Multiple Primary Tumors Originating From the Prostate and Colorectum A Clinical-Pathological and Therapeutic Challenge

Considering that the incidence of colorectal (CRC) and prostatic cancer (PC) increases with age, metachronous and synchronous tumors can often affect the same patient. Despite the importance of this subject for the diagnosis and management of oncologic patients, in medical literature the data are scarce. The aim of the study was to evaluate the incidence and the characteristics of double/multiple primary malignant tumors (D/MPMTs) with colorectal and prostatic origin, in patients admitted to a reference hospital in West Romania. A 4-year retrospective observational study (2016–2019) was conducted by analyzing the medical records of all patients admitted in the hospital. Demographic and clinical data, as well as tumor-related parameters, were extracted. We identified 413 consecutive hospitalized patients with PC, and 21 (5%) of them also had a primary CRC. At the time of diagnosis, the mean age of the patients with PC was 71.2 ± 6 years, and 71.8 ± 10 years for patients with CRC. Synchronous PC and CRC tumors were identified in 3/21 cases and metachronous tumors in 18/21 cases. Prostate cancer was the first tumor to be diagnosed in 13/18 cases and CRC in 5/18 cases. The most frequent subtype of PC was acinar adenocarcinoma (90%) and for CRC cases, conventional adenocarcinoma (90%). Prostate and colorectal cancers tend to co-occur in a single patient. The diagnosis of one of these two types of tumors should imply the screening for the other one, because these patients require a multidisciplinary and personalized approach.

MBRS-54. POOR SURVIVAL IN REPLICATION REPAIR DEFICIENT HYPERMUTANT MEDULLOBLASTOMA AND CNS EMBRYONAL TUMORS: A REPORT FROM THE INTERNATIONAL RRD CONSORTIUM

BACKGROUND Mutations in mismatch repair (MMR) and DNA-polymerase (POL) genes lead to DNA replication repair deficiency (RRD), resulting in a growing group of previously under-recognized childhood brain tumors. Medulloblastoma and embryonal tumors are rarely reported in RRD. Their biological and clinical significance is unknown. METHODS We analyzed the clinical and genomic data of embryonal tumors registered in the International RRD Consortium. RESULTS Twenty-six tumors were centrally reviewed to confirm medulloblastoma (n=18), embryonal-tumor, NOS (n=5), and three glioblastoma (excluded). Embryonal tumors were observed at a young age (median: 7-years, IQR: 5;11), and all but one exhibited clinical cues (café-au-lait macules/ family history) of germline RRD. Medulloblastomas with RRD exhibited high-risk features, including anaplastic histology (50%), and SHH-subgroup with TP53-mutation (50%). Importantly, 68% harbored POLE/POLD1 mutations, resulting in median tumor mutation burden of 164 mut/mb. POL-mutated tumors were significantly ultra-hypermutated (>100 mut/mb) than tumors with MMR-deficiency alone (p=0.015). Synchronous and metachronous tumors were observed in 40%. However 90% of the deaths were related to the diagnosis of embryonal CNS tumor. Median survival for the entire cohort was 17-months (95% CI: 10 to 23). Predicted 3-year survival was 37% for medulloblastoma, with no survivors among other embryonal tumors. CONCLUSIONS This is the largest cohort of replication repair deficient medulloblastoma reported till date. The tumors are hypermutated, harbor somatic mutations in TP53 and/or POLE/POLD1, and have very poor survival with current chemo-irradiation based approaches. These biologically unique tumors expand the spectrum of high-risk TP53-mutant SHH-medulloblastoma, and need novel strategies for treatment.

SYNCHRONOUS AND METACHRONOUS TUMORS – A LITERATURE REVIEW

This paper aims to present the results of extensive studies on synchronous and metachronous tumors, both in order to optimize the surgical treatment of these, but also to concretize some suitable and useful screening measures for their early detection. The prognosis of cancer patients has improved over time. On the other hand, investigative methods have advanced considerably so that today are discovered tumors that could have gone unnoticed in the past. These data show why there are currently more cases of multiple cancers and their rate is steadily rising. The review will consider several studies focused on multiple tumors in terms of their localizations, manifestations, and risk factors. The first primary tumor found in a patient is called the index tumor, and the following tumors can be considered synchronous if they occurred in less than 6 months and metachronous if they occurred more than 6 months. Also, for the tumors of group IA, a variable of 4 centimeters was imposed13. Thus multiple tumors of the same tissue / organ (multicenter type A) are considered, tumors that are located at 4 cm or more of the index tumor, are histopathologically confirmed as malignant and are not metastasis or relapses of the first tumor.

Clinicopathologic Characterization of Bilateral Testicular Germ Cell Tumors With Immunohistochemical Evaluation of Mismatch Repair and BRAF (V600E) Genes Mutations

The incidence of bilateral testicular germ cell tumor (TGCT) is 1% to 5%. Despite the high rate of treatment success, resistance to chemotherapy has a detrimental effect. Some studies found MMR and BRAF gene mutations to be associated with chemotherapy resistance, which has not been found by others. However, the role of microsatellite instability (MSI) and BRAF mutations in bilateral disease has not been investigated. In this article, we studied the clinicopathologic characteristics and immunohistochemical expressions of MMR and BRAF in 13 patients with bilateral TGCT. Bilateral tumors were found in 4% of patients in our data. The mean ages at the first and subsequent diagnoses were 26.9 and 28.3 years, respectively. Eleven patients had metachronous disease; and the mean period between both tumors was 4.9 years. Six had mixed GCTs (MGCT) initially and later developed contralateral seminoma, 3 had bilateral MGCTs; 1 initially had pure embryonal carcinoma and subsequently MGCT and finally, 1 patient had initial seminoma and contralateral germ cell neoplasia in situ only. Of the patients with synchronous GCT, 1 had a MGCT and contralateral non-seminoma and 1 had seminoma and contralateral MGCT. In metachronous cases, 40% and 78% had an initial and subsequent stage of pT1, respectively. Hormonal and/or metastatic recurrence was observed in 30% of metachronous tumors. Six patients received chemotherapy, including patients with metastasis. No progression occurred after therapy. MLH1, PMS2, MSH2, and MSH6 staining was retained in all tumors. No BRAF staining was found. In conclusion, we found no association between bilateral TGCT and the MMR/MSI pathway and that subsequent metachronous tumors behaved much more indolently.

EFFICIENCY OF MALIGNENT EPITHELIAL SKIN TUMORS TREATMENT METHODS

The article analyzes the data of 307 patients, who have solitary, primary-multiple synchronous or metachronous tumors. It considers the advantages and disadvantages of the main methods of treatment of malignant epithelial skin tumors, in particular, short-range X-ray, electro-excision, cryotherapy and scalpel excision. The authors compare treatment methods and propose modern recommendations for choosing treatment tactics based on risk groups. The short-range X-ray method is found to be the least effective compared to the other methods of treatment of malignant epithelial skin tumors.

Polineoplasia in patients with cervical cancer in the Chelyabinsk region of Russia

The purpose of the study was to analyze the incidence of primary-multiple cancer (PMC) of the female reproductive system according to the population cancer register of the Chelyabinsk region for 15 years (1999-2013) using the example of PMC of the cervix. Carry out an analysis of the adjusted cumulative survival in the group of patients with PMC of the cervix as compared with solitary cervical cancer.Material and methods. The material was processed using the classification of Zisman I. F. and Kirichenko G. D. (1978) on the sequence of tumors: metachronous, synchronous, mechatronic-synchronous and synchronous-metachronous. The interval of metachronousness is 6 months. The survival rates of cancer patients in the Chelyabinsk region were calculated automatically with the use of the computer program "Calculation of survival rates" — an application to the population-based cancer registry of OOO Novell-SPb. Using the method of continuous sampling, we carried out a retrospective analysis of the case histories of patients with PMC of the female reproductive system treated in the SBEO CRCOD for 15 years (1999-2013).Results. During the period under review, 82 patients with PMC of the cervix uteri were examined, metachronous tumors prevailed in 55 (67.1%), synchronous tumors developed in 27 (33.75%). In the group of metachronous tumors in 12 (21.8%) patients had a combination of three tumors. Three (5.45%) patients had a combination of four tumors. Analysis of combinations of cervical cancer showed that more often, the cervical cancer metachronically met with breast cancer 35% (14 patients), endometrial cancer 17.5% (7 patients), ovarian cancer 7.5% (3 patients). Synchronously cervical cancer was more often combined with breast cancer 42.8% (9 patients), endometrium 28.6% (6 patients), ovaries 23.8% (5 patients) and rectal cancer 4.8% (1 patient).The results of calculation of the index of the adjusted cumulative survival of the study group of the PMC of the cervix showed that in the group of metachronous tumors, survival rates were significantly higher than in the group of synchronous tumors: single-year survival was 84.8 ± 6.3% against 82.4 ± 9.2, three-year survival — 66.8 ± 7.8% against 47, 1 ± 12.1, and five years after the diagnosis, 53.8 ± 8.6% of patients survived.Conclusion. Thus, patients with cervical cancer are at risk of developing cancer of other localizations that share common etiopathogenetic factors, such as HPV infection in women, hormonal disorders.

Multiple Primary Cancers in North Tunisia, 2000 - 2009

Background and Objective: To evaluate and report the frequency, epidemiologic and anatomic - clinical features of patients who developed MPM from the data of North Tunisia Cancer Registry, during the period 2000-2009.Materials and methods: From a population of 53757 new patients of the North Tunisia National Cancer Registry database presenting new cases of cancers during the period 2000-2009 in North Tunisia, we collected and analyzed those with MPMTs. We used for MPMT the international IARC diagnosis criteria are published in ICD-O Third Edition. Results: In the 53757 new cancer cases registered from 2000-2009, we collected 528 cases (1.0%) of MPM. Mean age at diagnosis of the 1st cancer was 61 years (22-99) and sex-ratio at 1.08 (275M/253F) while mean age at the 2nd cancer diagnosis was 62 years(29 to 99). Among the 528 cases, the most frequent 1 st cancer site was breast in females (147 pts, 58.1%) and urinary tract for males (56 patients, 20.4%). In the 528 MPM cases, 321 (60.8%) were synchronous and 207 cases (39.2%) were metachronous tumors. The median time from 1 st to 2 nd cancer was 1.98 months (range 0-140). The most associated 1 st -2 nd cancer sites were breast in 110 patients (43.3%) in females and for males' urinary tract -prostate cancers (45 patients, 16.3%). Conclusions: The coexistence of a synchronous or metachronous MPM is possible and have to be considered during pretreatment evaluation. A close follow-up should be recommended to detect second malignancies in patients treated for a 1 st cancer.

CLINICAL AND IMMUNOHISTOCHEMICAL FEATURES OF PRIMARY BREAST CANCER AND METACHRONOUS OVARIAN AND ENDOMETRIAL TUMORS

The aim of the study was to assess the patterns of development of metachronous cancer (endometrial cancer, EC, and ovarian cancer, OC) in breast cancer (BC) patients dependent of receptor phenotype of breast tumors. Materials and Methods: In the study, 63 patients with ВС, who developed metachronous EC (n = 47) or OC (n = 16) were enrolled. Expression of estrogen receptor (ER), progesterone receptor (PR), HER/2neu was assessed using immunohistochemical approach. Results: BC in patients with metachronous EC and OC was characterized by a different frequency of molecular subtypes with the dominance of luminal A (36%) and B (43%) subtypes. In primary BC, we have established a correlation between ER expression and regional lymph nodes status (r = −0.50, p < 0.05); negative correlation between HER2/neu expression and tumor stage (r = −0.48, p < 0.05); between the molecular subtype of BC and its size (r = −0.33, p <0.05), the molecular subtype of primary BC and metastases in regional lymph nodes (r = 0.27, p <0.05). In the patients with luminal subtype BC metachronous tumors developed with the highest frequency (OC — 50%, EC — 50%). After treatment of primary BC metachronous tumors developed at different period: EC (22.2%) — most often in 3–5 years, OC (11.0%) — after 10 years and more. Conclusion: Our data evidence on the clinical significance of the individual characteristics of the BC, especially its molecular subtype, and the need to calculate the personalized risk of development of metachronous tumors of the reproductive system in patients with the BC.