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Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over recent years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. There is ongoing discussion amongst oncology professionals about how best to optimise treatments in terms of sequencing to maximise the potential number of lines or to give the best treatments first. A previous south-west UK audit was completed in 2021 reviewing the drop off rates across 5 UK sites identifying that 69% of patients were able to receive second line therapy and 34% were able to receive third line therapy. Method(s): In this study we conducted retrospective analysis of all patients who commenced treatment with SACT for mRCC between 1st January 2018 and 30th June 2021 in 18 centres across the 4 nations of the United Kingdom. All NHS reimbursed treatment options including the COVID interim treatment guideline options were included. Patients who received SACT as part of a clinical trial were also included. Patients who continued on their respective lines of treatment were censored. We also identified patients who had been on a period of active surveillance before staring SACT in this cohort. Result(s): 1549 patients (71% male: 29% female) were included. IMDC subgroup patients included 21.6%favourable, 52.3% intermediate, 25.1%poor and 1% unavailable. 9.1% of patients had been on active surveillance before starting SACT - defined as a period of longer than 3 months from mRCC diagnosis to starting SACT. Of those patients that started SACT 60.5% of eligible patients had 2nd line therapy, 25.3% had 3rd line, 7.2% received 4th line therapy and only 1% had 5th line therapy. In the 1st line setting 58.9% received single agent VEGF TKI, 24.5% received combination ipilimumab and nivolumab (IO-IO) immunotherapy, 14 % received IO/ VEGF TKI combination and 2.6% received other/trial treatment. The single agent VEGF TKI ratio for 1st line SACT declined year by year with rising IO-IO and IO/VEGF TKI combination ratios seen. In the secondand third-line settings cabozantinib (33.2% 2nd line and 44.4% 3rd line) and nivolumab (32.8% 2nd line and 22.6% 3rd line) were the most common options. Disease progression or death was the most common cause of SACT discontinuation amounting to 57.4%, 62.5% and 79% of SACT cessation in the 1st, 2nd and 3rd lines respectively. Treatment toxicity SACT discontinuation rates were 22.8%, 21.4% and 10.9% for 1st, 2nd and 3rd lines respectively. Conclusion(s): These results suggest that with more treatment options available, including combination/immunotherapy therapies, more patients are able to receive second- and third-line therapies. That said there remains significant drop off rates mostly driven by disease progression that would support the use of our most effective therapies in the upfront setting.
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SESSION TITLE: Lung Nodule Biopsy: Yield and Accuracy SESSION TYPE: Original Investigations PRESENTED ON: 10/16/2022 10:30 am - 11:30 am PURPOSE: A variety of endpoints have been used to evaluate the diagnostic performance of navigational bronchoscopy for sampling peripheral pulmonary lesions (PPLs), including diagnostic yield (rate of biopsies with a specific diagnosis that facilitates clinical decisions) and diagnostic accuracy (yield plus a follow-up to assess for false negative/positive initial results). There is also significant variation in what non-malignant findings are considered diagnostic, especially regarding nonspecific inflammatory changes. We hypothesized a diagnostic yield definition excluding nonspecific findings as diagnostic would lead to few false negative PPL biopsies. METHOD(S): Our center maintains a prospective cohort of consecutive PPLs targeted via navigational bronchoscopy. Diagnostic yield was defined as specific findings readily explaining the presence of a PPL (malignancy, organizing pneumonia, granulomatous inflammation, frank purulence, other specific finding) permitting management without immediate additional diagnostic intervention. "Other specific finding" required pulmonologist and lung pathologist agreement. All other findings were considered non-diagnostic. RESULT(S): A total of 450 PPLs biopsied 2017-2019 with complete two-year follow-up were included in the analysis. Ultimately, 274 of 450 (60.9%) PPLs were determined to be malignant. Diagnostic biopsies were obtained in 331 cases (73.6%). There was a single false-positive among 228 malignant biopsies (0.4%, carcinoid tumor on cytopathology, alveolar adenoma on resection surgical pathology). Among 223 PPLs without malignant diagnosis at initial bronchoscopy, 48 were later determined to be malignant. Most (n=39) exhibited nonspecific abnormalities on initial pathology. Two of 104 specific benign biopsies were false negative (1.9%). Both demonstrated organizing pneumonia on initial pathology but re-biopsy months after index bronchoscopy revealed Hodgkin's lymphoma and metastatic renal cell carcinoma, respectively. The sensitivity, specificity, and positive predictive value of specific benign findings for an ultimately benign nodule were 58% (95% CI, 51-66%), 95% (86-99%), and 90% (70-97%). The sensitivity, specificity, and positive predictive value of nonspecific benign findings for an ultimately benign PPL diagnosis were 32% (95% CI, 25-39%), 19% (9-33%), and 20% (16-24%). CONCLUSION(S): A definition of diagnostic yield excluding nonspecific benign findings had low false positive/negative rates. If bronchoscopy is not diagnostic of malignancy, a specific benign finding was highly predictive of an ultimately benign PPL, while nonspecific findings poorly predicted benignity. CLINICAL IMPLICATIONS: This definition of diagnostic yield could be used as the primary outcome in future studies, permitting distribution of reliable diagnostic results without requiring years of follow-up. DISCLOSURES: No relevant relationships by Joyce Johnson No relevant relationships by Robert Lentz No relevant relationships by Kaele Leonard No relevant relationships by See-Wei Low PI ofan investigator-initiated study relationship with Medtronic Please note: >$100000 by Fabien Maldonado, value=Grant/Research Support PI on investigator-initiated relationship with Erbe Please note: $5001 - $20000 by Fabien Maldonado, value=Grant/Research Support Consulting relationship with Medtronic Please note: $5001 - $20000 by Fabien Maldonado, value=Honoraria co-I industry-sponsored trial relationship with Lung Therapeutics Please note: $5001 - $20000 by Fabien Maldonado, value=Grant/Research Support Board of director member relationship with AABIP Please note: $1-$1000 by Fabien Maldonado, value=Travel Consultant relationship with Medtronic/Covidien Please note: $1001 - $5000 by Otis Rickman, value=Consulting fee No relevant relationships by Briana Swanner Copyright © 2022 American College of Chest Physicians
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SESSION TITLE: Using Imaging for Diagnosis Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Immunotherapy is now a standard of care in solid-tumor oncology following the approvals of CTLA-4 and PD-1 inhibitors. Belzutifan, a small-molecule HIF-2a inhibitor, has recently gained FDA-approval for the treatment of advanced von Hippel-Lindau (VHL) associated renal cell carcinomas. CASE PRESENTATION: A 63-year-old female presented to our hospital with a one-day history of progressive dyspnea. Medical history is significant for metastatic renal cell carcinoma with pulmonary metastasis. Family and social history were noncontributory. Her cancer diagnosis was established in 2019 and had undergone cytoreductive nephrectomy and treatment with axitinib/pembrolizumab. As she had little improvement with immunotherapy, she was enrolled in a clinical trial at Memorial Sloan Kettering. Due to further disease progression, she was transitioned to lenvatinib/everolimus, though the treatment was discontinued due to anorexia and worsening pulmonary symptoms. Further work up revealed that she had ERG, MPL, VHL gene mutations. Thus, she was started on belzutifan two weeks prior to her presentation. Initial vitals were significant for hypoxia on room air that recovered with high flow nasal cannula (40L/80%). Physical examination was remarkable for severe respiratory distress with coarse breath sounds bilaterally. Laboratory studies revealed an acute leukocytosis with a neutrophilic prominence and a chronic metabolic alkalosis. COVID, flu PCR were negative. Chest x-ray demonstrated diffuse bilateral reticulonodular opacities. CTA revealed innumerable pulmonary nodules with areas of mass-like consolidation and a loculated left-sided pleural effusion. She was covered with azithromycin/ceftriaxone along with high-dose steroids and was admitted to the stepdown unit for further management. While in stepdown, she had a left PleurX catheter placed given her large effusion which was complicated by bloody output that required one unit of blood. Despite high-dose steroids, she had persistent hypoxia. As she remained unstable, goals of care discussions were held, which ultimately led to a change in code status to comfort measures. All aggressive measures were discontinued. She was started on comfort medications and ultimately passed away. DISCUSSION: Currently, neoplasms associated with VHL mutations are managed surgically to minimize the risk of metastatic disease. Nearly 70% of all patients with VHL mutations will develop renal cell carcinomas which means most patients undergo numerous surgical procedures. HIF-2a inhibition therefore offers an effective alternative that could reduce surgical burden and offer a new approach to management of VHL-associated disease. However due to its new approval, several adverse effects have yet to be documented. CONCLUSIONS: We report the only known case of Belzutifan-induced hypersensitivity pneumonitis and hope this case will become a useful contribution to the literature. Reference #1: Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R;MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425. PMID: 34818478. DISCLOSURES: No relevant relationships by Garrett Fiscus No relevant relationships by Niala Moallem No relevant relationships by Raj Parikh