Immune checkpoint inhibitor (ICI)-related pneumonitis among patients with lung cancer admitted to an Oncology Hospitalist Service: Treatment patterns and hospitalization outcomes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21054-e21054
Author(s):  
Hadeel Neamat Sahar ◽  
Jeffrey Aldrich ◽  
Christine B. Peterson ◽  
Norman Brito-Dellan ◽  
Maggie Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mortality Rate ◽  
Median Time ◽  
Immune Checkpoint ◽  
Readmission Rate ◽  
Treatment Patterns ◽  
Comprehensive Cancer Center ◽  
Study Population ◽  
The Mean ◽  
Grade 3

e21054 Background: Immune checkpoint inhibitors (ICI) have gained success in the treatment of multiple malignancies including lung cancer. However, immune-related adverse events (irAE) are common with pneumonitis being one of the most fatal having a 10% mortality rate. As such, early identification and treatment of irAEs are important. We describe the treatment patterns and hospitalization outcomes of patients with lung cancer with grade ≥3 ICI-related pneumonitis (ICI-P) admitted to an oncology hospitalist service at a comprehensive cancer center. Methods: We performed a retrospective review of patients with lung cancer admitted to our oncology hospitalist service with a suspicion of ICI-P between January 1, 2019 and November 30, 2019. ICI-P was confirmed if the patient received irAE-specific management, or if there was multidisciplinary consensus among treating providers. Descriptive statistics were utilized. Here we present the demographic and clinical characteristics of the study population as well as hospitalization outcomes. Results: We identified 49 patients with lung cancer who received at least one dose of ICI before being admitted with a suspicion of ICI-P. The mean age was 67y, with 63% being male and 86% having a diagnosis of non-small cell lung cancer. The most common ICI received by patients was pembrolizumab (67%). 84% were on active ICI treatment at the time of hospitalization and the median time from the 1st ICI dose to hospitalization was 3.5 months. Pulmonology was consulted in 88% of patients. Only 63% (n=31) of those admitted with a suspicion of ICI-P were confirmed to have ICI-P. The mean time to first ICI-P directed treatment was 2.2 days from admission with all 31 patients receiving corticosteroids. 23% required infliximab and 10% required IVIG. Patients with confirmed ICI-P had a median length of stay of 8 days, with 19% requiring ICU stay. The ICI-P inpatient mortality rate was 32%. Of those discharged alive (n=21), 90% were discharged on oral corticosteroids. GI and PJP prophylaxis were prescribed for 95% and 81% of the discharged patients, respectively. The 30-day readmission rate for this subgroup was 29%. 86% were seen by their oncologist within a median time of 8 days from discharge. Conclusions: Studies have shown that patients with grade ≥3 ICI-related pneumonitis (i.e. requiring hospitalization) have high mortality rates and this was consistent with our findings. Treatment for ICI-related pneumonitis was started >2 days from admission in our study population. A high index of suspicion is necessary to expedite work-up, and a multidisciplinary approach is key to confirm diagnosis and promptly initiate treatment. Readmission rate was high. Care coordination and strategies for safe transitions of care at discharge should be ensured to improve the overall outcome.

scholarly journals 237 Infectious complications in patients with non-small cell lung cancer treated with anti-PD(L)1 immune checkpoint inhibitors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A253-A253
Author(s):  
Matthew Guo ◽  
Aanika Balaji ◽  
Joseph Murray ◽  
Joshua Reuss ◽  
Seema Mehta Steinke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Infectious Complications ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

BackgroundImmune checkpoint inhibitors (ICI) are standard treatment for stage III/IV non-small cell lung cancer (NSCLC). ICIs may cause immune-related adverse events (irAEs) often requiring corticosteroids or other immunosuppressive therapy and are associated with increased risk of opportunistic infections.1 2 The burden of infectious complications in NSCLC patients (pts) treated with ICIs is poorly described.MethodsWe retrospectively reviewed NSCLC pts treated with ICIs between 2016–2020 at a large tertiary academic center. An infectious complication related to ICIs was defined as a pathogen-confirmed or clinically diagnosed infection requiring antimicrobials during or within 3 months of ICI discontinuation. High-grade infections were defined as those requiring IV antibiotics (grade 3), life-threatening or requiring ICU stay (grade 4), or resulting in death (grade 5). irAEs were defined by the treating provider and treated according to standard guidelines. Patient demographics, treatment data, cancer outcomes, infectious complications, and irAE details were annotated in an IRB-approved database. An AE treated as both an infection and/or irAE with antibiotics and immunosuppression was coded as a concomitant irAE/infection event. The association between patient features and infectious complications was examined using logistic regression. Treatment and disease characteristics for concomitant irAE with infection were also described.Results302 ICI-treated NSCLC pts were included. 211 pts received PD-1 monotherapy and 91 received PD-1 therapy with CTLA-4 therapy, chemotherapy, or other investigational therapy. The majority (175/302, 57.9%) had a documented infection (bacterial=138, viral=17, fungal=19, mycobacterial=1) during or within 3 months of ICI discontinuation. Grade ≥3 infections occurred in 33.4% of pts (101/302). Pulmonary infections were most common (35.4%), followed by gastrointestinal, urinary, and skin (<10%, each). A subset of pts were treated as having concomitant irAE/infection events (63/302, 20.9%). Among 63 pts who experienced irAEs, pneumonitis occurred most commonly (47/63, 74.6%) followed by colitis (7/63, 11.1%); other irAEs (hepatitis, myocarditis, thyroiditis) occurred in <3 patients each. A concomitant event was associated with a trend toward higher odds of hospitalization (OR 3.91, CI 0.5–30.76) when adjusted for grade ≥3 infection. Similarly, steroid use within one month prior to infection, was also associated with a trend toward higher odds of hospitalization (OR 8.88, CI 0.81–97.15), adjusted for grade ≥3 infection.ConclusionsIn this retrospective study of NSCLC pts treated with ICIs, the majority experienced infections during or within 3 months of ICI discontinuation. The most common infections were bacterial pulmonary in origin. Concomitant irAE/infection was associated with trend toward higher odds of hospitalization.ReferencesHamashima R, Uchino J, Morimoto Y, et al. Association of immune checkpoint inhibitors with respiratory infections: a review. Cancer Treatment Reviews 2020;90:102109. doi:10.1016/j.ctrv.2020.102109Lu M, Zhang L, Li Y, et al. Recommendation for the diagnosis and management of immune checkpoint inhibitor related infections. Thorac Cancer 2020;11(3):805–809. doi:10.1111/1759-7714.13313Ethics ApprovalThis retrospective chart review study has obtained ethics approval from the Institutional Review Board at the Johns Hopkins School of Medicine (number: IRB00129424).

scholarly journals Neurologic autoimmunity and immune checkpoint inhibitors

Neurology ◽  
2020 ◽  
Vol 95 (17) ◽  
pp. e2442-e2452
Author(s):  
Elia Sechi ◽  
Svetomir N. Markovic ◽  
Andrew McKeon ◽  
Divyanshu Dubey ◽  
Teerin Liewluck ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Mayo Clinic ◽  
Checkpoint Inhibitors ◽  
Cns Involvement ◽  
Neurologic Symptom ◽  
Clinical Cohort ◽  
Severity Grade ◽  
Systemic Autoimmunity ◽  
Grade 3

ObjectiveTo describe neural autoantibody profiles and outcomes in patients with neurologic autoimmunity associated with immune checkpoint inhibitor (ICI) cancer immunotherapy.MethodsIn this retrospective descriptive study, 63 patients with ICI-related neurologic autoimmunity were included: 39 seen at the Mayo Clinic Neurology Department (clinical cohort) and 24 whose serum/CSF was referred to the Mayo Clinic Neuroimmunology Laboratory for autoantibody testing. Serum/CSF samples were tested for neural-specific autoantibodies. Predictors of unfavorable outcome (residual adverse event severity grade ≥3) were explored (logistic regression).ResultsMedian age at neurologic symptom onset was 65 years (range 31–86); 40% were female. Neurologic manifestations were CNS-restricted (n = 26), neuromuscular (n = 30), combined (n = 5), or isolated retinopathy (n = 2). Neural-specific autoantibodies were common in patients with CNS involvement (7/13 [54%] in the unbiased clinical cohort) and included known or unidentified neural-restricted specificities. Only 11/31 patients with CNS manifestations had neuroendocrine malignancies typically associated with paraneoplastic autoimmunity. Small-cell lung cancer (SCLC)–predictive antibodies were seen in 3 patients with non-neuroendocrine tumors (neuronal intermediate filament immunoglobulin G [IgG] and antineuronal nuclear antibody 1 with melanoma; amphiphysin IgG with non-SCLC). A median of 10 months from onset (range, 0.5–46), 14/39 in the clinical cohort (36%) had unfavorable outcomes; their characteristics were age ≥70 years, female, CNS involvement, lung cancer, higher initial severity grade, and lack of systemic autoimmunity. By multivariate analysis, only age remained independently associated with poor outcome (p = 0.01). Four of 5 patients with preexistent neurologic autoimmunity experienced irreversible worsening after ICI.ConclusionsNeural-specific autoantibodies are not uncommon in patients with ICI-related CNS neurologic autoimmunity. Outcomes mostly depend on the pre-ICI treatment characteristics and clinical phenotype.

Paclitaxel and Carboplatin in the Treatment of Small-Cell Lung Cancer Patients Resistant to Cyclophosphamide, Doxorubicin, and Etoposide: A Non–Cross-Resistant Schedule

1999 ◽  
Vol 17 (3) ◽  
pp. 927-927 ◽  
Author(s):  
Harry J.M. Groen ◽  
Eelco Fokkema ◽  
Bonne Biesma ◽  
Bibi Kwa ◽  
John W.G. van Putten ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Time ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Group Performance ◽  
Small Cell ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: To evaluate the efficacy of paclitaxel and carboplatin (PC) in small-cell lung cancer (SCLC) patients resistant to cyclophosphamide, doxorubicin, and etoposide (CDE). PATIENTS AND METHODS: We performed a phase II study with PC in SCLC patients who relapsed within 3 months after first-line treatment with CDE. Paclitaxel administration (175 mg/m2 by a 3-hour intravenous infusion) was followed by a 30-minute infusion of carboplatin (area under the curve 7; Chatelut formula) once every 3 weeks for five cycles. Dexamethasone, clemastine, and ranitidine were standard premedication before every cycle. RESULTS: Included were 35 patients (median age, 59 years; 16 with limited disease and 19 with extensive disease; Eastern Cooperative Oncology Group performance status of ≤ 1; median time off treatment 6 weeks) who were previously treated with CDE (n = 33), oral etoposide (n = 2), and reinduction CDE (n = 15); only one patient had received three CDE treatments of five cycles. The CDE regimen was followed by local thoracic radiotherapy in seven patients. Hematologic toxicity of grade 3 or 4, for leukopenia was 27% and 6%, for thrombocytopenia 21% and 13%, and for anemia 17% and 0%, respectively, for a total of 132 cycles. Two patients had neutropenic fever; no toxic death occurred. Nonhematologic toxicity was paresthesia CTC grade 3, diarrhea grade 4, and myalgia grade 3 in one patient each. Reversible paresthesia (CTC grade 1 and 2) in toes and fingers was reported in 69% of patients. Thirty-four patients were assessable for response: complete response in two patients, partial response in 23 patients, stable disease in eight patients, and progressive disease in one patient (response rate, 73.5%; 95% confidence interval, 59% to 88%). One patient was found to have atypical carcinoid at pathologic review and was excluded. Median time to progression was 21 weeks (range, 3 to 40 weeks). Median survival was 31 weeks (range, 6 to 112 weeks). One-year survival was 9%. CONCLUSION: Second-line PC in CDE-resistant SCLC patients yields a high response rate and seems non–cross-resistant to CDE. Toxicity was mild in these poor-prognosis patients.

What is the value added of patient reported outcomes relative to physician rated symptom assessments?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8580-8580 ◽  
Author(s):  
S. J. Mandrekar ◽  
M. M. Huschka ◽  
P. L. Schaefer ◽  
J. R. Jett ◽  
A. A. Adjei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Median Time ◽  
Patient Reported Outcomes ◽  
Percent Agreement ◽  
Patient Reported ◽  
Lung Cancer Symptom Scale ◽  
Multiple Item ◽  
First Occurrence ◽  
Grade 3 ◽  
Distress Scale

8580 Background: This pooled analysis examined the relationship between single-item and multiple-item quality of life (QOL) measures and assessed the agreement between changes in QOL and patient-reported adverse events (AE). Methods: Data from six lung cancer clinical trials involving 358 patients were pooled. All trials incorporated the UNISCALE and one of three multiple-item assessments: the Functional Assessment for Cancer Therapy-Lung, the Lung Cancer Symptom Scale, or the Symptom Distress Scale. A clinically significant decline (CSD) in QOL was defined as a 10-point drop from baseline. A CSD in AE was defined as a change from ≤ grade 2 at baseline to ≥ grade 3 post-baseline. Spearman rank correlations and Bland-Altman approach were used to assess agreement. The Kaplan-Meier method was used to evaluate the time to the first occurrence of a severe (grade 3+) AE and first CSD in QOL. Results: Correlations between the UNISCALE and multi-item assessments were modest (rho=0.49–0.66). At least one 10-point decline in the UNISCALE and multi-item assessments were reported by 58% and 40% respectively. At least one severe AE was reported in 44% of patients post-baseline. The percent agreement between experiencing a severe AE and a CSD in QOL was 49% and 59% for UNISCALE and the multi-item tools. For individual AE, the percent agreement between a CSD in AE and a CSD in QOL ranged from 37% to 50% for UNISCALE and 44% to 69% for the multi-item tools. The median time to the first CSD in QOL for UNISCALE and multi-item tools was 67 and 142 days respectively. The median time to the first occurrence of a severe AE was 304 days. Conclusions: QOL and AE provide quantifiably different information. A 10-point decline in QOL occurs earlier than CTC AE reporting. Patient reported outcomes may be more sensitive in identifying clinically relevant problems than physician rated symptom assessments. No significant financial relationships to disclose.

scholarly journals Combination of Immune Checkpoint Inhibitors and Radiotherapy for Advanced Non-Small-Cell Lung Cancer and Prostate Cancer: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zexi Xu ◽  
Jia Feng ◽  
Yiming Weng ◽  
Yao Jin ◽  
Min Peng
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Fixed Effects ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Clinical Manifestations ◽  
Grade 3

Objectives. Immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) have emerged as a breakthrough therapy in the treatment of various cancers. The combination has a strong rationale, but data on their efficacy and safety are still limited. Hence, we comprehensively searched the database and performed this study to elucidate the clinical manifestations of this combined strategy. Methods. We performed a meta-analysis of randomized trials that compared ICI plus RT with placebo plus RT or ICI alone for the treatment of advanced nonsmall-cell lung cancer (NSCLC) and prostate cancer. The outcomes included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events. A fixed-effects or random-effects model was adopted depending on between-study heterogeneity. Results. Three trials involving 1584 patients were included. ICI plus RT was significantly associated with improvement of OS (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.70–0.94, P = 0.004 ), PFS (HR = 0.64; 95% CI 0.56–0.72, P < 0.00001 ), and DCR (relative risk [RR] = 1.38; 95% CI 1.03–1.84, P = 0.03 ). A significant predictor for PFS with the combination of ICI and RT was age, as a significant improvement in PFS (HR = 0.49; 95% CI 0.37–0.64, P < 0.00001 ) was observed in NSCLC patients aged under 65 years. In safety analyses, patients receiving ICI plus RT had a significantly higher incidence of dyspnea (RR = 2.43; 95% CI 1.16–5.08, P = 0.02 ) and pneumonitis of grade 3 or higher (RR = 2.78; 95% CI 1.32–5.85, P = 0.007 ). Conclusion. The combination of ICI and RT was associated with improved OS, PFS, and DCR. Patients under 65 years will be the dominant beneficiaries. However, the incidence of dyspnea and pneumonia of grade 3 or higher also increased, which deserves our vigilance.

scholarly journals Gambaran Teknik Menyikat Gigi dan Indeks Plak pada Siswa SD GMIM Siloam Tonsealama

e-GIGI ◽  
2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Princess Keloay ◽  
Christy N. Mintjelungan ◽  
Damajanty H. C. Pangemanan
Keyword(s):  
Sampling Method ◽  
Tooth Brushing ◽  
Plaque Index ◽  
Cross Sectional ◽  
Combination Technique ◽  
Control And Prevention ◽  
Study Population ◽  
The Mean ◽  
Cross Sectional Design ◽  
Grade 3

Abstract: In Indonesia, children dental and mouth health is on the apprehensive level. The caries prevalence in children of 5 to 9 years old is 92.6% and the proportion of brushing their teeth properly is only 1.4%. The control and prevention of plaque forming can be done in a simple, effective, and practical way through brushing the teeth thoroughly and regularly. This study was aimed to obtain the tooth brushing technique and plaque index among students at SD GMIM Siloam Tonsealama (elementary school). This was a descriptive study with a cross sectional design. Study population consisted of elementary students og grade 3 to 5. We used total sampling method. There were 42 students as subjects. Data were obtained by observing their tooth brushing techniques. The results showed that all students used combination technique of tooth brushing. Most students had plaque index of moderate category. The mean plaque index of the subjects was 2.67. In conclusion, students at GMIM in Tonsealama used combination technique of tooth brushing, and their plaque index was categorized as moderate.Keywords: plaque index, brushing teeth technique Abstrak: Kesehatan gigi dan mulut anak di Indonesia masih sangat memrihatinkan. Prevalensi karies pada anak usia 5-9 tahun dilaporkan mencapai 92,6%, dan proporsi waktu menyikat gigi dengan benar sebesar 1,4%. Usaha untuk mengontrol dan mencegah pemben-tukan plak dapat dilakukan secara sederhana, efektif, dan praktis yaitu dengan cara menggosok gigi secara teliti dan teratur. Penelitian ini bertujuan untuk mengetahui gambaran teknik menyikat gigi dan indeks plak siswa SD GMIM Siloam Tonsealama. Jenis penelitian ialah deskriptif dengan desain potong lintang. Populasi penelitian terdiri dari siswa sekolah dasar kelas 3 sampai dengan 5. Pengambilan sampel menggunakan total sampling. Terdapat seba-nyak 42 siswa sebagai subyek penelitian. Pengumpulan data menggunakan formulir pemeriksaan. Hasil penelitian menunjukkan bahwa teknik menyikat kombinasi digunakan oleh seluruh subyek. Indeks plak paling banyak pada kategori sedang. Rerata nilai indeks plak yaitu 2,67. Simpulan penelitian ini ialah teknik menyikat gigi yang digunakan oleh siswa SD GMIM di Tonsealama ialah teknik kombinasi dengan indeks plak tergolong kategori sedangKata kunci: indeks plak, teknik menyikat gigi

Immune checkpoint inhibitor induced hepatitis: Risk factors, outcomes, and impact on survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14525-e14525
Author(s):  
Abdul Miah ◽  
Songzhu Zhao ◽  
Sandip H. Patel ◽  
Andrew Johns ◽  
Madison Grogan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Grade 3

e14525 Background: Immune checkpoint inhibitors (ICIs) have improved the survival of patients with multiple cancer types, however ICI treatment is associated with a unique set of immune-related adverse events (irAEs) that can affect any organ. Few studies have evaluated the risk factors and outcomes of ICI induced hepatitis (ICIH). Methods: We utilized an institutional database of patients with advanced cancers treated with ICI between 2011 and 2017 at The OSU Comprehensive Cancer Center to identify patients with ICIH. Any patient who received at least one dose of ICI alone or in combination with other systemic therapies either as part of clinical trial or standard of care were included. Clinical data were extracted through chart abstraction. irAEs were graded using the Common Terminology Criteria for Adverse Events v5. Overall survival (OS) was calculated from the date of ICI initiation to death from any cause or the date of the last follow-up. OS with 95% confidence intervals were estimated using the Kaplan–Meier method. OS was also evaluated by occurrence of ICIH using the log-rank test. Results: We identified 1,096 patients treated with at least one dose of ICI. Most common cancers included lung (n=224, 20%) and melanoma (n=342, 31%). The most common ICIs were PD1/L1 (n=774, 71%) and CTLA-4 inhibitors (n=195, 18%). ICIH of any grade occurred in 64 (6%) patients. Overall, 46 (71%) were male and median age was 60 years. Severity of hepatitis was grade 1-2 in 30 patients (47%) (Table 1). The incidence of ≥grade 3 ICIH in the entire cohort was 3.1%. Median time to ICIH diagnosis was 63 days. ICIH occurred alone in 24 patients, and co-occurred with other irAEs in 40 patients. The most common co-occurring irAEs were pneumonitis (n=7); colitis (n=15), thyroid abnormality (n=14); and dermatitis (n=15). ICIH was more common in women (p=0.038), in patients treated with combination ICIs (p<0.001), and among patients receiving first line therapy (p=0.018). Patients who developed ICIH had significantly longer OS than patients who did not develop ICIH; there was no difference in OS between patients with ≥grade 3 ICIH vs grade 1-2 (Table). 33 out of 34 patients with ≥grade3 ICIH were treated with steroids; 3 received mycophenolate and one received infliximab. Of patients with ≥grade 3 ICIH, 11 resumed ICI therapy without recurrent ICIH. Conclusions: Female sex, combination immunotherapy, and line of therapy were associated with ICIH. Patients with ICIH had improved clinical outcomes compared to those that did not develop ICIH, even those with higher grade toxicity. Further study is needed to assist in developing risk stratification models and optimal treatment for ICIH. OS of patients with and without immune checkpoint inhibitor hepatitis.[Table: see text]

scholarly journals An orthotopic murine model of human spinal metastasis: histological and functional correlations

2009 ◽  
Vol 10 (6) ◽  
pp. 501-512 ◽  
Author(s):  
Claudio E. Tatsui ◽  
Frederick F. Lang ◽  
Joy Gumin ◽  
Dima Suki ◽  
Naoki Shinojima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Median Time ◽  
Murine Model ◽  
Spinal Canal ◽  
Spinal Metastasis ◽  
Histological Studies ◽  
Neural Canal ◽  
Left And Right ◽  
The Mean

Object There is currently no reproducible animal model of human spinal metastasis that allows for laboratory study of the human disease. Consequently, the authors sought to develop an orthotopic model of spinal metastasis by using a human lung cancer cell line, and to correlate neurological decline with tumor growth. Methods To establish a model of spinal metastasis, the authors used a transperitoneal surgical approach to implant PC-14 lung tumors into the L-3 vertebral body of nude mice via a drill hole. In 24 animals, motor function was scored daily by using the validated semiquantitative Basso-Beattie-Bresnahan (BBB) scale. A second group of 26 animals (6 or 7 per time point) were sacrificed at specific times, and the spines were removed, sectioned, and stained. Canal compromise was analyzed quantitatively by determining the ratio of the area of the neural elements to the area of the spinal canal on histological sections (neural/canal ratio). Correlations between BBB score and histological evaluation of tumor growth were assessed. Results Lung cancer xenografts grew in all animals undergoing functional evaluation (24 mice) according to a reliable and reproducible time course, with paraplegia occurring at a median interval of 30 days following tumor implantation (95% CI 28.1–31.9 days). Importantly, the analysis defined 4 key milestones based on components of the BBB score; these were observed in all animals, were consistent, and correlated with histological progression of tumor. From Days 1 to 14, the mean BBB score declined from 21 to 19. The animals progressed from normal walking with the tail up to walking with the tail constantly touching the ground (milestone 1). The median time to tail dragging was 12 days (95% CI 10.8–13.2). Histological studies on Day 14 demonstrated that tumor had progressed from partial to complete VB infiltration, with initial compression of the neural elements and epidural tumor extension to adjacent levels (mean neural/canal ratio 0.32 ± 0.05, 7 mice). From Days 15 to 20/21 (left/right leg), the mean BBB score declined from 19 to 14. Animals showed gait deterioration, with the development of dorsal stepping (milestone 2). The median time to dorsal stepping was 21 days (95% CI 19.4–22.6) in the left hindlimb and 23 days (95% CI 20.6–25.4) in the right hindlimb. Histological studies on Day 21 demonstrated an increase in the severity of the neural element compression, with tumor extending to adjacent epidural and osseous levels (mean neural/canal ratio 0.19 ± 0.05, 6 mice). From Days 22 to 26/27 (left/right leg), the mean BBB score declined from 14 to 8. Animals had progressive difficulty ambulating, to the point where they showed only sweeping movements of the hindlimb (milestone 3). The median time to hindlimb sweeping was 26 days (95% CI 23.6–28.4) and 28 days (95% CI 27.1–28.9) in the left and right hindlimbs, respectively. Histological studies on Day 28 revealed progressive obliteration of the spinal canal (mean neural/canal ratio 0.09 ± 0.01, 7 mice). From Days 29 to 36, the animals progressed to paralysis (milestone 4). The median time to paralysis was 29 days (95% CI 27.6–30.4) and 30 days (95% CI 28.1–31.9) in the left and right hindlimbs, respectively. Conclusions The authors have developed an orthotopic murine model of human spinal metastasis in which neurological decline reproducibly correlates with severity of tumor progression. Although developed for lung cancer, this model can be expanded to study other types of metastatic or primary spinal tumors. Ultimately, this will allow testing of targeted therapies against specific tumor types.

scholarly journals Immune Checkpoint Inhibitors with or without Radiotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: A Systematic Review and Meta-Analysis

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1098
Author(s):  
Dong Yeong Kim ◽  
Pyeong Hwa Kim ◽  
Chong Hyun Suh ◽  
Kyung Won Kim ◽  
Ho Sung Kim
Keyword(s):  
Lung Cancer ◽  
Adverse Event ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Event Rates

This study aimed to evaluate the radiologic response and adverse event rates of immune checkpoint inhibitor (ICI) therapy with or without radiotherapy for the treatment of non-small cell lung cancer (NSCLC) brain metastases. A systematic literature search was performed up to January 3, 2020. Studies evaluating the intracranial objective response rates (ORR) and/or disease control rates (DCR) of ICI with or without radiotherapy for treating NSCLC brain metastases were included. Consequently, twelve studies satisfied inclusion criteria. ICI combined with radiotherapy (pooled ORR, 95%; DCR, 97%) showed better local efficacy compared to ICI monotherapy (pooled ORR, 24%; DCR, 44%; p < 0.01 for both ORR and DCR). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (5% vs. 4%; p = 0.93). In conclusion, ICI combined with radiotherapy showed better intracranial efficacy than ICI monotherapy for treating NSCLC brain metastases. CNS-related grade 3 or 4 adverse event rate was not statistically different between the two groups. Several prospective trials are needed to compare the efficacy of ICI combined with radiotherapy and ICI monotherapy.

Tamponade during immune checkpoint inhibitors therapy in lung cancer: case-reports and systematic review of the literature

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Mustafic ◽  
A Celebic ◽  
S Lannou ◽  
S Mallet ◽  
A Vieillard Baron ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Smoking Cessation ◽  
Cancer Therapy ◽  
Mortality Rate ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Immune Therapy ◽  
Pericardial Fluid

Abstract Introduction Immune therapy is a new option that has revolutionized cancer therapy. Immune checkpoint inhibitors target mostly either PD-1 (Pembrolizumab, Nivolumab) or PD-L1 (Durvalumab). Immune-related cardiotoxic side effects, among them, tamponade, initially thought to be rare, seem to be increasingly cited in the literature. Moreover, tobacco smoking is linked to 80% of lung cancers. Smoking during cancer therapy may influence on radiotherapy and chemotherapy outcomes but little is known on immunotherapy. Purpose We aimed to review all the published cases of tamponade during immune therapy for lung cancer and to report all the cases that occurred in the University Hospital Ambroise Paré. We also wanted to highlight the possible impact of tobacco on immunotherapy. Methods We conducted a literature review in the PubMED database, from database inception up to 02/14/2020, with a combination of the following terms: “tamponade AND ((immune checkpoint inhibitors) OR (PD-1) OR (PD-L1))”. We also reported all the tamponade cases occurred in our hospital from the beginning of immune checkpoint inhibitors therapy existence up to 02/14/2020. Results Seventeen cases citing tamponade were identified in the literature to which we added 3 cases from our hospital. Mortality rate at 1 month was of 20%. Nivolumab was involved in 80%, Pembrolizumab in 10% and Durvalumab in 10%. In 75%, lung cancer was with a stage IV. Men accounted for 85% and mean age was of 62 years. Active smokers represented 85% and passive smokers existed in 5%, after diagnosis, smoking cessation was done in 10%. Tamponade occurred either shortly after the first administrations but also after several doses. Pericardial fluid cytology revealed malignant cells in half of the cases and microbiology was always negative. For all the cases, excepted for one who was directly considered as palliative, an evacuation of the pericardial fluid was done. In 45% a corticotherapy was initiated. Two cases quickly worsened after pericardial evacuation by unmasking a probable myocarditis with cardiogenic shock which needed the use of a veno-arterial extracorporeal membrane oxygenation. Conclusions Tamponade under immune checkpoint inhibitors therapy appears less rare than initially thought and mortality rate at one month was not negligible. The use of regular echocardiography during this immune therapy may be crucial in detecting early stages of the disease process and smoking cessation should also be advised for these patients. The prevalence of complications among all the patients both exposed to immune therapy and tobacco could not be calculated in this work (case-reports), but some recent studies may indicate survival gains of smoking cessation. Further research establishing more specific guidelines is naturally necessary in dealing with this potentially fatal effect but also in establishing the possibly additional role of smoking in the cardiotoxicity of immunotherapy. Funding Acknowledgement Type of funding source: None

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