Squamous Cell Lung Cancer Research Articles

Up-regulated DDX39 in Adrenocortical Carcinoma Is Associated With Patient Survival.

Adrenocortical carcinoma is a very rare tumor characterized by poor prognosis and high mortality. The origin of this tumor is primarily the adrenal cortex. The 5-year overall survival rate of patients with adrenocortical carcinoma has not improved despite therapeutic advances. Early detection of this malignancy remains difficult, and no standard curative therapy currently exists. Therefore, it is important to understand the biology of adrenocortical carcinoma, and to identify prognostic biomarkers and molecular targets for its therapy. DDX39 is an Asp-Glu-Ala-Asp (DEAD)-box RNA helicase, which is required for transcription, splicing and transport of mRNA. There are some reports about overexpression of DDX39 in tumor tissues and cells (lung squamous cell cancer, gastrointestinal stromal tumor, urinary bladder cancer, malignant pleural mesothelioma). However, the clinicopathological involvement of DDX39 in adrenocortical carcinoma has not yet been documented. The GEPIA, GEPIA2, and UALCAN platforms were used to analyze DDX39 mRNA expression and survival in patients with adrenocortical carcinoma. DDX39 was found to be significantly up-regulated in adrenocortical carcinoma tissues, and this up-regulation inversely correlated with prolonged patient survival. DDX39 may be a potential prognostic biomarker in patients with adrenocortical carcinoma.

Immunological characteristics of peripheral T cells as prognostic markers for Camrelizumab and Apatinib combination therapy in advanced squamous non-small-cell lung cancer.

To determine the characteristic changes of peripheral blood T cells and identify potential biomarkers that associated with the clinical efficacy of combined immunotherapy and anti-angiogenic therapy in patients with advanced squamous non-small cell lung cancer (NSCLC). We performed a comprehensive immunological assessment of peripheral blood mononuclear cell samples from advanced squamous NSCLC patients before and after combination of immunotherapy (Camrelizumab) and anti-angiogenic therapy (Apatinib) using spectral flow cytometry. Correlations between these immunological features and clinical efficacy were analyzed. Our findings revealed that, following two treatment cycles, the concentration of type 1 T helper (Th1) cells in the peripheral circulation was significantly higher in the responder group than in the non-responder group, correlating with a statistically significant improvement in survival outcomes. Post-treatment, CD137 expression within Th1 cells in the responders, whereas TIM-3 expression was significantly reduced. In the validation cohort, elevated CD4+ CXCR3+ CD137+ cells in the peripheral blood were associated with a positive clinical reaction to the treatment and extended survival. Our findings suggest that peripheral blood circulating CD4+ CXCR3+ CD137+ cells serve as biomarkers of response to combined immunotherapy and anti-angiogenic therapy in patients with advanced squamous NSCLC, providing potential guidance for improving clinical outcomes.

An open-label, randomized phase III study of early switch maintenance vs delayed second-line nivolumab in advanced stage squamous non-small cell lung cancer (NSCLC) patients after standard first-line platinum-based chemotherapy-EDEN trial GOIRC 04-2016.

As for squamous (Sq)-NSCLC, Checkmate-017 trial showed a significant overall survival (OS) improvement in favor of Nivolumab (Nivo) over Docetaxel in 2nd-line. We hypothesized that anticipating Nivo use, as early switch maintenance after 1st-line chemotherapy (CHT), might have improved survival as compared to delayed 2nd-line treatment. EDEN was an open-label, 2-arm, phase III study which randomized (1:1) stage IIIB/IV Sq-NSCLC pts non-progressive after 1st-line platinum-based CHT, to receive early Nivo as switch maintenance (Arm A) or standard best supportive care followed by 2nd-line Nivo at disease progression (Arm B). In both arms, Nivo was administered at the dose of 240mg i.v. every 2weeks until progressive disease, intolerable toxicity, or for a maximum of 2years. The primary endpoint was OS. From Sep 2017 to Aug 2020 125 patients (62 Arm A vs 63 Arm B) were randomized from 32 Italian centers. Accrual was stopped early, before the planned sample size (388 pts) was reached, because of registration of ICPIs in 1st-line. Most patients were male (79.2%), current/former smokers (93.6%), had stage IV (74.4%), performance status 0-1 (98.4%). mOS (95% CI) was 14.9 (10.4-18.6) months in arm A vs 18.8 (14.4-21.1) months in arm B (HR 1.09, 95%CI 0.74-1.62, p=0.659). In advanced Sq-NSCLC, the use of Nivo as switch maintenance after 1st-line CHT, does not improve OS compared to its use as 2nd-line. Although the optimal use of ICPIs remains in 1st-line, its role as maintenance has to be better investigated. gov: registration number: NCT03542461.

Comprehensive molecular profiling of squamous non-small cell lung cancer reveals high incidence of actionable genomic alterations among patients with no history of smoking

Comprehensive molecular profiling of squamous non-small cell lung cancer reveals high incidence of actionable genomic alterations among patients with no history of smoking

Artificial neural network systems to predict the response to sintilimab in squamous-cell non-small-cell lung cancer based on data of ORIENT-3 study

BackgroundExisting biomarkers and models for predicting response to programmed cell death protein 1 monoclonal antibody in advanced squamous-cell non-small cell lung cancer (sqNSCLC) did not have enough accuracy. We used data from the ORIENT-3 study to construct artificial neural network (ANN) systems to predict the response to sintilimab for sqNSCLC.MethodsFour ANN systems based on bulk RNA data to predict disease control (DC), immune DC (iDC), objective response (OR) and immune OR (iOR) were constructed and tested for patients with sqNSCLC treated with sintilimab. The mechanism exploration on the bulk and the spatial level were performed in patients from the ORIENT-3 study and the real world, respectively.FindingssqNSCLC patients with different responses to sintilimab showed each unique transcriptomic spectrum. Four ANN systems showed high accuracy in the test cohort (AUC of DC, iDC, OR and iOR were 0.83, 0.89, 0.93 and 0.94, respectively). The performance of ANN systems was better than that of linear model systems and showed high stability. The mechanism exploration on the bulk level suggested that patients with lower ANN system scores (worse response) had a higher ratio of immune-related pathways enrichment. The mechanism exploration on the spatial level indicated that patients with better response to immunotherapy had fewer clusters of both tumor and cytotoxicity T cell spots.InterpretationThe four ANN systems showed high accuracy, robustness and stability in predicting the response to sintilimab for patients with sqNSCLC.

Blood laboratory parameters can predict relapse-free survival of patients with advanced squamous cell lung cancer and adenocarcinoma

The aim of the work was to study the relationship between the concentration of cells and proteins in the blood of patients with Stage III squamous cell lung cancer (SCLC) and adenocarcinoma (AC) before surgical treatment and the duration of the relapse-free period after tumor resection to develop prognostic models for relapse-free survival in these diseases. Using logistic regression equations, the models incorporated variables included cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) concentration, the proportion of lymphocytes expressing the C-X-C motif chemokine receptor 1 (CXCR1), and monocytes expressing the C-X-C motif chemokine receptor 2 for SCLC. For AC, the models included the CYFRA 21-1 concentration, lymphocytes expressing the CXCR1 receptor, and the eosinophil-to-monocyte ratio. These models can predict the probability of tumor recurrence based on measurements of blood parameters in the pre-operative period, with a prediction efficiency of 87.7% for SCLC and 89.0% for AC.

Pneumonitis with amivantamab in squamous cell lung cancer with EGFR exon 20 insertion mutation: a case report

Abstract Background Amivantamab is a human antibody targeting epidermal growth factor receptor (EGFR) and c-MET. It is approved in patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion after progression with platinum-based chemotherapy. The most frequent adverse effects (AEs) are rash, infusion-related reactions, paronychia, and peripheral edema. Pneumonitis is a rare side effect, and there is no evidence about the possibility of reintroducing amivantamab after pulmonary toxicity. Clinical case A 56-year-old male was diagnosed with squamous cell lung cancer in 2021, with brain metastasis at diagnosis. The brain lesion was resected, and histopathologic assessment revealed metastasis from squamous cell lung cancer, and an exon 20 insertion mutation was identified. Chemotherapy with immunotherapy (carboplatin + paclitaxel + pembrolizumab) was initiated in October 2021, and progression was observed after three maintenance cycles. Amivantamab was started in May 2022, and partial response was observed after 2 months of treatment. In September 2022, the patient complained of dyspnea on exertion and dry cough. Computed tomography (CT) scan showed scattered ground-glass opacities. A pneumonitis grade 2 CTCAE was assumed, and corticosteroid therapy was started, with improvement in both symptoms and imaging abnormalities. After discussion with a multidisciplinary team, it was decided to restart treatment with amivantamab in January 2023 and there is no evidence of pulmonary toxicity to this date. Conclusion Amivantamab-related pneumonitis is a rare side effect and usually predicts drug discontinuation. In this clinical case, it was possible to reintroduce the drug without reoccurrence of the toxicity successfully. This possibility of reintroducing treatment after non-life-threatening toxicity occurs can be of great importance as therapeutic options for these patients are limited.

Survival prediction and molecular subtyping of squamous cell lung cancer based on network embedding

Squamous cell lung cancer (SQCLC), which is fatal to humans, is heterogeneous with different genetic and histological features. We used SBMOI, a multi-omics data integration method from previous study, to integrate clinical, gene expression, and somatic mutation data of SQCLC to construct new patient features. Next, random survival forest (RSF) model and SimpleMKL model were constructed to predict the survival of SQCLC patients, and K-means model was constructed to perform molecular subtyping. The results of the RSF model showed that when the dimension of the patient features were 11 × 364 and the hard threshold was 0.2, we obtained the best results, and the AUC value of the 1-year time-dependent ROC curve was 0.706. The SimpleMKL model, constructed using the same patient features, performed exceptionally well, with 1-year, 5-year, and 10-year survival prediction AUC values of 0.944, 0.947 and 0.950, respectively. We used K-means analysis to identify three SQCLC molecular subtypes with significant survival differences. The patient features constructed by SBMOI were used to effectively predict the survival and molecular subtyping of SQCLC patients. In addition, our study further confirmed the effectiveness in multi-omics data integration task and broad applicability of SBMOI.

Association between the dietary inflammatory index and risk of lung cancer: a multi-centered case-control study.

Dietary factors might contribute to the risk of lung cancer by increasing the concentration of inflammatory markers. The literature-derived Dietary Inflammatory Index (DII) has been established to evaluate the inflammatory potential of diet correlated with inflammatory markers. The association between DII scores and the risk of lung cancer has been conflicting. So, in the current study, we aimed to assess the effect of pro-inflammatory dietary patterns measured with DII and the risk of lung cancer. A multi-center case-control study was carried out on 616 patients with lung cancer and 3412 healthy controls. Dietary intakes were collected using a 131-item food frequency questionnaire during a face-to-face interview. The DII scores including thirty-six nutrients were calculated after energy adjustments. Finally, the association between DII level and the risk of lung cancer was evaluated by performing a multi-variable regression method after adjusting for potential confounders. The risk of overall lung cancer, small cell, and squamous cell carcinoma was elevated in the third tertile compared to the first tertile of the DII score, (odds ratio [OR] T3 vs. T1 of overall lung cancer = 1.38 (95% confidence interval [CI] 1.08-1.77), P trend = 0.01, OR T3 vs. T1 of squamous cell lung cancer = 1.82 (95% CI 1.02-3.24), P trend = 0.04, OR T3 vs. T1 of small cell lung cancer = 1.66 (95% CI 1.08-2.54), P trend = 0.019). However, no increase was observed in the risk of adenocarcinoma by adherence to a pro-inflammatory dietary pattern. A positive link was found between DII and the risk of overall lung cancer, small-cell, and squamous-cell lung cancer. However, there was no association between DII and the risk of lung adenocarcinoma.

A Case Report of EGFR-TKIs Resistant Secondary MET Gene Amplified Lung Squamous Cell Carcinoma and Literature Review

With the rapid development of epidermal growth factor receptor (EGFR) gene testing of lung adenocarcinoma patients has been routinely carried out, EGFR mutations are also possible for some small samples of non-smoking female lung squamous cell carcinoma patients. This increases the opportunity for targeted therapy for this group of patients. However, drug resistance in patients with lung squamous cell carcinoma during targeted therapy is an important factor affecting subsequent treatment. There are multiple mechanisms of acquired drug resistance in targeted therapy, and the alteration of mesenchymal-epithelial transition factor (MET) signaling pathway is one of the common mechanisms of drug resistance. At present, some selective tyrosine kinase inhibitors (TKIs) of MET has been approved for non-small cell lung cancer with MET gene 14 exon skipping mutation, such as Glumetinib, Savolitinib, Tepotinib, Capmatinib, etc. Drugs that target secondary MET amplification are still in clinical trials. This paper retrospectively analyzed the clinical data of a female patient with EGFR-TKIs resistant secondary MET amplified squamous cell lung cancer, and reviewed relevant literature to explore how to optimize the treatment of lung squamous cell carcinoma patients with EGFR mutation, so as to provide clinical reference for the diagnosis and treatment of such patients. .

Establishing a new human lung squamous cell carcinoma cell line, OMUL-1, expressing insulin-like growth factor 1 receptor and programmed cell death ligand 1.

Squamous cell carcinoma is the second most prevalent type of non-small cell lung cancer. Analyzing the molecular mechanisms underlying lung carcinoma requires useful tools, such as squamous lung cancer cell lines. A novel new lung squamous cell carcinoma cell line, OMUL-1, was developed from the primary lung cancer of a 74-year-old man. We assessed the characteristics and behavior of OMUL-1 cells were examined, including their growth kinetics, tumorigenicity in mice, histological properties, gene expression profiles using reverse transcription polymerase chain reaction (RT-PCR), and RNA sequencing and invasion assays. OMUL-1-an adherent cell line-resulted in 100% tumor formation when subcutaneously injected into mice. Histological analysis of the subcutaneous tumor using hematoxylin and eosin staining revealed squamous cell carcinoma with characteristics similar to those of the primary tumor (p40 and p63 were positive, and TTF-1 was negative). An invasion assay demonstrated that OMUL-1 had a lower invasion ability compared to that of other developed cell lines. RT-PCR analysis and RNA sequencing indicated that OMUL-1 cells expressed FGFR1, FGFR2, FGFR3, FGFR4, EGFR, HER2, ErbB3, ErbB4, VEGFR3, IGF1R, c-MET, PDGFRa, and PDGFRb. Additionally, picropodophyllin (an IGF1R inhibitor) significantly inhibited the growth of OMUL-1 cells. Immunohistochemistry revealed that IGF1R and PD-L1 were expressed in both the primary and subcutaneous tumors. We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1.

A causal association between chemokines and the risk of lung cancer: a univariate and multivariate mendelian randomization study

BackgroundObservational studies and experimental evidence have shown that chemokines play important roles in lung cancer development, progression, and treatment. However, few studies have examined the causal association between them.MethodsSummary data of chemokines and lung cancer were obtained from genome-wide association studies. Mendelian randomization (MR) analyses were performed by five methods, Inverse variance weighted (IVW), Weighted median estimation, MR-Egger, Simple mode and Weighted, with IVW as the primary analysis method. Sensitivity analysis was used to assess the reliability of the MR results. Multivariate Mendelian randomization studies were used to infer whether causality was influenced by potential mediators. The expression levels of CCL21 were analyzed by quantitative real-time PCR.ResultsWe found that CCL21 was negatively associated with lung adenocarcinoma risk. CCL25 was positively associated with lung squamous cell carcinoma risk. CCL5 was negatively associated with small cell lung cancer risk. CCL21, CCL24, CCL27, and CCL28 was positively associated with small cell lung cancer risk. After multivariate Mendelian randomization adjustment for smoking behavior, it was found that the effect of CCL25 on lung squamous cell cancer disappeared, and the effect of CCL21 on small cell lung cancer was quite opposite to the univariate. The receiver operating characteristic curve indicated that chemokines had high accuracy in the diagnosis of lung cancer. CCL21 expression levels showed large differences in lung adenocarcinoma cells.ConclusionThese results highlighted the causal effects of chemokines on lung cancer and suggested a mediating role of smoking behavior in the association between chemokines and lung cancer.

Clinical Efficacy and Safety of Anlotinib Combined with Immune Checkpoint Inhibitors in the Treatment of Advanced Squamous Cell Lung Cancer: A Retrospective Single-Center Study in China.

There is a relative lack of real-world data regarding the treatment of advanced squamous cell lung cancer (SqCLC) with anlotinib. This study aimed to investigate the clinical efficacy and safety of combining anlotinib with ICIs for the treatment of advanced SqCLC. Sixty patients with advanced SqCLC from December, 2017 to December, 2022, were retrospectively recruited in the final analysis. The overall survival (OS), adverse events (AEs), and short-term clinical effectiveness, including complete remission (CR), partial remission (PR), stable disease (SD), and progression disease (PD) of the study populations, were observed. Objective response rate (ORR) was defined as the combined percentage of CR and PR in all patients. Disease control rate (DCR) was defined as the combined percentage of CR, PR, and SD in all patients. Subgroups were classified based on age (<65 or ≥65), sex (female or male), and the eastern cooperative oncology group (ECOG) score (0-1 or 1-2). The median age of the study population was 65 years, and 41 (68.3%) of the participants were male. ORR was 21.67%, and DCR was 83.33%. The median PFS and OS were 7.5 and 19.5 months, respectively. Furthermore, the Kaplan-Meier curves demonstrated no significant difference (P >0.05) in PFS and OS between different age groups, sex, and ECOG scores. Bone marrow suppression was the most common AE, followed by immune pneumonia. The findings of this study confirmed the effectiveness and safety of anlotinib and ICIs for advanced SqCLC.

Squamous Cell Lung Cancer Presenting with Initial Rare Paraneoplastic Hematological Findings

Squamous Cell Lung Cancer Presenting with Initial Rare Paraneoplastic Hematological Findings

Non-small cell lung carcinoma. Clinical case

In 2020, 2.2 million new cases of lung cancer were reported. The main form of lung cancer is non-small cell carcinoma (85%). Non-small cell lung cancer has 3 subtypes: adenocarcinoma, large cell and squamous cell carcinoma. Squamous cell lung cancer occurs in 20-40% of all lung cancers. Squamous cell lung cancer is associated with an unfavorable outcome. 5-year survival rate not exceeding 18%.

P3.12D.09 Trial in Progress: A Phase Ib Study of HMBD-001, An Anti-HER3 Antibody, in Advanced Squamous Non-Small Cell Lung Cancer

P3.12D.09 Trial in Progress: A Phase Ib Study of HMBD-001, An Anti-HER3 Antibody, in Advanced Squamous Non-Small Cell Lung Cancer

Living for the Moment - How Important Is It in the End of Life?

This essay investigates the role of present-moment living in end-of-life care, drawing on reflections from a personal patient encounter in a palliative care setting, Mrs. B, a 63-year-old patient with terminal squamous cell lung cancer, whose experience underscores the impact of living with a sense of fulfillment and joy despite a life-limiting diagnosis. Mrs. B's approach to her illness-marked by an optimistic acceptance of mortality and a focus on daily joys-challenges traditional palliative care paradigms that emphasize somberness and future-oriented care. Through detailed narrative and reflective analysis, the essay highlights how Mrs. B's resilience and spiritual beliefs contributed to her ability to maintain a positive outlook in the face of terminal illness. This case study illustrates the potential for joy and present-moment living to coexist with palliative care practices, offering a nuanced perspective on patient care. The discussion extends to the implications for healthcare professionals, advocating for a more adaptable and empathetic approach that aligns with individual patient values and preferences. This reflection calls for a shift in palliative care practices towards recognizing and supporting the diverse ways patients navigate their end-of-life experiences.

Classification of histological subtypes of non-small cell lung cancer using computerized tomography texture analysis

Objective: This study aimed to differentiate between the two main histological subtypes of non-small cell lung cancer using a non-invasive technique, computerized tomography texture analysis. Method: We included 53 patients. All patients were histopathologically proven non-small cell lung cancer cases. All patients underwent thorax CT scans. In CT images, the differences present in the texture features of adenocarcinoma and squamous cell carcinoma, which are the two main histological subtypes of non-small cell lung cancer, were determined by the consensus of two radiologists for computerized tomography-based texture analysis. Results: A total of 44 texture features were extracted, including 12 first-order features and 32 second-order features derived from gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), neighborhood gray-level different matrix (NGLDM), and gray-level zone length matrix (GLZLM) features in 51 CT images. None of the evaluated texture parameters were statistically significant. However, in patients with squamous cell lung cancer, the values of Intensity Histogram, NGTDM Complexity, and Intensity Based Robust Mean Absolute Deviation higher from adenocarcinoma patients and had the highest area under the curve in roc analyses (0.727, 0.664, 0.666 respectively) Conclusion: Intensity Histogram, NGTDM Complexity, and Intensity Based Robust Mean Absolute Deviation features can be used to differentiate between the subtypes of non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma. These features were highly associated with the high intratumoral heterogeneity of squamous cell lung cancer.

Adaptive stereotactic radiosurgery for cerebral metastases of non-small cell lung cancer: a retrospective study

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cause of brain metastases (BM). Adaptive stereotactic radiosurgery (ASRS) may be a useful option in the treatment of patients with large unresectable brain metastases (BM), but to date there are only a limited number of studies evaluating the effectiveness of this method.OBJECTIVE: To analyze the effectiveness of ASRS in patients with large BM NSCLC not subject to surgical resection.MATERIAL AND METHODS: We retrospectively analyzed data from 37 patients suffering from NSCLC with 45 large (&gt;2 cm in diameter, volume &gt;4 cm3) unresectable BM treated with the Gamma Knife Perfexion model using two- and three-fraction ASRS. Of these, 14 foci (31.1%) were metastases of squamous cell lung cancer, 31 (68.9%) were metastases of adenocarcinoma. The median volume of lesions treated with ASRS was 9.8 (range 4.6–30.6 cm3). The dynamics of volume changes between fractions and the cumulative incidence of local relapses (CILR) were studied, and ROC analysis was performed for the tumor volume parameter. Intracranial progression-free survival (iPFS) and overall survival (OS) were assessed. Statistics: To establish statistical significance of differences for related variables, the Wilcoxon test for pairwise comparisons and the Friedman test for three or more groups were used. The Kaplan-Meier method was used to calculate local control, PFS, and OS rates. The log-rank test was used to compare survival data in two groups.RESULTS: The median follow-up period was 19.4 months. With two-fraction ASRS, the median volume of metastasis decreased by 28.6% by the second session, with three-fraction — by 40.0% by the third session. The 1-year and 2-year CILR rates were 8.6±6.1%, respectively; 26.1±12.3%. In ROC analysis, the area under the curve (AUC) for tumor volume was 0.80 (95% CI 0.6– 1.0) with an optimal cutoff of 18.5 cm3. The differences in CILR between the groups with metastasis volume &lt;18.5 cm3 and ≥18.5 cm3 were statistically significant (p&lt;0.001). Median iPFS was 8.3 (95% CI 5.9–10.7) months, 1-year iPFS was 33.5±8.1%;2-year — 7.8±5.2%. Median OS was 13.2 (95% CI 9.0–17.4) months; 1-year OS — 52.9±8.7%, 2-year — 22.4±8.8%.DISCUSSION: Using two- and three-fraction ASRS, we delivered doses to large BM sufficient for a high level of local control with an acceptable risk of neurotoxicity: 1-year local control was 91.4%; 2-year — 73.9%; the incidence of radionecrosis is 8.5%. A statistically significant effect of lesion volume ≥18.5 cm3 on the risk of local recurrence was found. The iPFS and OS indicators after ASRS can be considered satisfactory for this group of patients.CONCLUSION: ASRS is an effective and perhaps optimal strategy for the treatment of large unresectable BM in patients with NSCLC, but comparison with other modern radiotherapy modalities such as stereotactic hypofractionated radiotherapy and WBRT with simultaneous integrated boost is needed.

Cancer Incidence among Marines and Navy Personnel and Civilian Workers Exposed to Industrial Solvents in Drinking Water at US Marine Corps Base Camp Lejeune: A Cohort Study.

Drinking water at US Marine Corps Base Camp Lejeune, North Carolina, was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. A cohort cancer incidence study was conducted of Marines/Navy personnel who began service and were stationed at Camp Lejeune () or Camp Pendleton, California () between 1975 and 1985 and civilian workers employed at Camp Lejeune () or Camp Pendleton () between October 1972 and December 1985. Camp Pendleton's drinking water was not contaminated with industrial solvents. Individual-level information on primary invasive cancers and in situ bladder cancer diagnosed between 1996 and 2017 was obtained from 54 US cancer registries. Proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) comparing cancer incidence between the Camp Lejeune and Camp Pendleton cohorts, adjusted for sex, race, education, and rank (or blue-collar work), with age as the time variable. Precision of aHRs was evaluated using the 95% confidence interval (CI) ratio (CIR). Cancers among Camp Lejeune Marines/Navy personnel and civilian workers totaled 12,083 and 1,563, respectively. Cancers among Camp Pendleton Marines/Navy personnel and civilian workers totaled 12,144 and 1,416, respectively. Compared with Camp Pendleton, Camp Lejeune Marines/Navy personnel had aHRs with CIRs for all myeloid cancers (; 95% CI: 1.03, 1.49), acute myeloid leukemia (; 95% CI: 1.03, 1.85), myelodysplastic and myeloproliferative syndromes (; 95% CI: 1.07, 2.62), polycythemia vera (; 95% CI: 0.94, 2.11), and cancers of the esophagus (; 95% CI: 1.03, 1.56), larynx (; 95% CI: 0.98, 1.50), soft tissue (; 95% CI: 0.92, 1.59), and thyroid (; 95% CI: 1.03, 1.45). Lymphoma subtypes mantle cell and marginal zone B-cell and lung cancer subtypes adenocarcinoma and non-small cell lung cancer also had aHRs with CIRs . Compared with Camp Pendleton, Camp Lejeune civilian workers had aHRs with CIRs for all myeloid cancers (; 95% CI: 0.83, 2.36), squamous cell lung cancer (; 95% CI: 1.10, 2.41), and female breast (; 95% CI: 0.97, 1.52) and ductal cancer (; 95% CI: 1.02, 1.71). Increased risks of several cancers were observed among Marines/Navy personnel and civilian workers exposed to contaminated drinking water at Camp Lejeune compared with Camp Pendleton. https://doi.org/10.1289/EHP14966.