Multiple Primary Malignancies in Patients with Gynecologic Cancer

Objective: To investigate the prevalence and oncologic outcomes of patients with multiple primary malignant tumors (MPMT) with gynecologic cancer. Methods: This retrospective study included 1929 patients diagnosed with gynecologic cancer at a tertiary medical center between August 2005 and April 2021. The clinical data included cancer location, age at primary malignancy diagnosis, interval between primary and secondary cancer, stage of cancer, family history of cancer, genetic testing, dates of last follow-up, recurrence, and death. Results: The prevalence of MPMT with gynecologic cancer in patients was 8.6% and the mean diagnostic period between primary and secondary cancer was 60 months. Furthermore, 20 of the 165 patients with MPMT had multiple primary gynecologic cancers (MPGC), whereas 145 had gynecologic cancer coexisting with non-gynecologic cancer (GNC). Endometrial-ovarian cancer (60%) was the most common coexisting cancer in the MPGC group, whereas the most common non-gynecologic cancer in the GNC group was breast cancer (34.5%). There were 48 patients with synchronous cancer and 117 patients with metachronous cancer. The incidence of synchronous cancer was higher in the MPGC group than in the GNC group (p = 0.037). Significantly more patients had early-stage ovarian cancer in the MPGC group than in the GNC group (p = 0.031). The overall recurrence and mortality rates were 15.8% and 8.5%, respectively, in patients with MPMT. Conclusion: Synchronous cancer incidence was significantly higher in the MPGC than in the GNC group. Early-stage ovarian cancer was more highly diagnosed in patients with MPGC than in those with GNC. A systematic examination after primary cancer diagnosis could facilitate the early diagnosis of secondary primary malignancy, thereby improving patient prognosis.

Estimating Radiotherapy-Induced Secondary Cancer Risk Arising from Brain Irradiation at High Energy: A Monte Carlo Study

Background: The present study aims to determine the whole-body out-of-field photon dose equivalents of high-energy conventional radiation therapy treatment. Also, it is tried to estimate the probability of fatal secondary cancer risk for the susceptible organs using a Monte Carlo (MC) code. Materials and methods: An Monte Carlo N-Particle eXtended (MCNPX)-based model of 18-MV Medical Linear Accelerator (LINAC) was created to calculate the out-of-field photon dose equivalent at the locations of fascinating organs in the mathematical female Medical Internal Radiation Dosimetry (MIRD) phantom. Then, the secondary malignancies risk was estimated based on out-of-field doses and radiation risk coefficients according to the National Council of Radiation Protection and Measurements (NCRP). Results: The average photon equivalent dose in out-of-field organs was about 3.25 mSv/Gy, ranging from 0.23 to 37.2 mSv/Gy, respectively, for the organs far from the Planning Target Volume (PTV) (Eyes) and those close to the treatment field (rectum). The entire secondary cancer risk for the 60 Gy prescribed dose to isocenter was obtained as 2.9987%. Here, the maximum doses among off-field organs were related to stomach (0.0805%), lung (0.0601%), and thyroid (0.0404%). Conclusion: Regarding the estimated values for the probability of secondary cancer risk, it is suggested to perform a long-term follow-up of brain cancer patients regarding the prevalence of thyroid, stomach, and lung cancer after completing the treatment course.

Monte Carlo evaluation of out-of-field dose in 18-MV pelvic radiotherapy using a simplified female MIRD phantom

This study was devoted to determining the unwanted dose due to scattered photons to the out-of-field organs and subsequently estimate the risk of secondary cancers in the patients undergoing pelvic radiotherapy. A typical 18-MV Medical Linear Accelerator (Varian Clinac 2100 C/D) was modeled using MCNPX® code to simulate pelvic radiotherapy with four treatment fields: anterior-posterior, posterior-anterior, right lateral, left lateral. Dose evaluation was performed inside Medical Internal Radiation Dose (MIRD) revised female phantom. The average photon equivalent dose in out-of-field organs is 8.53 mSv/Gy, ranging from 0.17 to 72.11 mSv/Gy, respectively, for the organs far from the Planning Treatment Volume (Brain) and those close to the treatment field (Colon). Evidence showed that colon with 4.3049 % and thyroid with 0.0020 % have the highest and lowest risk of secondary cancer, respectively. Accordingly, this study introduced the colon as an organ with a high risk of secondary cancer which should be paid more attention in the follow-up of patients undergoing pelvic radiotherapy. The authors believe that this simple Monte Carlo (MC) model can be also used in other radiotherapy plans and mathematical phantoms with different ages (from childhood to adults) to estimate the out-of-field dose. The extractable information by this simple MC model can be also employed for providing libraries for user-friendly applications (e.g. “.apk”) which in turn increase the public knowledge about fatal cancer risk after radiotherapy and subsequently decrease the concerns in this regard among the public.

ANALYSIS OF CYCLOPHOSPHAMIDE-INDUCED N5-NITROGEN MUSTARD FORMAMIDOPYRIMIDINE ADDUCT IN DRIED BLOOD SPOT USING LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

Cyclophosphamide is one of the nitrogen mustard agents that is frequently used in cancer chemotherapy. Nevertheless, long-term use of high dosage cyclophosphamide has been proven to increase the risk of secondary cancer. This can be traced by the mutagenic DNA adduct formation, for instance, N5-nitrogen mustard formamidopyrimidine (NM-Fapy-G). Therefore, it may serve as one of the secondary cancer biomarkers in patients receiving cyclophosphamide. Several NM-Fapy-G analysis methods employ Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) developed by experts. However, it was discovered not applicative for patients because cells and tissues were utilized as the biospecimens. Therefore, this summary is presented to emphasize the idea of adopting Dried Blood Spot (DBS) as the blood bio sampling method, DNA extraction and hydrolysis method that is suitable for enriching NM-Fapy-G adduct; and method that is proper for NM-Fapy-G analysis. Based on the literature study, DBS has been proven beneficial for this analysis; DNA can be extracted from the DBS cards using the QIAamp DNA Mini Kit. Therefore, research with a little bit of adjustment can be applied for NM-Fapy-G analysis.

Estimation of aggregate losses of secondary cancer cases using PH Panjer class (a,b,1) distributions,

This research in-cooperates phase type distributions of Panjer class \((a,b,1)\) in estimation of aggregate loss probabilities of secondary cancer. Matrices of the phase type distributions are derived using Chapman-Kolmogorov equation and transition probabilities estimated using modified Kaplan-Meir and consequently the transition intensities and transition probabilities. Stationary probabilities of the Markov chains represents $\vec{\gamma}$. Claim amount are modeled using OPPL, TPPL, Pareto, Generalized Pareto and Wei-bull distributions. PH ZT Poisson with Generalized Pareto distribution provided the best fit.

Challenge and Outcome for the Prostate Squamous Cell Carcinoma Which Developed 8 Years after Low-Dose-Rate Brachytherapy Approached by a Combined Multimodal Treatment with High-Dose-Rate Interstitial Brachytherapy, External Beam Radiation Therapy, and Chemotherapy

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT.

CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer Outcomes: Analysis of a Large Cohort, Systematic Review of Endoscopic Surveillance and Secondary Cancer Risk Postulation

Hereditary diffuse gastric cancer (HDGC) is a rare signet-ring cell adenocarcinoma (SRCC) linked to CDH1 (E-cadherin) inactivating germline mutations, and increasingly other gene mutations. Female CDH1 mutation carriers have additional risk of lobular breast cancer. Risk management includes prophylactic total gastrectomy (PTG). The utility of endoscopic surveillance is unclear, as early disease lacks macroscopic lesions. The current systematic biopsy protocols have unknown efficacy, and other secondary cancer risks are postulated. We conducted a retrospective study of consecutive asymptomatic HDGC patients undergoing PTG, detailing endoscopic, pathologic, and outcome results. A systematic review compared endoscopic biopsy foci detection via random sampling versus Cambridge Protocol against PTG findings. A population-level secondary-cancer-risk postulation among sporadic gastric SRCC patients was completed using the Surveillance, Epidemiology, and End Results database. Of 97 patients, 67 underwent PTG, with 25% having foci detection on random endoscopic biopsy despite 75% having foci on final pathology. There was no improvement in the endoscopic detection rate by Cambridge Protocol. The postulated hazard ratio among sporadic gastric SRCC patients for a secondary colorectal SRCC was three-fold higher, relative to conventional adenocarcinoma patients. Overall, HDGC patients should not rely on endoscopic surveillance to delay PTG, and may have secondary SRCC risks. A definitive determination of actual risk requires collaborative patient outcome data banking.