Feature Paper in Section 'Cancer Epidemiology and Prevention' in 2024

Background: Individually personalized reconstructive microsurgery is more and more universally recognized and applied as a one-time, part of a few, or even the only highly effective treatment of patients with locally advanced midface cancer. Among the increasing number of publications focused on this field, most present different reconstructive techniques used for a single patient (case reports), and fewer papers evaluate a group including more than 100 patients. Methods: A dataset of 119 locally advanced midface cancers in stage T₃ or T₄ was used to analyze whether there is any correlation between clinical factors, resection defect parameters, and the free flaps chosen for reconstruction. Results: In general, the 5-year OS was 95% and 77% for the DFS, which inversely correlated with the increasing Cordeiro’s type of resective defects. Local recurrence occurred in 23% of cases. Taxonomic dendrograms allow the selection of four (A–D) different case clusters. Cluster B, which characterizes a tumor size of 8–18 cm², Cordeiro type IIIA, and an uncertain radicalism of resection, has the worst prognosis with a very high (89%) risk of local recurrence. On the contrary, the most favorable was found in cluster C, characterized by Cordeiro type IIA, a tumor size of 8 cm², and negative resective margins, because it has a very low (6%) risk of local recurrence. Conclusions: The results of the present analysis have led to design algorithms for midface resection and reconstruction. However, these should not be considered obligatory but rather as a useful general guideline. Full article

Background: In cancer, age and sex are often studied individually, but the impact of the intersection of these factors on cancer incidence and survival remains unclear. Using population-level data, we provide an up-to-date analysis of the impact of sex and age on cancer incidence and survival. Methods: Using data from the United States Cancer Statistics public use research database and the Centers for Disease Control and Prevention’s National Program of Cancer Registries Survival database, we assessed sex and age differences in the incidence and survival of malignant cancers diagnosed from 2001 to 2020. Results: Males experienced higher cancer incidence than females in all sites and age groups, excluding 20–29- and 30–39-year-olds. The highest Male-to-female (M:F) age-adjusted incidence rates (IRR) were observed in mesothelioma within ages 80+ (IRR: 5.48; 95% CI: 5.25–5.71; p < 0.001), and lowest in endocrine cancer within ages 20–29 years (M:F IRR: 0.20; 95% CI: 0.20–0.21; p < 0.001). Among all sites and age groups, excluding 0–9 years, males experienced worse survival than females, particularly within ages 20–29 years (Hazard Ratio (HR): 2.19; 95% CI: 2.15–2.23; p < 0.001). Highest M:F HRs were observed in endocrine system cancers within ages 20–29 (HR: 3.52; 95% CI: 3.15–3.94; p < 0.001), and lowest among lymphomas within ages 0–9 (HR: 0.74; 95% CI: 0.63–0.87; p < 0.001). Conclusions: Significant age and sex differences in cancer incidence and survival were observed across the US from 2001 to 2020. Males had a higher cancer incidence compared to females, with notable exceptions for younger age groups among certain types, suggesting age may be a critical component in further understanding the biology of sex differences in cancer. Full article

Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States (U.S.). Mississippi has the highest rate of CRC incidence in the U.S. and has large populations of black and white individuals, allowing for studies of racial disparities. Methods: We conducted an ecological study using the county as the unit of analysis. CRC incidence data at the county level for black and white populations in Mississippi, covering the years 2003 to 2020, were retrieved from the Mississippi Cancer Registry. Age-adjusted incidence rate differences and their corresponding 95% confidence intervals (CIs) were then calculated for these groups. Getis–Ord Gi* hot and cold spot analysis of CRC incidence rate racial disparities was performed using ArcGIS Pro. We used global ordinary least square regression and geographically weighted regression (MGWR version 2.2) to identify factors associated with racial differences in CRC incidence rates. Results: Age-adjusted CRC incidence rate in the black population (median = 58.12/100,000 population) and in the white population (median = 46.44/100,000 population) varied by geographical area. Statistically significant racial differences in CRC incidence rates were identified in 28 counties, all of which showed higher incidence rates among the black population compared to the white population. No hot spots were detected, indicating that there were no spatial clusters of areas with pronounced racial disparities. As a post hoc analysis, after considering multicollinearity and a directed acyclic graph, a parsimonious multiple regression model showed an association (β = 0.93, 95% CI: 0.25, 1.62) indicating that a 1% increase in food insecurity was associated with a 0.93/100,000 differential increase in the black–white CRC incidence rate. Geographically weighted regression did not reveal any local patterns in this association. Conclusions: Black–white racial disparities in CRC incidence were found in 28 counties in Mississippi. The county-level percentage of food insecurity emerged as a possible predictor of the observed black–white racial disparities in CRC incidence rates. Individual-level studies are needed to clarify whether food insecurity is a driver of these disparities or a marker of systemic disadvantage in these counties. Full article

Background: Recent publications suggest that the threshold for validation of the learning curve is 25 procedures. The aim of this study was to evaluate this threshold using another rarely used method, based on a composite quality indicator. Methods: We included all patients from the French medico-administrative database receiving robot-assisted surgery for lung cancer, with a focus on hospitals performing at least 25 procedures over the period 2019–2022. For postoperative complication analysis, we used the Clavien–Dindo classification. We used the sequential probability ratio test to estimate the number of procedures at which a hospital achieved its learning curve. Results: In France, the number of robotic-assisted procedures has risen steadily in the past few years: 195 in 2019 and 1567 in 2022 (overall, 3706 Robot-Assisted surgeries). The total number of patients with Clavien–Dindo classification > II was 833 (24.7%). Among the 28 hospitals performing at least 25 procedures, eight achieved their learning curve with thresholds ranging from 94 to 174 procedures, and the median was 110. Severe complications such as acute respiratory distress syndrome, respiratory failure, heart failure, acute ischemia of the lower limbs, or pulmonary embolism were significantly more frequent in the group of hospitals that did not validate the learning curve threshold. Conclusions: This study suggests that the threshold of 25 procedures may not be sufficient to validate the robot-assisted surgery learning curve in lung cancer surgery. To significantly reduce postoperative complications, a hospital would need to perform 94 to 174 procedures to guarantee patient safety. Full article

Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next (“third”) generation of offspring. Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI. Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36–1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37–32.42). Based on mothers’ reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49–1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70–2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported. Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed. Full article

Background & Aims: Reports of a rise in childhood cancer incidence in Australia and globally prompted the investigation of cancer incidence and survival in South Australia (SA) and the Northern Territory (NT) over a 28-year period, with emphasis on Indigenous peoples. Methods: This cross-sectional analysis of two prospective longitudinal databases, the SA and NT Cancer Registries (1990–2017), included all reported cases of childhood cancers. Poisson regression provided estimates of incidence rate ratios and survival was modelled using Cox proportional hazard models for children aged <5 and ≥5 years. Results: A total of 895 patients across SA (N = 753) and the NT (N = 142) were ascertained. Overall and in the NT, childhood cancer incidence was higher in males compared with females (IRR 1.19 [1.04–1.35] and 1.43 [1.02–2.01], respectively). Lymphocytic leukemia was the most reported cancer type across all locations. With reference to the 1990–1999 era (181.67/100,000), cancer incidence remained unchanged across subsequent eras in the combined cohort (SA and NT) (2000–2009: 190.55/100,000; 1.06 [0.91–1.25]; 2010–2017: 210.00/100,000; 1.15 [0.98–1.35]); similar outcomes were reflected in SA and NT cohorts. Cancer incidence amongst non-Indigenous children significantly decreased from the 1990–1999 era (278.32/100,000) to the 2000–2009 era (162.92/100,000; 0.58 [0.35–0.97]). Amongst 39 Indigenous children in the NT, incidence rates remained unchanged across eras (p > 0.05). With reference to the 1990–1999 era, overall survival improved in subsequent eras in SA (2000–2009: HR 0.53 [0.38–0.73]; 2010–2017: 0.44 [0.28–0.68]); however, remained unchanged in the NT (2000–2009: 0.78 [0.40–1.51]; 2010–2017: 0.50 [0.24–1.05]). In the NT, overall survival of Indigenous patients was significantly lower compared with the non-Indigenous cohort (3.42 [1.92–6.10]). While the survival of Indigenous children with cancer significantly improved in the last two eras (p < 0.05), compared to the 1990–1999 era, no change was noted amongst non-Indigenous children in the NT (p > 0.05). Conclusions: The incidence of childhood cancers has remained unchanged over 28-years in SA and the NT. Encouragingly, improved survival rates over time were observed in SA and amongst Indigenous children of the NT. Nevertheless, survival rates in Indigenous children remain lower than non-Indigenous children. Full article

Background: Helicobacter pylori (H. Pylori) eradication has been the mainstream for preventing and treating gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Prior data showed disparities in eradication rates of H. Pylori between different populations. This can potentially impact the occurrence of gastric MALT lymphoma. There are limited data on the incidence and mortality rates and trends of gastric MALT lymphoma in the US. Therefore, the aim of the current study was to conduct a time-trend analysis of gastric MALT lymphoma incidence and mortality rates in different populations. Methods: The incidence rates of gastric MALT lymphoma were calculated from the United States Cancer Statistics (USCS) database (which covers nearly 98% of the US population) between 2001–2020 and were age-adjusted to the standard 2000 US population using SEER*Stat software (version 8.4.3, national cancer institute “NCI”). Incidence-based mortality (IBM) rates, also age-adjusted to the standard 2000 US population, were calculated from the Surveillance Epidemiology and End Results (SEER) database. Tumor location was specified using ICD-O-3 codes C 160–C 169 with malignant behavior. Histopathology was specified using the ICD-O-3 code 9699. The rates were categorized by sex, age, race/ethnicity, and tumor stage at diagnosis. Age groups were older adults (aged 55 years or older) and younger adults (aged younger than 55 years). Race/ethnic groups included Non-Hispanic White (White), Non-Hispanic Black (Black), Hispanic, Non-Hispanic Asian/Pacific Islander (API), and Non-Hispanic American Indian/Alaska Native (AI/AN), as reported in the database. Stage at diagnosis included early stage (in situ and localized tumors) and late stage (regional and distant site tumors). Joinpoint Regression Software (version 5.0.2, NCI) using the weighted Bayesian Information Criteria method was used to generate time trends. Trends were reported as annual percentage change (APC) and average APC (AAPC). Parametric estimations were used with a two-sided t-test to evaluate the trends with a p-value cutoff at 0.05. Results: There were 21,625 patients diagnosed with gastric MALT lymphoma in the US between 2001 and 2020. Overall, incidence rates were significantly decreasing over the study period (AAPC = −1.93). This decrease was seen in males (AAPC = −1.67) and in females (AAPC = −1.66) (Figure). When categorized by age groups, older adults also experienced a significant decrease in gastric MALT lymphoma incidence rates (AAPC = −1.66). While this was also seen in younger adults, the rates were decreasing at a slower pace (AAPC = −1.38). When categorizing the trends by race/ethnicity, incidence rates were significantly decreasing in White (AAPC = −2.09), Hispanic (AAPC = −1.61), and API (AAPC = −3.92) populations. However, the rates were stable among Blacks. While early-stage tumors experienced a significant decrease (AAPC = −1.10), the rates were stable for late-stage tumors. When evaluating mortality, there were 11,036 patients whose death was attributed to gastric MALT lymphoma between 2000 and 2020. IBM rates were decreasing in males (AAPC = −1.47), older adults (AAPC = −1.55), Whites (AAPC = −1.23), Hispanics (AAPC = −1.73), APIs (AAPC = −2.30), and early-stage tumors (AAPC = −1.08). On the other hand, IBM rates were stable in females, younger adults, Blacks, and late-stage tumors. Discussion: An extensive nationwide data analysis encompassing nearly 98% of patients diagnosed with gastric MALT lymphoma in the US unveils a declining trend in the incidence of cancer overall over the past two decades. This decline is observed in both sexes and various age groups. When stratifying by race and ethnicity, this incidence has been decreasing in all populations except among Black individuals. While early-stage tumors have also demonstrated a significant decrease in incidence rates, late-stage tumors have shown no parallel decline. Mortality evaluation also revealed an improvement in most of the US population except among females, younger adults, Black individuals, and late-stage tumors. While the cause of our findings is unclear, it could be driven by disproportionate exposure to risk factors, including H. Pylori, and disparities in screening, management, and outcomes. Future studies are warranted to investigate factors contributing to worse outcomes of gastric MALT lymphoma, especially in the Black population. Full article

Pericardial disease is increasingly recognized in cancer patients, including acute pericarditis, pericardial effusion, and constrictive pericarditis, often indicating a poor prognosis. Acute pericarditis arises from direct tumor involvement, cancer therapies, and radiotherapy. Immune checkpoint inhibitor (ICI)-related pericarditis, though rare, entails significant mortality risk. Treatment includes NSAIDs, colchicine, and corticosteroids or anti-IL1 drugs in refractory cases. Pericardial effusion is the most frequent manifestation, primarily caused by lung cancer, followed by breast cancer, lymphoma, leukemia, gastrointestinal tumors, and melanoma. Chemotherapy, immunotherapy, and radiotherapy may also cause fluid accumulation in the pericardial space. Symptomatic relief for pericardial effusion may require pericardiocentesis, prolonged catheter drainage, or a pericardial window. Instillation of intrapericardial cytostatic agents may reduce recurrence. Constrictive pericarditis, though less common, often develops from radiotherapy and requires multimodality imaging for diagnosis, with pericardiectomy as the definitive treatment. Primary pericardial tumors are rare, with metastases being more frequent. Patients with cancer and pericardial disease generally have poor survival, emphasizing the need for early detection. A multidisciplinary approach involving hematologists, oncologists, and cardiologists is crucial to tailoring pericardial disease treatment to a patient’s clinical status, thereby improving the quality of life and prognosis. Full article

Background: Most randomized controlled trials (RCTs) assessing the impact of diet on cancer have been short term (<1 year), mostly evaluating breast cancer survivors. Given the many-year interval that is generally required for an intervention to have an impact on cancer risk or prognosis, as well as the fact that lifestyle strategies such as diet modification frequently fail due to lack of adherence over the long term, we focused this systematic review only on longer-term (≥1 year) intervention reports. Diet intervention reports focused on reducing cancer risk in overweight and obese individuals target caloric restriction (every day, some days, or most hours of each day). Methods: This study is a systematic review of RCTs lasting at least 1 year, testing dietary interventions with a primary or secondary endpoint of cancer or a biomarker linked to cancer. Results: Fifty-one reports met our review criteria. Twenty of fifty-one (39%) reports are RCTs where the primary endpoint was cancer or a cancer-related biomarker, while the other reports evaluated reports where cancer or a cancer-related biomarker was a secondary endpoint. Thirteen of twenty (65%) primary reports evaluated isocaloric, and the remaining eight evaluated low-calorie diets. All but one of the primary and two secondary isocaloric diet reports evaluated the benefit of a low-fat diet (LFD), with the other three evaluating a Mediterranean diet (MedD). More LCD vs. isocaloric diet primary reports (71% vs. 38%) demonstrated cancer or cancer-related biomarker benefit; the difference in chance of benefit with secondary reports was 85% for LCD vs. 73% for isocaloric diets. Three of three MedD reports demonstrated benefit. Sixty-nine percent (20/29) of the secondary reports came from two large reports: the WHI diet modification trial (15 secondary reports) and the polyp prevention trial (5 secondary reports). Nineteen of twenty-two (86%) primary reports enrolled only women, and three enrolled both men and women. No study that met our criteria enrolled only men, comprising 1447 men in total vs. 62,054 women. Fifteen of twenty (75%) primary reports focus on healthy women or women with breast cancer. Adherence findings are discussed when provided. Conclusions: More long-term RCTs evaluating cancer and cancer-related biomarker endpoints are needed, especially for cancers at sites other than the breast. Full article

The use of radioactive iodine (RAI) after total thyroidectomy for patients at the American Thyroid Association (ATA) who are at intermediate risk of recurrence is controversial. This is due to the lack of prospective randomized trials proving a benefit to recurrence or survival of RAI therapy in this group. In the absence of such evidence, clinicians struggle to recommend for or against this therapeutic approach which frequently results in overtreatment. This review describes key elements in the decision-making process that help clinicians more comprehensively evaluate the need for RAI therapy in patients with thyroid cancer at intermediate risk of recurrence. A clear definition of the purpose of RAI therapy should be conveyed to patients. In this sense, adjuvant RAI therapy intends to decrease recurrence, and ablation therapy is used to facilitate surveillance. Better stratification of the intermediate risk category into a low–intermediate subgroup and an intermediate–high-risk subgroup results in less heterogeneity and a more precise prediction of recurrence risk. The evaluation of post-operative thyroglobulin levels may prevent the overtreatment of low–intermediate-risk patients when their thyroglobulin level is <2.5 ng/mL. the integration of tumor genomics (when available) alongside pathologic features can enhance the ability of the clinician to predict iodine concentration in thyroid cancer cells. Finally, a detailed consideration of the adverse effects of RAI, patients’ comorbidities, and patient preferences will result in a patient-centered personalized approach. Systematic examination of these variables will ultimately provide a framework for making more educated decisions on the use of RAI in patients at intermediate risk of recurrence that will prevent overtreatment and minimize harm. Full article

Purpose: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. Results: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy. Full article

Background: Incidence of breast cancer (BrCa) may be correlated with country development, with a rise in cases anticipated in regions of the world that are currently undergoing an economic transformation. Herein, differences with regard to the occurrence of breast cancer between individual countries may depend on the distribution of risk factors, the level of early detection, also ethnicity and race, as well as clinical characteristics. The aim of our study was to identify and then investigate observational studies in which the risk of breast cancer was associated with the use of oral hormonal contraceptives (OCs), with particular emphasis on geographic region, and to conduct a systematic review and meta-analysis of the obtained data. Methods: RR (relative risk) was calculated and displayed in forest plots for visual interpretation. Accordingly, 74 studies involving a total of 198,579 women were eligible for inclusion in the meta-analysis. This is the first meta-analysis to comprehensively summarize the evidence between OC use and BrCa risk in connection with geographical region. Results: The cumulative results of the meta-analysis for specific parts of the world are: Africa (RR = 1.16, p = 0.216) and the Americas (RR = 1.03, p = 0.597); Asia (RR = 1.29, p = 0.014); European countries (RR = 1.01, p = 0.904); and Middle East countries (RR = 1.29, p = 0.043). Subgroup analyses showed an increased risk of BrCa for the analyzed variables that depended upon the geographical region. Conclusions: Our meta-analysis suggests that OC use may be associated with a higher BrCa risk, although a statistically significant association was not found for all geographical regions of the world. Full article

Introduction: Prostate cancer is the second most commonly diagnosed malignant tumor worldwide and poses a significant challenge to public health. This systematic review and meta-analysis aims to investigate the association between diabetes mellitus and the risk of developing prostate cancer. Methods: We conducted a search of PubMed, Embase, and the Cochrane Library from 1998 to 2024. The risk of bias within the included studies was assessed using the Newcastle–Ottawa Scale. The DerSimonian–Laird random-effect model was employed for the meta-analysis. Heterogeneity was evaluated using a forest plot and statistically assessed via the Q test, I² index, and p-values. Results: Forty-three studies involving a total of 3,746,769 patients were included. Both case–control (pOR = 0.68, 95% CI: 0.61–0.97; I² = 92.24%) and cohort studies (pRR = 0.71, 95% CI: 0.59–0.99; I² = 85.41%) suggest that diabetes mellitus is associated with a reduced risk of prostate cancer, though with significant heterogeneity (p < 0.05). Subgroup analysis revealed that the risk of developing prostate cancer was significantly higher in patients with a family history of prostate cancer (pRR = 1.25, 95% CI: 1.16–1.35; I² = 69.51%). Conclusions: Our meta-analysis of recent observational studies indicates that diabetes mellitus is associated with a reduced risk of developing prostate cancer. Full article