One cycle of immunization + chemotherapy, the elderly patients with lung squamous cell carcinoma develop purulent pericarditis, whose "pot" is it?

*Only for medical professionals to read and refer to "Jinling Lung Cancer Network Forum" MDT case sharing takes you to see the key issues of purulent pericarditis in patients with advanced lung squamous cell carcinoma! Lung cancer is the cancer with the highest morbidity and mortality in China.
According to the latest clinical studies, immunotherapy can bring more survival benefits to patients with early stage lung cancer and operable locally advanced lung cancer patients
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Immune checkpoint inhibitors (ICI) have become one of the most important first-line and second-line treatment strategies for advanced non-small cell lung cancer (NSCLC)
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The Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Xuzhou Medical University once encountered a case of lung cancer with purulent pericarditis.
Was the purulent pericarditis caused by immunotherapy or infection after chemotherapy? With these questions in mind, at the MDT site of the Jinling Lung Cancer Network Forum on November 24, experts discussed the lung cancer treatment cases reported by Professor Zuo Lina from the Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Xuzhou Medical University
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Basic information of the patient Li xx, male, 64 years old
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From February 20 to March 6, 2021, he was admitted to the hospital for "cough and sputum for more than one month"
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History of present illness and past history: Cough, sputum, less white sputum, no fever, no asthma, no obvious cause before 1 month, no improvement after anti-infection treatment in the local hospital, chest CT showed that the right lower lobe is near the spine Positional lesions
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He has a history of hypothyroidism, has taken oral medications, but has not taken the medications regularly
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Deny the history of heart disease, diabetes, hypertension; deny the history of hepatitis
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A history of smoking 20 cigarettes/day*40 years, a small amount of alcohol consumption
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Five examinations of the patient’s thyroid revealed abnormalities.
On February 24, he asked the endocrinologist for a consultation.
He was given levothyroxine 50 μg orally once a day, and his thyroid function was rechecked after one month
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On February 22, the chest enhanced CT ultrasound bronchoscopy (EBUS) and pathological results: hemorrhage and edema of the right middle segment of the bronchial mucosa, color Doppler ultrasound, swollen lymph nodes in the right neck area IV
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The pathology report showed: squamous cell carcinoma
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Pathological supplementary diagnosis: PD-L1 low expression (<1%)
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Currently diagnosed: right lung cancer (squamous cell carcinoma, T2N3M0, stage IIIB); hypothyroidism
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Treatment process: 1 cycle of immunotherapy + chemotherapy, multi-organ function involvement ▎Guide recommendation: immunotherapy + chemotherapy
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According to the recommendations of the 2021 Chinese Society of Clinical Oncology (CSCO) guidelines, patients were given a treatment plan of 200 mg pembrolizumab, 60 mg cisplatin d1-2 + paclitaxel liposome 240 mg d1
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The chemotherapy process went smoothly and was discharged from the hospital on March 6 after the cycle ended
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After discharge, he continued to take levothyroxine 50 μg once a day to monitor his thyroid function
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▎Fever, diarrhea, wheezing, chest pain, etc.
occurred after 3 days
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The 2021 CSCO guidelines for non-small cell lung cancer recommend that patients be admitted to the hospital for treatment from March 9th to March 25th due to heavy breathing, forced semi-recumbent position, fever, diarrhea, respiratory failure, and excessive pericardial effusion
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On March 9th, a pericardiocentesis was performed under the guidance of color Doppler ultrasound, and a gray-white purulent fluid was drained
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The blood test on March 10 showed: white blood cell count (WBC) 1.
2×109/L, neutrophils 77%, C-reactive protein (CRP)>370 mg/L
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Blood biochemistry showed: aspartate aminotransferase (AST) 124 u/l, alanine aminotransferase (ALT) 206 u/l, procalcitonin (PCT) 7.
8ng/mL, troponin T 31.
9 ng/L, type B natriuresis Peptide (BNP) 3396 pg/mL, creatine kinase and CK-MB were normal
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The patient had paroxysmal atrial fibrillation.
On the 4th day after pericardial drainage, reexamination of cardiac color Doppler showed that the volume of pericardial effusion decreased, but the EF value decreased from 56% to 48%
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The patient’s current diagnosis includes: right lung cancer (squamous cell carcinoma, T2N3M0, stage IIIB), bone marrow suppression after chemotherapy, purulent pericarditis, type I respiratory failure, liver and kidney cardiac insufficiency, atrial fibrillation, hypothyroidism, diarrhea, and electrolyte imbalance
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The patient’s pericardial effusion was fully drained and treated with biapenem 0.
6 g (twice a day) + linezolid 0.
6 g (twice a day).
Later, the patient’s platelet (PLT) decreased, and the treatment plan was adjusted to Abpenem combined with tigecycline 50 mg (twice a day)
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 As well as caspofungin 50 mg (1 time a day), methylprednisolone 50 mg (2 times a day), symptomatic and supportive treatments such as protecting the liver and lowering enzymes, increasing whiteness, increasing platelets, and nutritional support
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Laboratory examination trend chart The patient's body temperature was normal, no diarrhea, suffocation, and chest pain alleviated.
He was transferred to the general ward on March 15 and was discharged from the hospital on March 25
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Chest CT for the first visit on February 22, emergency chest CT on March 9, and chest CT chemotherapy on March 19 after infection or immune adverse reactions? After one cycle of immunotherapy and chemotherapy, the patient developed multiple organ functions including digestive tract, kidney function, liver function, and heart
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Is it an infection after chemotherapy or an adverse immunotherapy (irAE)? Immunotherapy may cause a series of irAEs, most of which are mild to moderate, and occasionally life-threatening adverse reactions occur
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Combined with the "Guidelines for the Management of Toxicity Related to CSCO Immune Checkpoint Inhibitors" and the relevant indicators of patient laboratory tests, it may appear rectal toxicity, renal toxicity, liver toxicity, pulmonary toxicity, and cardiotoxicity after treatment
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Thrombocytopenia or bone marrow suppression caused by chemotherapy
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In addition, combined with the patient's past history of hypothyroidism, and the thyroid function has not changed significantly, the patient will continue to take levothyroxine orally
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Cardiotoxicity cannot be ignored.
Regarding this patient, the prominent problem is purulent pericarditis
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The mechanism of immune-related cardiotoxicity is not fully understood, and the reasons are complicated
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According to relevant literature reports, initially, the incidence of cardiotoxicity was estimated to be less than 1%, but due to the lack of prospective evaluation of cardiac parameters, the actual incidence was underestimated
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Typical pericardial pain, electrocardiogram changes accompanied by diffuse ST-segment elevation and PR decline, or cardiac color Doppler ultrasound suggesting a new pericardial effusion
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In a single-center retrospective study of stage IIB/IV NSCLC patients, compared with standard chemotherapy, the incidence of pericardial effusion increased, but the possibility of myocarditis should be ruled out by increased troponin; pericardial effusion complicated by pericardial tamponade , The mortality rate is 21.
1%
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Pericarditis is the second most common manifestation of cardiotoxicity; it can be manifested as isolated pericardial effusion and cardiac tamponade
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For a median of 30 days after the start of ICI treatment, pericardial toxicity may occur, which is more common in male cases
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The patient has difficulty breathing after progressively aggravated activities, and the chest radiograph shows an enlarged flask-like heart shadow, and echocardiography can confirm the diagnosis
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Short-term rapid pericardial effusion will cause pericardial tamponade, 81% will cause abnormal hemodynamics, and emergency pericardiocentesis is required
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At present, the best treatment strategy for pericardial diseases is still steroid hormones
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After discharge from the hospital, the patient suffered from suffocation again, without fever, CT and heart color showed increased pericardial effusion, and was admitted to the hospital for the third time; after the pericardial catheter was placed, the pericardial effusion was drained and the pericardial effusion and blood second-generation sequencing (NGS) )
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The results suggest that CRP and PCT increased again
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However, NGS did not suggest a meaningful pathogen
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The patient was discharged after treatment improved
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The patient was admitted to the hospital again on May 10, and a reexamination of CT showed that the right lower lobe lesion was enlarged.
After eliminating the contraindications, systemic chemotherapy was performed on May 12.
The specific plan was adjusted to: carboplatin 400 mg + paclitaxel (albumin-bound type) 300 mg
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On July 17, the patient received systemic chemotherapy again and continued to receive the treatment plan of carboplatin 400 mg + paclitaxel (albumin-bound type) 300 mg
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At the same time, long-acting recombinant human granulocyte stimulating factor was used, and agranulocytosis reappeared 1 week after discharge, accompanied by gastrointestinal symptoms such as nausea and vomiting
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At the same time, using long-acting recombinant human granulocyte stimulating factor, agranulocytosis reappeared one week after discharge, accompanied by nausea and vomiting and other gastrointestinal symptoms, which improved after symptomatic treatment
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On October 17, the patient felt his coughing symptoms worsened and was admitted to the hospital again
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Chest CT on May 10 (before chemotherapy), chest CT on June 7 (after chemotherapy), and chest CT on July 10 (enlarged) Does this patient have an immune adverse reaction or an infectious disease? Or is it a merger of the two? Is there a link between infectious diseases and immune checkpoint inhibitor therapy? How to choose the patient's follow-up treatment plan? With these questions, many experts from Subei People's Hospital, Nanjing Chest Hospital, and Jinling Hospital affiliated to Nanjing University School of Medicine discussed
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●Professor Xu Xingxiang from Subei People’s Hospital pointed out: “During treatment, patients may have irAEs
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For
example, the symptoms of diarrhea can be explained as immune-related enteritis
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Immune-related cardiotoxicity refers more to myocarditis, combined with its muscles.
Calprotein does not increase significantly, so purulent pericarditis cannot be explained by irAE
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However, it should be noted that the patient has intestinal flora imbalance, and there is also the possibility of blood-borne infection, and this infection is mostly Gram-negative bacilli Infection
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Therefore, the patient needs to undergo baseline assessments such as purulent tonsillitis, blood sugar, skin ulcers, perianal abscess, etc.
The problem of bone marrow suppression after chemotherapy should also not be ignored
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" ● Professor Zhang Yu from Nanjing Chest Hospital explained: "Immunity Most of the related heart injuries are early-onset events
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The patient’s cardiotoxicity is not only manifested as pericardial effusion, but also paroxysmal atrial fibrillation, increased BNP and decreased EF value
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As for why the patient’s pericarditis is purulent, this after chemotherapy and bone marrow suppression overlap
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patients may cause bone marrow suppression immunocompromised, into purulent pericarditis from autoimmune pericarditis
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It is worth mentioning that the liver of a patient adverse reactions may be associated with pericarditis, and chemotherapy may also be poor Response is related, and pericarditis is more related to immunotherapy
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Patients' follow-up treatment should be rescheduled, and follow-up treatment options should be discussed in MDT
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"● Professor Sun Qian from Jinling Hospital Affiliated to Nanjing University School of Medicine analyzed: "This patient has a history of hypothyroidism with severe hypothyroidism
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After a cycle of sufficient chemotherapy, it may be an infection caused by bone marrow suppression based on hypothyroidism, which is manifested as purulent pericarditis
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The patient developed fever, diarrhea, and suffocation within 3 days after a cycle of immunization + chemotherapy, which are obvious symptoms of infection
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"● Professor Yin Jie of Jinling Hospital, Nanjing University School of Medicine also emphasized the influence of the patient’s previous history of hypothyroidism on the treatment process: “It is more common for hypothyroidism with pericardial effusion.
The patient’s purulent pericarditis may be caused by Caused by multiple factors
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The patient's hypothyroidism was not well controlled, and immunotherapy was started
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Purulent pericarditis cannot be explained solely as immunotherapy-related or infection-related
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"Professor Song Yong from Jinling Hospital, Nanjing University School of Medicine, analyzed and summarized: "Why does the patient have purulent pericarditis?" First of all, it is necessary to consider the underlying medical history of hypothyroidism, and the patient's immune function is low
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Second, there may be operations that increase the risk of infection, such as ultrasound bronchoscopy (EBUS)
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Furthermore, the impact of chemotherapy during treatment cannot be ignored
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As for whether immunotherapy played a role in this process? The conclusion is not clear yet
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How to choose the patient's follow-up treatment plan? Restarting immunotherapy and chemotherapy is not recommended.
I personally suggest that after the general condition of the patient improves, a cardiopulmonary function assessment should be performed, and then return to the treatment path of surgery, and then perform a condition assessment after the surgery
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Before surgery, it is strongly recommended that patients undergo PET-CT examination to determine whether the patient has brain metastases
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If the patient does not have the conditions for surgery, radiotherapy is recommended
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"