ABSTRACT
Introduction: Acromegaly is an uncommon pituitary disorder with an incidence of six per million persons. While hypertension is often encountered in these patients, heart failure rarely is seen with an incidence rate under 10%. We describe a case of an individual who was diagnosed with acromegaly after an acute exacerbation of heart failure with subsequent management requiring an LVAD to perform Transsphenoidal Surgery (TSS). Case Description: 37-year-old male otherwise healthy initially presented to an emergency room and was found to be in acute heart failure exacerbation. Concerning acromegaly features included macrognathia, enlarged hands and feet, swollen phalanges, widened spacing of teeth, and frontal bossing. IGF-1 level was found 455 ng/mL. MRI showed a 10mm macroadenoma. A right heart catheterization showed elevated filling pressures. Cardiac MRI showed no defects or enhancement. Endomyocardial biopsy showed no inflammatory infiltrates or evidence of infiltrative diseases. Patient had an ejection fraction of 15% corroborated by cardiac MRI along with the presence of aortic root dilatation and mitral regurgitation. The patient started on 0.5mg of Cabergoline twice weekly and 120mg weekly Lanreotide injections. Patient stabilized with plans for further close monitoring and outpatient neurosurgical evaluation. The COVID-19 pandemic and insurance gaps led the patient to spend two years off his medicines and he was unable to be seen by his medical team. Patient was seen by our system after recurrent hospitalizations for heart failure at our sister hospital, AICD was unable to be placed due to the patient's anatomy, he was placed on wearable cardiac defibrillator and required milrinone infusion for progression to end-stage heart failure with cardiac cachexia. At our institution, the patient was evaluated for Orthotopic Heart Transplant (OHT) but due to active GH secreting macroadenoma there was concern for OHT failure without TSS. Decision was made to utilize LVAD as Bridge-to-Transplant for OHT so the patient could be stabilized and safely undergo TSS. The patient tolerated surgeries well and is currently on the active transplant list. Discussion(s): Heart failure is an uncommon presentation of severe acromegaly requiring multidisciplinary management. We describe a case of a patient who initially presented with heart failure too unstable for surgery. Due to the COVID-19 pandemic the patient's disease progressed resulting in end-stage heart failure requiring LVAD placement for further treatment. We would like to draw attention to the use of LVAD placement in acromegalic patients who develop severe cardiovascular disease who are not candidates for OHT.Copyright © 2023
ABSTRACT
Introduction: The PACIFIC trial demonstrated that a year of consolidation PD-(L)1 inhibition following concurrent chemoradiation (CRT) for unresectable stage III NSCLC improves overall survival (OS). The optimal duration of consolidation IO therapy in this setting is undefined. Studies in metastatic NSCLC demonstrate that combination PD-(L)1/CTLA-4 inhibition improves OS over chemotherapy alone. This trial evaluated the use of combination Nivolumab (N) plus Ipilimumab (IPI) or N alone for up to 6 months in unresectable stage III NSCLC after concurrent CRT. Methods: This is a randomized phase II, multicenter trial of 105 pts with unresectable stage IIIA/IIIB NSCLC. All pts received concurrent CRT and were then enrolled and randomized 1:1 to receive N 480mg IV q4wks (Arm A) for up to 24 weeks or N 3mg/kg IV q2 wks + IPI 1mg/kg IV q6 wks (Arm B) for up to 24 weeks. The primary endpoint is 18-month PFS compared to historical controls of CRT alone for arm A (30%) and CRT followed by Durva for arm B (44%). Secondary endpoints include OS and toxicity. Results: From 9/2017 to 4/2021, 105 pts were enrolled and randomized, 54 to N alone (A) and 51 to N + IPI (B). The baseline characteristics for arm A/B: median age (65/63), male (44.4%/56.9%), stage IIIA (55.6%/56.9%), stage IIIB (44.4%/43.1%), non-squamous (57.4%/54.9%), and squamous (42.6%/45.1%). The percentage of pts completing the full treatment was 70.4% in A and 56.9% in B (p=0.15). Median f/u was 24.5 and 24.1 months on A and B, respectively. The 18-month PFS was 62.3% on A (p <0.1) and 67% on B (p <0.1), and median PFS was 25.8 months and 25.4 months, respectively. Median OS was not reached on either arm, but the 18- and 24-month OS estimates were 82.1% and 76.6% for A and 85.5% and 82.8% for B, respectively. Treatment-related adverse events (trAE) on arm A/B were 72.2%/80.4%, and grade ≥3 trAEs on arm A/B were 38.9%/52.9%. There was 1 grade 5 event in each arm (COVID19-A, Cardiac Arrest-B). The number of pts with grade ≥2 pneumonitis were 12 (22.2%) in A and 15 (29.4%) in B, with 5 (9.3%) and 8 (15.7%) grade ≥3 events, respectively. The most common (>10%) non-pneumonitis trAEs in A were fatigue (31.5%), rash (16.7%), dyspnea (14.8%), and hypothyroidism (13%), and in B were fatigue (31.4%), diarrhea (19.6%), dyspnea (19.6%), pruritus (17.7%), hypothyroidism (15.7%), rash (15.7%), arthralgia (11.8%), and nausea (11.8%). Conclusions: Following concurrent CRT for unresectable stage III NSCLC, both N and N + IPI demonstrated improved 18-month PFS compared with historical controls despite a shortened interval (6 months) of treatment. OS data are still maturing but 18- and 24-month OS estimates compare favorably to prior consolidation trials. Toxicity for N alone was similar to prior single-agent trials, and the combination of N + IPI resulted in a higher incidence of trAE’s, although consistent with prior reports. Keywords: Consolidation Immunotherapy, Stage III NSCLC
ABSTRACT
Background. Infectious respiratory-track pathogens are a common trigger of healthcare capacity strain, e.g. the COVID19 pandemic. Patient risk stratification models to identify low-risk patients can help improve patient care processes and allocate limited resources. Many existing deterioration indices are based entirely on structured data from the Electronic Health Record (EHR) and ignore important information from other data sources. However, chest radiographs have been demonstrated to be helpful in predicting the progress of respiratory diseases. We developed a joint EHR and chest x-ray (CXR) model method and applied it to identify low-risk COVID19+ patients within the first 48 hours of hospital admission. Methods. All COVID19+ patients admitted to a large urban hospital between March 2020 and February 2021 were included. We trained an image model using large public chest radiograph datasets and fine-tuned this model to predict acute dyspnea using a cohort from the same hospital. We then combined this image model with two existing EHR deterioration indices to predict the risk of a COVID19+ patient being intubated, receiving a nasal cannula, or being treated with a vasopressor. We evaluated models' ability to identify low-risk patients by using the positive predictive value (PPV). Results. The image-augmented deterioration index was able to identify 12% of 716 COVID-19+ patients as low risk with 0.95 positive predictive value in the first 48 hours of admission. In contrast, when used individually, the EHR and CXR models each identified roughly 3% of the patients with a PPV of 0.95. Predicting Low Risk Patients Aggregated predictions for COVID19 positive patients within the first 48 hours of admission, shown with exponential weight moving average and 95% CIs. Each plot shows the number of patients flagged as low-risk by lowest aggregated prediction and the resulting accuracy for that fraction of patients. The bottom plot compares the MCURES fused model to the MCURES model. The top plot compares the EDI fused model to the EDI model. Conclusion. Our multi-modal models were able to identify far more patients at low-risk of COVID19 deterioration than models trained on either modality alone. This indicates the importance of combining structured data with chest X-rays when creating a deterioration index performance for infectious respiratory-track diseases.
ABSTRACT
Clinical outcomes for limited stage small cell lung cancer (LS-SCLC) remain suboptimal. Standard of care chemoradiation with platinum/etoposide and thoracic radiation to 45 Gy delivered twice daily followed by prophylactic cranial irradiation yields a median overall survival of 30 months. LU005 is a randomized phase II/III trial designed to test the addition of atezolizumab to concurrent chemoradiation. Patients with LS-SCLC (Tx-T4, N0-N3, M0) are randomly assigned in a 1:1 ratio to either standard chemoradiation, consisting of thoracic radiation (45 Gy twice daily or 66 Gy daily) with concurrent platinum/etoposide chemotherapy, or the experimental arm, consisting of the same chemoradiation regimen plus the addition of atezolizumab delivered concurrently with thoracic radiation, every 3 weeks for 12 months duration. Thoracic radiation begins with the second cycle of chemotherapy in both treatment arms. Stratification variables include radiation schedule (once daily vs. twice daily), chemotherapy (cisplatin vs. carboplatin), gender, and performance status (PS 0/1 vs. 2). Prophylactic cranial radiation is recommended for patients who have a response to treatment. The phase II primary endpoint is progression free survival (PFS) and the phase III primary endpoint is overall survival (OS). The overall sample size for phase II/III will be 506. Secondary endpoints include objective response rates, local control, distant metastases free, and quality of life. Correlative studies will include blood and tissue based tumor mutational burden analysis, with the hypothesis that higher mutational burden will predict for improved PFS in the experimental arm. As of 3/01/2021, 374 sites are approved to enroll patients. Two-hundred patients have been accrued. Current enrollment is ahead of projected accrual. LU005 is a randomized II/III trial testing the addition of atezolizumab to standard chemoradiation for LS-SCLC. Accrual remains robust in spite of the ongoing COVID 19 pandemic. Funding: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI) and Genentech. [ABSTRACT FROM AUTHOR] Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)