PURPOSE A substantial proportion of cancers are preventable through established risk factor modification and evidence-based screening strategies. However, emerging screening technologies have created new challenges for clinicians in identifying which individuals may benefit most and how to contextualize these approaches within existing prevention frameworks. METHODS We projected individualized probabilities of 10-year and lifetime cancer risk across a population as well as potential improvement with healthy behaviors in the UK Biobank (UKB). RESULTS A total of 118 distinct variables were included across 38 cancer-specific models. The distribution of lifetime cancer risk had a rightward skew and wide variation for both men and women. The median lifetime cancer risk was 29.5% for men (IQR, 8.4%) and 21.0% for women (IQR, 8.8%). If all modifiable risk factors were set to the ideal state, this decreased to 20.5% for men (IQR, 3.9%) and 16.5% for women (IQR, 4.9%). There was considerable overlap between age groups, with men age 50-59 years at the 90th percentile having greater risk (11.9%) compared with men age 60-70 years at the 25th percentile (11.8%), and women age 40-49 years at the 90th percentile having greater risk (7.4%) compared with women age 50-59 years at the 60th percentile (6.8%) and women age 60-70 years at the 20th percentile (7.3%). CONCLUSION Lifetime cancer risk varies widely across the UKB cohort, but this risk decreases substantially with risk factor modification. There was considerable overlap in 10-year cancer risk between age groups, suggesting that discussion regarding future screening guidelines should account for more than age and sex as more evidence becomes available in the future.
PURPOSE Bispecific antibodies (BsAbs) targeting B-cell maturation antigen show remarkable efficacy in relapsed/refractory multiple myeloma (rrMM), but real-world data on treatment failure and severe infections remain limited. MATERIALS AND METHODS This multicenter, retrospective study evaluated the efficacy, infection rates, and adverse events of BsAb therapy (teclistamab and elranatamab) in patients with rrMM, compared with a propensity score-matched historical control cohort. A total of 201 patients (148 teclistamab, 53 elranatamab) from 10 hospitals were analyzed alongside 162 matched controls. Outcomes included progression-free survival (PFS), overall survival (OS), infection rates, and adverse events, adjusted using inverse probability weighting. RESULTS Over a median follow-up of 13 months, the median PFS was 17.9 months in the BsAb cohort (not reached for teclistamab, 9.3 months for elranatamab). Grade ≥3 infections were significantly higher in BsAb-treated patients (98.2/100 patient-years v 27.1/100, P < .001), mostly bacterial or viral. Intensive care admissions were more frequent in BsAb patients. Teclistamab showed superior 12-month OS (73.4% v 53.9%, P < .05). Key adverse events included cytokine release syndrome (50.2%, 2% grade ≥3) and neurotoxicity (8.5%, 5.9% grade ≥3). CONCLUSION BsAb therapy improves rrMM outcomes but increases severe infection risk, necessitating proactive management. Teclistamab demonstrated a more favorable survival profile, highlighting the need for individualized treatment strategies.
PURPOSE Trifluridine/tipiracil (FTD/TPI) plus ramucirumab may improve survival as a later-line therapy for advanced gastric cancer (GC); however, prospective evidence is limited. PATIENTS AND METHODS We conducted a multicenter, prospective phase II trial of FTD/TPI plus ramucirumab in patients with unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma who had received at least two previous systemic regimens for advanced disease, including a ramucirumab-containing regimen. Eligible patients had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Patients received oral FTD/TPI (35 mg/m 2 , days 1-5 and 8-12) and ramucirumab (8 mg/kg, days 1 and 15) every 28 days. The primary end point was time to treatment failure (TTF), and the secondary end points were progression-free survival (PFS), overall survival (OS), response, disease control rate (DCR), relative dose intensity (RDI), and safety. RESULTS Between February 2022 and March 2024, 32 patients were enrolled (median age, 72.5 years; 53.1% male). The median TTF was 4.0 months (95% CI, 2.8 to 5.0), meeting the primary end point. Median PFS and OS were 4.8 (95% CI, 2.8 to 8.3) and 12.2 months (95% CI, 7.8 to 17.2), respectively. Among 26 patients with measurable disease, objective response rate was 11.5%, and DCR was 76.9%. Mean RDI was 78.6% for FTD/TPI and 93.1% for ramucirumab, supporting feasibility in this cohort. Grade ≥3 neutropenia occurred in 53.1% and febrile neutropenia in 9.4%. Frequent nonhematologic events were anorexia (68.8%) and fatigue (59.4%), mostly grade 1 to 2. A modified FTD/TPI schedule was introduced in 15 patients and maintained dose delivery while reducing neutropenia, with no febrile events. CONCLUSION FTD/TPI plus ramucirumab met its primary end point and was feasible with manageable safety in heavily pretreated advanced GC. Given the single-arm design, the efficacy findings are hypothesis-generating and warrant confirmation in larger randomized trials.
PURPOSE To determine factors and survival of patients with ovarian cancer after primary debulking surgery followed by adjuvant chemotherapy (PDS) versus neoadjuvant chemotherapy followed by interval cytoreduction (NAC). METHODS GOG-262 was a prospective randomized trial evaluating once per week dose dense chemotherapy. The physicians were given the option of performing PDS versus NAC. Chi-squared tests and Kaplan-Meier procedures were used for analyses. RESULTS Of 192 patients from centers offering both treatment options, 119 (62%) patients had PDS and 73 (38%) underwent NAC. Compared with the PDS group, NAC patients were older (60 years and older) age (67% v 47%; P < .01) and had more advanced (stage IV) disease (41.1% v 26.1%, P < .01) and peritoneal versus ovarian or fallopian tube cancers (16.4% v 5.0%, P < .001). The 5-year unadjusted overall survival of patients after NAC was 41.9 versus 47.8 months in the PDS group. After adjusting for prognostic factors, PDS was not an independent predictor for survival (hazard ratio [HR], 1.08 [95% CI, 0.67 to 1.7]; P = .75), whereas more advanced (IV v II/III)-stage (HR, 1.9 [95% CI, 0.93 to 3.89]; P = .079) and peritoneal versus ovarian or fallopian tube cancers (HR, 4.36 [95% CI, 1.45 to 13.1]; P = .009) were associated with poorer survival. CONCLUSION Compared with primary surgery followed by chemotherapy, neoadjuvant chemotherapy followed by interval surgery patients were older and had more advanced disease (stage IV v II-III) and more primary peritoneal cancer ( v ovarian and fallopian tube cancer). The survival of these two groups was comparable after adjusting for prognostic factors.
PURPOSE Yttrium-90 (Y-90) radioembolization continues to be used in the treatment of colorectal cancer liver metastases (CRLMs), despite the lack of improvement in overall survival (OS) in randomized trials. Here, to our knowledge, we report the first study to assess the trend in utilization and investigate patient characteristics associated with the receipt of Y-90 for CRLM. METHODS Patients with CRLM were identified from the National Cancer Database (NCDB) from 2010 to 2020. CRLM was defined as stage IV colorectal cancer with hepatic metastases. Patients were categorized based on whether they received Y-90 radioembolization. Multivariate models were used to identify factors associated with Y-90 receipt. The annual trend in Y-90 usage was evaluated, and OS was compared between the two groups using the Kaplan-Meier method and Cox proportional hazards models. RESULTS Among 82,161 patients with CRLM, 398 (0.5%) received Y-90 radioembolization. Between 2010 and 2020, Y-90 utilization increased 400%, from 216 to 874 events per 100,000 patients. Y-90 was more likely for patients who were younger (18-54 years), were predominantly White non-Hispanic, and had private insurance and lower comorbidity scores ( P < .05). Patients who received chemotherapy were also more likely to receive Y-90 (adjusted odds ratio, 1.25 [95% CI, 1.64 to 3.07]; P < .01). After adjusting for covariates, receipt of Y-90 was not associated with improved OS (hazard ratio, 1.03 [95% CI, 0.91 to 1.17]; P = .59). CONCLUSION To our knowledge, in this first report of Y-90 from the NCDB, we identified a four-fold increase in utilization of Y-90 in a 10-year period. Similar to several randomized controlled trials, we observed no improvement in OS for patients with CRLM. Further investigation into the drivers of this trend will be necessary.
PURPOSE For patients with advanced biliary tract cancer (BTC), cancer-related time spent in health care systems, time toxicity, represents a critical but understudied burden affecting quality of life. This study aimed to quantify time toxicity in patients receiving first-line systemic therapy and evaluate whether the addition of durvalumab to gemcitabine plus cisplatin (GC) increases health care contact time. METHODS This international, multicenter, retrospective cohort study included patients with advanced BTC seen between January 2019 and April 2024 at Mayo Clinic Enterprise (US), and between January 2021 and April 2024 at Kyorin University Hospital (Japan), and Hospital Israelita Albert Einstein (Brazil). Patients received GC plus durvalumab (GCD) or GC. Time toxicity was recorded from treatment initiation until discontinuation or last follow-up during first-line systemic therapy. Multiple regression analysis identified factors associated with high time toxicity. RESULTS Among 193 patients (102 GCD, 91 GC; median age 65 years; 50% male; 49% Eastern Cooperative Oncology Group performance status [PS] 0), median time on treatment (TOT) was 156 days (95% CI, 122 to 190). The median proportion of total time toxicity was 14.4% (IQR, 10.9-20.6). Planned visits accounted for 11.9%, while unplanned visits were infrequent (1.8%). Time toxicity strongly correlated with TOT ( r = 0.824) and progression-free survival ( r = 0.827). Despite longer treatment in the GCD group than the GC group (212 v 134 days; P = .027), total time toxicity was similar (27 v 18 days; P = .19). Younger age and poor PS were independent factors of higher time toxicity. CONCLUSION Time toxicity represents a meaningful metric that allows for more comprehensive integration of the net benefit in patients with advanced BTC with a limited lifespan.
Cancer genetic counseling and testing have become integral to medicine given expanding knowledge of genetic risk and recognition that a substantial fraction of cancer is hereditary. Access to genetic testing and precision medicine breakthroughs have led to new standards of care for diagnosis and treatment. Many tumor types, both common (eg, breast cancer) and rare (eg, pheochromocytoma), are associated with hereditary cancer syndromes. Even common tumors typically explained by exposures might have important genetic underpinnings (eg, lung cancer in nonsmokers, skin cancer in dark-complexioned individuals). Cancer genetics referral determination is nuanced, requiring consideration of specific tumor characteristics and other factors (eg, age at diagnosis, personal and/or family history). This publication is intended as a resource for oncology providers to make such determinations.
PURPOSE The treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) has evolved with the recent approvals of lutetium Lu 177 vipivotide tetraxetan and poly (ADP-ribose) polymerase inhibitors, adding new layers of complexity to treatment sequencing. Cabazitaxel is an approved option in patients with disease progression on docetaxel. Real-world data on the effectiveness of cabazitaxel by line of therapy remain limited. To address this gap, we evaluated survival outcomes based on line of therapy in patients with mCRPC receiving single-agent cabazitaxel in a large real-world database. METHODS This retrospective study used the US-based Flatiron Health electronic health record–derived deidentified database. Patients who were diagnosed with mCRPC and received single-agent cabazitaxel for the first time were eligible and included. Real-world time to next treatment (rwTTNT) and real-world overall survival (rwOS) were calculated from the date patients initiated the first cycle of cabazitaxel. Survival rates were summarized using medians and 95% CI using the Kaplan-Meier method. RESULTS Among 24,105 patients with metastatic prostate cancer in the data set, 1,315 patients with mCRPC were eligible and included. The median age was 73 years (IQR, 67-78). The majority were non-Hispanic White (62%), treated in community practice (84%), had commercial insurance (81%), and received treatment in fourth line or later (58%). For the overall cohort, the median rwTTNT was 4.7 months (95% CI, 4.4 to 5.0), and the median rwOS was 8.6 months (95% CI, 8.0 to 9.3). The median rwTTNT ranged from 4.2 months to 6.8 months, and rwOS ranged from 6.3 months to 14 months based on the line of therapy. CONCLUSION In this large, real-world study of patients with mCRPC, cabazitaxel retained its effectiveness regardless of its line of therapy.
PURPOSE National Comprehensive Cancer Network guidelines recommend weekly cisplatin and weekly carboplatin with paclitaxel as alternative concurrent systemic therapy regimens among patients with head and neck cancer undergoing definitive chemoradiation. However, there is a paucity of literature comparing outcomes with these two regimens. We performed an observational cohort study of patients with head and neck cancer treated with definitive chemoradiation receiving either cisplatin or carboplatin with paclitaxel. METHODS A single-institution database was queried for patients with head and neck cancer diagnosed between October 2011 and December 2023 who underwent chemoradiation with either once a week cisplatin (40 mg/m 2 ) or once a week carboplatin (AUC 1) with paclitaxel (30 mg/m 2 ). Cox multivariable analysis (MVA), Kaplan-Meier, Fine-Gray MVA, logistic MVA, and propensity score matching were performed to evaluate treatment outcomes. RESULTS A total of 488 patients were identified. Median follow-up was 43.1 months (95% CI, 41.0 to 45.4). The majority of patients received at least five cycles. Those with older age, former smoking history, and worse performance status were more likely to undergo carboplatin and paclitaxel. Carboplatin and paclitaxel were associated with no statistically significant overall survival (adjusted hazards ratio [aHR], 1.12 [95% CI, 0.69 to 1.82]; P = .64), progression-free survival (aHR, 1.45 [95% CI, 0.96 to 2.19]; P = .08), locoregional failure (aHR, 1.91 [95% CI, 0.85 to 4.32]; P = .12), and distant failure (aHR, 1.33 [95% CI, 0.70 to 2.54]; P = .39) compared with cisplatin. Similar findings were noted on 109 matched pairs as well as subgroups stratified by p16 status. CONCLUSION Our study suggested that those treated with weekly carboplatin and paclitaxel had no statistically significant survival and tumor control outcomes compared with those with weekly cisplatin. Older age and poor performance status were independently associated with the receipt of weekly carboplatin and paclitaxel.
PURPOSE Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor with high rates of delta-like ligand 3 (DLL3) expression. MTC has limited treatment options after failure of kinase inhibition. DLL3-targeting therapies such as tarlatamab may be effective treatments for MTC. METHODS After providing informed consent, four patients with MTC were treated with tarlatamab after progression on all established therapies. Patients were treated using the step-up dosing described in patients with small cell lung cancer (SCLC). Efficacy was measured using RECIST v1.1, as well as changes in biomarkers, calcitonin, and carcinoembryonic antigen. Safety was evaluated by the rates of treatment-related adverse events (TRAEs) and the rate of severe (grade ≥3) TRAEs based on Common Terminology Criteria for Adverse Events v5.0. RESULTS Tarlatamab showed antitumor activity in 4 of 4 (100%) patients with MTC. In the three patients with RECIST evaluable disease, two experienced partial responses and one had stable disease. Three of four patients experienced biochemical responses. One patient who did not have a biochemical response had a RECIST partial response. All four patients experienced at least one grade ≥3 TRAE. Severe TRAEs included grade 5 colon perforation, grade 4 cytokine release syndrome (CRS), grade 4 immune effector cell–associated neurotoxicity syndrome (ICANS), and grade 3 leukopenia, neutropenia, hypophosphatemia, and anorexia. The grade 4 CRS and grade 4 ICANS were refractory to standard treatments. CONCLUSION Tarlatamab showed encouraging antitumor activity in patients with MTC, and it may be an effective treatment for this population. However, the safety data from these initial patients raise concern that the step-up dosing established for patients with SCLC may not be optimal for patients with MTC and potentially other neuroendocrine tumors. More research is needed to evaluate the safety and efficacy of tarlatamab in other populations.
PURPOSE Coordinated social care networks (CSCN) could improve patient access to community-based organizations (CBOs) that address cancer disparities and health-related social risks. However, little is known about CBO leaders' perspectives regarding serving patients with cancer, addressing health-related social risks, or participating in CSCNs. METHODS We conducted a qualitative study using the most common CBO referrals from 2020 to 2021 in a New Haven CT-based hospital system to guide sampling. We compiled a list of relevant CBOs and conducted semistructured interviews with CBO leaders from June 2021 to January 2023. The interview guide explored CBO leaders' awareness of cancer-related service needs, the CBO referral process, and perceived barriers and facilitators of CSCN participation. Thematic analysis identified emerging themes related to CBO ability to support needs of clients with cancer, challenges in accessing services, and interest in joining a CSCN. RESULTS Leaders from 13 CBOs participated, representing food pantries (n = 4), financial assistance and medical equipment (n = 3), cancer-specific advocacy groups (n = 2), homeless shelters (n = 2), transportation agencies (n = 2), and general services (n = 2). We identified five themes related to context and needs of CBOs and their clients: cancer-specific service needs, challenges accessing services in community, service gaps in community, CBOs' ability to address client needs, and challenges referring clients to other services. Two themes emerged in CSCN participation: perceived value of participation and key barriers to CSCN engagement including lack of resources, staff, and training and prior experiences with existing referral platforms. CONCLUSION Although CSCNs could be a helpful mechanism for addressing service gaps and improve CBO collaboration in cancer care, critical barriers such as awareness of specific needs for patients with cancer and limited CBO resources for engaging with and supporting CSCNs may hinder implementation.
PURPOSE Limited information exists regarding outcome severity among gynecologic cancer patients with SARS-CoV-2 infection. The objective of this study was to describe patient, cancer, and COVID-19 characteristics, and to identify factors associated with COVID-19 severity. METHODS Gynecologic cancer patients with SARS-CoV-2 infection were identified from the international COVID-19 and Cancer Consortium registry. We estimated odds ratios (ORs) for associations with severity of COVID-19 outcomes. Multivariable models included adjustment for age, race, cancer status, and time period of COVID-19 diagnosis. RESULTS Of 920 patients, 438 patients (48%) had endometrial, 249 (27%) had ovarian, 198 (22%) had cervical, and 44 (5%) had vulvar/vaginal cancers. Most were from the United States (86%) and non-Hispanic White (48%). Median age was 62 years (IQR, 52-71). When diagnosed with COVID-19, 457 (49%) patients were in remission and 343 (37%) had active disease. Outcomes included hospitalization in 452 patients (49%), intensive care unit admittance in 107 patients (12%), mechanical ventilation in 70 patients (8%), and death within 30 days of testing positive for SARS-CoV-2 in 91 patients (10%). In multivariable models, increasing age (adjusted OR, 1.35 [95% CI, 1.23 to 1.49]) and non-Hispanic Black race (adjusted OR, 1.75 [95% CI, 1.24 to 2.48]) were associated with increased COVID-19 severity, as were cardiac (adjusted OR, 1.85 [95% CI, 1.36 to 2.52]), pulmonary (adjusted OR, 1.58 [95% CI, 1.12 to 2.22]), and renal (adjusted OR, 2.18 [95% CI, 1.48 to 3.19]) comorbidities. Patients in remission <5 years had decreased COVID-19 severity (adjusted OR, 0.60 [95% CI, 0.42 to 0.87]). Other cancer characteristics associated with increased severity included progression (adjusted OR, 2.91 [95% CI, 1.92 to 4.40]), stage (adjusted OR, 1.57 [95% CI, 1.11 to 2.22]), and metastatic disease (adjusted OR, 1.60 [95% CI, 1.10 to 2.34]). CONCLUSION Patients with gynecologic cancer experience significant morbidity and mortality related to infection with SARS-CoV-2. Age, race, cancer status, comorbidities, and COVID-19 complications were associated with more severe COVID-19 outcomes.
PURPOSE The human microbiome is increasingly recognized as a key modifier of carcinogenesis, immune regulation, and treatment response. In lung cancer, characterization of both respiratory and gut microbiomes offers opportunities to identify biomarkers and therapeutic targets. However, methodologic variability limits reproducibility and clinical translation. The objective was to systematically evaluate current microbiome testing methodologies in lung cancer, focusing on sequencing-based profiling and short-chain fatty acid (SCFA) analysis. METHODS A systematic search of PubMed, Scopus, and Web of Science identified human lung cancer studies (2014-2023) employing 16S rRNA gene sequencing, shotgun metagenomics, metatranscriptomics, or SCFA quantification. Eligible studies were assessed per PRISMA guidelines for design, analytic workflow, and key findings. RESULTS Eighty-seven studies met inclusion criteria. Most (86%) used 16S rRNA sequencing, primarily on bronchoalveolar lavage, bronchial brushings, or stool. Shotgun metagenomics (9%) provided higher taxonomic and functional resolution, while SCFA analysis (14%), mainly via gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry, explored gut-lung interactions. Substantial heterogeneity was noted in DNA extraction, targeted 16S regions, sequencing platforms, and bioinformatic pipelines, complicating cross-study comparison. Across studies, lung cancer samples showed reduced alpha diversity and enrichment of taxa such as Streptococcus and Veillonella . SCFA studies suggested higher fecal butyrate and propionate levels were associated with favorable immunotherapy responses. CONCLUSION Methodologic inconsistency across microbiome testing platforms remains a major barrier to validation of microbial biomarkers in lung cancer. Standardized protocols for sampling, sequencing, and SCFA quantification are essential for reproducibility. Incorporating harmonized microbiome assays into immuno-oncology trials could improve biomarker reliability, refine patient stratification, and advance precision cancer care.
PURPOSE Gemcitabine-based chemotherapy is standard for metastatic pancreatic ductal adenocarcinoma (PDAC), but resistance limits its efficacy. Bacteria in the PDAC tumor microenvironment may contribute to resistance. Hence, the coadministration of an antibiotic to chemotherapy may potentiate antitumor drug responses. This study evaluates the safety and efficacy of adding ciprofloxacin to gemcitabine-based chemotherapy. Secondary aims included stool microbiome and exhaled breath volatile analysis. MATERIALS AND METHODS This single-arm study at the National University Cancer Institute, Singapore, enrolled patients with treatment-naïve advanced PDAC. Patients received nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1,000 mg/m 2 ) administered weekly on days 1, 8, and 15 of each 4-week cycle, together with oral ciprofloxacin (500 mg twice daily) until disease progression or intolerable toxicity. Stool and tumor samples were subjected to 16S rRNA sequencing. Primary end points were response rate and safety. Secondary end points included progression-free survival (PFS), overall survival (OS), and microbiome changes. RESULTS From March 2019 to February 2021, 8 patients were recruited. Best response was stable disease in 5 (62.5%) patients, and 3 patients had progressive disease (PD). The median PFS and OS were 4.3 and 15.4 months, respectively. Two patients developed grade 4 neutropenia and one had grade 3 febrile neutropenia. A total of 50% of patients developed grade 1/2 rash. No additional toxicities from ciprofloxacin were observed. PD correlated with increased Gammaproteobacteria and decreased cytidine deaminase functional potential. Response to therapy was associated with baseline increased abundances of Firmicutes species. CONCLUSION Gemcitabine-based chemotherapy plus ciprofloxacin demonstrated clinical activity and an acceptable safety profile in PDAC. Lack of response to treatment was associated with increased abundances of Gammaproteobacteria .
PURPOSE Pamrevlumab demonstrated favorable safety and therapeutic potential in locally advanced pancreatic cancer (LAPC) in phase I/II trials (ClinicalTrials.gov identifiers: NCT01181245 ; NCT02210559 ). LAPIS (phase III; ClinicalTrials.gov identifier: NCT03941093 ) evaluated the efficacy and safety of adding pamrevlumab versus placebo to chemotherapy for patients with LAPC. METHODS Eligible patients (randomly assigned 1:1) received investigator's choice of chemotherapy (gemcitabine plus nab-paclitaxel or folinic acid, fluorouracil, irinotecan, and oxaliplatin per the standard protocol) with either pamrevlumab (35 mg/kg every 2 weeks on days 1 and 15 before chemotherapy; additional dose on day 8 of cycle 1; arm A) or placebo (arm B) for up to six cycles. Patients were assessed for surgical eligibility based on a composite of biomarkers (carbohydrate antigen 19-9, fluorodeoxyglucose positron emission tomography [FDG-PET] imaging, RECIST v1.1 response criteria, and resectability status), guided by an independent surgical review panel. The primary end point was overall survival (OS). Treatment-emergent adverse events were monitored to evaluate safety. RESULTS Of 284 patients, 143 and 141 were randomly assigned to arms A and B, respectively (median [range] age, 65.0 [31-90] years; 53.2% male). The median OS was 17.3 versus 17.9 months for arms A and B, respectively, and the primary end point was not met (hazard ratio [95% CI], 1.08 [0.83 to 1.41]; P = .5487). No appreciable increase in toxicity was noted in the pamrevlumab arm. One pamrevlumab-related death occurred in arm A. CONCLUSION LAPIS did not meet its primary end point in this large, phase III trial featuring a design including FDG-PET imaging for response assessment, defined surgical eligibility criteria, an independent surgical review panel, and a composite event-free survival end point, collectively enhancing assessment rigor and clinical applicability and potentially establishing future standards for LAPC trials.
PURPOSE Biomarkers that facilitate detection of pancreatic cancer during a potentially curable stage are a significant public health need. We designed a 5-plex serum biomarker signature to detect stage I and II pancreatic ductal adenocarcinoma (PDAC) in high-risk surveillance populations. In two previous validations performed in two independent cohorts, the assay signature distinguished stage I and II PDAC from high-risk individuals in surveillance with high sensitivity and specificity. In this study, we evaluated assay performance in stage III and IV PDAC and non–high-risk individuals. METHODS Signature analytes were retrospectively measured in 619 serum samples from a blinded independent cohort of stage III and IV PDAC cases (n = 224) and non–high-risk controls (n = 395). A positive or negative result for PDAC was generated from a predefined cutoff established during assay development. The assay's performance in this study was compared with its performance in the previous validations. RESULTS The signature panel distinguished stage III and IV PDAC from controls with 87.9% sensitivity (95% CI, 82.9 to 91.9) and 97.7% specificity (95% CI, 95.7 to 99.0). The assay demonstrated significantly higher sensitivity in stage III and IV PDAC than stage I and II cases (77.3% [95% CI, 72.3 to 81.8]; P = .002) and significantly higher specificity in non–high-risk controls (97.7%) compared with high-risk controls (92.2% [95% CI, 90.4 to 93.7]; P < .001). CONCLUSION These results demonstrate high assay performance in patients with stage III and IV PDAC and non–high-risk individuals. Although the test is intended for detection of stage I and II PDAC in high-risk surveillance populations, it can be used to detect all stages of PDAC, including advanced disease.
