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Van Loon, Katherine; Breithaupt, Lindsay; Ng, Dianna; DeBoer, Rebecca J; Buckle, Geoffrey C; Bialous, Stella; Hiatt, Robert A; Volberding, Paul; Hermiston, Michelle L; Ashworth, Alan
doi: 10.1093/jnci/djad255pmid: 38060289
As the burden of cancers impacting low- and middle-income countries is projected to increase, formation of strategic partnerships between institutions in high-income countries and low- and middle-income country institutions may serve to accelerate cancer research, clinical care, and training. As the US National Cancer Institute and its Center for Global Health continue to encourage cancer centers to join its global mission, academic cancer centers in the United States have increased their global activities. In 2015, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, responded to the call for international partnership in addressing the global cancer burden through the establishment of the Global Cancer Program as a priority initiative. In developing the Global Cancer Program, we galvanized institutional support to foster sustained, bidirectional, equitable, international partnerships in global cancer control. Our focus and intent in disseminating this commentary is to share experiences and lessons learned from the perspective of a US-based, National Cancer Institute–designated cancer center and to provide a roadmap for other high-income institutions seeking to strategically broaden their missions and address the complex challenges of global cancer control. Herein, we review the formative evaluation, governance, strategic planning, investments in career development, funding sources, program evaluation, and lessons learned. Reflecting on the evolution of our program during the first 5 years, we observed in our partners a powerful shift toward a locally driven priority setting, reduced dependency, and an increased commitment to research as a path to improve cancer outcomes in resource-constrained settings.
doi: 10.1093/jnci/djad266pmid: 38113418
When diagnosed with cancer or any other life-threatening condition, people must negotiate 2 once-separate but now integrated realms—a medical care industrial complex and an everyday life now lived in conscious awareness of mortality—a state of being subject to death. Life becomes a series of challenges and disruptions to relationships, body image and integrity, autonomy and independence, life goals, hopes, and dreams for the future. Whether one physically, emotionally, or spiritually survives, thrives, or succumbs to cancer is dependent on a treatment plan that accounts for the multiple and varied ways in which people experience dual citizenship in the realms of the well and the sick. A theory of cancer survivorship that integrates both medical and patient perspectives into a cogent and coherent framework has the potential to enhance the quality of cancer care and the patient experience.“Everyone who is born holds dual citizenship in the kingdom of the well and in the kingdom of the sick.… Although we prefer to use the good passport, sooner or later each of us is obliged … to identify ourselves as citizens of that other place” (1).
Huang, Ryan S; Mihalache, Andrew; Nafees, Abdulwadud; Hasan, Asad; Ye, Xiang Y; Liu, Zhihui; Leighl, Natasha B; Raman, Srinivas
doi: 10.1093/jnci/djad268pmid: 38123515
BackgroundMultidisciplinary cancer conferences consist of regular meetings between diverse specialists working together to share clinical decision making in cancer care. The aim of this study was to systematically review and meta-analyze the effect of multidisciplinary cancer conference intervention on the overall survival of patients with cancer.MethodsA systematic literature search was conducted on Ovid MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials for studies published up to July 2023. Studies reporting on the impact of multidisciplinary cancer conferences on patient overall survival were included. A standard random-effects model with the inverse variance–weighted approach was used to estimate the pooled hazard ratio of mortality (multidisciplinary cancer conference vs non–multidisciplinary cancer conference) across studies, and the heterogeneity was assessed by I2. Publication bias was examined using funnel plots and the Egger test.ResultsA total of 134 287 patients with cancer from 59 studies were included in our analysis, with 48 467 managed by multidisciplinary cancer conferences and 85 820 in the control arm. Across all cancer types, patients managed by multidisciplinary cancer conferences had an increased overall survival compared with control patients (hazard ratio = 0.67, 95% confidence interval = 0.62 to 0.71, I2 = 84%). Median survival time was 30.2 months in the multidisciplinary cancer conference group and 19.0 months in the control group. In subgroup analysis, a positive effect of the multidisciplinary cancer conference intervention on overall survival was found in breast, colorectal, esophageal, hematologic, hepatocellular, lung, pancreatic, and head and neck cancer.ConclusionsOverall, our meta-analysis found a significant positive effect of multidisciplinary cancer conferences compared with controls. Further studies are needed to establish nuanced guidelines when optimizing multidisciplinary cancer conference integration for treating diverse patient populations.
de Munck, Linda; Eijkelboom, Anouk H; Otten, Johannes D M; Broeders, Mireille J M; Siesling, Sabine
doi: 10.1093/jnci/djad230pmid: 37935443
BackgroundLittle is known about the impact of screen-detected breast cancer compared with clinically detected breast cancer on the disease-free interval (ie, free from locoregional recurrences, distant metastasis, contralateral breast cancer). Moreover, it is thought that most studies overestimate the beneficial effect of screening, as they do not adjust for lead time. We investigated the association between method of breast cancer detection and disease-free interval, taking lead time into account.MethodsWomen aged 50-76 years, diagnosed with breast cancer between 2005 and 2008 were selected from the Netherlands Cancer Registry. Women diagnosed in 2005 were divided into screen-detected and clinically detected cancer and had a follow-up of 10 years (2005 cohort). Women diagnosed in 2006-2008 were divided into screen-detected, interval, and nonscreen-related cancer and had a follow-up of 5 years (2006-2008 cohort). A previously published method was used to adjust for lead time. Analyses were repeated correcting for confounding variables instead of lead time.ResultsThe 2005 cohort included 6215 women. Women with screen-detected cancer had an improved disease-free interval compared with women with clinically detected cancer (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.68 to 0.87). The 2006-2008 cohort included 15 176 women. Women with screen-detected or interval cancer had an improved disease-free interval compared with women with nonscreen-related cancer (HR = 0.76, 95% CI = 0.66 to 0.88; HR = 0.88, 95% CI = 0.78 to 0.99, respectively). Correcting for confounders instead of lead time did not change associations.ConclusionWomen with screen-detected cancer had an improved disease-free interval compared with women with a nonscreen-related or clinically detected cancer, after correction for lead time.
Etemadi, Arash; Poustchi, Hossein; Chang, Cindy M; Calafat, Antonia M; Blount, Benjamin C; Bhandari, Deepak; Wang, Lanqing; Roshandel, Gholamreza; Alexandridis, Apostolos; Botelho, Julianne Cook; Xia, Baoyun; Wang, Yuesong; Sosnoff, Connie S; Feng, Jun;
Pan, Changqing; Zhai, You; Wang, Chen; Liao, Zhiyi; Wang, Di; Yu, Mingchen; Wu, Fan; Yin, Yiyun; Shi, Zhongfang; Li, Guanzhang; Jiang, Tao; Zhang, Wei
doi: 10.1093/jnci/djad226pmid: 37944044
BackgroundPoliovirus receptor interacts with 3 receptors: T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif, CD96, and DNAX accessory molecule 1, which are predominantly expressed on T cells and natural killer (NK) cells. Many solid tumors, including IDH wild-type glioblastoma, have been reported to overexpress poliovirus receptor, and this overexpression is associated with poor prognosis. However, there are no preclinical or clinical trials investigating the use of cell-based immunotherapies targeting poliovirus receptor in IDH wild-type glioblastoma.MethodsWe analyzed poliovirus receptor expression in transcriptome sequencing databases and specimens from IDH wild-type glioblastoma patients. We developed poliovirus receptor targeting chimeric antigen receptor T cells using lentivirus. The antitumor activity of chimeric antigen receptor T cells was demonstrated in patient-derived glioma stem cells, intracranial and subcutaneous mouse xenograft models.ResultsWe verified poliovirus receptor expression in primary glioma stem cells, surgical specimens from IDH wild-type glioblastoma patients, and organoids. Accordingly, we developed poliovirus receptor–based second-generation chimeric antigen receptor T cells. The antitumor activity of chimeric antigen receptor T cells was demonstrated in glioma stem cells and xenograft models. Tumor recurrence occurred in intracranial xenograft models because of antigen loss. The combinational therapy of tyrosine-based inhibitory motif extracellular domain–based chimeric antigen receptor T cells and NK-92 cells markedly suppressed tumor recurrence and prolonged survival.ConclusionsPoliovirus receptor–based chimeric antigen receptor T cells were capable of killing glioma stem cells and suppressing tumor recurrence when combined with NK-92 cells.
Jackson, Sarah S; Pfeiffer, Ruth M; Hsieh, Mei-Chin; Li, Jie; Madeleine, Margaret M; Pawlish, Karen S; Zeng, Yun; Yu, Kelly J; Engels, Eric A
doi: 10.1093/jnci/djad224pmid: 37944040
BackgroundMales have 2–3-fold greater risk of cancer than females at most shared anatomic sites, possibly reflecting enhanced immune surveillance against cancer in females. We examined whether these sex differences remained among immunocompromised adults.MethodsUsing the Transplant Cancer Match (TCM) study, we estimated the male-to-female incidence rate ratio in TCM (M:F IRRTransplant) for 15 cancer sites diagnosed between 1995 and 2017 using Poisson regression. Male to female IRRs in the general population (M:F IRRGP) were calculated using expected cancer counts from the Surveillance, Epidemiology, and End Results Program, standardized to the transplant population on age, race and ethnicity, and diagnosis year. Male to female IRRs were compared using a chi-square test.ResultsAmong 343 802 solid organ transplants, 211 206 (61.4%) were among men and 132 596 (38.6%) among women. An excess cancer incidence in males was seen in transplant recipients, but the sex difference was attenuated for cancers of the lip (M:F IRRTransplant: 1.81 vs M:F IRRGP: 3.96; P < .0001), stomach (1.51 vs 2.09; P = .002), colorectum (0.98 vs 1.43; P < .0001), liver (2.39 vs 3.44; P = .002), kidney (1.67 vs 2.24; P < .0001), bladder (2.02 vs 4.19; P < .0001), Kaposi sarcoma (1.79 vs 3.26; P = .0009), and non-Hodgkin lymphoma (1.34 vs 1.64; P < .0001). The M:F IRRTransplant was not statistically different from the M:F IRRGP for other cancer sites.ConclusionsAlthough male solid organ transplant recipients have higher cancer incidence than female recipients, the attenuation in the male to female ratio for many cancers studied relative to the general population might suggest the importance of immunosurveillance, with some loss of advantage in female recipients due to immunosuppression after transplantation.
Goldberg, Jason F; Hyun, Geehong; Ness, Kirsten K; Dixon, Stephanie B; Towbin, Jeffrey A; Rhea, Isaac B; Ehrhardt, Matthew J; Srivastava, Deo Kumar; Mulrooney, Daniel A; Hudson, Melissa M; Robison, Leslie L; Jefferies, John L; Rohatgi, Anand; Armstrong, Gregory T
Ma, Tianfang; Jin, Lianjin; Bai, Shanshan; Liu, Zhan; Wang, Shuo; Shen, Beibei; Cho, Yeyoung; Cao, Subing; Sun, Meijuan J S; Fazli, Ladan; Zhang, David; Wedderburn, Chiyaro; Zhang, Derek Y; Mugon, Gavisha; Ungerleider, Nathan; Baddoo, Melody;
Showing 1 to 10 of 16 Articles
doi: 10.1093/jnci/djad218pmid: 37856326
BackgroundStudying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer.MethodsThe Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma.ResultsAmong individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N’-Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users.ConclusionThese novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications.
doi: 10.1093/jnci/djad222pmid: 37952244
BackgroundChildhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors.MethodsComprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls.ResultsPreviously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non–high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy.ConclusionsPreviously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population.
doi: 10.1093/jnci/djad215pmid: 37847647
BackgroundAlthough the fusion of the transmembrane serine protease 2 gene (TMPRSS2) with the erythroblast transformation-specific-related gene (ERG), or TMPRSS2-ERG, occurs frequently in prostate cancer, its impact on clinical outcomes remains controversial. Roughly half of TMPRSS2-ERG fusions occur through intrachromosomal deletion of interstitial genes and the remainder via insertional chromosomal rearrangements. Because prostate cancers with deletion-derived TMPRSS2-ERG fusions are more aggressive than those with insertional fusions, we investigated the impact of interstitial gene loss on prostate cancer progression.MethodsWe conducted an unbiased analysis of transcriptome data from large collections of prostate cancer samples and employed diverse in vitro and in vivo models combined with genetic approaches to characterize the interstitial gene loss that imposes the most important impact on clinical outcome.ResultsThis analysis identified FAM3B as the top-ranked interstitial gene whose loss is associated with a poor prognosis. The association between FAM3B loss and poor clinical outcome extended to fusion-negative prostate cancers where FAM3B downregulation occurred through epigenetic imprinting. Importantly, FAM3B loss drives disease progression in prostate cancer. FAM3B acts as an intermediator of a self-governing androgen receptor feedback loop. Specifically, androgen receptor upregulates FAM3B expression by binding to an intronic enhancer to induce an enhancer RNA and facilitate enhancer-promoter looping. FAM3B, in turn, attenuates androgen receptor signaling.ConclusionLoss of FAM3B in prostate cancer, whether through the TMPRSS2-ERG translocation or epigenetic imprinting, causes an exit from this autoregulatory loop to unleash androgen receptor activity and prostate cancer progression. These findings establish FAM3B loss as a new driver of prostate cancer progression and support the utility of FAM3B loss as a biomarker to better define aggressive prostate cancer.