Three novel rare TP53 fusion mutations in a patient with multiple primary cancers:a case report

As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.

Synchronous gastric cancer complicated with chronic myeloid leukemia (multiple primary cancers):A case report

BACKGROUND With the advancement of medical technology and improvement in living standards,the incidence of multiple primary cancers has gradually increased.In particular,tumors of the digestive system account for a large proportion of multiple primary cancers.The diagnosis and treatment of chronic myeloid leukemia,particularly with synchronous gastric cancer,at the first consultation is relatively rare.CASE SUMMARY Herein,we present the case of a middle-aged man who was referred to the Department of Hematology owing to an elevated white blood cell count.After the examination,he was diagnosed with chronic myeloid leukemia and was administered imatinib.Three months after the initial diagnosis,he visited our hospital again for abdominal pain,and further examination revealed gastric malignancy.After discussion with a multidisciplinary team,S-1(Tegafur,Gimeracil,and Oteracil Potassium Capsules) combined with oxaliplatin—SOX regimen—was initiated.Later,the patient’s condition rapidly progressed.He developed colonic obstruction and underwent an ostomy;however,he died less than 6 months after the initial diagnosis.CONCLUSION Multiple primary cancers are influenced by environmental and genetic factors;a standardized multidisciplinary discussion plays a key role in treatment.

Dual primary gastric and colorectal cancer:A complex challenge in surgical oncology

The intricate interplay of colorectal cancer(CRC)and gastric cancer(GC)as dual primary malignancies presents a significant challenge in surgical oncology.CRC is the most common secondary malignancy in GC patients,and vice versa,evidence highlighted by advances in diagnostic procedures and therapy modalities that impact patient survival.A recent study titled“Features of synchronous and metachronous dual primary gastric and colorectal cancer”explores this enigmatic dual malignancy,uncovering crucial insights into the clinical characteristics and prognostic distinctions between synchronous and metachronous presentations.Notably,metachronous cases with a second primary cancer discovered more than six months after the first diagnosis have a better outcome,emphasizing the importance of early detection and treatment.This study underscores the prognostic role of GC stage in patient outcomes.It also sheds light on the complexities faced by synchronous cases,often presenting with unresectable CRC.Surgery-related procedures,like gastrectomy and colon resection,stand out as important predictors of increased survival,necessitating a reevaluation of current therapeutic approaches.A tailored and patient-centered strategy,considering the health of each patient individually and the feasibility of radical treatments,is essential.Continuous follow-up and monitoring are crucial as most second primary cancers arise within five years.In conclusion,early diagnosis,surgical intervention,and watchful surveillance are pivotal in managing dual primary gastric and colorectal cancer patients.Since the incidence of gastric and colorectal cancers continues to rise,the imperative need for further research,ideally with larger sample sizes,becomes evident in our pursuit of comprehensive insights that will refine clinical approaches for this intricate dual malignancy.

BRAF mutation in multiple primary cancer with colorectal cancer and stomach cancer

Aims:Recently,BRAF mutation testing has been introduced as a marker in differentiating Lynch syndrome from sporadic colorectal cancers or in predicting colorectal cancers with worse prognosis.Individuals with hereditary predisposition to cancer development are at an increased risk of developing multiple primary cancers.The purpose of this study is to identify mutation in the BRAF gene in multiple primary cancers with colorectal cancer and stomach cancer.Methods:BRAF mutation was analysed in 45 patients with colorectal cancer and stomach cancer,synchronously or metachronously.Results:Mean age was 64.07 years(range:47–83 years).For the colorectal cancer,tumors were located at the sigmoid colon in eight patients(17.8%)and at the rectum in 22 patients(48.9%).Twenty-three patients(51.1%)had synchronous cancer.Four patients(8.9%)had family members with cancer.BRAF mutation was identified in three patients(6.7%).All three of these patients had metachronous cancers.The colorectal cancers were located in the sigmoid colon(1 patient)and the rectum(2 patients).Conclusions:BRAF mutation rate was low in the multiple primary cancer with colorectal cancer and stomach cancer.With only BRAF gene study,it was not possible to identify any correlation with family history of colorectal cancer.Further study means considering other genes–MSI,MSH2,MLH1,MSH6.

Multiple primary colorectal cancer: Individual or familial predisposition?

Colorectal carcinoma(CRC) is one of the most frequent cancers. Along the surface of the large bowel, several foci of CRC may appear simultaneously or over the time. The development of at least two different tumours has been defined as multiple primary CRC(MPCRC):When more than one tumour is diagnosed at the same time, it is known as synchronous CRC(SCRC), while when a second neoplasm is diagnosed some time after the resection and/or diagnosis of the first lesion, it is called metachronous CRC(MCRC). Multiple issues can promote the development of MPCRC, ranging from different personal factors, such as environmental exposure, to familial predisposition due to hereditary factors. However, most studies do not distinguish this dichotomy. High- and low-pentrance genetic variants are involved in MPCRC. An increased risk for MPCRC has been described in Lynch syndrome, familial adenomatous polyposis, and serrated polyposis. Non-syndromic familial CRCs should also be considered as risk factors for MPCRC. Environmental factors can promote damage to colon mucosae that enable the concurrence of MPCRC. Epigenetics are thought to play a major role in the carcinogenesis of sporadic MPCRC. The methylation state of the DNA depends on multiple environmental factors(e.g., smoking and eating foods cooked at high temperatures), and this can contribute to increasing the MPCRC rate. Certain clinical features may also suggest individual predisposition for MPCRC. Different etiopathogenic factors are suspected to be involved in SCRC and MCRC, and different familial vs individual factors may be implicated. MCRC seems to follow a familial pattern, whereas individual factors are more important in SCRC. Further studies must be carried out to know the molecular basis of risks for MPCRC in order to modify, if necessary, its clinical management, especially from a preventive point of view.

Simultaneous Bilateral Thoracoscopic Pneumonectomy for Early Multiple Primary Lung Cancer Feasibility Analysis

Objective:To analyze the feasibility of simultaneous bilateral thoracoscopic lung resection in the treatment of multiple primary lung cancers in the early stage.Methods:The study time range is between March 2019 and March 2021.A sample of 30 patients with early multiple primary lung cancer admitted to this hospital were included,and they were divided into a study group,a control group,and samples within the group using a random number table scheme n=15,patients in the control group underwent staged bilateral thoracoscopic pneumonectomy,and patients in the study group underwent bilateral thoracoscopic pneumonectomy at the same time.The indicators of the two groups were compared and analyzed.Results:There was no significant difference in the operation time and intraoperative blood loss between the two groups(P>0.05).There were significant differences in the VAS score,total length of hospital stay,and total surgical costs on the first day after surgery(P<0.05);there was no significant difference in the two groups'postoperative recovery indicators and the incidence of complications(P>0.05).Conclusion:It is safe and feasible to treat patients with multiple primary lung cancer in both lungs at the same time with simultaneous bilateral thoracoscopic surgery,and is suitable for promotion.

METACHRONOUS SECOND PRIMARY CANCERS: CLINICAL ANALYSES OF 506 CASES IN A SINGLE INSTITUTION

Objective: To elucidate the clinical features and prognosis of multiple primary cancers, in order to make improvement of diagnosis and treatment. Methods: A total of 506 patients with two primary cancers admitted from 1973 to 2004 were analyzed retrospectively. Results: These cases accounted for 0.9% of all the hospitalized cases in the same period among which 126 were males, with the ratio of male to female 1:3. The median age at the onset of the first disease was 48 y (ranged from 24 to 77). The interval between the two cancers was longer in patients under 50 y and in males, but without statistical significance. The onset age of the two primary cancers was mainly centered around 40 to 60 y, while 70% of the second cancer occurred within 80 m after the first cancer but half of them occurred within five years. The interval between the two cancers played crucial role in affecting the prognosis (P<0.005). Conclusion: Fewer lethal cancers are involved in either the primary or the secondary malignancies. The interval between the two primaries contributes most to the prognoses.

Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy

Multiple primary lung cancer(MPLC)is an increasingly prevalent subtype of lung cancer.According to recent genomic studies,the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence.We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found.Using our own and other relevant public data,evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk,indicating evolutionary contingency rather than adaptive convergence.Additionally,tumors from the same MPLC patient are as genetically diverse as those from different patients,while within-tumor genetic heterogeneity is significantly lower.Furthermore,the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor,but not with samples from other tumors or other patients.Overall,there is no evidence of adaptive convergence during the evolution of MPLC.Most importantly,the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient.To fully exploit the strategic value of precision medicine,targeted therapies should be designed and delivered on a per-lesion basis.

A pairwise radiomics algorithm–lesion pair relation estimation model for distinguishing multiple primary lung cancer from intrapulmonary metastasis

Background:Distinguishing multiple primary lung cancer(MPLC)from intrapulmonary metastasis(IPM)is critical for their disparate treatment strategy and prognosis.This study aimed to establish a non-invasive model to make the differentiation pre-operatively.Methods:We retrospectively studied 168 patients with multiple lung cancers(307 pairs of lesions)including 118 cases for modeling and internal validation,and 50 cases for independent external validation.Radiomic features on computed tomography(CT)were extracted to calculate the absolute deviation of paired lesions.Features were then selected by correlation coefficients and random forest classifier 5-fold cross-validation,based on which the lesion pair relation estimation(PRE)model was developed.A major voting strategy was used to decide diagnosis for cases with multiple pairs of lesions.Cases from another institute were included as the external validation set for the PRE model to compete with two experienced clinicians.Results:Seven radiomic features were selected for the PRE model construction.With major voting strategy,the mean area under receiver operating characteristic curve(AUC),accuracy,sensitivity,and specificity of the training versus internal validation versus external validation cohort to distinguish MPLC were 0.983 versus 0.844 versus 0.793,0.942 versus 0.846 versus 0.760,0.905 versus 0.728 versus 0.727,and 0.962 versus 0.910 versus 0.769,respectively.AUCs of the two clinicians were 0.619 and 0.580.Conclusions:The CT radiomic feature-based lesion PRE model is potentially an accurate diagnostic tool for the differentiation of MPLC and IPM,which could help with clinical decision making.

Younger age of onset and multiple primary lesions associated with esophageal squamous cell carcinoma cases with a positive family history of the cancer suggests genetic predisposition

Background Previous epidemiological studies have consistently found a positive family history of esophageal cancer is associated with a significantly increased risk of the cancer.However,whether the elevated risk could be attributed to common household exposure or inherited susceptibility is uncertain.This study aimed to highlight the effect of genetic predisposition by noting the significant differences in onset age and multiple primary cancers between esophageal squamous cell carcinoma （ESCC） cases with or without a positive family history of the cancer.Methods Age at onset and the percentage of multiple primary cancers were compared between ESCCs with （n=766） or without （n=1 776） a positive family history of the cancer in a consecutive surgery cohort at the Department of Thoracic Surgery of Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University.Results Overall,ESCCs with a positive family history of the cancer featured both a significantly younger age of onset and significantly more multiple primary cancers than those with a negative family history （onset age 51.83 vs.53.49 years old,P 〈0.01; percent of multiple primary cancers 5.50% vs.1.70%,x2=25.42,P 〈0.01）.Both the differences were evident in subgroup analyses,but did not correlate.While age at onset differed significantly by family history among the male,smoking,and drinking groups,the difference of multiple primary cancers was significant among the otherwise nonsmoking,nondrinking,and younger onset age groups.Conclusions Younger age of onset and multiple primary cancers associated with ESCCs with a positive,as opposed to a negative family history of the cancer,suggest a genetic predisposition.The results of subgroup analyses indicate a younger age of ESCC development results from the interaction of environmental and genetic risk factors,but multiple primary cancers may be related only to genetic predisposition.

Multiple primary malignancies including colon, stomach, lung, breast, and liver cancer： a case report and literature review

Multiple primary malignancies in a single patient are relatively rare but have increase in frequency in recent decades. This may be a result of medical advancements in diagnostic and therapeutic strategies, a possible effect of new carcinogens in the industrial environment, and longer life span allowing another primary cancer to develop. Among those with multiple primary malignancies, double cancer is commonly seen, while triple cancers occur in 0.5% of patients, and quadruple or quintuple cancers occur in only less than 0.1% of the population.

Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China

Background In China, esophageal squamous cell carcinoma （ESCC） and gastric cardia adenocarcinoma （GCA） share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal. Methods The percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University. Results A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males （P 〈0.000） and 25.0%, 22.3%, 23.9%, and 9.8% in females （P 〈0.0001）. Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females （ both P 〈0.0001） for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2：1 for upper, middle, lower third ESCC and GCA （P〈0.0001）. For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age 〉50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist. Conclusions The proportion of familial cancer in upper gastrointestinal carcinomas decreases by the priamry site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.

Coincidence of three solid tumors in a patient with multiple myeloma

Multiple primary cancers （MPC） are specific .malignant tumors type, manifesting as more than one primary tumor diagnosed in the same patient, either simultaneously or sequentially. The diagnostic criteria include： the cancer must be clearly malignant as determined by histological evaluation; each cancer must be geographically separate and distinct;