Findings

Advancements in Oncology

Systemic Therapy Combinations

• According to the latest American Society of Clinical Oncology's (ASCO) "Clinical Cancer Advances" report, one of the major advances in cancer therapy is the systemic therapy combination that includes surgeries and other treatment modalities. If the surgery is postponed until after the targeted therapy or immunotherapy, it becomes significantly less invasive or even not needed, depending on how much the tumor will shrink.
• Systemic therapy combinations are advancing cancer treatment because they are decreasing the risk associated with having surgery while also making the procedure more effective.
• Two examples of such systemic combinations that have shown promising results in 2019 studies include treating melanoma with dabrafenib and trametinib or ipilimumab and nivolumab before surgery and using a targeted therapy drug before removing a cancerous kidney.
• In patients with melanoma, 86% of study participants had their tumors shrunk after taking dabrafenib and trametinib, while 46% had no signs of them.
• For those who took ipilimumab and nivolumab, "the tumors shrank in 57% of patients when checked with imaging scans and in 77% of patients when checked using tissue samples."
• In the group of patients with kidney cancer, those who preceded the surgery with the targeted therapy (sunitinib) lived with a median of 32.4 months, while those who had the surgery right away lived for 15 months.

Highly-Targeted Drug Combinations

• Effectiveness of targeted therapies and immunotherapies has urged researchers to look for powerful combinations that could improve the outcomes without elevating toxicity.
• So far, the combination that has been showing positive result involves complimenting immunotherapy with tyrosine kinese inhibitors in the treatment of renal cell calcinoma (RCC). It is advancing cancer treatment because it may extend the survival of patients with kidney cancer.
• In a recent study, combining axitinib and pembrolizumab showed significantly better results compared to using a standard therapy, sunitinib. Specifically, "the estimated 18-month overall survival was 82.3% and 72.1%, respectively, for the combination of axitinib and pembrolizumab compared with sunitinib. Progression-free survival was also greater for the combination therapy—15.1 v 11.1 months. Grade 3 or greater adverse events from any cause were 75.8% for combination therapy and 70.6% for sunitinib."
• In JAVELIN Renal 101 trial, patients with advanced RCC who took the combination of avelumab and axitinib had progression-free survival of 13.8 months, while those who took sunitinib - 7.2 months.

Progress In the Treatment of Rare Cancers

• According to the 2019 "Clinical Cancer Advances" report by the American Society of Clinical Oncology, the most significant advance of 2018 was the progress in the treatment of rare cancers, which account for around 20% of cancers diagnosed each year. It was especially significant because the development of new therapies in this area had been slower compared to other types of cancer.
• The advances can be attributed to several major trials conducted in 2018, out of which the majority had federal funding.
• In the first study, more than two-thirds of patients responded to the new targeted therapy for rare thyroid cancer.
• In another trial, sorafenib was the first medication to improve progression-free survival in patients with desmoid tumors, an uncommon type of sarcoma.
• In the same year, researchers discovered that trastuzumab, a standard treatment for a type of breast cancer, slows the progression of HER2-positive uterine serous carcinoma.

• A different study identified the first promising treatment for tenosynovial giant cell tumor, a rare cancer of the joints. The colony-stimulating factor-1 (CSF-1) inhibitor pexidartinib had a response rate of 39.3%, compared to 0% in the placebo group.

Additional Information

• Multiple other advancements in oncology are included in "Clinical Cancer Advances" reports from 2019 and 2020. They include advances related to immunotherapy, targeted therapies, CAR-T cell immunotherapies, precision medicine, and molecular diagnostics.

Proton Therapy

How It Works

• The basic principles of standard radiation and proton therapy are the same. Both are based on damaging the cellular DNA, destroying cancer cells, and preventing their proliferation. However, while the former irradiates with high-energy electromagnetic waves, the latter works with "positively charged nuclei of elementary hydrogen."
• In proton therapy, protons are taken "out of the hydrogen atoms and then accelerated in the particle accelerator by electromagnetic fields up to about two-thirds of the speed of light." They reach the patient right away, with the technology allowing for highly precise irradiation within the body.
• Due to the phenomenon called the Bragg Peak, protons release most of their energy on the last millimeters of their trajectory. The point of release can be set with calculating acceleration.
• Thanks to this effect, compared to traditional radiation, proton therapy significantly reduces the body's exposure to radiation. Because of the way protons interact within the body, their full energy goes to the tumor, which decreases effects on the heart, lungs, bones, and healthy tissue.
• This type of treatment is non-invasive and can be combined with chemotherapy and surgery. It can also be a second treatment after radiation and recurrence in the treated area.
• A typical treatment is based on an individual plan, which consists of choosing the treatment area, radiation dose, and session schedule. Additionally, it is crucial to find the optimal body position for the right penetration of protons in the body. It is done with robotic control.
• As a patient can't move during the session, dedicated treatment centers tend to use immobilizing contour mattresses. Such outpatient sessions "range from 15 – 45 minutes in length, 5 days a week, for 4-8 weeks depending on the specific cancer diagnosis."
• It is worth noting that proton therapy can only be conducted in such facilities, which require significant investments. At the same time, the cost of individual treatment tends to be above $30,000-$40,000, though it is often covered by insurance.
• Still, cost-related issues are significant barriers to using proton therapy. There are currently around 30 proton therapy centers in the US, with many others under construction. However, many of them are at risk of bankruptcy due to demand-supply mismatch.

What It Is Used For

• The US is considered a pioneer in proton therapy. Unlike in many other places around the world, it is already used to treat patients, not only for research purposes.
• According to MD Anderson, a proton therapy center, it can be effective on solid tumors that have well-defined borders, i.e., ones that haven't spread to other parts of the body.
• Types of diseases that are currently treated with proton therapy include brain tumors, breast cancer, cancer in children, eye melanoma, esophageal cancer, head and neck cancers, liver cancer, lung cancer, pituitary gland tumors, prostate cancer, sarcoma, tumors affecting the spine, tumors in the base of the skull, as well as selected eye diseases.
• The website of the National Association for Proton Therapy, a non-profit focused on educating about proton therapy, includes information on why the therapy is appropriate for each type of cancer or tumor.
• For example, it is recommended for pediatric patients because it decreases the long-term side effects of radiation, including secondary cancers in healthy tissues.
• In breast cancer, it limits the possibility of damage to lungs and heart, which makes it especially recommended for patients with preexisting cardiovascular or pulmonary conditions.
• In eye cancers, as well as some other eye conditions such as macular degeneration, proton therapy reduces radiation that can be potentially harmful to brain tissue and the optic nerve.
• It is also used for conditions in which the use of traditional radiation is dangerous due to the proximity of the spinal cord, the brain stem, and brain tissue, including head and neck cancers, skull-based cancers, and brain tumors.
• However, it currently has limited effectiveness in metastatic cancers, when secondary tumors are already present.
• So far, in the US, around 75,000 people have been treated with proton therapy (which accounts for 44% of global proton therapy patients).

Advancements

Proton Therapy and Hypofractionation for Prostate Cancer

• In recent years, there have been studies that combined proton therapy and hypofractionation in the treatment of prostate cancer. "In hypofractionation, the prescribed radiation dose is delivered in larger portions (fractions) over fewer treatment sessions than in traditional radiotherapy."
• While the method has been tested for the treatment of prostate cancer, most large trials used the traditional radiotherapy together with hypofractionation.
• However, the 4-year study by Penn Medicine showed that hypofractionated proton therapy for prostate cancer doesn't affect bowel and urinary health while remaining less toxic compared to typical radiotherapy.
• There is also an ongoing stage 3 clinical trial that compares the effectiveness of hypofractionated proton therapy and proton therapy with androgen suppression therapy, sponsored by Proton Collaborative Group.

Other Advancements

• While we didn't find detailed descriptions of other advancements in proton therapy in research papers, medical media, and websites of proton treatment centers and non-profit organizations, we decided to include any relevant findings we came across.
• Researchers predict that advancements in proton therapy intensity modulation may improve outcomes for meningiomas near the pituitary gland.
• At the same time, they hope that the advancements in technology and the growth in the number of proton treatment centers will eventually lead to lowering the cost of proton therapy and increasing its accessibility.