Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

[Evaluation of thyroid cancer data completeness and quality at a population-based cancer registry, Algeria]. / Évaluation de l'exhaustivité et de la qualité des données du cancer de la thyroïde dans un registre du cancer dans la population algérienne.

BACKGROUND: Over the last three decades the incidence of thyroid cancer (TC) has increased in many regions of the world, however little is known about TC incidence and trends in Algeria. MATERIAL AND METHODS: Using data from the Oran cancer registry (OCR) we assessed TC incidence and trends in Oran for the period 1996-2013 with the historical data method. The incidence curves were unstable and did not show any clear trend. Therefore, we actively collected data on TC for the period 1996-2013 using the multisource approach and the independent case ascertainment method. RESULTS: Analysis of actively collected and validated data showed a significant increase in the incidence of TC. We compared the two databases to identify differences. There were 558 TC cases during the period 1996-2013 in the OCR, while our active data collection enabled us to find 1,391 TC cases during the same period. The completeness rate in the OCR was 40.1%. These differences were due to our approach that consisted in the inclusion of a greater number of health facilities and laboratories (44 versus 23 in the OCR), and the active data collection in the nuclear medicine facility of the University Hospital of Tlemcen that we undertook. CONCLUSIONS: The application of the recommendations of the International Agency for Research on Cancer (IARC) to enhance data completeness and quality, and an active collection of TC data in the nuclear medicine facility of the University Hospital of Tlemcen should make the OCR an essential tool for decision-making in public health and for directing health policy towards health priorities.

Thyroid cancer incidence and trends by demographic and tumor characteristics in Oran, Algeria: 1993-2013, a population-based analysis.

OBJECTIVES: Incidence rates of thyroid cancer have dramatically increased over recent decades in many countries, particularly the papillary histotype and microcarcinomas. We examined thyroid cancer incidence and trends by demographic and tumor characteristics based on 1443 patients with thyroid cancer diagnosed between 1993 and 2013 in Oran district, in Northwest Algeria. METHODS: All thyroid cancer cases were abstracted from medical records and pathology reports and classified according to the International Classification for Diseases in Oncology, third edition. Age-specific, age-standardized incidence rates per 100 000 person-years, and annual percent changes (APC) in the incidence were calculated. RESULTS: Age-standardized incidence was 11.7 per 100 000 for women and 2.0 per 100 000 for men. Thyroid cancer incidence increased over time significantly in women (APC: +3.72%; P < 0.05), mostly due to an increased incidence of the papillary histotype (APC: +5.48%; P < 0.05), and microcarcinomas (APC: +17.34%; P < 0.05). During the same time period, the incidence of follicular thyroid carcinomas decreased (APC: -3.74%; P < 0.05). CONCLUSIONS: The results of our study showing an upward trend of thyroid cancer incidence driven largely by increases in the papillary histotype are consistent with previous studies. The higher increase has coincided with the introduction of fine needle aspiration and thyroid ultrasound in the 1990s, and may have led to overdiagnosis. However, the increased papillary-to-follicular ratio observed over time is possibly a late effect of iodine supplementation implemented in Algeria in 1967 to combat endemic goiter. Further larger-scale population-based research is needed to gain insight into thyroid cancer etiology.

Changes in the Demographic and Clinicopathological Characteristics of Thyroid Cancer: A Population-Based Investigation in Algeria, 1993-2013.

Over the last three decades, the incidence of thyroid cancer has increased worldwide. The reasons for this increase remain controversial. In Algeria, however, to date, information on thyroid cancer has been limited to a hospital-based case series. We analyzed data from a population-based cohort study in Oran District, Algeria, to describe demographic and clinicopathological characteristics of patients diagnosed with thyroid cancer between 1993 and 2013. Medical records and pathology reports of thyroid cancer patients who had surgery were reviewed. Changes in demographic and clinicopathological features over the 21-year period are described. During the study period, thyroid cancer was diagnosed in 1248 women (86.5%, mean age 43.7 ± 15.2 years) and 195 men (23.4%, mean age 48.1 ± 15.9 years). Most cases (83.1% for women and 69.8% for men) sought a diagnosis following a self-neck check. The most common histologic types were papillary (58.3%), follicular (29.7%), anaplastic (4.1%), and medullary (0.8%) carcinomas. The incidence of papillary carcinomas significantly increased (p < 0.001) while the incidence of other histologic types significantly decreased over time. Tumor size overall significantly decreased (p < 0.001) while the frequency of small (≤20 mm) and larger (>20 mm) carcinomas significantly increased (p < 0.05). The frequency of thyroid cancers with capsular effractions and angioinvasions also decreased over time. Thyroid cancer incidence in Algeria has increased substantially in line with international trends with changes in clinical practice being a possible contributing factor. However, the increasing papillary-to-follicular cancer ratio may be due to changes in iodine nutrition status in Algeria. Further research, including exploration of biological and molecular features of thyroid cancer, will enable a better understanding of risk factors and etiopathogenetic mechanisms.

Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects.

OBJECTIVES: The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose-response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors. METHODS: This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site-specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR). RESULTS: Linear dose-response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries. CONCLUSIONS: The results suggest that the effect of high-dose irradiation is consistent with a linear dose-response for most organs, but they also reveal important organ-specific and host-specific differences in susceptibility and interactions between different aspects of treatment.

Risk of salivary gland cancer after childhood cancer: a report from the Childhood Cancer Survivor Study.

PURPOSE: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). METHODS AND MATERIALS: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. RESULTS: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. CONCLUSION: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.

Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissues following the Chernobyl accident.

The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131) doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T) and normal (N) tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria. We first hybridized 32 randomly allocated RNA specimen pairs (T/N) on 64 whole genome microarrays (Agilent, 4×44 K). Associations of differential gene expression (log(2)(T/N)) with dose were assessed using Kruskall-Wallis and trend tests in linear mixed regression models. While none of the genes withstood correction for the false discovery rate, we selected 75 genes with a priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the remaining 31 RNA specimen pairs (T/N). The qRT-PCR data were analyzed using linear mixed regression models that included radiation dose as a categorical or ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12, FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493) were confirmed to have a statistically significant differential dose-expression relationship. Our study is among the first to provide direct human data on long term differential gene expression in relation to individual I-131 doses and to identify a set of genes potentially important in radiation carcinogenesis.

Incidence of carcinoma of the major salivary glands according to the WHO classification, 1992 to 2006: a population-based study in the United States.

BACKGROUND: Carcinomas of the major salivary glands (M-SGC) comprise a morphologically diverse group of rare tumors of largely unknown cause. To gain insight into etiology, we evaluated incidence of M-SGC using the WHO classification schema (WHO-2005). METHODS: We calculated age-adjusted incidence rates (IR) and IR ratios (IRR) for M-SGC diagnosed between 1992 and 2006 in the Surveillance, Epidemiology and End Results Program. RESULTS: Overall, 6,391 M-SGC (IR, 11.95/1,000,000 person-years) were diagnosed during 1992 to 2006. Nearly 85% of cases (n = 5,370; IR, 10.00) were encompassed within WHO-2005, and among these, males had higher IRs than females [IRR, 1.51; 95% confidence interval (95% CI), 1.43-1.60]. Squamous cell (IR, 3.44) and mucoepidermoid (IR, 3.23) carcinomas occurred most frequently among males, whereas mucoepidermoid (IR, 2.67), acinic cell (IR, 1.57), and adenoid cystic (IR, 1.40) carcinomas were most common among females. Mucoepidermoid, acinic cell, and adenoid cystic carcinomas predominated in females through age approximately 50 years; thereafter, IRs of acinic cell and adenoid cystic carcinomas were nearly equal among females and males, whereas IRs of mucoepidermoid carcinoma among males exceeded IRs among females (IRR, 1.57; 95% CI, 1.38-1.78). Except for mucoepidermoid and adenoid cystic carcinomas, which occurred equally among all races, other subtypes had significantly lower incidence among Blacks and Asians/Pacific Islanders than among Whites. Adenoid cystic carcinoma occurred equally in the submandibular and parotid glands, and other M-SGC histologic subtypes evaluated had 77% to 98% lower IRs in the submandibular gland. Overall M-SGC IRs remained stable during 1992 to 2006. CONCLUSION: Distinct incidence patterns according to histologic subtype suggest that M-SGC are a diverse group of neoplasms characterized by etiologic and/or biological heterogeneity with varying susceptibility by gender and race.

Expression of cell cycle biomarkers and telomere length in papillary thyroid carcinoma: a comparative study between radiation-associated and spontaneous cancers.

OBJECTIVE: Radiation exposure during childhood is the only well-established risk factor for papillary thyroid carcinoma (PTC). To better define the biologic profile of radiation-induced and sporadic PTC, we compared in these two groups of PTC the expression of cell cycle regulatory proteins and telomere length. METHODS: Cell cycle markers (cyclin A, B1, D1, E, and Ki67) were evaluated on 100 PTC specimens (26 radiation-induced and 74 sporadic PTCs). The expression of cell cycle regulators was studied using immunohistochemistry; telomere length heterogeneity was studied using in situ hybridization in a subset of 16 formalin-fixed samples (8 radiation-induced and 8 sporadic PTCs). RESULTS: At multivariate analysis, only cytoplasmic cyclin E staining was overexpressed in sporadic cases (P = 0.006). The other cell cycle markers and telomere length did not differ significantly between sporadic PTC and radiation-induced PTC. CONCLUSIONS: These markers cannot be used to differentiate radiation-induced from sporadic PTCs.

Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma.

Survival of metastatic gastroenteropancreatic well-differentiated endocrine carcinoma (GEP WDEC) is not well characterized. We evaluated the long-term outcome and prognostic factors for survival in 118 patients with distant metastases from GEP WDEC. Inclusion criteria were 1) pathological review by a single pathologist according to the present WHO criteria, 2) absence of previous therapy apart from surgery, 3) complete morphological evaluation within 3 months including somatostatin receptor scintigraphy, and 4) follow-up at Gustave-Roussy Institute until death or study's end. Clinical, biological marker, and pathological parameters were analyzed in univariate and multivariate statistical models. Survival after the first complete imaging work-up of the metastatic disease was determined using Kaplan-Meier method. Overall, survival for 5 years after the diagnosis of metastatic disease was 54%. In multivariate analysis, age (hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.01-1.08, P = 0.01), the number of liver metastases (HR: 3.4, 95% CI: 1.4-8.3, P = 0.01), tumor slope (HR: 1.1, 95% CI: 1.0-1.1, P = 0.001), and initial surgery (HR: 0.3, 95% CI: 0.1-0.8, P = 0.01) were predictive of survival. Five-year survival was 100%, 91% (95% CI, 51-98%), 62% (95% CI, 37-83%), and 9% (95% CI, 6-32%) when patients had 0, 1, 2, 3 or more poor prognostic features respectively. This study enables the stratification of metastatic GEP WDEC patients into distinct risk groups. These risk categories can be used to tailor therapeutic approaches and also to design and interpret clinical trials.

Risk of radiation-related salivary gland carcinomas among survivors of Hodgkin lymphoma: a population-based analysis.

BACKGROUND: Radiotherapy for Hodgkin lymphoma (HL) increases the risk of salivary gland carcinomas (SGC). To the authors' knowledge, however, the magnitude of the risk has not been assessed to date. METHODS: The risks of SGC among 20,928 1-year survivors of HL who were diagnosed between 1973 and 2003 were evaluated in 11 population-based cancer registry areas of the Surveillance, Epidemiology, and End Results (SEER) program. Observed-to-expected ratios (O/E) were assessed by radiation treatment, sex, age at the time of HL diagnosis, calendar year of diagnosis, attained age, time since HL diagnosis, histologic type of SGC, and site of occurrence in the major salivary glands. RESULTS: Among 11,047 HL patients who received radiotherapy as part of their initial treatment for HL, 21 developed subsequent invasive SGC (O/E = 16.9; 95% confidence interval [95% CI], 10.4-25.8). The risk of radiation-related SGC was highest for younger HL patients (age <20 years) (O/E = 45.5; 95% CI, 12.4-116.5) and among 10-year survivors (O/E = 23.9; 95% CI, 13.1-40.1), with risks remaining elevated for at least 2 decades after irradiation. Significant differences in risk by histologic type were observed, with a particularly high risk of developing mucoepidermoid carcinomas (O = 14; O/E = 44.2 [95% CI, 24.2-74.2]) and adenocarcinomas (O = 4; O/E = 30.6 [95% CI, 8.3-78.2]) noted. CONCLUSIONS: HL patients treated with radiotherapy experienced a significantly increased risk of SGC, particularly when exposed at young ages or for at least 2 decades after exposure. Although the results of the current study reflect the late effects of former HL treatment approaches, they point to the importance of long-term follow-up and a heightened awareness of SGC risk in this population.

Long-term mortality in a cohort study of 6,800 French breast cancer patients treated between 1954 and 1983.

PURPOSE: To investigate the impact of initial tumour characteristics and loco-regional radiotherapy on long-term survival following breast cancer diagnosis. METHODS AND MATERIALS: This study was conducted among 6,800 French women from a cohort of 7 711 subjects diagnosed at the IGR with breast cancer between 1954 and 1983 and followed-up until January 2004. Overall mortality in the cohort was compared with that in the French general population using Standardized Mortality Ratios (SMR) and the Absolute Excess Risk (AER) estimated by Poisson regression. RESULTS: During the 1954-2004 follow-up period, 5,436 women died. Mortality was 3.15-fold higher in the cohort than in the general female population in France. It decreased from 6.86 to 1.26 during the first 30 years of follow-up then rose again to 1.60. Both SMRs and AERs were more than 2-fold higher in women who had received radiotherapy during initial treatment than in those who had not, this difference being higher for women treated before 1976 than afterwards (p < 0.0001). They (SMRs and AERs) were also higher for subjects who had stage II, III or IV lesions than for those with less advanced tumours. CONCLUSION: The results of this study suggest that the excess deaths observed during the first two decades are closely linked to the initial clinical characteristics of the tumour and to radiotherapy. The late increase in mortality may be partially due to deleterious late effects of radiotherapy.

Poorly differentiated follicular thyroid carcinoma: prognostic factors and relevance of histological classification.

OBJECTIVE: Poorly differentiated follicular thyroid carcinoma (PDFC) is a tumor of follicular cell origin with attributes intermediate between well-differentiated carcinomas and anaplastic carcinomas, but neither a clear histological description nor an established definition of prognostic indicators are available. DESIGN: This study correlates the clinical outcome and survival of 40 PDFC patients with histological architecture, cytological characteristics, and expression of various markers of cell proliferation and differentiation (cyclin A, cyclin B1, cyclin D1, cyclin E, Ki67, thyroperoxidase, galectin 3, dual oxidase [Duox], vascular endothelial growth factor, epidermal growth factor receptor, and p53). MAIN OUTCOME: At 5 years, the overall survival rate was 63% and the metastasis-free survival rate was 57%. An older age at the time of diagnosis and a larger tumor size were associated with an increased risk of distant metastases and of cancer-related death. Polymorph architecture was associated with a reduced risk of metastases, whereas a high expression of Duox was associated with a reduced risk of death. In these patients with PDFC, no other histological features or expression of any other marker had a prognostic significance. CONCLUSION: PDFC has a more aggressive behavior than well-differentiated carcinomas; prognosis is related to indicators that are also relevant in patients with well-differentiated carcinomas.