The Knowledge Connector decision support system for multiomics-based precision oncology.

Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS (P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.

Background Tumor complexity and heterogeneity require matching of actionable genomic alterations with available therapy to increase response rates and prolong survival in patients. However, it has been a long-standing challenge for treating oncologists to select an effective patient-specific therapeutic strategy due to the molecular rationale, disease relevance, and patient-specific issues. To provide a decision-support tool to aid oncologists and educate patients, we have developed a set of molecular and clinical evidence-based criteria as an algorithm for ranking therapeutic strategies in order to deliver optimal care and improve outcomes in patients with malignancy. Methods History of present illness (HPI) and comprehensive genomic profiling (CGP) results of 203 patients with malignant tumors were reviewed by our multidisciplinary Molecular Tumor Board (MTB) from June 2021 to August 2022, and therapeutic recommendations were provided with Matching Score based on molecular matching only as well as with Ranking Score calculated by our molecular and clinical evidence-based algorithm with the criteria not only focusing on molecular matching, but also including disease relevance, patient-specific clinical considerations and treatment availability as weighting factors (Cohort 2). The other 50 patients with previously treated solid tumors reviewed by MTB (before 2018) and treatment recommendations provided with Matching Score only, were used as a control group (Cohort 1). The matching rates from recommendations and treatment outcomes of the patients were then assessed. Results In Cohort 1, of the 50 patients, 33 patients (66%) received matched therapeutic plans recommended by our MTB. The other 17 patients were not on a matched plan from the MTB. Twelve patients (36.4% of 33 patients) achieved progression-free survival (PFS) at 12-week time point, including 8 patients (24.2%) achieved PFS at 6-month time point. The other 21 patients (63.6% of 33 patients) could not be assessed due to treatment termination per drug toxicity or death before the follow-up time point. The median PFS/overall survival (OS) for patients with a Matching Score &amp;gt; 50% (N = 17) were 7.5/10.5 months, whereas with Matching Score ≤ 50% (N = 16) were 3/7.35 months. In Cohort2, of the 203 patients, 89 (43.8%) patients have initiated matched therapeutic plans and follow-up is ongoing. Updated results will be presented at the meeting. Conclusion Our novel molecular and clinical evidence-based algorithm may be used to support oncologists decision-making to utilize the most clinically appropriate and effective therapeutic options. Further validation studies and development of an user-friendly computational ranking platform based on the algorithm are planned in order. Citation Format: Yuliang Sun, Tobias Meissner, Rachel Elsey, Leah Theisen, Crystal Hattum, Bing Xu, John Lee, Casey Williams. Development/validation of a molecular and clinical evidence-based algorithm for selecting optimal precision therapeutic strategy for cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1057.

BackgroundThere is growing evidence supporting multidisciplinary molecular tumor boards (MTB) in solid tumors whereas hematologic malignancies remain underrepresented in this regard.ObjectiveThe present study aimed to assess the clinical relevance of MTBs in primary refractory diffuse large B-cell lymphomas/high-grade B-cell lymphomas with MYC and BCL2 rearrangements (prDLBCL/HGBL-MYC/BCL2) (n = 13) and HGBL, not otherwise specified (NOS), with MYC and BCL6 rearrangements (prHGBL, NOS-MYC/BCL6) (n = 6) based on our previously published whole-exome sequencing (WES) cohort.Patients and MethodsFor genomic analysis, the institutional MTB WES pipeline (University Cancer Center Schleswig-Holstein: UCCSH), certified for routine clinical diagnostics, was employed and supplemented by a comprehensive immunohistochemical work-up. Consecutive database research and annotation according to established evidence levels for molecularly stratified therapies was performed (NCT-DKTK/ESCAT).ResultsMolecularly tailored treatment options with NCT-DKTK evidence level of at least m2A were identified in each case. We classified mutations in accordance with biomarker/treatment baskets and detected a heterogeneous spectrum of targetable alterations affecting immune evasion (IE; n = 30), B-cell targets (BCT; n = 26), DNA damage repair (DDR; n = 20), tyrosine kinases (TK; n = 13), cell cycle (CC; n = 7), PI3K-MTOR-AKT pathway (PAM; n = 2), RAF-MEK-ERK cascade (RME; n = 1), and others (OTH; n = 11).ConclusionOur virtual MTB approach identified potential molecularly targeted treatment options alongside targetable genomic signatures for both prDLBCL/HGBL-MYC/BCL2 and prHGBL, NOS-MYC/BCL6. These results underline the potential of MTB consultations in difficult-to-treat lymphomas early in the treatment sequence.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11523-023-00983-5.

SummaryNext Generation Sequencing (NGS) is increasingly used in diagnostic centers for the assessment of genomic alterations to select patients for precision oncology. The Italian Society of Anatomic Pathology and Diagnostic Cytopathology (SIAPEC) through the Molecular Pathology and Predictive Medicine Study Group (PMMP) has been following the progressive development of centers that have adopted NGS technology in diagnostics over time. In July 2017, a study network on massive parallel sequencing was activated in Italy and recognized as the NGS SIAPeC National Network by the SIAPeC Scientific Society Board. Since then, activities have been implemented within the network that provide for alignment of laboratories through diagnostic concordance analysis and monitoring of centers adhering to the Network. Recently, considering the growing need for extended genomic analyses, the PMMP distributed a national survey to assess activities related to the use of genomic diagnostics in oncology within the NGS SIAPEC National Network.Thirty centers participated in the survey. Eighty percent of the centers are laboratories within Pathology Departments. The distribution of laboratories in the country, the diagnostic laboratory/population ratio, the staff dedicated, the type and number of sequencing and mechatronics platforms available, the genomic panels utilized, and the type and number of diagnostic tests carried out in the last year in each center, are reported.The centers were also asked whether they participated in a multidisciplinary Molecular Tumor Board (MTB) for management of patients. Thirty percent of the centers had a MTB that was ratified by regional decree. The professionals most frequently involved in the core team of the MTB are the pathologist, oncologist, molecular biologist, geneticist, pharmacologist, and bioinformatician.The data from this survey indicate that NGS diagnostics in Italy is still heterogeneous in terms of geographical distribution and the characteristics of laboratories and diagnostic test performed. The implementation of activities that favors harmonization, the logistics and the convergence of biological material in reference centers for molecular analyses is a priority for the development of a functional laboratory network.

Neuroblastoma (NB) is the most common extracranial solid tumor encountered in childhood. Although there has been significant improvement in the outcomes of patients with high-risk disease, the prognosis for patients with metastatic relapse or refractory disease is poor. Hence, the clinical integration of genome sequencing into standard clinical practice is necessary in order to develop personalized therapy for children with relapsed or refractory disease. The PeRsonalizEdMEdicine (PREME) project focuses on the design of innovative therapeutic strategies for patients suffering from relapsed NB. We performed whole exome sequencing (WES) of patient-matched tumor-normal samples to identify genetic variants amenable to precision medicine. Specifically, two patients were studied (First case: a three-year-old male with early relapsed NB; Second case: a 20-year-old male who relapsed 10 years after the first diagnosis of NB). Results were reviewed by a multi-disciplinary molecular tumor board (MTB) and clinical reports were issued to the ordering physician. WES revealed the mutation c.G320C in the CUL4A gene in case 1 and the mutation c.A484G in the PSMC2 gene in case 2. Both patients were treated according to these actionable alterations, with promising results. The effective treatment of NB is one of the main challenges in pediatric oncology. In the era of precision medicine, the need to design new therapeutic strategies for NB is fundamental. Our results demonstrate the feasibility of incorporating clinical WES into pediatric oncology practice.

The STREAM (Strategic TREatment And Magic for pediatric cancers) program, launched in March 2023, is the first nationwide precision medicine initiative for pediatric solid tumors in Korea. The platform integrates high-depth whole-genome sequencing of matched tumor–germline samples with transcriptomic, methylomic, and in vitro drug-response profiling. All findings undergo centralized pathology review and are discussed at a multidisciplinary molecular tumor board (MTB). Between March 2023 and December 2024, 308 children with malignant solid tumors were enrolled (243 newly diagnosed, 65 relapsed/refractory), meeting predefined quality criteria. Diagnoses included 123 CNS tumors, 54 sarcomas, 38 germ cell tumors (GCTs), 38 neuroblastomas, 22 bone tumors, 9 renal, 7 hepatic, and 17 miscellaneous tumors. Somatic driver alterations were identified in 253 patients (82.1%, median two per patient), totaling 1,082 events across 404 genes, including single-nucleotide variants (n=521), copy-number variants (n=238), and structural variants (n=323) with 65 gene fusions. The most frequently altered genes included TP53, BRAF, CTNNB1, and CDKN2A. Pathogenic germline variants were detected in 32 patients (10.4%) across 25 known cancer predisposition genes (e.g., TP53, BRCA1/2, BRIP1, VHL). Molecular profiling contributed to diagnosis in 85 patients, impacted risk stratification in 20, and revealed 117 actionable targets in 99 cases (Tier 1: 48; Tier 2: 61; Tiers 3–5: 8). Drug sensitivity testing in 58 cases across 76 agents yielded 496 sensitive and 1,376 resistant drug–tumor interactions, informing therapeutic potential in 53 and resistance in 54 patients. Unsupervised multi-omic clustering aligned with histopathology and uncovered pathway-dominant molecular subsets: MAPK pathway activation in pilocytic astrocytoma, Langerhans-cell histiocytosis, and polymorphous low-grade neuroepithelial tumor of the young (PLNTY); cell cycle and epigenetic dysregulation in atypical teratoid/rhabdoid tumor and supratentorial ependymoma; both patterns aligned with observed drug sensitivities. Further stratification of medulloblastomas confirmed WNT- and SHH-driven signatures in medulloblastoma Groups 1 and 2, while Groups 3–4 were molecularly diverse, marked by SBS39 mutational signatures suggestive of homologous recombination deficiency (HRD). Similar HRD-associated signatures were enriched in neuroblastoma and osteosarcoma with high-level copy-number alterations (CNAs). Intracranial GCTs demonstrated greater CNA burden and whole-genome duplication compared to gonadal tumors, indicating distinct evolution. STREAM marks a milestone for precision oncology in Asia, and confirms that real-world, genome-guided oncology is feasible in routine pediatric care and can complement histologic diagnosis to inform treatment. Building on this experience, sustained efforts are needed to implement genome-driven workflows in routine clinical practice and ultimately improve treatment outcomes for pediatric cancer patients. Citation Format: Ji Won Lee, Chang Yeon Kim, Joo Whan Kim, June-Young Koh, Jung Yoon Choi, Seung-Ah Choi, Seung-Ki Kim, Se Hoon Kim, Ji Hoon Phi. Nationwide Genome-Guided Precision Oncology in Pediatric Solid Tumors: Results from the STREAM Program [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr A005.

P-269 Malignant tumors of the appendix: A retrospective study

e17123 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of endometrial cancer (EC) patients assayed in a nationwide cancer network. Methods: 278 Pts with advanced EC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 59 years (range, 37-85), 58% were Caucasian. GA were identified in 97% (271/278) of EC, of which 218 (80%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most common, present in 63.8% of EC. CRGA in other targetable pathways were identified: 28.4% in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) , 12.5% in HRD (BRCA1/2, ATM, PALB2, BRIP1 ) and 9.9% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). 26 patients are MSI-high 9.5% (26/271) and 21 patients are TMB-high 7.7% (21/271). 29.8% (65/218) of EC patients were ordered a genomically-matched treatment, and 61 of these patients received the treatment. 69.2% (45/65) were agents that were FDA approved in a different tumor type, and 24.6% (16/65) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The median PFS for non-clinical trial study patients was 9 weeks, and the median OS was 27 weeks. Conclusions: In a large series of Endometrial and Uterine cancer patients assayed with CGP, 27.9% (61/218) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

BackgroundIn the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy.MethodsA FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients.ResultsSamples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0–86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0–117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48–2.26)].ConclusionsThis study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.

1531 Background: Relative lack of prior success of genomic technology has been a function of suboptimal target detection and poor timely implementation. We set out to improve patient access to targeted therapy through use of whole genome sequencing (WGS) to optimize targets and operational implementation to identify clinical trials and secure off-label drugs. Methods: We performed a retrospective analysis of our first 100 patients (Feb-Nov 2016) with metastatic disease whose tumors and matched blood were analyzed using whole genome (WGS) and transcriptome sequencing, as well as targeted proteomic analysis in a CLIA setting (NantOmics). Most common tumor types were Colorectal (20%), Breast (15%), and Ovarian (10%). Patients were seen in dedicated precision genomics clinics with results reviewed by a multi-disciplinary molecular tumor board. A dedicated service line with staff to match patients to clinical trials, medication acquisition, and genetic counseling for germline findings was provided. Results: 85% of patients had a finding either on WGS or proteomic analysis that pointed to an FDA approved drug or clinical trial. Common findings included: mutations in the PI3K pathway (15%), BRCA1&amp;2/ATM (15%), and cell cycle genes (11%). Other markers of note include: HER2, TMB/MSI for immune checkpoint therapy, IDH1/2, and MET. WGS also enabled identification of rare actionable findings, particularly translocations, and viral integration for trials requiring HPV-positivity. Cancer predisposition germline findings were observed in 3 patients. Of the 85 patients with actionable findings, 22 went on to be treated with a genomically-directed agent, 13 did not follow recommendations or were sent to hospice, 4 were lost to follow-up, and 46 still remain on their therapy prescribed prior to sequencing. Conclusions: A higher proportion of patients in our program went on to be treated with a genomically-directed agent than previously reported in the literature secondary to comprehensive whole genome multi-omics profiling and a clinical service line dedicated to medication acquisition and matching to clinical trials.

Although genetic profiling of tumors is a potentially powerful tool to predict drug sensitivity and resistance, its routine use has been limited because clinicians are often unfamiliar with interpretation and incorporation of the information into practice. We established a Molecular Tumor Board (MTB) to interpret individual patients' tumor genetic profiles and provide treatment recommendations. DNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments-certified laboratory to identify coding mutations in a 50-gene panel (n = 34) or a 255-gene panel (n = 1). Cases were evaluated by a multidisciplinary MTB that included pathologists, oncologists, hematologists, basic scientists, and genetic counselors. During the first year, 35 cases were evaluated by the MTB, with 32 presented for recommendations on targeted therapies, and 3 referred for potential germline mutations. In 56.3% of cases, MTB recommended treatment with a targeted agent based on evaluation of tumor genetic profile and treatment history. Four patients (12.5%) were subsequently treated with a MTB-recommended targeted therapy; 3 of the 4 patients remain on therapy, 2 of whom experienced clinical benefit lasting >10 months. For the majority of cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. The most common reasons that MTB-recommended therapy was not administered stemmed from patient preferences and genetic profiling at either very early or very late stages of disease; lack of drug access was rarely encountered. Increasing awareness of molecular profiling and targeted therapies by both clinicians and patients will improve acceptance and adherence to treatments that could significantly improve outcomes. Case evaluation by a multidisciplinary Molecular Tumor Board (MTB) is critical to benefit from individualized genetic data and maximize clinical impact. MTB recommendations shaped treatment options for the majority of cases evaluated. In the few patients treated with MTB-recommended therapy, disease outcomes were positive and support genetically informed treatment.

BACKGROUNDComprehensive molecular characterization of pediatric brain tumors has led to a more refined diagnosis. However, the feasibility of performing multi-omic and functional precision medicine approaches using ex-vivo drug screening in the clinical setting is unknown. METHODSPatients with newly diagnosed or recurrent central nervous system tumors were enrolled in a feasibility study of multi-omic analysis including whole genome trio germline sequencing, tumor whole exome/RNA sequencing, RNA-based DiSCoVER analysis, methylation profiling, immunogenic potential analysis, and ex-vivo drug screening utilizing a customized panel of 175 FDA approved/investigational drugs. Findings were presented at a multidisciplinary molecular neuro-oncology tumor board. RESULTSEighteen patients (9 female; average age 9.4 years; 12 newly diagnosed, 6 with recurrent disease; 5 high grade gliomas, 4 ependymomas, 4 embryonal tumors, 3 low grade gliomas, 2 others) were enrolled between 2020-2022. Whole genome germline testing (N=18) was normal in half of patients (pathogenic germline mutations in 3 patients, variants of unknown significance in 6 patients). Ex-vivo drug screening results (N=14) varied among patients, however sub-micromolar efficacy was commonly observed for proteosome inhibitors, HDAC inhibitors, and topoisomerase II inhibitors. Average time from surgery to receipt of finalized results varied across platforms (drug screening 5.7 days, whole exome/RNA sequencing 14.8 days, whole genome germline 10.6 days, methylation 21 days). Fifteen patients had a modification in diagnosis and 4 patients had a change in tumor classification. Multi-omic and functional precision medicine results alone or in combination led to changes in management in 50% of patients (Tumor Molecular Sequencing 6/18, Ex-Vivo Drug Screening 4/14, RNA DiSCoVER Analysis 2/15, Methylation 1/14). CONCLUSIONOur studies demonstrate the feasibility of timely ex-vivo drug screening and multi-omic analysis and show that these data may lead to changes in patient diagnosis/management. These findings are the basis of an ongoing trial for recurrent medulloblastoma (NCT05057702).

Cancer is characterized by an extremely complex biological background, which hinders personalized therapeutic interventions. Precision medicine promises to overcome this obstacle through integrating information from different ‘subsystems’, including the host, the external environment, the tumor itself and the tumor micro-environment. Immunogenetics is an essential tool that allows dissecting both lymphoid cancer ontogeny at both a cell-intrinsic and a cell-extrinsic level, i.e. through characterizing micro-environmental interactions, with a view to precision medicine. This is particularly thanks to the introduction of powerful, high-throughput approaches i.e. next generation sequencing, which allow the comprehensive characterization of immune repertoires. Indeed, NGS immunogenetic analysis (Immune-seq) has emerged as key to both understanding cancer pathogenesis and improving the accuracy of clinical decision making in oncology. Immune-seq has applications in lymphoid malignancies, assisting in the diagnosis e.g. through differentiating from reactive conditions, as well as in disease monitoring through accurate assessment of minimal residual disease. Moreover, Immune-seq facilitates the study of T cell receptor clonal dynamics in critical clinical contexts, including transplantation as well as innovative immunotherapy for solid cancers. The clinical utility of Immune-seq represents the focus of the present contribution, where we highlight what can be achieved but also what must be addressed in order to maximally realize the promise of Immune-seq in precision medicine in cancer.

Precision medicine is the most modern contemporary medicine approach today, based on great amount of data on people's health, individual characteristics, and life circumstances, and employs the most effective ways to prevent and cure diseases. Precision medicine in cancer is the most precise and viable treatment for every cancer patient based on the disease's genetic profile. Precision medicine changes the standard one size fits all medication model, which focuses on average responses to care. Consolidating modern methodologies for streamlining and checking anticancer drugs can have long-term effects on understanding the results. Precision medicine can help explicit anticancer treatments using various drugs and even in discovery, thus becoming the paradigm of future cancer medicine. Cancer biomarkers are significant in precision medicine, and findings of different biomarkers make this field more promising and challenging. Naturally, genetic instability and the collection of extra changes in malignant growth cells are ways cancer cells adapt and survive in a hostile environment, for example, one made by these treatment modalities. Precision medicine centers on recognizing the best treatment for individual patients, dependent on their malignant growth and genetic characterization. This new era of genomics progressively referred to as precision medicine, has ignited a new episode in the relationship between genomics and anticancer drug development.

This article discusses the role of PET/CT in contributing to precision medicine in lung cancer, and provides the perspective of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) on this process. The mission and vision of SNMMI are listed, along with the guidance provided by SNMMI to promote best practice in precision medicine. Basic principles of PET/CT are presented. An overview of the use of PET/CT imaging in lung cancer is discussed. In lung cancer patients, PET/CT is vitally important for optimal patient management. PET/CT is essential in determining staging and re-staging of disease, detecting recurrent or residual disease, evaluating response to therapy, and providing prognostic information. PET/CT is also critically important in radiation therapy planning by determining the extent of active disease, including an assessment of functional tumor volume. The current approach in tumor imaging is a significant advance over conventional imaging. However, recent advances suggest that therapeutic response criteria in the near future will be based on metabolic characteristics and will include the evaluation of biologic characteristics of tumors to further enhance the effectiveness of precision medicine in lung cancer, producing improved patient outcomes with less morbidity.