"Doctor, what should I do?" 67-year-old Aunt Zhang (not her real name) sat in the consultation room, her eyes full of confusion and fear.
As an advanced melanoma patient, Aunt Zhang had undergone 15 months of immunotherapy, and the tumor was almost completely gone, and she thought she had finally defeated the cancer. However, fate played a cruel joke on her - the side effects of the treatment actually threatened her life.
This once optimistic and strong old man has to face a difficult choice at this moment: whether to continue immunotherapy or stop taking the drug? Do you put up with the side effects of high doses of hormones, or take the risk of trying a new drug?
Aunt Zhang's experience is a microcosm of a dilemma faced by modern medicine. How can immunotherapy, a "double-edged sword", kill cancer cells without harming the innocent? And how do we balance treatment outcomes with quality of life?
Let's walk into Auntie Zhang's story to explore the pros and cons of immunotherapy and how the medical community is tackling this challenge.
- Immunotherapy: a new hope for cancer treatment
"When the doctor told me I could try immunotherapy, I felt hopeful." Aunt Zhang recalled.
In 2011, the first immune checkpoint inhibitor was approved by the FDA, ushering in a new era of cancer treatment. These drugs fight cancer by activating the body's own immune system and are known as "lighting the switch on the immune system".
Immunotherapy usually has fewer side effects than conventional chemotherapy. It is estimated that about 40% of cancer patients in the United States are currently eligible for this treatment. For patients with advanced melanoma like Aunt Zhang, immunotherapy brings unprecedented hope.
- Bonus: the tumor is gone!
Aunt Zhang was started with pembrolizumab, a PD-1 inhibitor injected every 3 weeks.
"At first I was worried about serious side effects, but apart from a slight feeling of fatigue, I had almost no discomfort." Aunt Zhang said, "What surprised me the most was that the examination a few months later showed that the tumor was shrinking!"
After 15 months of treatment, Aunt Zhang's condition is exciting: the brain metastases are gone, and the lymph node metastases are no longer visible. PET-CT showed no signs of active tumors throughout the body.
"I couldn't believe my eyes," Auntie Zhang's attending doctor recalled, "and such a complete remission is not common in patients with advanced melanoma." "
- Sudden Blows: Immune-Related Adverse Effects
However, just when Aunt Zhang thought she could breathe a sigh of relief, trouble came.
"I started feeling tired, chills, loss of appetite, night sweats, nausea, diarrhea, dry cough and chest pain," said Auntie Zhang, "At first I thought it was a cold and went to the emergency room twice, but the symptoms did not improve. "
A routine PET-CT scan revealed the truth of the problem: Aunt Zhang had inflammation of the aortic arch, a rare but dangerous immune-related adverse reaction (irAE) - aoritis.
"The side effects of immunotherapy can affect any organ system," Auntie Zhang's doctor explains, "and while most of the side effects are mild, some, such as aortitis can be life-threatening." "
- The dilemma: continue or stop?
Faced with this situation, the medical team had to make a difficult decision: stop immunotherapy.
"It was a dilemma," said the attending doctor, "on the one hand, the immunotherapy controlled Aunt Zhang's cancer; On the other hand, continued treatment may worsen aortitis and be life-threatening. "
For Aunt Zhang, this decision is undoubtedly a heavy blow. "I felt like I was walking a tightrope," she said, "with the risk of cancer recurrence on one side and the threat of aortitis on the other." "
- Treatment of aortitis : hormonal troubles
To control the aortitis, doctors began to give Aunt Zhang a large dose of prednisone (a glucocorticoid).
"At first, the hormones did alleviate my symptoms," says Auntie Zhang, "but the side effects that followed bothered me – I started to gain weight like crazy and couldn't sleep well at night." "
After two months of hormone therapy, Aunt Zhang's weight increased by nearly 10 kilograms, and her insomnia problem became increasingly serious. "I felt like I was a different person," she said, "and while the aortitis was under control, my quality of life was compromised." "
- New Hope: Tocilizumab
Just when Aunt Zhang was bothered by hormone side effects, the doctor proposed a new option: tocilizumab to replace the hormone.
Tocilizumab is an IL-6 inhibitor commonly used to treat rheumatoid arthritis and other inflammatory diseases. Although it has never been used to treat aortitis caused by immunotherapy, doctors think it's worth a try.
"Our decision was based on two factors," the attending physician explained, "first, tocilizumab has a good effect in treating giant cell arteritis, another type of vasculitis that can affect the aorta." Second, some guidelines recommend it for the treatment of refractory vasculitis. "
- Surprise: Symptoms are relieved and the cancer does not recur
After starting tocilizumab, Aunt Zhang's condition began to improve.
"I feel more relaxed," she says, "not only are the symptoms of aortitis gone, but the annoying side effects of hormones are gradually lessening." "
What's even more gratifying is that despite the cessation of immunotherapy, Aunt Zhang's cancer has not returned. Follow-up PET-CT showed complete resolution of aortitis without any signs of metastasis.
"This is a real bonus," says the attending physician, "and it not only demonstrates the potential of tocilizumab in the treatment of immune-associated aoritis, but also gives us a long-term benefit of immunotherapy." "
- Takeaway: The importance of individualized care
Aunt Zhang's experience has brought us profound enlightenment:
(1) Although immunotherapy is effective, it may also bring serious side effects. Patients and doctors need to be vigilant to detect and manage these side effects in a timely manner.
(2) For rare immune-related adverse reactions, conventional treatment may not be sufficient. Doctors need to be flexible in their choice of treatment based on the patient's specific situation.
and (3) the need to balance treatment efficacy and quality of life when dealing with immune-related adverse reactions. Sometimes, innovative treatments can lead to unexpectedly good results.
(4) Even if immunotherapy is stopped, some patients can still achieve sustained anti-tumor effects. This provides a new perspective for understanding the mechanism of action of immunotherapy.
- Future outlook: safer and more effective immunotherapy
Aunt Zhang's story is just the tip of the iceberg. With the widespread clinical application of immunotherapy, there may be more and more similar cases. This poses a new challenge for the medical community: how to minimize side effects while ensuring the effectiveness of treatment?
Some possible directions include:
(1) Develop more precise biomarkers to better predict which patients may have serious immune-related adverse effects.
(2) To study the pathogenesis of immune-related adverse reactions and develop targeted prevention and treatment strategies.
and (3) explore the best combination of immunotherapy with other treatment modalities to improve efficacy and reduce side effects.
(4) Strengthen the understanding and research of rare immune-related adverse reactions, and establish more comprehensive treatment guidelines.
- Conclusion: The Way of Balance
Three years have passed, and Aunt Zhang is still in good shape. "Despite all the twists and turns, I am grateful for life," she says, "and this experience has taught me that medicine is not a panacea, but as long as we don't give up hope, we can always find a solution to the problem." "
Aunt Zhang's story is a microcosm of the challenges and opportunities facing modern medicine. While pursuing a cure, we also need to pay attention to the quality of life of our patients. We need to be open and innovative when dealing with the unknown.
Immunotherapy is undoubtedly a "double-edged sword", but through continuous exploration and efforts, we will eventually find a way to harness it and bring hope and new life to more patients.
参考资料：Bloomer CH, Annabathula RV, Aggarwal V, Upadhya B, Lycan TW. A Case Report of Immune Checkpoint Inhibitor-Induced Aortitis Treated with Tocilizumab. Case Reports Immunol. 2022 Oct 12;2022:7971169. doi: 10.1155/2022/7971169. PMID: 36277471; PMCID: PMC9581648.