Searched for: person:shume01
in-biosketch:true
Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action
Meyer, M-L; Peters, S; Mok, T S; Lam, S; Yang, P-C; Aggarwal, C; Brahmer, J; Dziadziuszko, R; Felip, E; Ferris, A; Forde, P M; Gray, J; Gros, L; Halmos, B; Herbst, R; Jänne, P A; Johnson, B E; Kelly, K; Leighl, N B; Liu, S; Lowy, I; Marron, T U; Paz-Ares, L; Rizvi, N; Rudin, C M; Shum, E; Stahel, R; Trunova, N; Ujhazy, P; Bunn, P A; Hirsch, F R
BACKGROUND:Lung cancer remains a critical public health issue, presenting multifaceted challenges in prevention, diagnosis, and treatment. This article aims to review the current landscape of lung cancer research and management, delineate the persistent challenges, and outline pragmatic solutions. MATERIALS AND METHODS/METHODS:Global experts from academia, regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the National Cancer Institute (NCI), professional societies, the pharmaceutical and biotech industries, and patient advocacy groups were gathered by the New York Lung Cancer Foundation to review the state of the art in lung cancer and to formulate calls to action. RESULTS:Improving lung cancer management and research involves promoting tobacco cessation, identifying individuals at risk who could benefit from early detection programs, and addressing treatment-related toxicities. Efforts should focus on conducting well-designed trials to determine the optimal treatment sequence. Research into innovative biomarkers and therapies is crucial for more personalized treatment. Ensuring access to appropriate care for all patients, whether enrolled in clinical trials or not, must remain a priority. CONCLUSIONS:Lung cancer is a major health burden worldwide, and its treatment has become increasingly complex over the past two decades. Improvement in lung cancer management and research requires unified messaging and global collaboration, expanded education, and greater access to screening, biomarker testing, treatment, as well as increased representativeness, participation, and diversity in clinical trials.
PMID: 39413875
ISSN: 1569-8041
CID: 5718592
Race, age at diagnosis and histological characteristics of lung cancer in never-smokers (LCINS) and ever-smokers in low-dose computed tomography (LDCT) screening: a systematic review and meta-analysis
Triphuridet, Natthaya; Nagasaka, Misako; Shum, Elaine; Ou, Sai-Hong Ignatius
BACKGROUND/UNASSIGNED:We previously demonstrated in a meta-analysis there was no difference in risk ratio (RR) of lung cancer detected by low-dose computed tomography (LDCT) screening among female never-smokers (NS) and male ever-smokers (ES) in Asia. LDCT screening significantly decreased lung cancer death among Asian NS compared to Asian ES (RR =0.27, P<0.001). METHODS/UNASSIGNED:We investigated if race, age at diagnosis, and histology further differentiate lung cancer diagnosed by LDCT among in NS and ES using the 14 studies from our previous meta-analysis. RESULTS/UNASSIGNED:70.37%). CONCLUSIONS/UNASSIGNED:Among normal-risk individuals, LCINS had a significantly higher likelihood of being diagnosed among Asians than non-Asians, predominantly manifesting as ADC and diagnosed approximately 2 years younger than ES suggesting that the age limit to initiate lung cancer screening in NS may be set lower compared to LDCT lung cancer screening among ES.
PMCID:11157373
PMID: 38854936
ISSN: 2218-6751
CID: 5668792
Top 20 EGFR+ NSCLC Clinical and Translational Science Papers That Shaped the 20 Years Since the Discovery of Activating EGFR Mutations in NSCLC. An Editor-in-Chief Expert Panel Consensus Survey
Ou, Sai-Hong Ignatius; Le, Xiuning; Nagasaka, Misako; Reungwetwattana, Thanyanan; Ahn, Myung-Ju; Lim, Darren W T; Santos, Edgardo S; Shum, Elaine; Lau, Sally C M; Lee, Jii Bum; Calles, Antonio; Wu, Fengying; Lopes, Gilberto; Sriuranpong, Virote; Tanizaki, Junko; Horinouchi, Hidehito; Garassino, Marina C; Popat, Sanjay; Besse, Benjamin; Rosell, Rafael; Soo, Ross A
The year 2024 is the 20th anniversary of the discovery of activating epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Since then, tremendous advances have been made in the treatment of NSCLC based on this discovery. Some of these studies have led to seismic changes in the concept of oncology research and spurred treatment advances beyond NSCLC, leading to a current true era of precision oncology for all solid tumors. We now routinely molecularly profile all tumor types and even plasma samples of patients with NSCLC for multiple actionable driver mutations, independent of patient clinical characteristics nor is profiling limited to the advanced incurable stage. We are increasingly monitoring treatment responses and detecting resistance to targeted therapy by using plasma genotyping. Furthermore, we are now profiling early-stage NSCLC for appropriate adjuvant targeted treatment leading to an eventual potential "cure" in early-stage EGFR+ NSCLC which have societal implication on implementing lung cancer screening in never-smokers as most EGFR+ NSCLC patients are never-smokers. All these advances were unfathomable in 2004 when the five papers that described "discoveries" of activating EGFR mutations (del19, L858R, exon 20 insertions, and "uncommon" mutations) were published. To commemorate this 20th anniversary, we assembled a global panel of thoracic medical oncology experts to select the top 20 papers (publications or congress presentation) from the 20 years since this seminal discovery with December 31, 2023 as the cutoff date for inclusion of papers to be voted on. Papers ranked 21 to 30 were considered "honorable mention" and also annotated. Our objective is that these 30 papers with their annotations about their impact and even all the ranked papers will serve as "syllabus" for the education of future thoracic oncology trainees. Finally, we mentioned potential practice-changing clinical trials to be reported. One of them, LAURA was published online on June 2, 2024 was not included in the list of papers to be voted on but will surely be highly ranked if this consensus survery is performed again on the 25th anniversay of the discovery EGFR mutations (i.e. top 25 papers on the 25 years since the discovery of activating EGFR mutations).
PMCID:11208875
PMID: 38938224
ISSN: 1179-2728
CID: 5733402
Berzosertib Plus Topotecan vs Topotecan Alone in Patients With Relapsed Small Cell Lung Cancer: A Randomized Clinical Trial
Takahashi, Nobuyuki; Hao, Zhonglin; Villaruz, Liza C; Zhang, Jun; Ruiz, Jimmy; Petty, W Jeffrey; Mamdani, Hirva; Riess, Jonathan W; Nieva, Jorge; Pachecho, Jose M; Fuld, Alexander D; Shum, Elaine; Chauhan, Aman; Nichols, Samantha; Shimellis, Hirity; McGlone, Jessie; Sciuto, Linda; Pinkiert, Danielle; Graham, Chante; Shelat, Meenakshi; Kattappuram, Robbie; Abel, Melissa; Schroeder, Brett; Upadhyay, Deep; Krishnamurthy, Manan; Sharma, Ajit Kumar; Kumar, Rajesh; Malin, Justin; Schultz, Christopher W; Goyal, Shubhank; Redon, Christophe E; Pommier, Yves; Aladjem, Mirit I; Gore, Steven D; Steinberg, Seth M; Vilimas, Rasa; Desai, Parth; Thomas, Anish
IMPORTANCE/UNASSIGNED:Patients with relapsed small cell lung cancer (SCLC), a high replication stress tumor, have poor prognoses and few therapeutic options. A phase 2 study showed antitumor activity with the addition of the ataxia telangiectasia and Rad3-related kinase inhibitor berzosertib to topotecan. OBJECTIVE/UNASSIGNED:To investigate whether the addition of berzosertib to topotecan improves clinical outcomes for patients with relapsed SCLC. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Between December 1, 2019, and December 31, 2022, this open-label phase 2 randomized clinical trial recruited 60 patients with SCLC and relapse after 1 or more prior therapies from 16 US cancer centers. Patients previously treated with topotecan were not eligible. INTERVENTIONS/UNASSIGNED:Eligible patients were randomly assigned to receive topotecan alone (group 1), 1.25 mg/m2 intravenously on days 1 through 5, or with berzosertib (group 2), 210 mg/m2 intravenously on days 2 and 5, in 21-day cycles. Randomization was stratified by tumor sensitivity to first-line platinum-based chemotherapy. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included overall survival (OS) in the overall population and among patients with platinum-sensitive or platinum-resistant tumors. The PFS and OS for each treatment group were estimated using the Kaplan-Meier method. The log-rank test was used to compare PFS and OS between the 2 groups, and Cox proportional hazards models were used to estimate the treatment hazard ratios (HRs) and the corresponding 2-sided 95% CI. RESULTS/UNASSIGNED:Of 60 patients (median [range] age, 59 [34-79] years; 33 [55%] male) included in this study, 20 were randomly assigned to receive topotecan alone and 40 to receive a combination of topotecan with berzosertib. After a median (IQR) follow-up of 21.3 (18.1-28.3) months, there was no difference in PFS between the 2 groups (median, 3.0 [95% CI, 1.2-5.1] months for group 1 vs 3.9 [95% CI, 2.8-4.6] months for group 2; HR, 0.80 [95% CI, 0.46-1.41]; P = .44). Overall survival was significantly longer with the combination therapy (5.4 [95% CI, 3.2-6.8] months vs 8.9 [95% CI, 4.8-11.4] months; HR, 0.53 [95% CI, 0.29-0.96], P = .03). Adverse event profiles were similar between the 2 groups (eg, grade 3 or 4 thrombocytopenia, 11 of 20 [55%] vs 20 of 40 [50%], and any grade nausea, 9 of 20 [45%] vs 14 of 40 [35%]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial, treatment with berzosertib plus topotecan did not improve PFS compared with topotecan therapy alone among patients with relapsed SCLC. However, the combination treatment significantly improved OS. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03896503.
PMCID:10570917
PMID: 37824137
ISSN: 2374-2445
CID: 5628102
Selective Personalized Radioimmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial
Ohri, Nitin; Jolly, Shruti; Cooper, Benjamin T; Kabarriti, Rafi; Bodner, William R; Klein, Jonathan; Guha, Chandan; Viswanathan, Shankar; Shum, Elaine; Sabari, Joshua K; Cheng, Haiying; Gucalp, Rasim A; Castellucci, Enrico; Qin, Angel; Gadgeel, Shirish M; Halmos, Balazs
PURPOSE/OBJECTIVE:Standard therapy for locally advanced non-small-cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. For biomarker-selected patients with LA-NSCLC, we hypothesized that sequential pembrolizumab and risk-adapted radiotherapy, without chemotherapy, would be well-tolerated and effective. METHODS:Patients with stage III NSCLC or unresectable stage II NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible for this trial. Patients with a PD-L1 tumor proportion score (TPS) of ≥50% received three cycles of induction pembrolizumab (200 mg, once every 21 days), followed by a 20-fraction course of risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic volume exceeding 20 cc, 48 Gy delivered to smaller lesions), followed by consolidation pembrolizumab to complete a 1-year treatment course. The primary study end point was 1-year progression-free survival (PFS). Secondary end points included response rates after induction pembrolizumab, overall survival (OS), and adverse events. RESULTS:Twenty-five patients with a PD-L1 TPS of ≥50% were enrolled. The median age was 71, most patients (88%) had stage IIIA or IIIB disease, and the median PD-L1 TPS was 75%. Two patients developed disease progression during induction pembrolizumab, and two patients discontinued pembrolizumab after one infusion because of immune-related adverse events. Using RECIST criteria, 12 patients (48%) exhibited a partial or complete response after induction pembrolizumab. Twenty-four patients (96%) received definitive thoracic radiotherapy. The 1-year PFS rate is 76%, satisfying our efficacy objective. One- and 2-year OS rates are 92% and 76%, respectively. The most common grade 3 adverse events were colitis (n = 2, 8%) and esophagitis (n = 2, 8%), and no higher-grade treatment-related adverse events have occurred. CONCLUSION/CONCLUSIONS:Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with LA-NSCLC with a PD-L1 TPS of ≥50%.
PMID: 37988638
ISSN: 1527-7755
CID: 5608482
Neoadjuvant Targeted Therapy in Resectable Non-Small Cell Lung Cancer: Current and Future Perspectives
Lee, Jay M; McNamee, Ciaran J; Toloza, Eric; Negrao, Marcelo V; Lin, Jules; Shum, Elaine; Cummings, Amy L; Kris, Mark G; Sepesi, Boris; Bara, Ilze; Kurtsikidze, Nino; Schulze, Katja; Ngiam, Celina; Chaft, Jamie E
The standard of care (SoC) for medically operable patients with early-stage (stage I-IIIB) non-small cell lung cancer (NSCLC) is surgery combined with (neo)adjuvant systemic therapy for patients with II-IIIB disease and some stage IB or, rarely, chemoradiation (stage III disease with mediastinal lymph node metastases). Despite these treatments, metastatic recurrence is common and associated with poor survival, highlighting the need for systemic therapies that are more effective than the current SoC. Following the success of targeted therapy (TT) in patients with advanced NSCLC (aNSCLC) harboring oncogenic drivers, these agents are being investigated for the perioperative (neoadjuvant and adjuvant) treatment of patients with early-stage NSCLC (eNSCLC). Adjuvant osimertinib is the only TT approved for use in the early-stage setting and there are no approved neoadjuvant TTs. We discuss the importance of comprehensive biomarker testing at diagnosis to identify individuals who may benefit from neoadjuvant targeted treatments and review emerging data from neoadjuvant TT trials. We also address the potential challenges for establishing neoadjuvant TTs as SoC in the early-stage setting, including the identification and validation of early response markers to guide care and accelerate drug development, and discuss safety considerations in the perioperative setting. Initial data indicate that neoadjuvant TTs are effective and well tolerated in patients with EGFR- or ALK-positive eNSCLC. Data from ongoing trials will determine whether neoadjuvant targeted agents will become a new SoC for individuals with oncogene-addicted resectable NSCLC.
PMID: 37451404
ISSN: 1556-1380
CID: 5537892
Extended Survival in Patients With Non-Small-Cell Lung Cancer-Associated Brain Metastases in the Modern Era
Berger, Assaf; Mullen, Reed; Bernstein, Kenneth; Alzate, Juan Diego; Silverman, Joshua S; Sulman, Erik P; Donahue, Bernadine R; Chachoua, Abraham; Shum, Elaine; Velcheti, Vamsidhar; Sabari, Joshua; Golfinos, John G; Kondziolka, Douglas
BACKGROUND:Brain metastases (BM) have long been considered a terminal diagnosis with management mainly aimed at palliation and little hope for extended survival. Use of brain stereotactic radiosurgery (SRS) and/or resection, in addition to novel systemic therapies, has enabled improvements in overall and progression-free (PFS) survival. OBJECTIVE:To explore the possibility of extended survival in patients with non-small-cell lung cancer (NSCLC) BM in the current era. METHODS:During the years 2008 to 2020, 606 patients with NSCLC underwent their first Gamma Knife SRS for BM at our institution with point-of-care data collection. We reviewed clinical, molecular, imaging, and treatment parameters to explore the relationship of such factors with survival. RESULTS:The median overall survival was 17 months (95% CI, 13-40). Predictors of increased survival in a multivariable analysis included age <65 years (P < .001), KPS ≥80 (P < .001), absence of extracranial metastases (P < .001), fewer BM at first SRS (≤3, P = .003), and targeted therapy (P = .005), whereas chemotherapy alone was associated with shorter survival (P = .04). In a subgroup of patients managed before 2016 (n = 264), 38 (14%) were long-term survivors (≥5 years), of which 16% required no active cancer treatment (systemic or brain) for ≥3 years by the end of their follow-up. CONCLUSION/CONCLUSIONS:Long-term survival in patients with brain metastases from NSCLC is feasible in the current era of SRS when combined with the use of effective targeted therapeutics. Of those living ≥5 years, the chance for living with stable disease without the need for active treatment for ≥3 years was 16%.
PMID: 36722962
ISSN: 1524-4040
CID: 5420082
Low dose computed tomography (LDCT) screening in Asian female never-smokers is as efficacious in detecting lung cancer as in Asian male-ever-smokers: a systematic review and meta-analysis
Triphuridet, Natthaya; Zhang, Shannon S; Nagasaka, Misako; Gao, Yanfei; Zhao, Joseph J; Syn, Nicholas L; Hanaoka, Takaomi; Ou, Sai-Hong Ignatius; Shum, Elaine
INTRODUCTION/BACKGROUND:Lung cancer in never-smokers is the major cancer cause of death globally. We compared the efficacy of low-dose computed tomography (LDCT) lung cancer screening among never-smokers versus ever-smokers using systematic review and meta-analysis. METHODS:LDCT lung cancer screening studies simultaneously included both ever-smoker and never-smoker participants published by April 30, 2021 were searched via Pubmed/Scopus. Primary outcome measure was relative risk (RR) of lung cancer diagnosed among never-smokers versus ever-smokers. RESULTS:Fourteen studies (13 from Asia) were included (141,396 ever-smokers, 109,251 never-smokers, 1961 lung cancer cases diagnosed). RR of lung cancer diagnosed between ever-smokers versus never-smokers overall was 1.21 (95%CI: 0.89 - 1.65), 1.37 (95%CI: 1.08 - 1.75) among males, and 0.88 (95%CI: 0.59 - 1.31) among females. RR was 1.78 (95%CI: 1.41 - 2.24) and 1.22 (95%CI: 0.89 - 1.68) for Asian female never-smokers versus male never-smokers and versus male ever-smokers respectively, and 0.99 (95%CI: 0.65 - 1.50) versus high-risk ever-smokers (≥30 pack-years). Proportional meta-analysis showed significantly more lung cancers diagnosed at first scan (95.4% {95%CI: 84.9 - 100.0} versus 70.9% {95%CI: 54.6 - 84.9}, P = 0.010) and at stage 1 (88.5% {95%CI: 79.3 - 95.4} versus 79.7% {95%CI: 71.1 - 87.4}, P = 0.071) among never-smokers versus ever-smokers, respectively. RR of lung-cancer death and 5-years all-cause mortality in never-smokers versus ever-smokers was 0.27 (95%CI: 0.1 - 0.55, p<0.001), and 0.13 (95%CI: 0.05 - 0.33) respectively. CONCLUSIONS:The RR of lung cancer detected by LDCT screening among female never-smokers and male ever-smokers in Asia was statistically similar. Mortality from the lung cancer diagnosed was significantly reduced among never-smokers versus ever-smokers.
PMID: 36775191
ISSN: 1556-1380
CID: 5421172
In vivo metabolomics identifies CD38 as an emergent vulnerability in LKB1 -mutant lung cancer
Deng, Jiehui; Peng, David H; Fenyo, David; Yuan, Hao; Lopez, Alfonso; Levin, Daniel S; Meynardie, Mary; Quinteros, Mari; Ranieri, Michela; Sahu, Soumyadip; Lau, Sally C M; Shum, Elaine; Velcheti, Vamsidhar; Punekar, Salman R; Rekhtman, Natasha; Dowling, Catríona M; Weerasekara, Vajira; Xue, Yun; Ji, Hongbin; Siu, Yik; Jones, Drew; Hata, Aaron N; Shimamura, Takeshi; Poirier, John T; Rudin, Charles M; Hattori, Takamitsu; Koide, Shohei; Papagiannakopoulos, Thales; Neel, Benjamin G; Bardeesy, Nabeel; Wong, Kwok-Kin
UNLABELLED:. Surprisingly, compared with other genetic subsets, murine and human LKB1-mutant NSCLC show marked overexpression of the NAD+-catabolizing ectoenzyme, CD38 on the surface of tumor cells. Loss of LKB1 or inactivation of Salt-Inducible Kinases (SIKs)-key downstream effectors of LKB1- induces CD38 transcription induction via a CREB binding site in the CD38 promoter. Treatment with the FDA-approved anti-CD38 antibody, daratumumab, inhibited growth of LKB1-mutant NSCLC xenografts. Together, these results reveal CD38 as a promising therapeutic target in patients with LKB1 mutant lung cancer. SIGNIFICANCE/CONCLUSIONS:tumor suppressor of lung adenocarcinoma patients and are associated with resistance to current treatments. Our study identified CD38 as a potential therapeutic target that is highly overexpressed in this specific subtype of cancer, associated with a shift in NAD homeostasis.
PMCID:10153147
PMID: 37131623
ISSN: 2692-8205
CID: 5507602
The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial (SPRINT) [Meeting Abstract]
Ohri, N; Jolly, S; Cooper, B T; Kabarriti, R; III, W R B; Klein, J; Viswanathan, S; Kaufman, R; Shum, E; Sabari, J K; Cheng, H; Gucalp, R; Castellucci, E; Qin, A; Gadgeel, S M; Halmos, B
Purpose/Objective(s): Standard therapy for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy (chemoRT), which is usually followed by adjuvant durvalumab. We performed a prospective trial testing sequential pembrolizumab and risk-adapted radiotherapy without chemotherapy for biomarker-selected LA-NSCLC patients. Materials/Methods: Patients with AJCC version 8 stage III NSCLC or unresectable stage II NSCLC and ECOG performance status 0-1 were eligible for this trial. Subjects with PD-L1 tumor proportion score (TPS) >= 50% received three cycles of induction pembrolizumab (200 mg, every 21 days), underwent restaging FDG-PET/CT, received risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic tumor volume exceeding 20 cc and 48 Gy delivered to smaller lesions, all in 20 daily fractions), and then received up to 13 cycles of additional pembrolizumab. Subjects with PD-L1 TPS < 50% received concurrent chemoRT, and adjuvant durvalumab was recommended for patients without disease progression. The primary study endpoint was one-year progression-free survival (PFS) for subjects treated with pembrolizumab and radiotherapy (pembroRT), which we hypothesized would exceed 65%. Other study endpoints included 1-year overall survival (OS) and rates of clinician-scored (CTCAE v. 4.03) and patient-reported (PRO-CTCAE) adverse events observed over one year.
Result(s): Twenty-five subjects with PD-L1 TPS >= 50% and 12 subjects with PD-L1 TPS < 50% from three institutions were enrolled between August 2018 and November 2021. Median age was 70. Twenty-four subjects had stage II-IIIA disease, and 13 had stage IIIB-IIIC disease. Except for PD-L1 TPS, subject characteristics did not differ significantly across treatment groups. Ten out of the 12 subjects with ChemoRT received adjuvant durvalumab, and one received adjuvant osimertinib for EGFR mutation. The median follow-up duration is 15 months. Compared to patients treated with chemoRT, treatment with pembroRT has yielded numerically higher 1-year PFS (72% v. 46%, log rank p=0.232) and OS (91% v. 73%, log rank p=0.213) rates. Similar rates of grade 3 physician-scored adverse events have been observed with pembroRT (24%) and chemoRT (25%). Less severe patient-reported adverse events occurred with pembroRT compared to chemoRT (See Table).
Conclusion(s): Treatment with pembrolizumab and risk-adapted radiotherapy without chemotherapy is a promising approach for LA-NSCLC patients with PD-L1 TPS >= 50%. In addition to yielding high disease control rates, this strategy appears to reduce patient-reported adverse events compared to standard chemoRT and adjuvant therapy.
Copyright
EMBASE:2020264048
ISSN: 1879-355x
CID: 5366302