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Lung cancer is the leading cause of cancer-related death worldwide. However, lung cancer incidence and mortality rates differ substantially across the world, reflecting varying patterns of tobacco smoking, exposure to environmental risk factors and genetics. Tobacco smoking is the leading risk factor for lung cancer. Lung cancer incidence largely reflects trends in smoking patterns, which generally vary by sex and economic development. For this reason, tobacco control campaigns are a central part of global strategies designed to reduce lung cancer mortality. Environmental and occupational lung cancer risk factors, such as unprocessed biomass fuels, asbestos, arsenic and radon, can also contribute to lung cancer incidence in certain parts of the world. Over the past decade, large-cohort clinical studies have established that low-dose CT screening reduces lung cancer mortality, largely owing to increased diagnosis and treatment at earlier disease stages. These data have led to recommendations that individuals with a high risk of lung cancer undergo screening in several economically developed countries and increased implementation of screening worldwide. In this Review, we provide an overview of the global epidemiology of lung cancer. Lung cancer risk factors and global risk reduction efforts are also discussed. Finally, we summarize lung cancer screening policies and their implementation worldwide.Lung cancer is the commonest cancer globally. Reflecting patterns of smoking and other risk factor exposures, both the incidence of and mortality from lung cancer are highest in economically developed countries. Nonetheless, developing and less economically developed countries are likely to have the biggest increases in lung cancer in the coming years. In this Review, the authors describe the global epidemiology of lung cancer, and how changes in exposures, socioeconomic status, public health interventions and better treatment strategies are influencing both the incidence of and mortality from lung cancer.

Randomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of locoregional non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however. We used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in locoregional NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases. Adjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with Stage IB and IIA cancers. For patients with CHF and Stage IB and IIA disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for more advanced stages for younger patients with CHF. For stages IIB and IIIA NSCLC, most patient groups benefited from adjuvant chemotherapy. However, In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts. Older, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients.

BackgroundHypophysitis is a well-recognized immune-related adverse event in patients treated with immune checkpoint inhibitors for cancer. Some anterior pituitary hormones may recover; however, secondary adrenal insufficiency is usually permanent.Case presentationA 26-year old male with metastatic clear cell renal cell carcinoma was started on treatment with the anti-programmed cell death-1 monoclonal antibody (anti-PD-1 mAb) nivolumab, followed by combined nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb, ipilimumab. After starting nivolumab monotherapy the patient developed thyroiditis, which resolved without treatment. Prior to commencing combined ICI therapy, a random serum cortisol drawn at 1:30 pm and was 15.0 μg/dL (414 nmol/L). Three weeks after starting combined ICI therapy he developed sudden onset of severe fatigue and 1 pm serum cortisol was 2.0 μg/dL (55.2 nmol/L), adrenocorticotropic hormone (ACTH) was 16 pg/mL (3.52 pmol/L). A diagnosis of hypophysitis was made, and he was immediately started on prednisone 1 mg/kg. His symptoms resolved rapidly, and he continued immune checkpoint inhibitor therapy. He was noted to also have low gonadotropic hormones and testosterone (nadir testosterone 81.19 ng/dL). The prednisone was tapered slowly over the next six weeks to a maintenance dose of 5 mg daily. Four months after the initial presentation his cortisol remained low, but his testosterone level had increased to 973.43 ng/dL. After five months his random serum cortisol (1 pm) increased to 11.0 μg/dL (303.6 nmol/L). The prednisone was cautiously discontinued with close monitoring. Two months off glucocorticoid replacement he remained asymptomatic with an ACTH of 24.1 pg/mL (5.3 pmol/L), and cortisol of 13.0 μg/dL (358.8 nmol/L).ConclusionsThis case documents the unusual recovery from secondary adrenal insufficiency in a patient who developed hypophysitis from immune checkpoint inhibitor therapy. Repeated pituitary hormone testing every three months for the first year after the development of hypophysitis may identify more patients with hypothalamic-pituitary-adrenal axis recovery.

Background Gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) are increasingly common malignancies and tend to have favorable long‐term prognoses. Somatostatin analogues (SSA) are a first‐line treatment for many NETs. Short‐term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality. Aim In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment. Methods and Results Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991‐2016), we identified patients age 65+ with no prior DM diagnosis and a GEP‐NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ2 tests to compare SSA‐treated and SSA‐untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP‐NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95‐1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. Conclusion DM was very common in GEP‐NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA‐treated and SSA‐untreated GEP‐NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

Objectives Response to immune checkpoint inhibitor (ICI) remains limited to a subset of patients and predictive biomarkers of response remains an unmet need, limiting our ability to provide precision medicine. Using real-world data, we aimed to identify potential clinical prognosticators of ICI response in solid tumor patients. Methods We conducted a retrospective analysis of all solid tumor patients treated with ICIs at the Mount Sinai Hospital between January 2011 and April 2017. Predictors assessed included demographics, performance status, co-morbidities, family history of cancer, smoking status, cancer type, metastatic pattern, and type of ICI. Outcomes evaluated include progression free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Univariable and multivariable Cox proportional hazard models were constructed to test the association of predictors with outcomes. Results We identified 297 ICI-treated patients with diagnosis of non-small cell lung cancer (N = 81, 27.3%), melanoma (N = 73, 24.6%), hepatocellular carcinoma (N = 51, 17.2%), urothelial carcinoma (N = 51, 17.2%), head and neck squamous cell carcinoma (N = 23, 7.7%), and renal cell carcinoma (N = 18, 6.1%). In multivariable analysis, good performance status of ECOG ≤ 2 (PFS, ORR, DCR and OS) and family history of cancer (ORR and DCR) associated with improved ICI response. Bone metastasis was associated with worse outcomes (PFS, ORR, and DCR). Conclusions Mechanisms underlying the clinical predictors of response observed in this real-world analysis, such as genetic variants and bone metastasis-tumor microenvironment, warrant further exploration in larger studies incorporating translational endpoints. Consistently positive clinical correlates may help inform patient stratification when considering ICI therapy.

Nanosecond pulsed electric fields (nsPEF) induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns). An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7-30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five other types of cancer cell lines were used to detect the effect of nsPEF in vitro. Rate of cell death in these 12 different cancer cell lines was dependent on nsPEF voltage and pulse number. To examine the effect of nsPEF in vivo, carcinogen-induced cutaneous papillomas and squamous cell carcinomas in mice were exposed to nsPEF with three pulse numbers (50, 200, and 400 pulses), two nominal electric fields (40 KV/cm and 31 KV/cm), and two pulse durations (7 ns and 14 ns). Carcinogen-induced cutaneous papillomas and squamous carcinomas were eliminated efficiently using one treatment of nsPEF with 14 ns duration pulses (33/39 = 85%), and all remaining lesions were eliminated after a 2nd treatment (6/39 = 15%). 13.5% of carcinogen-induced tumors (5 of 37) were eliminated using 7 ns duration pulses after one treatment of nsPEF. Associated with tumor lysis, expression of the anti-apoptotic proteins Bcl-xl and Bcl-2 were markedly reduced and apoptosis increased (TUNEL assay) after nsPEF treatment. nsPEF efficiently causes cell death in vitro and removes papillomas and squamous cell carcinoma in vivo from skin of mice. nsPEF has the therapeutic potential to remove human squamous carcinoma.

Abstract Disclosure: D. Nudelman: None. M. Galsky: Janssen Research & Development Company, Merck, Seagen, Bristol-Myers Squibb, Gilead Sciences, Pfizer, Inc., Curis, AstraZeneca, Novartis, Abbvie, Janssen Oncology, Genentech, Inc., Bicycle Therapeutics, Dendreon. J. Wisnivesky: Sanofi, PPD, Banook, BioNTech, Regeneron, Axella. A. Leiter: None. Background: Diabetes mellitus (DM) is a significant comorbidity in PC survivors (prevalence ∼20%) and is associated with worse mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are DM drugs that lower glucose and reduce CV risk. SGLT2is reduce glucose reabsorption in the kidneys, inducing glucosuria. Due to this mechanism, they are associated with adverse genitourinary (GU) effects. How SGLT2is are tolerated by PC survivors, who have a high baseline burden of GU symptoms from PC treatments like prostatectomy and radiation therapy (RT), is unknown. We hypothesized that PC survivors with T2DM who received SGLT2is had higher rates of urinary tract infections (UTIs) and incontinence after PC treatment, than those not on SLGT2is. Methods: We retrospectively collected data from our institution’s health records linked to cancer registry data. Patients were included for analysis if they had PC diagnosed from 2005-2020, were treated with RT and/or prostatectomy, and had T2DM on non-insulin medications (based on claims codes). Patients with < 2-year follow-up after primary PC treatment and < 4 months of follow-up after beginning SGLT2is were excluded. We collected data on patient demographics, PC, and DM characteristics. We investigated prevalence of incontinence and UTIs 2 years after PC treatment (to ensure new symptoms were not primary treatment-related). We used descriptive statistics to assess population characteristics and compared groups using chi-square test. Results: 190 patients with PC and DM were analyzed. 40 patients (21%) received SGLT2is and 150 (79%) were on other DM drugs. Median follow-up after PC treatment was 5.2 years. Median age at diagnosis was 67, with similar distribution across patients on SLGT2is and other DM drugs (p=0.6). 33% of the cohort was White, 29% Black, 45% Hispanic, with no significant distribution difference (p=0.2). Most patients had localized disease (75%), followed by regional (20%) and metastatic (5%) at time of PC diagnosis, with no significant differences between groups (p=0.7). For PC treatments, 39% received RT, 57% received prostatectomy, and 4% got both (p=0.5). 10% of patients on SGLT2is and 10% of patients on other DM drugs developed a UTI at least 2 years after PC treatment (p=0.99). Incontinence was observed in 13% of patients receiving SGLT2i and in 17% of patients on other DM drugs (p=0.63). 3 patients (7.5%) receiving SGLT2is discontinued the medication due to GU side effects. Conclusions: In a cohort of PC survivors with T2DM, we found no association between SGLT2is and new adverse GU effects relative to those receiving other DM drugs, indicating SLGT2is are generally well-tolerated in this group. These insights can help make PC survivors make informed decisions about initiating SGLT2is and improve guideline-concordant DM care. Future studies should examine SGLT2i adverse GU effects in larger PC survivor populations. Presentation: Monday, July 14, 2025

Objective We describe a patient who presented with thyroid storm and severe gastrointestinal bleed (GIB) and aim to highlight the unique challenges in management. Case A 57-year-old man with a history of psoriasis presented to an outside hospital with palpitations, shortness of breath and diarrhea. Vitals included temperature 98.2F, blood pressure 127/77 mmHg, heart rate 142 bpm with an EKG confirming new onset atrial fibrillation with rapid ventricular rate. Labs included TSH 0.000 mIU/mL (0.35 - 5.50) with a free T4 5.42 ng/dL (0.61 - 1.12). The patient was started on a beta blocker and methimazole (MMI) 10 mg and transferred to our institution for possible cardioversion. Additional labs included Hgb 10.6 g/dL (14-18), platelets 84 K/cm (130-400), ALT 32 U/L (0-45), AST 67 U/L (0-41), ALP 289 U/L (30-115), TBr 5.1 mg/dL (0.2-1.2) and Dbr 4 mg/dL (0-0.2). Echocardiogram confirmed an ejection fraction of 35% and chest radiograph revealed bilateral pleural effusions and pulmonary edema. In preparation for cardioversion, a heparin drip was started resulting in hematemesis, melena and a repeat Hgb of 7.9 g/dL. The patient was intubated, transfused with pRBC’s and started on pantoprazole and octreotide. Endoscopy revealed multiple actively bleeding gastric ulcers treated with clipping. Endocrinology was consulted; the patient was diagnosed with thyroid storm (Burch-Wartofsky ≥ 70 based on known clinical parameters) and treated with an esmolol drip and dexamethasone 1 mg q6h. Due to concern for an active GIB, cholestyramine and SSKI/Lugols were held whereas the dose of MMI was not increased due to worsening transaminitis, doubling of DBr, and downtrending of free T4. After stabilization of the GIB, the patient was extubated with significant clinical improvement. He was discharged on MMI 10 mg and metoprolol tartrate 50 mg BID. Follow-up labs confirmed the diagnosis of Graves’ with TPO 346 IU/mL (0-34), anti-thyroglobulin Ab 31.4 IU/mL (0-0.9) and a TSH-receptor antibody of 15.97 (0-1.75). Thyroid ultrasound revealed heterogenous enlarged gland with no nodules. Conclusion Thyroid storm, a rare but life threatening endocrine emergency is treated by targeting thyroid hormone synthesis, release, conversion to its active form and effects. Active GIB complicates treatment of thyroid storm. First, SSKI/Lugol’s has been shown to be caustic to the GI lining and has been reported to induce a GIB during the treatment of thyroid storm. Second, cholestyramine and steroids have also been associated with an increased risk of GIB. The case was further complicated by worsening transaminitis and hyperbilirubinemia which prevented uptitration of MMI. Despite being limited in treatment options, the patient’s free T4 and clinical symptoms improved on an esmolol drip, dexamethasone and low dose MMI. Our case demonstrates that thyrotoxicosis can be managed despite the treatment limitations posed by an active GIB.

Randomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of locoregional non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however. We used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in locoregional NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases. Adjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with Stage IB and IIA cancers. For patients with CHF and Stage IB and IIA disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for more advanced stages for younger patients with CHF. For stages IIB and IIIA NSCLC, most patient groups benefited from adjuvant chemotherapy. However, In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts. Older, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients.

Randomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of locoregional non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however. We used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in locoregional NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases. Adjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with Stage IB and IIA cancers. For patients with CHF and Stage IB and IIA disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for more advanced stages for younger patients with CHF. For stages IIB and IIIA NSCLC, most patient groups benefited from adjuvant chemotherapy. However, In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts. Older, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients.