Synchronous Multiple Primary Cancers Research Articles

Genomic alterations in oral multiple primary cancers

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n = 202) and oral MPCs (n = 34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs. Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Analysis of clinicopathological features and prognosis of sporadic synchronous multiple primary colorectal cancers

Analysis of clinicopathological features and prognosis of sporadic synchronous multiple primary colorectal cancers

Synchronous multiple primary cancers involving rectal cancer and pelvic classical hodgkin lymphoma: the first case report

Synchronous multiple primary cancers involving rectal cancer and pelvic classical hodgkin lymphoma: the first case report

A case of synchronous double cancers consisting of maxillary gingival carcinoma and intraductal papillary mucinous carcinoma, invasive: case report

BackgroundThe development of synchronous multiple primary cancers is one of the major causes of death in patients with head and neck cancer. Herein, we report a case of synchronous intraductal papillary mucinous carcinoma (IPMC), invasive in a patient with maxillary gingival carcinoma.Case presentationA 73-year-old female visited our hospital complaining of a mass on the left side of the maxillary gingiva. Intraorally, an exophytic tumor, 50 × 25 mm in size, was found on the gingiva of the left maxillary posterior, and a diagnosis of squamous cell carcinoma was revealed by cytology. Emission tomography/ computed tomography with 18 Fluorodeoxyglucose-Positron (18FDG- PET/ CT) showed increased accumulation in the left maxillary gingiva, the left side of cervical lymph nodes, and the main pancreatic duct. The pancreatic ductal tumor was performed the biopsy at esophagogastroduodenoscopy (EGD) and resulted in a pathological diagnosis of IPMC, invasive. The patient was diagnosed as synchronous double primary cancers consisting of maxillary gingival carcinoma cT4aN2bM0 and IPMC, invasive cT3N0M0. She refused radical treatment, and died 11 months later.Conclusion18FDG- PET/ CT, EGD and multidisciplinary approach is required for the detection and determining the treatment strategy of synchronous double primary cancers.

Clinicopathological characteristics of synchronous multiple primary early esophageal cancer and risk factors for multiple lesions.

With the development of endoscopic technology, the detection rate of synchronous multiple primary early esophageal cancer (SMPEEC) is increasing; however, the risk factors remain unclear. We aimed to assess the clinicopathological characteristics of patients with SMPEEC and investigate the risk factors contributing to the development of multiple lesions. A retrospective cohort study was conducted on 911 consecutive patients who underwent Endoscopic submucosal dissection (ESD) for primary esophageal neoplasms from January 2013 to June 2021. The patients were divided into the SMPEEC group and the solitary early esophageal cancer (SEEC) group. We compared the differences in clinicopathological characteristics between the two groups and investigated the risk factors linked to multiple lesions. Additionally, we investigated the relationship between the main and accessory lesions. A total of 87 SMPEEC patients were included in this study, and the frequency of synchronous multiple lesions was 9.55% in patients with early esophageal cancer. The lesions in the SMPEEC group were mainly located in the lower segment of the esophagus (46[52.9%]), whereas those in the SEEC group were in the middle segment (412[50.0%]). The pathology type, tumor location, and circumferential rate of lesions were independent risk factors(P<0.05) for SMPEEC by logistic regression analysis. Significant positive correlations were observed between the main and accessory lesions in terms of morphologic type (r=0.632, P=0.000), tumor location(r=0.325, P=0.037), pathologic type (r=0.299, P=0.003), and depth of invasion (r=0.562, P=0.000). Pathology type, tumor location, and circumferential rate of lesions were identified as independent risk factors for SMEPPC. Understanding these risk factors and the correlation between the main and accessory lesions could significantly improve the detection rate of SMPEEC.

Developing prognostic nomograms to predict overall survival and cancer-specific survival in synchronous multiple primary colorectal cancer based on the SEER database.

Synchronous multiple primary colorectal cancer (SMPCC) is a rare subtype of CRC, characterized by the presence of two or more primary CRC lesions simultaneously or within 6months from the detection of the first lesion. We aim to develop a novel nomogram to predict OS and CSS for SMPCC patients using data from the SEER database. The clinical variables and survival data of SMPCC patients between 2004 and 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Appropriate inclusion and exclusion criteria were established to screen the enrolled patients. Univariate and multivariate Cox regression analyses were used to identify the independent risk factors for OS and CSS. The performance of the nomogram was evaluated using the concordance index (C-index), calibration curves, and the area under the curve (AUC) of a receiver operating characteristics curve (ROC). A decision curve analysis (DCA) was generated to compare the net benefits of the nomogram with those of the TNM staging system. A total of 6772 SMPCC patients were enrolled in the study and randomly assigned to the training (n = 4670) and validation (n = 2002) cohorts. Multivariate Cox analysis confirmed that race, marital status, age, histology, tumor position, T stage, N stage, M stage, chemotherapy, and the number of dissected LNs were independent prognostic factors.The C-index values for OS and CSS prediction were 0.716 (95% CI 0.705-0.727) and 0.718 (95% CI 0.702-0.734) in the training cohort, and 0.760 (95% CI 0.747-0.773) and 0.749 (95% CI 0.728-0.769) in the validation cohort. The ROC and calibration curves indicated that the model had good stability and reliability. Decision curve analysis revealed that the nomograms provided a more significant clinical net benefit than the TNM staging system. We developed a novel nomogram for clinicians to predict OS and CSS, which could be used to optimize the treatment in SMPCC patients.

Evaluation of synchronous multiple primary superficial laryngo-pharyngeal cancers that were treated by endoscopic laryngo-pharyngeal surgery

Evaluation of synchronous multiple primary superficial laryngo-pharyngeal cancers that were treated by endoscopic laryngo-pharyngeal surgery

A novel risk prediction nomogram for early death in patients with resected synchronous multiple primary colorectal cancer based on the SEER database

BackgroundSynchronous multiple primary colorectal cancer (SMPCC) involves the simultaneous occurrence of 2 or more independent primary malignant tumors in the colon or rectum. Although SMPCC is rare, it results in a higher incidence of postoperative complications and mortality compared to patients with single primary colorectal cancer (SPCRC).MethodsThe clinical factors and survival outcomes of SMPCC patients registered on the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2017 were extracted. The patients were divided into the training and validation cohorts using a ratio of 7:3. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for early death. The performance of the nomogram was evaluated using the concordance index (C-index), calibration curves, and the area under the curve (AUC) of a receiver operating characteristics curve (ROC). A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomogram and standard TNM system.ResultsA total of 4386 SMPCC patients were enrolled in the study and randomly assigned to the training (n = 3070) and validation (n = 1316) cohorts. The multivariate logistic analysis identified age, chemotherapy, radiotherapy, T stage, N stage, and M stage as independent risk factors for all-cause and cancer-specific early death. The marital status was associated with all-cause early death, and the tumor grade was associated with cancer-specific early death. In the training cohort, the nomogram achieved a C-index of 0.808 (95% CI, 0.784–0.832) and 0.843 (95% CI, 0.816–0.870) for all-cause and cancer-specific early death, respectively. Following validation, the C-index was 0.797 (95% CI, 0.758–0.837) for all-cause early death and 0.832 (95% CI, 0.789–0.875) for cancer-specific early death. The ROC and calibration curves indicated that the model had good stability and reliability. The DCA showed that the nomogram had a better clinical net value than the TNM staging system.ConclusionOur nomogram can provide a simple and accurate tool for clinicians to predict the risk of early death in SMPCC patients undergoing surgery and could be used to optimize the treatment according to the patient's needs.

Experience in the treatment of radioinduced angiosarcoma of the breast in a patient with primary multiple lesions of the breast and bladder. Case report

Among the multiple primary malignant tumors, breast cancer is the most common and in most cases it is combined with the second mammary gland, uterine body, stomach, colon, skin and ovary. Breast angiosarcoma is a very rare disease with unfavorable prognosis. Radiation therapy to the area of the breast is considered to be the main risk factor for the radiation-induced angiosarcoma. Diagnosis is based on the clinical aspect, the results of morphological and immunohistochemical findings. There are no uniform standards for the treatment of this pathology; a surgical method, systemic therapy, and radiation therapy are used. The article presents a clinical case of a female patient born in 1952, who was diagnosed with synchronous multiple primary cancer in 2014: stage 2A left breast cancer (cT2N0M0); bladder cancer stage I (cT1cN0M0). After the complex treatment, the patient received adjuvant endocrine therapy with Tamoxifen. In December 2018, single bluish formations appeared in the area of the postoperative scar, followed by a rapid growth of formations on the skin within a month, with a tendency to merge and necrosis. The patient was sent for biopsy of the formations with suspected recurrence of the disease. Immunomorphological patterns correspond to the angiosarcoma in the skin of the mammary gland. A simple mastectomy was performed. After 3 months, growth of angiomyosarcoma in the soft tissues of the anterior chest wall continued. Excision of the tumor in the soft tissues of the chest was performed and the patient underwent postoperative course of radiation therapy with a single focal dose (SFD) 2.5 Gy, total boost isodose of 50 Gy. At follow-up examinations held from January to December 2021, there is no evidence for continued growth and recurrence of the disease. The presented clinical observation demonstrates the experience of diagnostics and treatment of radiation-induced angiosarcoma in the patient with multiple primary synchronous lesions of the breast and bladder.

Molecular Typing and Clinical Characteristics of Synchronous Multiple Primary Colorectal Cancer

Synchronous multiple primary colorectal cancer (sMPCC) is clinically rare, but its incidence has increased over the past decade. However, little is known about the molecular and clinical features of sMPCC, which may differ from those of single primary colorectal cancer (SPCRC). To evaluate the clinical characteristics and pathogenic variations in lesions and the molecular typing of sMPCC. From November 2012 to April 2021, patients with colorectal cancer (CRC) treated at the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this cohort study. Follow-up ended on January 31, 2022. The primary outcome was mismatch repair (MMR) status of each lesion in all patients examined using immunohistochemistry (IHC). Microsatellite instability (MSI) and tumor mutation burden (TMB) were also calculated. A total of 13 276 patients with CRC were enrolled, and 239 patients with sMPCC (mean [SD] age, 63.3 [12.2] years; 173 men [72.4%]) with available clinical data were evaluated. Seventy-eight patients with sMPCC and 94 with SPCRC also underwent next-generation sequencing (NGS)-based molecular testing. The deficient MMR (dMMR)/MSI-H frequencies in sMPCC were significantly higher than those in SPCRC, which was confirmed by both IHC (50 of 239 patients vs 872 of 13 037 patients) and NGS (17 of 78 patients vs 5 of 94 patients). According to the MMR/MSI status of different lesions in patients with sMPCC, they were further divided into 3 subgroups: all dMMR/MSI-H, dMMR/MSI-H and proficient MMR (pMMR)/microsatellite stability (MSS), and all pMMR/MSS. The EGFR and PIK3CA variants were more common, whereas TP53 variants were less prevalent in patients with sMPCC than in those with SPCRC. Moreover, higher tumor mutation burden was associated with higher MSI in patients with sMPCC rather than in those with SPCRC. In this cohort study of sMPCC, the incidence of dMMR/MSI-H in patients with sMPCC was significantly higher than that in patients with SPCRC. These findings suggest that sMPCC can be classified into 3 subgroups according to the MMR/MSI status of each lesion, which might be applied to guide personalized therapies for better disease management.

Landscapes of synchronous multiple primary cancers detected by next-generation sequencing.

An increase in the detection rate of multiple primary cancers has been accompanied with declining cancer death rates over the past few decades. However, synchronous multiple primary tumors have gradually increased, and the molecular mechanisms involved in the synchronous occurrence of multiple primary cancers of different origins are unclear. To investigate these mechanisms, we sequenced cancer tissues by FoundationOne CDx. Data were annotated with annovar, and we then performed pathway enrichment analysis. A total of 109 genes that were mutated in all samples were clustered into different diseases, biological processes, and molecular functions. GO and KEGG analyses indicated that the P53 and PKB signaling pathways may be relevant to the occurrence of synchronous multiple primary cancers. In summary, patients with a concordance of mutations in pathogenetic genes may have a higher risk of developing a second cancer. Our research may provide a basis for the development of individualized treatments for synchronous multiple primary cancers.

Molecular typing and clinical characteristics of synchronous multiple primary colorectal cancer.

3061 Background: Synchronous multiple primary colorectal cancer (sMPCC) is clinically rare while its incidence was increasing in the past decade. However, little was known about molecular and clinical features of sMPCC, which might be different from single primary colorectal cancer (CRC). Methods: From November 2012 to April 2021, 239 sMPCC from a total of 13276 CRC patients operated in the 6th Affiliated Hospital of Sun Yat-sen University were enrolled in this study. Mismatch repair (MMR) status in each lesion of all 239 patients was examined by immunohistochemistry (IHC). Totally 78 sMPCC patients and 94 single primary CRC patients conducted an 831-gene panel based next-generation sequencing (NGS) (OncoPanscan, Genetronhealth). Somatic mutations and potential pathogenic germline variants were analyzed. Microsatellite instability (MSI) and tumor mutation burden (TMB) were calculated. Results: We found that dMMR/MSI-H frequencies in sMPCC were significantly higher than those in single primary CRC, which were confirmed by both IHC (50/239 vs 872/13037, p &lt; 0.001) and NGS (17/78 vs 5/94, p = 0.0022). According to the MMR/MSI status at different lesion in sMPCC patients, they were further divided into all MSI-H, MSI-H &amp; MSS and all MSS group, with incidences of 16.7%, 4.2% and 79.1%, respectively. With NGS analysis, we found that the most enriched gene mutation type in sMPCC patients was C &gt; T (G &gt; A), and their most frequently mutated genes were APC (65%), KRAS (46%), TP53 (31%), PIK3CA (25%), EGFR (23%), ARID1A (18%), NF1 (18%), SOX9 (18%), FAT4 (16%), and TCF7L2 (15%), whereas those genes in single primary CRC patients were APC (71%), TP53 (64%), KRAS (40%), FBXW7 (20%), PIK3CA (13%), SMAD4 (12%), ARID1A (11%), FAT4 (11%), CREBBP (11%), and NF1 (10%). Moreover, we found that higher TMB was correlated with higher MSI in sMPCC rather than single primary CRC patients. Furthermore, we found that the mutated genes were different among three subgroups. The top 5 mutated genes in MSI-H group were APC (68%), FAT4 (64%), TCF7L2 (59%), KMT2B (55%), ARID1A (45%), whereas those in MSI-H &amp; MSS group were APC (57%), KMT2B (43%), KMT2C (43%), ATM (43%), PRKDC (43%), and those in MSS group were APC (66%), KRAS (49%), TP53 (36%), PIK3CA (21%), EGFR (20%). Finally, we also found that patients with pathogenic/likely pathogenic germline mutations were comparable between sMPCC and single primary CRC, indicating that sMPCC may not be resulted from germline changes. Conclusions: Our results revealed that incidences of dMMR/MSI-H in sMPCC were significantly higher than those in single primary CRC. We proposed that MMR/MSI status of each lesion in sMPCC patients should be verified before treatment and these patients could be divided into three subgroups according to their MMR/MSI status. Our findings indicated that sMPCC patients with different MMR/MSI status might be treated with personalized therapies for better management of their disease.

The structure of synchronous multiple primary colorectal cancer

One of the problems of modern oncology is the lack of timely diagnosis of synchronous forms of colorectal cancer. Therefore, the aim of this study was to evaluate the structure of synchronous primary multiple forms of colorectal cancer. Methods: We analyzed the results of colorectal cancer diagnostics (n = 583) in the period 2010–2019. We did not include patients with metachronous colorectal cancer in the study. The average age of all patients was 71.6 ± 7.4 years. There were 1.5 times more men than women. Results: Synchronous colorectal cancer was detected in 171 (29.3%) patients. With synchronous primary multiple forms of colorectal cancer, 2 tumors were diagnosed in every second patient. In synchronous colorectal cancer, tumors were localized twice as often in the colon (n = 118) than in the rectum (n = 53). Conclusions: In patients with colorectal cancer, synchronous tumors occur in every third case. Synchronous colorectal cancer is more common in men. In the majority of patients (59.1%), synchronous colorectal cancer was detected within 6 months after imaging of the primary tumor.

Clinical characteristics and prognosis of patients with hypopharyngeal cancers with multiple primary cancers: A propensity score matched analysis

PurposeThis study aimed to identify the clinical characteristics of hypopharyngeal squamous cell carcinoma (HPSCC) patients with multiple primary cancers (MPCs) and to compare differences between patients with metachronous and synchronous MPCs. Material and methodsThis study included 219 patients with HPSCC treated at our center between 2008 and 2020; the clinical characteristics and prognosis of 66 patients with MPCs were analyzed. Propensity score matching (PSM) was used to balance the factors between patients with synchronous and metachronous MPCs. ResultsSixty-six patients with HPSCC (66/219, 30.1%) experienced MPCs, of which 29 were synchronous and 37 were metachronous. The esophagus (n = 39, 59.1%), lung (n = 10, 15.2%), and oropharynx (n = 4, 6.1%) were the three most common sites of MPCs in both the synchronous and metachronous groups. More patients with synchronous MPCs were stage T1–2 (82.8% vs. 59.5%, P = 0.041) compared to those with metachronous MPCs. Among the 24 pairs of patients after PSM, patients with metachronous MPCs had higher 3-year progression-free survival (PFS) (52.5% vs. 16.3%, P < 0.001) and overall survival (OS) (58.5% vs. 22.1%, P = 0.001) than those with synchronous cancers. Multivariate Cox analysis showed that patients with synchronous MPCs had shorter PFS (HR 4.45, 95% CI 1.819–10.885, P = 0.001) and OS (HR 3.918, 95% CI 1.591–9.645, P = 0.003). ConclusionMPCs are common among patients with HPSCC, and patients with metachronous MPCs had better survival than those with synchronous MPCs. Clinicians should be aware of the possibility of MPCs in patients with HPSCC and optimize treatment to improve outcomes.

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

BackgroundThe 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 methodsRetrospective 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.ResultsMultiple 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.ConclusionsThe 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.

Prevalence of cancer susceptibility variants in patients with multiple Lynch syndrome related cancers

Along with early-onset cancers, multiple primary cancers (MPCs) are likely resulting from increased genetic susceptibility; however, the associated predisposition genes or prevalence of the pathogenic variants genes in MPC patients are often unknown. We screened 71 patients with MPC of the stomach, colorectal, and endometrium, sequencing 65 cancer predisposition genes. A subset of 19 patients with early-onset MPC of stomach and colorectum were further evaluated for variants in cancer related genes using both normal and tumor whole exome sequencing. Among 71 patients with MPCs, variants classified to be pathogenic were observed in 15 (21.1%) patients and affected Lynch Syndrome (LS) genes: MLH1 (n = 10), MSH6 (n = 2), PMS2 (n = 2), and MSH2 (n = 1). All carriers had tumors with high microsatellite instability and 13 of them (86.7%) were early-onset, consistent with LS. In 19 patients with early-onset MPCs, loss of function (LoF) variants in RECQL5 were more prevalent in non-LS MPC than in matched sporadic cancer patients (OR = 31.6, 2.73–1700.6, p = 0.001). Additionally, there were high-confidence LoF variants at FANCG and CASP8 in two patients accompanied by somatic loss of heterozygosity in tumor, respectively. The results suggest that genetic screening should be considered for synchronous cancers and metachronous MPCs of the LS tumor spectrum, particularly in early-onset. Susceptibility variants in non-LS genes for MPC patients may exist, but evidence for their role is more elusive than for LS patients.

Experience on the diagnosis and treatment of multiple active primary cancers in our Institution.

e15097 Background: Multiple active primary cancers (MAPC) deal with synchronous multiple primary cancers and heterochronous multiple primary cancers needing concurrent treatment for each primary. There are no standards in the diagnosis and treatment of MAPC. Here, we report our experiences with MAPC cases. Methods: Overall, 31 patients with MAPC between Apr 2017 and Dec 2020 were included. All of them had received treatment for their MAPC, either local intervention or systemic treatment. Results: Of the 31 MAPC, 5 cases having triple and 26 having double primary neoplasms. The most common primary sites were breast (n = 20) and lung (n = 13). The contribution of each diagnostic approach in the establishment of MAPC diagnosis were as follows: atypical metastatic spread, lymphatic or vascular; lesions in other organ sites indicating suspected primary tumor by imaging (11/26) and PET-CT (5/17); atypical increase of tumor marker panel (3/24) or clinical manifestations (7/31) not parallel or specific to the prior documented primary tumor; and patients with genetic predisposition (one germline BRCA2 mutation and one TP53 mutation). If biopsy was not available, utilization of other optimal imaging techniques, such as FES- and PSMA-PET-CT could be helpful in selected patients. Treatment decisions of patients with MAPC should be made with joint effort of the multidisciplinary team. Radical surgery or radiotherapy (17/31) was done in the setting when any primary cancer was considered localized. The severity of each primary malignance (aggressiveness, symptom, staging and etc.) was also evaluated, and the predominant primary tumor was handled with priority. Systemic therapy was administered in consideration of each active cancer, and any new drug combinations should be evaluated for drug interactions. Unexpectedly, use of palbociclib in a patient with breast cancer and chronic lymphoblastic leukemia might aggravate the leukemia, because one week of palbociclib plus letrozole led to a sharp WBC increase with a lymphocyte predominance and quickly reduced to the baseline after drug discontinuation. Notably, NGS in circulating tumor DNA was also useful since it might indicate a common treatment strategy for MAPC and a hint to the predominant cancer. Six MAPC patients including 1 ROS-1 rearranged lung cancer, 4 EGFR mutant lung cancer, and 2 HER2 positive breast cancer were treated with corresponding targeted agents (crizotinib, gefitinib and lapatinib). Four responses (1 CR and 3 PR) and 2 stable disease (PFS 33+ and 132 months) were observed. Three of the four responders had a PFS of 1+, 29+ and 27 months, whereas Case 13 who had multiple combinations of EGFR-TKI, chemotherapy and anti-HER2 treatment for her simultaneously advanced breast and lung cancers, was alive at 66 months. Conclusions: The diagnosis and treatment of MAPC has no standards and should integrate all available resources by a specific multidisciplinary team.

Evaluation of synchronous multiple primary superficial laryngo-pharyngeal cancers that were treated by endoscopic laryngo-pharyngeal surgery

Objectivendoscopic laryngopharyngeal surgery (ELPS) is a useful surgery for superficial cancers of the head and neck region, but it has not yet been well evaluated for synchronous multiple primary cancers (multiple primaries). The purpose of this study was to clarify the safety and usefulness of ELPS for patients with multiple superficial primary cancers in the head and neck region. Methodsrom December 2009 to December 2016, 145patients with superficial head and neck cancers underwent ELPS. The patients were divided into two groups; a group consisting of patients with a single primary cancer (single primary) and another group consisting of patients with synchronous multiple primaries, and the incidences of postoperative complications and lymph node metastasis were retrospectively compared between the two groups. Resultsf the 145 patients, 107 had a single primary cancer and 38 had multiple primaries. There was no significant difference in the age, sex, or rate of intraepithelial cancer between the two groups. Postoperative complications included dysphagia in 6 (5.6%) patients with a single primary and 2 (5.3%) patients with multiple primaries. One patient with multiple primaries required gastrostomy because of aspiration pneumonia. In addition, the following complications were also observed. Laryngeal paralysis occurred in 2 (1.9%) patients with a single primary, and 1 (2.6%) patient with multiple primaries; tracheostomy because of postoperative bleeding in 1 (0.9%) patient with a single primary; infection occurred in 2 (5.3%) patients with multiple primaries. Postoperative lymph node metastasis was found in 7 (6.5%) patients with a single primary and 6 (15.8%) patients with multiple primaries. Lymphatic invasion of the primary cancer was noted in 3 (2.8%) patients with a single primary and 5 (13.2%) patients with multiple primaries, being significantly higher in the latter group. ConclusionELPS is also a safe surgery for patients with multiple primaries. However, the incidence of lymphatic invasion of the primary cancer was significantly higher in patients with multiple primaries.

Risk Factors and Genetic Biomarkers of Multiple Primary Cancers in Esophageal Cancer Patients.

Esophageal cancer (EC) is a deadly cancer that frequently develops multiple primary cancers (MPCs). However, the risk biomarkers of MPC in EC have hardly been investigated. We retrospectively enrolled 920 subjects with primary EC and analyzed the possible risk factors as well as MPC single-nucleotide polymorphisms (SNPs) from blood DNA. A total of 184 subjects (20.0%) were confirmed to have MPC, 59 (32.8%) had synchronous MPC, and 128 (69.6%) had head and neck cancer. Elderly EC patients have an increased risk of having gastrointestinal cancer (Odds ratio, OR[95% CI]=6.70 [1.49–30.19], p=0.013) and a reduced risk of developing HNC (OR[95% CI]=0.44 [0.24–0.81], p=0.008). MPC risk was also associated with betel nut chewing (OR[95% CI]=1.63, 1.14–2.32], p=0.008), the A allele of ALDH2:rs671 (p=0.074 and 0.030 for GA and AA, respectively), the CC genotype in CISH:rs2239751 (OR[95% CI]=1.99 [1.2–3.32], p=0.008), and the G allele of ERCC5:rs17655 (p=0.001 and 0.090 for GC and CC, respectively). ADH1B:rs1229984 also correlated with MPC risk (p=0.117). Patients carrying four risk SNPs had a 40-fold risk of MPC (OR[95% CI]=40.25 [6.77–239.50], p<0.001) and a 12.57-fold risk of developing second primary cancer after EC (OR[95% CI]=12.57 [1.14–138.8], p=0.039) compared to those without any risk SNPs. In conclusion, hereditary variations in ALDH2, CISH, ERCC5, and ADH1B have great potential in predicting the incidence of MPC in EC patients. An extensive cancer screening program during clinical follow-up would be beneficial for patients with high MPC susceptibility.

The analysis of multiple primary cancers in Ege University hospital database

Amaç: Ege Üniversitesi Hastanesi (EÜH) kanser veri tabanında birden çok sayıda kanserleri olanÇoklu Primer Kanser (ÇPK)’li olguların sayıca artışı dikkat çekici bulunmuş, bu artışın istatistik olarakanalizi planlanmıştır.Gereç ve Yöntem: EÜH’de EÜKAM tarafından CANREG-4 özel bilgisayar programına kayıt edilenkanser verileri WHO ve Surveillance, Epidemiology, and End Results (SEER) sistemleri temelindegruplanarak analizler yapılmıştır. İstatistik analizlerde Ki-kare, General Linear Model, Kaplan Meiersağkalım analizleri uygulanmıştır. Kaplan Meier Sağkalım analizinde Log Rank (Mantel-Cox), Breslow(Generalized Wilcoxon) ve Tarone-Ware istatistikleri kullanılmış, istatistik analizlerde p &amp;lt;0,05istatistiksel olarak anlamlı kabul edilmiştir.Bulgular: EÜH veri tabanında 1992-2018 yılları arasında kaydedilmiş 124.321 kanser olgusunun6.311’inde birden çok kanser (%5,1) saptanmıştır. ÇPK görülüşü erkeklerde daha belirgindir(p&amp;lt;0,0001). ÇPK’de yıllara göre bir artış saptanmıştır (p&amp;lt;0,0001). Her iki cinste en sık görülenGastrointestinal sistem (GİS) kanserlerinde ÇPK genellikle yine GİS ile ilgili olmakta, bunu ürogenitalsistem (ÜGS) kanserleri izlemektedir. Akciğer kanseri ile beraber görülen ÇPK’lerin başında diğersolunum sistemi kanserleri gelmekte, bunu mesane kanserleri izlemektedir. Meme kanserini izleyenÇPK’ler endometrium ve over kanseridir. ÇPK’lerde sağkalım tek primer kanserlilere göre daha kötüve çoklu ÇPK sayısı arttıkça sağkalımlar daha kötü olmaktadır (p&amp;lt;0,001). Olguların %18,2’si senkron,%81,8’i metakron olup sağkalım açısından istatistiksel olarak aradaki fark anlamlı değildir (p=0,506).Sonuç: EÜH Hastanesi veri tabanında %5,1 ÇPK saptanmış olup yıllara göre bir artış eğilimi vardır.Senkron veya metakron gelişen ÇPK’lar da sağkalım farkı bulunmamıştır. Çoklu primer kanserlerdesağkalım tekli kanserlere göre daha kötü olup ÇPK sayısı arttıkça GSK’lar daha kötü olmaktadır.