New Title: Advances in FLASH Proton Therapy: A Breakthrough in Cancer Treatment

Rewritten Article:

FLASH, which translates to "閃電" in Chinese, is commonly known as the English word "flash". However, with the continuous technological advancements in proton therapy, the latest cancer radiation treatment, FLASH now has a whole new meaning. Recently, Varian, one of the leading research institutions for cancer proton therapy devices, announced that the U.S. Food and Drug Administration (FDA) has approved their new proton radiation therapy called FLASH for clinical research. This therapy, known as FAST-02, is being used in human clinical trials to treat symptomatic bone metastatic cancer, further advancing the clinical research program for FLASH. Prior to FAST-02, researchers had already begun the FAST-01 clinical trial, which was the world's first human clinical trial of FLASH therapy. The research data from FAST-01 supported the application for the FAST-02 clinical trial.

Regarding proton FLASH therapy, we all know that it is a more advanced technology for cancer radiation therapy. The diagram below clearly explains the advantages of proton therapy compared to conventional radiation therapy. Proton therapy has a characteristic known as the "Bragg peak," where the energy of the particle beam is low when passing through the human skin and normal tissues, but suddenly increases when reaching the tumor site (blue rays in the diagram). The advantage of this is that proton therapy can minimize damage to normal tissues while delivering a higher dose of radiation to the tumor, achieving a "targeted explosion" on the tumor. The breakthrough achieved by the proton FLASH therapy takes the characteristics of proton beams to the extreme. FLASH radiation therapy is a cutting-edge technology that can complete tumor radiation therapy within fractions of a second. Its most prominent feature is that it can deliver a dose of radiation to the tumor in a unit of time that is over 300 times higher than that of conventional radiation therapy. In conventional radiation therapy, a palliative therapy dose is usually greater than 36Gy and requires approximately 10-15 sessions, while a curative therapy dose is usually greater than 60Gy and requires approximately 15-25 sessions. In the previous FAST-01 clinical trial, patients received radiation therapy at a speed of ≥40Gy per second, completing the entire treatment course within one-third of a second, significantly improving treatment efficiency compared to conventional radiation therapy. Among the 10 patients participating in the clinical trial, 7 experienced significant or complete pain relief, similar to conventional radiation therapy. This ultra-short time, ultra-high dose method induces a phenomenon known as the FLASH effect, which reduces the damage to normal tissues surrounding the tumor during radiation therapy and effectively kills tumor tissue and cancer cells. However, the clinical data from only 10 patients is insufficient, and we look forward to seeing more mature clinical data on proton FLASH therapy to support its superior clinical outcomes and help patients fight against cancer.

Currently, it is not recommended to blindly pursue "high-end" radiation therapy methods. After reading the information about FLASH clinical trials, many patients may be tempted to use this "high-end" treatment, believing that it is much more effective than conventional radiation therapy. However, is this conclusion really true? In fact, gamma knife, cyber knife, tomotherapy, and even the most advanced proton knife are all essentially radiation therapy methods used to kill cancer cells with radiation. The difference lies in the type of radiation used. The most common conventional radiation therapy usually uses photons, which are high-energy beams of light, and a complete course of treatment typically costs around 50,000 yuan, covered by national medical insurance. Gamma knife, cyber knife, and tomotherapy also use photons, but the machines used differ, with larger single doses and more precise targeting, costing around 100,000 yuan and may not be eligible for medical insurance reimbursement. Proton therapy uses protons, while heavy ion therapy uses heavy ions. Protons and heavy ions have a certain mass and carry a positive charge. After gaining high energy and speed, they form the so-called Bragg peak, allowing the energy for anti-cancer treatment to be accurately released within the tumor tissue, minimizing the impact on surrounding normal tissues. However, such high-end radiation therapy currently costs around 300,000 yuan and is not covered by medical insurance. After explaining the differences between these methods, the most important and practical question for patients remains unresolved: what is the difference in efficacy and side effects between the 300,000 yuan proton heavy ion therapy and the 40,000-50,000 yuan conventional radiation therapy? Is it a world of difference or just a minor one? Let me provide you with the answer: in the vast majority of cases, proton heavy ion therapy and conventional radiation therapy have similar efficacy, with a certain degree of reduction in side effects with proton therapy. This conclusion is not based on personal experience or speculation but is supported by multiple authoritative data. As early as 2016, the official journal of the European Society for Radiotherapy & Oncology, a top academic journal in the field of radiation therapy, reported the results of a group of case-control studies. The study compared proton heavy ion therapy with conventional intensity-modulated radiation therapy for the treatment of head and neck squamous cell carcinoma. The former included 50 cases, while the latter included 100 cases that were matched in terms of age, gender, race, and disease severity. The results showed that there was no difference in the disease-free survival period and overall survival period between the two treatment modes. However, the proportion of patients with adverse reactions such as oral mucositis, difficulty swallowing, and stenosis caused by radiation therapy significantly decreased in the head and neck squamous cell carcinoma patients receiving proton heavy ion therapy (from 24.7% to 8.0%). There were no statistically significant differences between the two groups in other adverse reactions such as oral mucositis, dry mouth, weight loss, fatigue, etc. The conclusion was that proton therapy did not improve efficacy but significantly reduced the side effects of radiation therapy. Of course, some readers may think that the above study included only 150 patients and only one type of cancer, head and neck squamous cell carcinoma, so it may not have broad persuasive power. In 2020, Professor James M Metz's team at the University of Pennsylvania provided another comparative study including 1483 cases, covering almost all common tumors. 1092 patients received conventional intensity-modulated radiation therapy, and 391 patients received proton heavy ion therapy. The results showed that there was no statistically significant difference in the median disease-free survival period and overall survival period between the two groups. The incidence of severe adverse reactions within 90 days in the proton heavy ion therapy group significantly decreased (the incidence of grade 3 or higher severe side effects decreased from 27.6% to 11.5%; the incidence of grade 2 or higher adverse reactions decreased from 84.8% to 74.2%). In summary, proton heavy ion therapy and conventional radiation therapy have almost the same efficacy in the vast majority of common cancers and situations. However, the former can to some extent reduce the incidence of adverse reactions. As for whether the degree of reduction in adverse reactions is worth the cost, it is up to individual patients to decide. However, proton heavy ion therapy has unique advantages in some special cancers (such as adenoid cystic carcinoma) and special locations (such as those near the brainstem or involving the spinal cord). Recently, the top medical journal JCO published a prospective randomized controlled clinical trial comparing the efficacy of proton heavy ion therapy and conventional intensity-modulated radiation therapy in patients with solid tumor brain metastases. The study included 42 patients in the proton heavy ion therapy group and 21 patients in the conventional radiation therapy group. The results showed that the proton heavy ion therapy group had a significantly longer time to disease progression in the brain (2.3 months compared to 7.5 months) and a longer median overall survival time (6.0 months compared to 9.9 months). The brain and spinal cord are the most precious organs in the human body, so proton heavy ion therapy has certain advantages in treating these special locations. Of course, we also look forward to seeing more and better clinical data on the new technology of proton therapy, FLASH, to provide practical help to patients!