapy is used for metastatic disease. Chemotherapy is considered on a case by case basis, as there is limited trial data on the positive effects of chemotherapy. Clinical studies are ongoing, however.