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Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.
An adjuvant used on its own specifically refers to an agent that improves the effect of a vaccine. used to help primary medications are known as add-ons.
The budding theory of using additional therapies to supplement primary surgery was put into practice by Gianni Bonadonna and his colleagues from the Instituto Tumori in Italy in 1973, where they conducted a randomized trial that demonstrated more favorable survival outcomes that accompanied use of cyclophosphamide methotrexate fluorouracil (CMF) after the initial mastectomy.
In 1976, shortly after Bonadonna's landmark trial, Bernard Fisher at the University of Pittsburgh initiated a similar randomized trial that compared the survival of breast cancer patients treated with radiation after the initial mastectomy to those who only received the surgery. His results, published in 1985, indicated increased disease-free survival for the former group.
Despite the initial pushback from the breast cancer surgeons who believed that their radical mastectomies were sufficient in removing all traces of cancer, the success of Bonadonna's and Fisher's trials brought adjuvant therapy to the mainstream in oncology. Since then, the field of adjuvant therapy has expanded to include a range of adjuvant therapies to include chemotherapy, immunotherapy, hormone therapy, and radiation.
In the context of breast cancer, neoadjuvant chemotherapy administered before surgery can improve survival in patients. If no active cancer cells are present in a tissue extracted from the tumor site after neoadjuvant therapy, physicians classify a case as "pathologic complete response" or "pCR." While response to therapy has been demonstrated to be a strong predictor of outcome, the medical community has still not reached a consensus in regard to the definition of pCR across various breast cancer subtypes. It remains unclear whether pCR can be used as a surrogate end point in breast cancer cases.
Adjuvant systemic therapy and radiotherapy are often given following surgery for multiple types of cancer, including colon cancer, lung cancer, pancreatic cancer, breast cancer, prostate cancer, and some gynaecological cancers. Some forms of cancer fail to benefit from adjuvant therapy, however. Such cancers include renal cell carcinoma, and certain forms of brain cancer.
Hyperthermia therapy or heat therapy is also a kind of adjuvant therapy that is sometimes given in combination with radiotherapy or chemotherapy to boost the effects of these conventional treatments in treating advanced cancers. Heating the tumour area sensitises it making it more responsive to the other therapies used. It is cost-effective and safe, and is seen to have a promising role in cancer treatment.
In the context of melanoma, certain treatments, such as Ipilimumab, result in high grade adverse events, or immune-related adverse events, in 10-15% of patients that parallel the effects of metastatic melanoma itself. Similarly, several common adjuvant therapies are noted for having the potential of causing cardiovascular disease. In such cases, physicians must weigh the cost of recurrence against more immediate consequences and consider factors, like age and relative cardiovascular health of a patient, before prescribing certain types of adjuvant therapy.
One of the most notable side effects of adjuvant therapy is the loss of fertility. For pre-pubescent males, testicular tissue cryopreservation is an option for preserving future fertility. For post-pubescent males, this side effect can be assuaged through semen cryopreservation. For pre-menopausal females, options to preserve fertility are oftentimes much more complex. For example, breast cancer patients of fertile age oftentimes have to weigh the risks and benefits associated with starting an adjuvant therapy regimen after primary treatment. In the some low-risk, low-benefit situations, forgoing adjuvant treatment altogether can be a reasonable decision, but in cases where the risk of metastasis is high, patients may be forced to make a difficult decision. Though options for fertility preservation exist (e.g., embryo preservation, oocyte cryopreservation, ovarian suppression, etc.), they are more often than not time-consuming and costly.
As a result of complications that can stem from liberal use of adjuvant therapy, the philosophy surrounding the use of adjuvant therapy in the clinical setting has shifted towards the goal of doing as little harm as possible to patients. The standards for dose intensity of adjuvant treatments and treatment duration are regularly updated to optimize regimen efficiency while minimizing toxic side effects that patients must shoulder.
In glioblastoma multiforme, adjuvant chemoradiotherapy is critical in the case of a completely removed tumor, as with no other therapy, recurrence occurs in 1–3 months.
In early stage one small cell lung carcinoma, adjuvant chemotherapy with gemcitabine, cisplatin, paclitaxel, docetaxel, and other chemotherapeutic agents, and adjuvant radiotherapy is administered to either the lung, to prevent a local recurrence, or the human brain to prevent metastases.
In testicular cancer, adjuvant either radiotherapy or chemotherapy may be used following orchidectomy. Previously, mainly radiotherapy was used, as a full course of cytotoxic chemotherapy produced far more side effects then a course of external beam radiotherapy (EBRT). However, it has been found a single dose of carboplatin is as effective as EBRT in stage II testicular cancer, with only mild side effects (transient myelosuppressive action vs severe and prolonged myelosuppressive neutropenic illness in normal chemotherapy, and much less vomiting, diarrhea, mucositis, and no alopecia in 90% of cases.
Adjuvant therapy is particularly effective in certain types of cancer, including colorectal carcinoma, lung cancer, and medulloblastoma. In completely resected medulloblastoma, 5-year survival rate is 85% if adjuvant chemotherapy and/or craniospinal irradiation is performed, and just 10% if no adjuvant chemotherapy or craniospinal irradiation is used. Prophylactic cranial irradiation for acute lymphoblastic leukemia (ALL) is technically adjuvant, and most experts agree that cranial irradiation decreases risk of central nervous system (CNS) relapse in ALL and possibly acute myeloid leukemia (AML), but it can cause severe side effects, and adjuvant intrathecal methotrexate and hydrocortisone may be just as effective as cranial irradiation, without severe , such as developmental disability, dementia, and increased risk for second malignancy.
Adjuvant chemotherapy has been used in melanoma, but there is little hard evidence to use chemotherapy in the adjuvant setting. However, melanoma is not a chemotherapy-resistant malignancy. Dacarbazine, temozolomide, and cisplatin all have a reproducible 10–20% response rate in metastatic melanoma.; however, these responses are often short-lived and almost never complete. Multiple studies have shown that adjuvant radiotherapy improves local recurrence rates in high-risk melanoma patients. The studies include at least two M.D. Anderson cancer center studies. However, none of the studies showed that adjuvant radiotherapy had a statistically significant survival benefit.
A number of studies are currently underway to determine whether immunomodulatory agents which have proven effective in the metastatic setting are of benefit as adjuvant therapy for patients with resected stage 3 or 4 disease.
Micometastases cannot be ruled out in locally advanced disease, and surgery alone is not always sufficient for complete cancer control. In certain situations, acquiring precise pathologic staging can make adjuvant chemotherapy (AC) an appealing option. Stage specific pathologic treatment and reduced time to surgery can predict prognosis and the absolute OS benefits in patients with at least cT3 disease A systematic review that studied 7,056 patients showed there was a known 9-11% absolute survival benefit at five years attributable to earlier administration of AC; there was a survival benefit seen with earlier administration, as well as a benefit that persisted when compared to controls who received no AC. One limitation of AC is that poor postoperative healing or complications can limit early administration, leading to a potential propagation of potential micrometastases, early recurrence, or reduction in cancer-specific survival. Enhanced recovery after surgery protocols have recently improved perioperative care and may make earlier time to AC administration less challenging. The recent approval of adjuvant immunotherapy for patients with adverse pathology may make earlier adjuvant administration more tolerable, and be provided to patients who received NAC prior to their RC.
Agents used include:
However, ethical concerns have been raised about the magnitude of benefit of this therapy since it involves further treatment of patients without knowing the possibility of relapse. Dr. Bernard Fisher, among the first to conduct a clinical trial evaluating the efficacy of adjuvant therapy on patients with breast cancer, described it as a "value judgement" in which the potential benefits must be evaluated against the toxicity and cost of treatment and other potential side effects.
Often related to fear of side effects, more recent work has indicated that women do not take adjuvant therapy as prescribed or may stop before they should. A study in 2023 exploring the extent to which an information leaflet could help women to understand the benefits and to reduce their concerns and found that quotes from other women with breast cancer contributes to more positive beliefs.
Most cases of ovarian cancers are detected at the advanced stages, when the survival is greatly reduced.
In advanced-stage endometrial cancer, adjuvant therapy is typically radiation, chemotherapy, or a combination of the two. While advanced-stage cancer makes up only about 15% of diagnoses, it accounts for 50% of deaths from endometrial cancer. Patients who undergo radiation and/or chemotherapy treatment will sometimes experience modest benefits before relapse.
For non-seminoma, the options include: active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection.
As is the case for all reproductive cancers, a degree of caution is taken when deciding to use adjuvant therapy to treat early stage testicular cancer. Though the 5-year survival rates for stage I testicular cancers is approximately 99%, there still exists controversy over whether to overtreat stage I patients to prevent relapse or to wait until patients experience relapse. Patients treated with standard chemotherapy regimens can experience "second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems." As such to minimize overtreatment and avoid potential long-term toxicity caused by adjuvant therapy, most patients today are treated with active surveillance.
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