Metachronous Malignancies Research Articles

Leiomyomas of the Gastrointestinal Tract: A Clinicopathologic Review

Abstract Introduction/Objective Leiomyomas are benign smooth muscle tumors that can be found anywhere along the gastrointestinal tract (GIT). We undertook a retrospective study to investigate the incidence of GIT leiomyomas and to gain better understanding of their clinicopathologic characteristics. Methods/Case Report The surgical pathology files at our institution were searched for GIT leiomyomas encountered between 07/1994 and 12/2023. The clinical and histopathological findings were recorded. Results (if a Case Study enter NA) 74 leiomyomas were identified in various GIT locations, including esophagus (8), stomach (20), duodenum (3), colon (37) and rectum (6). There were 40 females and 34 males, with an average age of 61.5 years. Esophageal leiomyomas showed a mean size of 2.2 cm. 5/8 patients had synchronous adenocarcinomas of gastroesophageal junction and 1/8 patient had synchronous squamous cell carcinoma of esophagus. Gastric leiomyomas showed a mean size of 2.0 cm. 6/20 patients had synchronous and 4/20 patients had metachronous GIT cancers. 2/6 patients who had leiomyomas with synchronous GIT cancers also presented with gastrointestinal stromal tumors (GIST). Duodenal leiomyomas showed a mean size of 0.7 cm. 1/3 patient had synchronous pancreatic adenocarcinoma. Colonic leiomyomas showed a mean tumor size of 0.6 cm. 2/37 patients had synchronous and 6/37 patients had metachronous GIT cancers. Rectal leiomyomas showed a mean tumor size of 0.9 cm. 1/6 patient had metachronous non-GIT sarcoma. Adenomatous polyps coexisted with 10/37 colonic leiomyomas, 2/6 rectal leiomyomas and 1/20 gastric leiomyoma. Immunohistochemical stains (αSMA, Desmin, CD117, DOG-1, CD34) were consistently utilized in diagnosis to exclude GIST. Conclusion Leiomyomas were most frequently found in the colon (50.0%), followed by the stomach (27.0%). Esophageal and gastric leiomyomas showed larger sizes (averaged 2.2 and 2.0 cm respectively) than duodenal, colonic, and rectal counterparts (averaged 0.7, 0.6, and 1 cm, respectively). This suggests an association between tumor locations and clinical features. Synchronous malignancies occurred in 20.2% of cases, mainly gastroesophageal/colonic adenocarcinomas. Metachronous malignancies were noted in 14.8% of cases. Given the high incidence of synchronous/metachronous malignancies (35.1%) in the gastrointestinal tract, close clinical surveillance is warranted for these patients.

Dual Malignancies in Geriatric Cancer Patients: A Radiation Oncologist’s Perspective of Clinical Care

Abstract Background: Data pertaining to dual malignancies in the geriatric population are not only sparse but also heterogeneous. The present study evaluated the pattern of care for geriatric dual malignancy patients at a tertiary care center. Materials and Methods: We retrospectively collected data from all dual malignancy patients of and above the age of 65 years registered in the radiation oncology department of a single tertiary care center. Results: 456 geriatric cancer patients were registered between January 2019 and July 2021,out of which 48 patients had dual malignancy (10.5%). The distribution of index malignancy was six (12.5%) patients each of carcinoma oropharynx and prostate. Thirty-two (66.7%) patients developed metachronous malignancies. The mean difference in the development of the second malignancy was 3.4 years. Eleven (22.9%) patients developed carcinoma lung as a second malignancy. The primary treatment received by 38 (79.2%) patients was radical. Conclusion: Geriatric patients with synchronous malignancies pose a therapeutic challenge and the decision is achieved by a multidisciplinary approach.

The Cellular Stress and Cutaneous Manifestations in Renal Cell Carcinomas-A Narrative Review.

The carcinomas originating from the renal cortex are the most aggressive renal malignancies, with a high tendency for metastasis. Understanding the incidence of cutaneous manifestations caused by renal carcinomas is a challenge. In the first part, this article summarizes a series of factors that promote oncogenesis, invasiveness, and the ability of renal cell carcinoma (RCC) to develop secondary cutaneous manifestations. It is postulated that the cellular stress response is one of the leading causes of developing dermatological events induced by cancers located at distant sites. Furthermore, the paper provides an overview of cutaneous complications associated with renal cancer, categorized as malignant manifestations (metastases, synchronous or metachronous cutaneous malignancies associated with renal cancer), non-malignant indirect cutaneous manifestations associated with renal cancer, and treatment consequences. The data presented in this article suggest that recognizing certain cutaneous disorders could assist the physician in the early identification of renal neoplasms and could lead to a better prognosis.

Retrospective study of qualitative assessment in detecting synchronous and metachronous malignancies in adult cancer patients by 18 F-FDG PET/CT.

The study aimed to evaluate the frequency of incidental suspicious lesions detected by flourine-18 fluorodeoxyglucose PET/computed tomography ( 18 F-FDG PET/CT) scans done for staging or restaging in adult cancer patients. We further determined the detection rate of synchronous and metachronous malignancies in these suspicious lesions after further investigations. This retrospective analysis evaluated the consecutive patients with 18 F-FDG PET/CT scans done in Queen Elizabeth Hospital (QEH), Hong Kong between July 2021 and June 2022. The adult cancer patients who underwent staging or restaging 8 F-FDG PET/CT were included while the remaining were excluded. Patients' demographics, primary cancer type, tumor markers, and pathological analyses for the incidental suspicious lesions were reviewed to establish the detection rate of synchronous and metachronous malignancies. A total of 2054 patients fulfilled inclusion criteria with age ranging from 18 to 93 years old. Out of the 2054 patients, 304 (14.8%) were found to have incidental suspicious lesions. Of these, 206 patients (67.8%) underwent further investigations including pathological analyses. Subsequently, 84 of these 206 patients (40.8%) had pathologically proven synchronous or metachronous malignancies. The detection rate of incidental suspicious lesions in adult cancer patients who underwent 18 F-FDG PET/CT scans for staging or restaging was 14.8% and the rate of synchronous and metachronous malignancies in these suspicious lesions was 40.8%. The treatment plan of these patients may potentially be altered, which should be included in the cost-benefit analysis of using this imaging modality.

Comparison of immediate germline sequencing and multi-step screening for Lynch syndrome detection in high-risk endometrial and colorectal cancer patients.

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome with a significantly increased risk of colorectal and endometrial cancers. Current standard practice involves universal screening for LS in patients with newly diagnosed colorectal or endometrial cancer using a multi-step screening protocol (MSP). However, MSP may not always accurately identify LS cases. To address this limitation, we compared the diagnostic performance of immediate germline sequencing (IGS) with MSP in a high-risk group. A total of 31 Taiwanese women with synchronous or metachronous endometrial and colorectal malignancies underwent MSP which included immunohistochemical staining of DNA mismatch repair (MMR) proteins, MLH1 promoter hypermethylation analysis, and germline sequencing to identify pathogenic variants. All patients who were excluded during MSP received germline sequencing for MMR genes to simulate IGS for the detection of LS. Our findings indicate that IGS surpassed MSP in terms of diagnostic yield (29.0% vs. 19.4%, respectively) and sensitivity (90% vs. 60%, respectively). Specifically, IGS successfully identified nine LS cases, which is 50% more than the number detected through MSP. Additionally, germline methylation analysis revealed one more LS case with constitutional MLH1 promoter hypermethylation, bringing the total LS cases to ten (32.3%). Intriguingly, we observed no significant differences in clinical characteristics or overall survival between patients with and without LS in our cohort. Our study suggests that IGS may potentially offer a more effective approach compared to MSP in identifying LS among high-risk patients. This advantage is evident when patients have been pre-selected utilizing specific clinical criteria.

Comparison of Short-term and Long-term Outcomes after Different Reconstructions between Totally Laparoscopic Distal Gastrectomy and Laparoscopic-assisted Distal Gastrectomy for Gastric Cancer: a Retrospective Analysis at a High-volume Center.

Background: The short-term and long-term outcomes of laparoscopic-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) have been subject to controversy with various reconstruction techniques of Billroth-I, Billroth-II, Roux-en-Y, and Uncut. This study aims to compare the short-term and long-term outcomes of LADG and TLDG as well as the outcomes of different anastomoses. Methods: This study enrolled patients with gastric cancer at the First Affiliated Hospital of Nanjing Medical University (NMUH) between 2017 and 2021. Postoperative complications were classified according to the Clavien-Dindo grade. Exclusion criteria included metachronous and synchronous malignancy and palliative surgery. The Kaplan-Meier analysis was applied to assess 5-year prognosis between two groups. Results: This study included 1221 cases with an overall complication rate of 17.37% for LADG, which was significantly higher than TLDG's 10.72%. The incidence of anastomosis-related complications was 4.79% for LADG and 1.13% lower for TLDG. LADG and TLDG did not show significant difference for Grade III-V complications and resected lymph nodes. The postoperative stay was shorter for TLDG than LADG, and R-Y had a longer postoperative stay than B-II and Uncut after combining LADG and TLDG. The operation time was shorter in TLDG cases than that in LADG cases. The 5-year OS of the TLDG group was not significantly better than that of the LADG group. Conclusion: TLDG is superior in overall complication rate, anastomosis-related complication rate, postoperative stay and operation time to LADG. No difference of OS was observed between LADG and TLDG. Four anastomoses had no convincing evidence of being superior in complications rates, post-op stay, and harvested lymph nodes to each other.

Long term outcomes beyond 5 years after pulmonary resection for non-small-cell lung cancer.

We investigated the incidence of late recurrence beyond 5years after pulmonary resection and aimed to identify candidates for long-term surveillance. We retrospectively reviewed the medical records of 978 non-small-cell lung cancer patients who underwent pulmonary resection between 2002 and 2015 and survived without recurrence for 5years. Clinicopathological factors associated with recurrence-free survival beyond 5years after surgery were investigated using univariate and multivariate analyses. The development of late metachronous malignancies was also investigated. The median follow-up period from 5years post-surgery was 27months in the whole cohort. Late recurrence occurred in 37 (3.8%) patients. Late metachronous malignancies were diagnosed in 116 patients (11.9%), including 57 (5.8%) with lung cancer. One-, three-, and five-year recurrence-free survival rates beyond 5years after surgery were 97.6%, 94.7%, and 94.7%, respectively. The recurrence-free survival of patients with pN1-2 was significantly poorer than that of patients with pN0 disease. Multivariate analysis revealed that adenocarcinoma and pN1-2 status were significantly associated with poor recurrence-free survival beyond 5years post-surgery (P = 0.009 and 0.007, respectively). Non-adenocarcinoma histology and pN0 status were significant favorable factors for recurrence-free survival beyond 5years post-surgery. The efficacies of long-term surveillance for the detection of late recurrence were considered limited for these populations. Twelve percent of the patients experienced late metachronous malignancies after pulmonary resection.

Pattern of Occurrence and Management of Dual Malignancy: Our Institutional Experience

Background: Management of dual malignancies is challenging in the present scenario of advanced techniques and increased life expectancy. Objectives: To determine the demographic and clinical profile of patients with dual malignancies and the management received. Methods: In this retrospective analysis of the data of patients presenting with histologically proven synchronous or metachronous dual malignancy, we evaluated the demographic and clinical profile of patients with dual malignancies and the management received. Results: In this study, 158 cases with multiple primary cancers, of whom 57 were synchronous and 101 were metachronous, were observed from January 2017 to December 2021. The maximum period for synchronous tumor occurrence was seen at 6 months (180 days). The interval of occurrence of metachronous tumors ranged from 1 to 15 years, with an average of 4.8 years for the entire group. Moreover, 73 (46.2%) were females, and 85 (53.8%) were males, with a male-to-female ratio of 1.2: 1. The most common site of primary tumor with dual malignancies was the head and neck (31%), followed by breast cancers (21%). The most frequent pathologic type was adenocarcinoma (40%), followed by squamous carcinoma (38%), hematopoietic and lymphoid tissues (7.5%), transitional cell carcinoma (6.3%), sarcomas and soft tissue tumors (2.5%). Conclusions: Even in complete clinical remission, every cancer patient must take into account the possibility of developing a second malignancy and must be closely monitored.

High Frequency of Mesenteric Panniculitis in Non-Hodgkin Lymphoma and Prostate Cancer: Study in 1,500 Oncologic Patients Undergoing Staging

To establish the frequency of MP in oncologic patients according to the type of cancer. Images of PET/CT performed between January 2008 and December 2019 on recently diagnosed oncologic patients were reviewed searching for MP. MP was defined as increased density and volume of mesenteric root fat, associated with nodules and/or lymph nodes, with or without pseudocapsule. Patients who had received previous cancer treatment or those with synchronous or metachronous malignancies were excluded. The frequency of MP in the total oncologic population was 5,3 % (82/1539). Types of cancer frequently associated with MP were non-Hodgkin lymphoma at 15,9% (31/195) and prostate cancer at 11,9% (16/134), both significantly higher than the rest of the malignancies (p < 0,01). Hodgkin Lymphoma (0/59), carcinoma of the cervix (0/45), and endometrial cancer (0/44) did not show MP. MP is more frequently associated with some malignant neoplasms, such as non-Hodgkin lymphoma and prostate cancer, and rare in others. This must be considered when studying patients with MP detected incidentally.

Clinical Outcome and Patterns of Failure in Patients with Solitary Plasmacytoma Treated with Radical Radiotherapy

We intended to assess the patterns of care and failure in patients with solitary plasmacytoma (SP), treated at our institute from 2011-21. Data pertaining to the management of patients with SP was abstracted by retrospective chart review. Progression free survival (PFS) and overall survival (OS) were defined as the time intervals from the date of diagnosis to the date of progression (local, systemic or both) and death or last follow up, respectively. PFS and OS were analyzed by Kaplan Meier method. Atotal of 72 patients were diagnosed with SP (61-bone plasmacytoma; 11-extramedullary plasmacytoma) in between 2011 and 2021. The median age at diagnosis was 52 years. The male: female ratio was 2.27. The ECOG PS were 0, 1, 2, 3, and 4 in 1, 46, 11, 10, and 3 patients, respectively. The median diameter of the lesion was 6.7 cm (range 2.3-18.4 cm). The median M protein was 0.375 g/dl (range 0.63-5.3 g/dl). On bone marrow examination, 8 and 64 patients had no and minimal marrow involvement, respectively (median bone marrow plasma cells 4%). Radical radiotherapy (RT) was administered in 71 patients, the techniques being 2D-conventional in 35, 3D-conformal in 14, IMRT in 8 and VMAT in 5 patients (details not available in 9). The median RT dose was 45 Gy in 25 fractions over 5 weeks (range 45-50 Gy). In addition, 5(7%) patients underwent surgery prior to RT and 6(8.5%) patients received systemic chemotherapy. After RT, the median quantum of symptom relief was 75% (range 0-100%). The best response to RT was CR, PR, SD and PD in 41(57.7%),18(25.4%),3(4.2%) and 4(5.6%) patients, respectively (response assessment could not be done in 5). Local control with primary RT was achieved in 58(81.7%) patients. No RT related grade 3/4 acute or late toxicity was reported. The median follow up was 48.3 months (range 1.3-141.6 months). A total of 28(39.4%) patients experienced disease progression (systemic in 15, local in 7 and both in 6), out of which 13 could be successfully salvaged with further systemic chemotherapy (mostly bortezomib, lenalidomide/pomalidomide and dexamethasone based) with or without local treatment. On progression to multiple myeloma, 9 patients underwent high dose chemotherapy(melphalan) followed by autologous stem cell transplant. Nine (12.7%) patients died, the causes being COVID-19 infection in 1, surgical complications in 1, PD in 2, second malignancies in 3 and unknown in 2. The actuarial rates of PFS & OS were 58.4% & 92.5% at 3 years and 50.3% & 89.4% at 5 years, respectively. Metachronous second malignancies were noted in 4 patients (B-ALL-1, lung cancer-1, metastatic carcinoma cervix-1, metastatic carcinoma gall bladder-1). In patients with SP, radical RT with a modest dose (45-50 Gy) leads to satisfactory symptom relief, response and local control. Close to 40% patients eventually progress to multiple myeloma, out of which 50% can be successfully salvaged with further systemic chemotherapy. The 5-year OS approaches 90% in this cohort.

A Single-center Experience of Synchronous and Metachronous Hematologic and Oncologic Tumors

The incidence of cancer is increasing in the world. With the developments in cancer treatment, the life expectancy of patients is prolonged and the incidence of secondary malignancies is increasing. We retrospetively patients with syncronous / metachronous oncological malignancies accompanying hematological malignancies in a newly established hematology center. Data were obtained from the medical records. Demographic data, treatments and overall survival of the patients were evaluated. Twenty eight (6%) of 433 patients hematological malignancies were included in the study. 12 patients (42.9) were diagnosed with syncronous and 16 (57.1%) patients with metachronous hematologic-oncologic tumors. Sixteen of the patients were male,twelve were female. In syncronous tumors, the most common hematologic malignancy was Non-hodgkın lymphoma (NHL), while the most common oncologic malignancies were thyroid papillary cancer and colon cancer. In metachronous tumors, the most common malignancies were NHL and breast cancer. The median time between diagnosis of metachronous tumors was 49.5 months (8-192 months). The median survival of patients with syncronous malignancies was 19 months (SE=12.19) (95% CI 0-42.89), with metachronous malignancies was 22 months (SE=14.0) (95% CI 0-49.44). There was no statistically significant difference in the comparison of survival curves of patients with syncronous and metachronous malignancies (p=0.382). Oncological malignancies accompanying hematological malignancies are not uncommon. There is no standart treatment for syncronous / metachronous hematologic malignancies. In the presence of syncronous multipl malignancies should be evaluated individually.

A Novel Mutation of MSH2 Gene in a Patient with Lynch Syndrome Presenting with Thirteen Metachronous Malignancies.

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), accounts for 2-3% of all colorectal cancers. This autosomal dominant disorder is associated with a predisposition to endometrial, stomach, small bowel, pancreatic, biliary tract, ovary, urinary tract, brain, and skin tumors. Lynch syndrome is caused by the mutation of the MLH1, MSH2 (EPCAM), MSH6, and PMS2 genes. In this article, a case study of a 70-year-old female patient with Lynch syndrome is presented. Over a span of 30 years, the patient underwent multiple surgical procedures for a total of thirteen different malignancies. She was found to have a deleterious pathogenic gene MSH2 (NM_000251.2) variant (mutation) c.1774_1775insT in the 12th exon. This variant, c.1774_1775insT, represents a novel finding, as it has not been previously reported in existing databases or literature. No other case of 13 metachronous tumors in a patient with Lynch syndrome was found in the literature.

Previous, simultaneous, or subsequent occurrence of malignant tumours in patients with primary hyperparathyroidism: a closer look at the single-tertiary-centre cases.

Our aims were to explore the relationship between primary hyperparathyroidism (pHPT) and malignant tumour development, to determine the frequency and the time of occurrence of malignant tumours in patients with pHPT, and to evaluate the characteristics of pHPT in these patients. This retrospective cohort study included consecutive individuals who were diagnosed with pHPT aged 18 years or older in a university hospital during a 7-year period. A total of 198 patients with pHPT were reviewed retrospectively. Demographic, clinical, biochemical, radiologic findings, and histopathological diagnosis were collected from the electronic medical records of the hospital system. The mean age of the study population was 58 ± 13 years and was predominantly female (female/male: 162/36). There were 42 (21.2%) patients with malignant tumours. Five (12%) out of 42 patients had metachronous double malignancies. The most common 2 concurrent malignancies were breast (36.1%) and thyroid (17.0%). Sixty-eight per cent of the malignant tumours occurred before the diagnosis of pHPT. A higher percentage (87.5%) of simultaneous tumours was seen in the thyroid gland. No statistically significant differences were observed between patients with and without malignant tumours in terms of demographic, clinical, biochemical, radiological, and histopathological features. The median follow-up duration was 24 months after parathyroid surgery. The results of this study revealed that pHPT was associated with various tumour types. The frequency of malignant tumours was 21.2%. Breast and thyroid cancers were the most common 2 cancers coexisting with pHPT. A large percentage of malignant tumours occurred before the diagnosis of pHPT. A higher percentage of simultaneous tumours was seen in the thyroid gland. pHPT patients with and without malignant tumours seemed to have similar characteristics.

Discussion article: do we understand the role of local treatments after oligoprogression of ovarian cancer on PARP inhibitors?

The development of poly(ADP‐ribose) polymerase (PARP) inhibitors has been the most significant breakthrough in the treatment of advanced ovarian cancer over recent decades, with olaparib being the first drug of this class. The drug showed its efficacy at many stages of the treatment of various oncological diseases, but its maximum clinical efficacy is demonstrated in the initial treatment of BRCA-associated or HRD-positive ovarian cancer. In the phase III SOLO1 (n = 391) and PAOLA-1 (n = 806) clinical trials, treatment with olaparib reduced the relative risk of disease progression by 67% and 59%, and the risk of death by 45% and 38%, respectively. At the same time, the treatment of patients with disease progression after therapy with PARP inhibitors causes reasonable concerns in clinicians, which is associated with many aspects, primarily with the lack of individually developed approaches to the management of this category of patients. This discussion article through the example of the treatment of a particular patient allows to summarize the current data on the features of the tumour process after disease progression on PARP inhibitors and possible ways to resolve the issue of drug resistance in such patients. In the clinical case under discussion, the maintenance therapy with olaparib after combination treatment in a 50-year-old woman with metachronous multiple primary BRCA-associated malignancies (breast cancer in 2005, ovarian cancer in 2018) allowed to achieve a 2-year cancer remission, after which the oligoprogression of ovarian cancer was observed. PET-CT showed a left iliac lymph node metastasis without other progressive manifestations of the disease, after which a left laparoscopic iliac lymphadenectomy was performed, and the olaparib therapy was continued until progression or intolerable toxicity. The duration of olaparib therapy from the date when the local treatment was performed is 23 months as of this writing. The article states the detailed rationale behind choosing the non-standard management and presents the results of recent studies that support the decisions made.

Metachronous Squamous Cell Carcinoma of the Esophagus After Resolution of Previous Adenocarcinoma

ABSTRACT Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Metachronous malignancies refer to multiple independent primary cancers diagnosed at least 6 months apart. The incidence of metachronous esophageal cancers with different histologic subtypes is extremely rare. This case presents an unprecedented occurrence of esophageal adenocarcinoma, followed by metachronous squamous cell carcinoma.

Case Report: Metachronous urothelial carcinoma of the renal pelvis following radical cystectomy: a rare case report

Introduction: Bladder carcinoma (BC) is the most common urinary tumor. The most common histologic type of BC is urothelial carcinoma of the bladder (UCB) According to GLOBOCAN 2020 data, there were 573,000 new cases and 213,000 deaths from bladder cancer in 2015. The likelihood of developing upper urinary tract cancer after a bladder tumor were being treated is minimal; nonetheless, such lesions can develop later. Case Report: A 52-year-old man with urothelial carcinoma of the renal pelvis, previously had UCB. Initially, in 2019, he developed hematuria. It was accompanied by dysuria. Every day, the patient smoked 2 packs. The patient denied having a chronic disease. No family history of cancer. At that time, it was discovered that the patient had urothelial bladder cancer following transurethral resection of bladder tumor (TURBT). Histopathology revealed bladder-invasive urothelial carcinoma. The patient then underwent radical cystectomy and ileal conduit. The patient was stable afterward, but during the pandemic period, the follow-up was disturbed. Early in 2021, the patient got hematuria. The patient was referred for a right radical nephrectomy due to a metachronous mass in the right renal pelvis. The histopathological result indicated a high-grade invasive upper urinary urothelial carcinoma. Conclusion: This study reported a case of metachronous urothelial bladder cancer in the upper urinary tract following radical cystectomy. Thorough surveillance in malignancy cases is a mandatory procedure to detect the recurrence of the malignancy and/or the uneventful spreading of the malignancy to other organs. The research regarding the pathophysiology of metachronous malignancy is still being conducted but has shown some promising results.

Synchronous and metachronous multiple primary cancers in melanoma survivors: a gender perspective.

Long-term survivors of cutaneous malignant melanoma (CMM) risk subsequent malignancies due to both host-related and environmental risk factors. This retrospective population-based study differentially assesses the risk of synchronous and metachronous cancers in a cohort of CMM survivors stratified by sex. The cohort study (1999-2018) included 9,726 CMM survivors (M = 4,873, F = 4,853) recorded by the cancer registry of all 5,000,000 residents in the Italian Veneto Region. By excluding subsequent CMM and non-CMM skin cancers, the incidence of synchronous and metachronous malignancies was calculated according to sex and tumor site, standardizing for age and calendar year. The Standardized Incidence Ratio (SIR) was calculated as the ratio between the number of subsequent cancers among CMM survivors and the expected number of malignancies among the regional population. Irrespective of the site, the SIR for synchronous cancers increased in both sexes (SIR = 1.90 in males and 1.73 in females). Both sexes also demonstrated an excess risk for synchronous kidney/urinary tract malignancies (SIR = 6.99 in males and 12.11 in females), and women had an increased risk of synchronous breast cancer (SIR = 1.69). CMM male survivors featured a higher risk of metachronous thyroid (SIR = 3.51, 95% CI [1.87, 6.01]), and prostate (SIR = 1.35, 95% CI [1.12, 1.61]) malignancies. Among females, metachronous cancers featured higher SIR values than expected: kidney/urinary tract (SIR = 2.27, 95% CI [1.29, 3.68]), non-Hodgkin's lymphoma (SIR = 2.06, 95% CI [1.24, 3.21]), and breast (SIR = 1.46, 95% CI [1.22, 1.74]). Females had an overall increased risk of metachronous cancers in the first 5 years after CMM diagnosis (SIR = 1.54 at 6-11 months and 1.37 at 1-5 years). Among CMM survivors, the risk of metachronous non-skin cancers is higher than in the general population and differs significantly by sex. These results encourage sex-tailored interventions for metachronous secondary cancer prevention.

Multiple Primary Malignancies: A Clinicopathological Profile of Patients at a Tertiary Center of North India—A Retrospective Hospital-Based Observational Study

Abstract Introduction The incidence, prevalence, as well as survival of cancer patients, is increasing day by day due to the use of screening and improved diagnostic modalities. Simultaneously, the development of multiple primary malignancies (MPMs) in cancer survivors is not uncommon in recent years, because of an improved understanding of biology and effective management of cancer in the form of local (i.e., surgery/radiotherapy) and systemic (chemotherapy/targeted therapy) treatment, leading to improved survival and subsequent development of more malignancies. The study was conducted to describe the clinicopathological profile of patients diagnosed with MPMs. Objective To study the clinicopathological profile of MPMs and to look for treatment patterns of these patients. Materials and Methods This was a retrospective hospital-based observational study. Medical records of 73 patients with MPMs, who were registered in the department of medical and surgical oncology between January 2016 and December 2018, were enrolled in the study. The statistical analysis was done by using IBM SPSS Statistics for Windows from IBM Corp. Categorical data were expressed in the form of frequencies and percentages. Results Out of the total 73 patients, 2 patients were diagnosed to have triple malignancies and were excluded from the study for discussion purposes. Among 71 patients with double malignancies, 19 patients had synchronous and 52 had metachronous malignancies with synchronous to metachronous ratio of 1:2.73. The study included 39 men and 32 women with a male to female ratio of 1.21:1. Gastrointestinal system was the most common system involved in first primary as well as in second primary malignancy. Squamous cell carcinoma and adenocarcinoma equally were the most common histologies seen in primary, whereas adenocarcinoma was the most common histology seen in second primary malignancy. Conclusions The phenomenon of MPMs is not an uncommon presentation due to longer survival and side effects of treatment (radiotherapy/chemotherapy). It should always be kept in consideration in any cancer survivor during surveillance in order to detect it and treat at the earliest.

Lessons learnt from the clinico-genomic profiling of families with Li Fraumeni syndrome at a tertiary care centre in North India.

Li Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome due to TP53 gene mutation. There is sparse literature on LFS in the Indian population. We conducted a retrospective study of patients diagnosed with LFS and their family members, registered at our Medical Oncology Department between September 2015 and 2022. 9 LFS families consisted of 29 patients diagnosed currently or historically with malignancies including 9 index cases and 20 first or second-degree relatives. Of these 29 patients, 7 (24.1%) patients developed their first malignancy before the age of 18 years, 15 (51.7%) were diagnosed between 18and and 60 years, and 7 (24.1%) were diagnosed at age more than 60 years. A total of 31 cancers occurred among the families, including 2 index cases who had metachronous malignancies. Each family had a median of three cancers (range 2-5); sarcoma (n = 12, 38.7% of total cancers) and breast cancer (n = 6, 19.3% of total cancers) being the commonest malignancies. Germline TP53 mutations were documented among 11 patients with cancers and 6 asymptomatic carriers. Of these nine mutations, the most common types were missense (n = 6, 66.6%) and nonsense (n = 2, 22.2%), and the commonest aberration was replacement of arginine with histidine (n = 4, 44.4%). Eight (88.8%) families met either classical or Chompret's diagnostic criteria and two (22.2%) satisfied both. Two (22.2%) families fit the diagnostic criteria prior to onset of malignancy in the index cases but were untested till the index cases presented to us. Four mutation carriers from three families are undergoing screening as per the Toronto protocol. No new malignancies have been detected so far during the mean surveillance duration of 14 months. The diagnosis of LFS has socio-economic implications for patients and their families. Delay in genetic testing misses out a crucial window wherein asymptomatic carriers could initiate surveillance in a timely fashion. Greater awareness on LFS and genetic testing in Indian patients is warranted for better management of this hereditary condition.

Clinicopathological analysis of patients with dual malignancies: A retrospective study.

This study aims to report the increasing incidence of second primary malignancies to better understand the association of multiple primary cancers and the duration of their occurrence. Keeping in view the current trends in dual malignancies and to further emphasize the importance of screening and follow-up diagnosis, we reviewed the records of patients who were diagnosed with dual malignancies. This is a retrospective observational study. We collected data from the hospital database, of patients presenting with either histologically proven synchronous or metachronous double primaries between January 1, 2017, and December 31, 2021. The time interval to differentiate between synchronous and metachronous has been taken as 6 months. During the period of five years, twenty-three patients presented with dual malignancy. Out of 23 cases, seven were synchronous (30.43%), and 16 were metachronous (69.56%). In the synchronous malignancy group, the most common site of first and second primary malignancy was breast [5 cases (71.4%) and 3 cases (42.8%), respectively]. In the metachronous malignancy group, the most common site of the first primary was breast (7 cases; 43.75%), followed by the head and neck (4 cases; 25%), and the most common site of the second primary was also the breast (6 cases; 37.5%), followed by the lung (5 cases; 31.25%). Second primary malignancies are not rare and can occur at any age. Regular follow-up and screening procedures by the treating oncologist can play a major role in early detection followed by appropriate treatment of second primary tumors.