Risks and cancer associations of metachronous and synchronous multiple primary cancers: a 25-year retrospective study

Background The situation of patients developing multiple primary cancers is becoming more frequent and graver. This study investigated the risks of developing second primary cancers that are related to first primary cancers, and the interval times of synchronous and metachronous multiple primary cancers. Patients and methods Retrospective data were retrieved from 109,054 patients aged ≥18 who were diagnosed with a first solid cancer and registered at Siriraj Cancer Center between 1991 and 2015. A two-month period between first- and second- primary cancers was used to differentiate metachronous and synchronous multiple primary cancers. The combinations of subsequent cancers and relative risks (RRs) of having multiple primary cancers versus having single primary cancer for the top-ten first and second primary cancers were examined. The RR was adjusted for age of the first primary cancer. A survival analysis of the time to second-primary-cancer development was performed. Results Multiple primary cancers were found in 1785 (1.63%) patients. Most (70.87%) second primary cancers occurred after 2 months of first breast, skin, colorectal, lung, head and neck, liver, male genital cancer–prostate, thyroid, and female genital cancer–non-uterine cancers, resulting in those cancers being classified as metachronous multiple primary cancer. After adjustment for age at first diagnosis, head and neck cancers had the highest metachronous association with second esophageal cancers (RR, 25.06; 95% CI, 13.41–50.77). Prostate cancer and second colorectal cancer also demonstrated a high metachronous association (RR, 2.00; 95% CI, 1.25–3.05). A strong synchronous association was found between uterine and ovarian cancers (RR, 27.77; 95% CI, 17.97–43.63). The median time from the first uterine cancer to second-cancer development was 55 days. Conclusions The top-ten most frequent multiple primary cancers were the following: breast; liver; head and neck; colorectal; male genital cancer–prostate; skin; female genital cancer–uterine; thyroid; lung; and female genital cancer–non-uterine. Second primary cancers showed specific associations that depended on the first primary cancer. Physicians should be cognizant of the most common combinations and the interval times of metachronous and synchronous multiple primary cancers.

Identification of Highly Frequent TP53 Germline Variations in a Cohort of Head and Neck Cancer Cases

TP53 tumour suppressor gene inactivation plays a significant role in molecular pathology of cancers. TP53 germline mutations/variations increase the risk of developing multiple primary cancers. However, the role of such TP53 genetic alterations in head and neck cancers (HNCs) is not well-established. HNCs comprise one of the most frequent cancers in Karachi, Pakistan. The pilot study reports the investigation of germline mutations in TP53 gene in a cohort of 30 HNC patients from Pakistan. Blood samples were collected and genomic DNA was extracted from white blood cells. After quality control, amplification of seven selected exons along with their splice sites, two intronic regions (introns 2-3 and 3-4), and 3'UTR were carried out. Sanger sequencing was carried out in order to identify germline variations. Comparison with wild type sequence revealed 11099C>G (intron 2-3) variation in 90%, PIN3 duplication (intron 3-4) in 95%, and exon 4 C>G (rs1042522) alteration in 93.4% of the cases. In 3'UTR, gDNAdelCC1558 was found in 13.4% of the analyzed cases. In conclusion, we report three highly frequent germline variations and a newly discovered variation in 3'UTR in TP53 germline DNA of head and neck cancer patients from Pakistan. These results shall contribute in delineating the genetic component of head and neck cancers.

SYSCHRONOUS PRIMARY THYROID, LUNG AND COLON CANCERS: A CASE REPORT

Multiple primary neoplasms are relatively rare, but their incidence has increased because of aging and improvements in diagnostic imaging. There are many ways to classify, but nowadays, multiple primary cancers are again classified as synchronous and metachronous, the time is 6 months after the first primary injury detection, some authors get 12 months. Our clinical case is a 66-year-old man, prolonged exposure to risk factors for cancer. The patient was diagnosed with different types of primary cancer, colon cancer, thyroid cancer, lung cancer, and stomach cancer. The patient was treated according to the general clinical guidelines suitable for the disease type and the stage of the disease at the time of detection. Lesson learned is the importance of screening tests, attitudes, and comprehensive views of doctors for cancer patients, avoiding missing injuries, affecting the quality of treatment for patients.

Prevalence of Germline Pathogenic Variants in Cancer Predisposing Genes in Czech and Belgian Pancreatic Cancer Patients

(1) Background: The proportion and spectrum of germline pathogenic variants (PV) associated with an increased risk for pancreatic ductal adenocarcinoma (PDAC) varies among populations. (2) Methods: We analyzed 72 Belgian and 226 Czech PDAC patients by multigene panel testing. The prevalence of pathogenic variants (PV) in relation to personal/family cancer history were evaluated. PDAC risks were calculated using both gnomAD-NFE and population-matched controls. (3) Results: In 35/298 (11.7%) patients a PV in an established PDAC-predisposition gene was found. BRCA1/2 PV conferred a high risk in both populations, ATM and Lynch genes only in the Belgian subgroup. PV in other known PDAC-predisposition genes were rarer. Interestingly, a high frequency of CHEK2 PV was observed in both patient populations. PV in PDAC-predisposition genes were more frequent in patients with (i) multiple primary cancers (12/38; 32%), (ii) relatives with PDAC (15/56; 27%), (iii) relatives with breast/ovarian/colorectal cancer or melanoma (15/86; 17%) but more rare in sporadic PDAC (5/149; 3.4%). PV in homologous recombination genes were associated with improved overall survival (HR = 0.51; 95% CI 0.34–0.77). (4) Conclusions: Our analysis emphasizes the value of multigene panel testing in PDAC patients, especially in individuals with a positive family cancer history, and underlines the importance of population-matched controls for risk assessment.

Nivolumab Effective for Gastric and Lung Cancers but Not for Multiple Myeloma in a Multiple Primary Cancer Patient

The case of a 76-year-old man with multiple primary cancers that were treated with nivolumab is presented. Six years earlier, he was diagnosed with multiple myeloma (MM) and was treated with several chemotherapies. He was also diagnosed with gastric cancer with liver metastasis and primary lung cancer by upper gastrointestinal endoscopy and computed tomography (CT). Nivolumab treatment was given as third-line therapy, and it was effective for gastric and lung cancers. But MM worsened, and the patient died. There is no standard treatment for multiple primary cancers, and the development of effective treatments for multiple primary cancers is important.

An Ontology to Model the International Rules for Multiple Primary Malignant Tumours in Cancer Registration

Population-based cancer registry data provide a key epidemiological resource for monitoring cancer in defined populations. Validation of the data variables contributing to a common data set is necessary to remove statistical bias; the process is currently performed centrally. An ontology-based approach promises advantages in devolving the validation process to the registry level but the checks regarding multiple primary tumours have presented a hurdle. This work presents a solution by modelling the international rules for multiple primary cancers in description logic. Topography groupings described in the rules had to be further categorised in order to simplify the axioms. Description logic expressivity was constrained as far as possible for reasons of automatic reasoning performance. The axioms were consistently able to trap all the different types of scenarios signalling violation of the rules. Batch processing of many records were performed using the Web Ontology Language application programme interface. Performance issues were circumvented for large data sets using the software interface to perform the reasoning operations on the basis of the axioms encoded in the ontology. These results remove one remaining hurdle in developing a purely ontology-based solution for performing the European harmonised data-quality checks, with a number of inherent advantages including the formalisation and integration of the validation rules within the domain data model itself.