Risk Of Second Primary Malignancies Research Articles

Exploring the risk of second primary malignancies in laryngeal cancer survivors: insights from the SEER database.

We intended to investigate the risk for second primary malignancy (SPM) development in Laryngeal Cancer (LC) survivors. We conducted a population-based analysis of SPM risk using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Data of selected LC survivors from the SEER database between 2000 and 2020 were examined. Standardized Incidence ratios (SIRs) for SPM development were calculated, followed by detailed stratification according to anatomical site and different latency periods. A total of 8413 SPMs were observed in our extracted cohort. The collective standardized incidence of SPMs was 2.12 (95% CI 2.07-2.17) compared to the US population, with an absolute excess risk (AER) of 201.73 per 10,000 individuals. The highest SPM risks were observed in patients with young age at diagnosis, females, and American Indians/Alaska natives. Increased SPM risks were reported in patients receiving all modalities of treatment including surgery, chemotherapy, and radiotherapy. Most SPMs were detected in solid organs such asthe lungs and bronchus, oral cavity and pharynx, and prostate. The highest increased risks of developing SPMs were observed in Trachea, larynx, oral cavity and pharynx, lung and bronchus, and esophagus. The risk of SPMs in LC survivors was significantly increased compared to the general US population. Accordingly, a more impactful cancer surveillance strategy for LC patients should be implemented.

Prognosis of Second Primary Malignancies in Pediatric Acute Lymphoblastic Leukemia Survivors: A Multicenter Study by the Turkish Pediatric Hematology Society.

The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.

Association between postoperative radiotherapy for young-onset non-small cell lung cancer and risk of second primary malignancies ----Comparative study.

The most common form of therapy for non-small cell lung cancer (NSCLC) in early stage is surgery-based combination therapy, including radiotherapy and immunotherapy. However, postoperative radiotherapy (PORT) of cancer is correlated with increasing risk of second primary malignancy (SPM), especially young-onset cancer cases. We aimed to quantify the risks of SPM associated with PORT treatment for young‑onset NSCLC in early stage. We screened for SPM that developed over 5 years since the diagnosis of NSCLC. Using the data from the Surveillance, Epidemiology and End Results database, PORT-correlated risks were estimated with multivariate Logistic regression analysis. Moreover, Fine-Gray's competing risk regression analysis was used to calculate the cumulative incidence of SPMs. Among the 30308 young-onset NSCLC patients in early stage undergoing surgery, a total of 3728 patients have received PORT. Logistic regression analyses showed that PORT showed substantial correlation with elevated risks of second solid malignancies (RR = 1.31; 95% CI: 1.17-1.46), lung cancer (RR=1.23; 95% CI: 1.07-1.42), breast cancer (RR=1.74; 95% CI: 1.16-2.74) and colon and rectum cancers (RR=1.37; 95% CI: 1.07-2.06) as well as a negligible risk of second hematologic malignancies (RR = 1.15; 95% CI: 0.82-1.67). The cumulative incidence of SPMs revealed similar findings. Higher RR was obtained in NSCLC patients aged 60 to 69 years (RR = 1.33), in white race (RR = 1.36), diagnosed in 1975-2000 (RR = 1.23) and 2001-2015 (RR = 1.40), or diagnosed with lung adenocarcinoma (RR = 1.55). PORT for young-onset NSCLC in early stage was correlated with elevated risks of SPMs (lung cancer, breast cancer as well as colon and rectum cancers), supporting the need for long-term surveillance of these patients.

Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy

ObjectivesWe primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors.MethodsWe retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs.ResultsA total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001).ConclusionsOur study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

The Role of Autologous Stem Cell Transplantation in the Treatment of Newly Diagnosed Multiple Myeloma: Is It Time to Rethink the Paradigm in the Era of Targeted Therapy?

High-dose melphalan (HDM) plus autologous stem cell transplant (ASCT) remains a standard-of-care treatment approach for eligible patients with newly diagnosed multiple myeloma (NDMM) based on demonstrated superiority in terms of progression-free survival (PFS) versus nontransplant approaches. Very high rates of minimal residual disease (MRD)-negative responses are also being seen with novel triplet and quadruplet induction regimens plus HDM-ASCT. However, recent clinical trials have shown no overall survival benefit with transplant versus nontransplant approaches. Furthermore, HDM is associated with several important downsides, including acute and long-term toxicities, transient decreases in quality of life, the need for hospitalization, an increased mutational burden at relapse, and an elevated risk of second primary malignancies. In this context, given the highly heterogeneous nature of MM in the NDMM patient population, as well as the continued emergence of novel agents and treatment approaches, there is an increasing rationale for considering deferred HDM-ASCT approaches in selected patients. Approaches under investigation include MRD-adapted therapy and the use of novel immune-based therapies as alternatives to HDM-ASCT. Ongoing developments in understanding the pathobiology and prognostic factors in NDMM, plus immune profiling and routine MRD evaluation, will result in novel, HDM-sparing treatment paradigms, enabling further improvement in patient outcomes.

Incidence, risk and prognosis of second primary malignancy of patients with gastric adenocarcinoma

Due to the long-term low survival rates of gastric adenocarcinoma (GAC) patients, the occurrence and prognosis of second primary malignancies (SPMs) are often underreported and overlooked as a significant concern.To date, only a few studies have addressed this issue in the context of GAC. These studies, however, are limited by their small patient cohorts and lack of substantial, meaningful findings. Our study aims to fill this gap by investigating the incidence, risk factors, and prognostic significance of SPMs among GAC survivors. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we analysed data from patients diagnosed with GAC between 2000 and 2020. The study employs the standardized incidence ratio (SIR) to assess the relative risk of SPMs, competing risk regression to identify risk factors for SPM development after GAC, and Kaplan-Meier and COX regression analyses for survival outcomes. Out of 44,041 GAC patients analyzed, 2,032 (4.3%) developed SPMs, with a median latency period of 36 months. The incidence of SPMs was significantly higher in GAC patients (SIR 1.36, 95% CI 1.32-1.4, EAR 53.57) compared to the general population. Key factors including older age, sex, tumor grade, summary stage, and history of surgical and radiation therapy were related to the higher risk of developing SPMs following GAC. Interestingly, GAC patients without SPMs exhibited poorer overall survival compared to those with SPMs. Age, summary stage, and surgical history were identified as independent prognostic factors for GAC patients with SPMs. This comprehensive analysis underscores the necessity of vigilant monitoring and tailored follow-up for SPMs in GAC survivors, highlighting the study's contribution to enhancing GAC survivors care strategies.

Secondary primary malignancies among patients with GU cancer.

98 Background: The risk of secondary primary malignancies (SPM) among the survivors of GU cancer is not well-established. In this study, we attempt to describe the patterns of SPMs in patients diagnosed with GU cancers. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (SEER*Stat 8.4.2) was searched to obtain data on the incidence of SPM in adult patients (age &gt;18 years) diagnosed with GU cancers, including prostate, renal, and bladder cancer. Standardized incidence ratios (SIRs) with a 95% confidence interval (CI) were calculated. SIR was defined as the observed SPMS from each category divided by the expected number of SPMs in the age-matched US population for the same period. The data was further stratified by age (&lt;50y, 50-70y, &gt;70y), race (White, Black, Asian/Pacific Islander), ethnicity (Hispanic, non-Hispanic), chemotherapy, and radiotherapy exposure. Results: A total of 1,041,217 patients were included in this analysis. In patients diagnosed with GU cancer, the incidence of overall SPM was 11%. Particularly, patients with GU cancers were observed to have a high incidence of Endocrine system SPM (1.52; 1.45-1.59), and urinary system SPM (1.51; 1.49-1.53) These results were consistent by different sociodemographic groups. In patients diagnosed with prostate cancer, the incidence of thyroid SPM was increased (1.31; 1.23-1.39). Particularly, prostate cancer patients treated with radiation therapy had increased incidence rates of SPM in the peritoneum, omentum and mesentery (1.57; 0.79-2.81) and urinary bladder (1.36;1.32-1.40) was higher as compared to those with no exposure to radiation therapy (1.11;1.08-1.13 and 1.03;1-1.06 respectively). Bladder cancer patients had an overall increased incidence of SPM in the esophagus (1.21; 1.08-1.35), lung, bronchus, trachea, and other respiratory organs (1.97;1.92-2.01), prostate (3.50;3.4-3.6) and kidney (1.86;1.76-1.97). A higher incidence of renal pelvis, ureter and other urinary organ SPM (11.08;10.48-11.07) was also notable in this population. Similarly, kidney cancer patients had a higher incidence of the endocrine system (3.00;2.74-3.27), prostate (1.24;1.2-1.29) and bladder 1.78;1.68-1.79 SPMs. Conclusions: This population-based study shows an increased risk of SPM development in GU cancer survivors compared to the general population. Clinicians should keep a high index of suspicion for SPMs and initiate appropriate workups at early warning signs.

Effectiveness and risk of second primary malignancies after radiotherapy in major salivary gland carcinomas: A retrospective study using SEER database.

To investigate the effectiveness of radiotherapy and its association with second primary malignancies (SPMs) risk in major salivary gland carcinomas (MSGCs) patients. Cohort 1 included 7274 surgically treated MSGC patients from the Surveillance, Epidemiology, and End Results database, assessing the effectiveness of radiotherapy. Cohort 2 (n = 4213) comprised patients with ≥5-year survival in Cohort 1 to study SPMs. Radiotherapy decreased overall survival in MSGCs patients, but improved it in high-grade MSGCs. Cumulative SPMs incidences at 25 years were 16.5% in the radiotherapy (RT) group compared to 14.5% in the non-radiotherapy (NRT) group. For second head and neck carcinomas (SHNCs), incidences were 3.4% in RT versus 1.6% in NRT. Radiotherapy increased the relative risks of tumors, particularly SHNCs (RR = 1.78). The 10-year OS rates of SHNCs after radiotherapy were significantly lower. Radiotherapy improves survival in advanced-stage MSGCs but increases the risk of developing SPMs, particularly SHNCs.

Lifetime risks of second primary malignancies after pediatric Hodgkin lymphoma and non-Hodgkin lymphoma

ObjectivesSurvivors after pediatric Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are with lifetime risk for second primary malignancy (SPM). This necessitates a thorough analysis to better understand the potential long-term health implications for these individuals.MethodsWe used a US-wide population-based cancer registry data to quantify the SPM risk and identify its incidence patterns among pediatric lymphoma patients.ResultsWe observed 4.74-fold (95% CI 4.27–5.25) and 3.40-fold (95% CI 2.78–4.10) increased risks of SPM in survivors after pediatric HL and NHL, respectively. Through over 40 years’ follow-up, the cumulative incidence of SPM for pediatric lymphoma was persistently increasing, and here we firstly report the high 40-year cumulative incidence rates of SPM, 22.2% for HL and 12.6% for NHL, suggesting that SPM accounts for a great proportion of deaths among survivors. Of 6805 pediatric lymphomas, 462 (6.36%) developed a SPM, especially second breast and thyroid cancer, followed by hematologic neoplasms including leukemia and NHL. The competing risk analysis demonstrated gender, lymphoma subtype and radiotherapy were significantly associated with SPM. Different risk patterns of SPM were identified between pediatric HL and NHL. Chemotherapy accelerated SPM development but did not increase its incidence risk.ConclusionOverall, patients after pediatric lymphoma can be with high lifetime risk of SPM, and more attention should be paid to SPM-related signs for early detection and intervention.

T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy.

We report a T cell lymphoma (TCL) occurring 3 months after anti-CD19 chimeric antigen receptor (CAR) T cell immunotherapy for non-Hodgkin B cell lymphoma. The TCL was diagnosed from a thoracic lymph node upon surgery for lung cancer. The TCL exhibited CD8+ cytotoxic phenotype and a JAK3 variant, while the CAR transgene was very low. The T cell clone was identified at low levels in the blood before CAR T infusion and in lung cancer. To assess the overall risk of secondary primary malignancy after commercial CAR T (CD19, BCMA), we analyzed 449 patients treated at the University of Pennsylvania. At a median follow-up of 10.3 months, 16 patients (3.6%) had a secondary primary malignancy. The median onset time was 26.4 and 9.7 months for solid and hematological malignancies, respectively. The projected 5-year cumulative incidence is 15.2% for solid and 2.3% for hematological malignancies. Overall, one case of TCL was observed, suggesting a low risk of TCL after CAR T.

Genotype-phenotype correlations of neurofibromatosis type 1: a cross-sectional study from a large Chinese cohort.

Neurofibromatosis type 1 (NF1) is a highly heterogeneous autosomal genetic disorder characterized by a broad spectrum of clinical and molecular manifestations. The correlations between genotype and phenotype in NF1 remain elusive. This study aimed to elucidate genotype-phenotype associations in a large Chinese cohort of NF1 patients. We included NF1 patients from our center who underwent genetic testing for NF1 variants and systemic examination. Genotype-phenotype correlation analyses were performed, focusing on variation types and involved neurofibromin domains. A total of 195 patients were enrolled, comprising 105 males and 90 females, with a median age of 18years. Truncating variants, single amino acid variations, and splicing variants accounted for 139/195 (71.3%), 23/195 (11.8%), and 33/195 (16.9%), respectively. Patients with splicing variants exhibited a significantly higher prevalence of spinal plexiform neurofibromas (spinal PNF) than those with truncating variants (76.4% vs. 51.8%; p = 0.022). Variations affecting the PKC domain were associated with higher rates of cutaneous neurofibromas (CNF) (100% vs. 64.9%, p < 0.001), Lisch nodules (100% vs. 61.2%, p < 0.001), plexiform neurofibromas (PNF) (100% vs. 95.7%, p = 0.009), and psychiatric disorders (11.8% vs. 1.6%, p = 0.042). Patients with mutations in the CSRD had an elevated risk of secondary primary malignancies (11.6% vs. 2.8%, p = 0.015). GRD involvement might enhance the risk of Lisch nodules (76.9% vs. 53.7%, p = 0.044). Variations in the Sec14-PH domain were correlated with a higher rate of CNF (76.8% vs. 58.6%, p = 0.014). Additionally, we found that the p.R1748* variants carry a high risk of malignancy. Our study suggested some novel genotype-phenotype correlations within a Chinese cohort, providing innovative insights into this complex field that may contribute to genetic counseling, risk stratification, and clinical management for the NF1 population.

Mortality patterns of patients with tonsillar squamous cell carcinoma: a population-based study.

Tonsillar squamous cell carcinoma (TSCC) and second primary malignancies (SPMs) are the most common causes of mortality in patients with primary TSCC. However, the competing data on TSCC-specific death (TSD) or SPM-related death in patients with TSCC have not been evaluated. This study aimed to analyze the mortality patterns and formulate prediction models of mortality risk caused by TSCC and SPMs. Data on patients with a first diagnosis of TSCC were extracted as the training cohort from the 18 registries comprising the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk approach of cumulation incidence function was used to estimate cumulative incidence curves. Fine and gray proportional sub-distributed hazard model analyses were performed to investigate the risk factors of TSD and SPMs. A nomogram was developed to predict the 5- and 10-year risk probabilities of death caused by TSCC and SPMs. Moreover, data from the 22 registries of the SEER database were also extracted to validate the nomograms. In the training cohort, we identified 14,530 patients with primary TSCC, with TSCC (46.84%) as the leading cause of death, followed by SPMs (26.86%) among all causes of death. In the proportion of SPMs, the lungs and bronchus (22.64%) were the most common sites for SPM-related deaths, followed by the larynx (9.99%), esophagus (8.46%), and Non-Melanoma skin (6.82%). Multivariate competing risk model showed that age, ethnicity, marital status, primary site, summary stage, radiotherapy, and surgery were independently associated with mortality caused by TSCC and SPMs. Such risk factors were selected to formulate prognostic nomograms. The nomograms showed preferable discrimination and calibration in both the training and validation cohorts. Patients with primary TSCC have a high mortality risk of SPMs, and the competing risk nomogram has an ideal performance for predicting TSD and SPMs-related mortality. Routine follow-up care for TSCC survivors should be expanded to monitor SPMs.

Longitudinal Screening of Mutant Hematopoietic Progenitor Cells (HPC) in Multiple Myeloma (MM) and Its Association with Secondary Primary Malignancies (SPM)

Background: The incidence of SPM in transplant eligible MM patients (pts) receiving lenalidomide maintenance is ≥ 12% and is associated with inferior overall survival (OS). Recent evidence suggests that while clonal hematopoiesis does not increase the risk of SPM, specific TP53 mutant HPC may expand under lenalidomide treatment and give rise to therapy related myeloid neoplasms and acute lymphoblastic leukemia. Genetic screening may facilitate personalized treatment to minimize the risk of SPM. However, there are no longitudinal studies in purified HPC to inform on the evolution of specific gene mutations and its association with clinical outcomes. Aim: Analyze the mutational landscape of HPC at diagnosis and throughout lenalidomide based regimens. Methods: This study included 335 pts: 43 with high risk smoldering MM, 223 transplant eligible and 69 ineligible active MM respectively enrolled in the CESAR, GEM2012MENOS/GEM2014MAIN and CLARIDEX clinical trials. Of the 335 pts analyzed at diagnosis, 60 were further investigated after induction, 30 at day 100 after autologous transplant (ASCT) and 47 during maintenance. Two or more studies were available throughout treatment in 36 pts. Fluorescence activated cell sorting of CD34+ HPC was performed in a total of 500 bone marrow aspirates. DNA was analyzed with a panel of 55 genes recurrently mutated in myeloid neoplasms. Sequencing depth was &amp;gt;1000x in 95% of nucleotides. Criteria to filter out included synonymous, intronic, invalid-transcript, 5'UTR, panel error and single nucleotide polymorphisms. The criteria to filter in was a AMP/ACMG classification of uncertain significance, likely pathogenic or pathogenic. Only the latter two were included in downstream analysis. Results: HPC from 184 of the 335 (55%) pts were mutated. The frequency in high-risk smoldering MM, transplant eligible and ineligible active MM was 46%, 26% and 35%, respectively. The genes more frequently mutated were DNMT3A (n=94, 52%), TP53 (n=29, 16%) and TET2 (n=28, 15%). The median variant allele frequency was 4.9, 7.5 and 7.0, respectively. In a pt-paired analysis between diagnosis and induction, 8 mutations were present in both time points, 25 became undetectable and 22 were acquired during treatment. The latter (eg, PPM1D and SF3B1) were observed in 14 of the 60 (23%) pts. In the 30 pts with paired samples at diagnosis and at day 100 after ASCT, 4 mutations were present in both time points, 48 became undetectable and only 3 were acquired during treatment ( ATRX, MPL and SAMDL9). Thus, the frequency of mutant HPC was higher at diagnosis vs ASCT (23% vs 5%, P &amp;lt;.001). In a pt-paired analysis between diagnosis and maintenance, 13 mutations were present in both time points, 12 became undetectable and 30 were acquired during treatment. The latter (eg, PPM1D and SF3B1) were observed in 24 of the 47 (51%) pts screened at both time points, and after a median of 5 years since diagnosis. With a median follow-up of 6 years, 17 of the 335 (5%) pts developed SPM. Mutant HPC were detected in 13 of the 17 pts. Accordingly, presence of mutant HPC was associated with a 2-fold increased risk of SPM (OR: 2.3; P = .03). Of the 13 pts, 3 showed mutations at diagnosis and in 8 these emerged during maintenance. The only case developing a myeloid neoplasm had a TP53 mutation present during maintenance that was undetectable at diagnosis. Pts with mutant vs non-mutated HPC at diagnosis showed similar OS (6y rates of 86% and 81%, respectively; P =.46). Similarly, there were no differences in OS of pts with emerging mutations vs those without mutant HPC after treatment (6y rates of 85% and 83%, respectively; P =.65). Specific mutations in DNMT3A, TP53 and TET2 and were not associated with inferior OS. Conclusions: To our knowledge this is the first study analyzing the mutational landscape of purified HPC throughout lenalidomide based regimens in high risk smoldering MM as well as transplant eligible and ineligible active MM. Deep sequencing of CD34+ HPC uncovered that the frequency of mutations is similar between precursor and malignant disease, and that TP53 is amongst the top mutated genes. There was considerable volatility with presence of both transient and emerging mutations throughout treatment. Importantly, the detection of mutant HPC was associated with increased risk of SPM without differences in survival. Thus, this study supports the longitudinal screening of HPC for the identification of patients at risk of developing SPM.

Incidence of Second Primary Malignancies in Medicare-Insured Patients in the US with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Background As therapeutic advances have increased life expectancy for patients (pts) with relapsed/refractory (RR) multiple myeloma (MM), second primary malignancies (SPMs) have become an increasingly important safety consideration. Prior studies have demonstrated that treatment with alkylators, autologous stem cell transplantation, and immunomodulatory drugs (IMiDs), specifically lenalidomide, are associated with increased risk of SPM. Pts who are triple-class exposed (TCE), defined as prior exposure to an IMiD, a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody (mAb), represent an increasingly large subgroup of RRMM pts. The objective of this study was to describe the incidence and characteristics of SPMs in Medicare-insured pts with TCE RRMM initiating a new line of therapy (LOT). Methods Adult pts with an incident diagnosis (Dx) of MM (≥2 outpatient Dx 30-365 days apart OR ≥1 inpatient Dx AND 6 months of continuous eligibility prior to initial Dx) during the study period (Nov 14, 2006-Dec 31, 2020) who were TCE (≥1 claim each for an IMiD, a PI, and an anti-CD38 mAb) were selected from the Center for Medicare and Medicaid Services Chronic Conditions Data Warehouse (TCE pts were assumed to have RRMM based on exposure). The first LOT after TCE was defined as the index LOT and the associated date of initiation was defined as the index date. Pts with SPMs prior to the index date were excluded. SPMs were identified based on having ≥2 outpatient Dx of SPM (of the same cancer type) 30-365 days apart OR ≥1 inpatient Dx of SPM. Dx of SPM included Dx of invasive malignancies or myelodysplastic syndromes (MDS), excluding MM, Waldenström macroglobulinemia, plasma cell leukemia, non-melanoma skin cancers, or primary bone malignancies that were preceded by a Dx of bone metastases. The incidence of SPM was calculated per 100 person years (PY) of follow-up, considering only the first SPM for each pt. Cumulative incidence of SPM (with death as a competing risk) was also calculated. For pts who experienced SPM, overall survival (OS) and measures of healthcare resource utilization (HRU) and costs (in 2021 USD, on a per patient per month [PPPM] basis) were calculated. Results A total of 3,088 TCE RRMM pts were identified, of whom 989 had no evidence of SPM prior to the index date (Table). These 989 pts had a mean age of 75.2 years, a mean of 2.9 prior LOTs and a mean of 3.1 years since MM Dx. Over a median follow-up of 7.1 months, 166 pts (19.3 per 100 PY) experienced an SPM, including 93 (10.8 per 100 PY) with a solid tumor and 73 (8.5 per 100 PY) with a hematologic malignancy. The latter included 27 (3.1 per 100 PY) with acute myeloid leukemia (AML) and 18 (2.1 per 100 PY) with MDS. The cumulative incidence of SPM (95% confidence interval [CI]) at 12, 24, and 36 months was 15.2% (12.8-17.9%), 19.7% (16.8-22.8%), and 23.8% (20.2-27.6%), respectively (Figure). Median (95% CI) OS from SPM Dx was 7.9 months (5.4-10.9). Kaplan-Meier estimated probability of survival (95% CI) at 12, 24, and 36 months following SPM Dx was 40.3% (31.6-48.9%), 27.6% (18.6-37.4%), and 9.5% (2.1-23.8%), respectively. Mean (95% CI) total costs after SPM were $22,514 ($19,105-$26,404) PPPM. Conclusions The incidence of SPM in Medicare-insured TCE RRMM pts is high. Many SPMs in these pts, such as AML, are life-threatening and may interfere with or prevent MM treatment. Pts with SPMs have poor survival and high HRU and costs. With increasing OS for RRMM pts due to therapeutic advancements, there is a need for effective treatments that are not associated with increased risk of SPMs.

Clinicopathological Features of Buccal Squamous Cell Carcinoma with Focus on Patients Who Never Smoke and Never Drink.

Introduction Oral carcinoma has been reported at a substantial proportion in patients who never smoke and never drink. However, the proportion may vary by subsite and ethnicity. Objective We aimed to determine the clinicopathological features of buccal squamous cell carcinoma (SCC) in a Japanese population. Methods We retrospectively analyzed the records of patients diagnosed with buccal SCC at our institution from September 2002 to November 2015. We reviewed the gender, age, tumor status, treatment, smoking, alcohol drinking, multiple primary cancers, and prognosis of the patients. The overall and cause-specific survival rates were calculated, and the effects of clinicopathological variables were assessed by univariate analysis. Furthermore, the cause of death was evaluated. Results Among the 63 patients (men: 38; women: 25) included in the present study, 29 (46.0%) never smoked or drank. Women were almost 5 years older than men ( p = 0.014). The number of women in the group who never smoked or drank was disproportionately higher than that of those in the smoker or drinker groups ( p < 0.001). In total, 29 patients (46.0%) had 59 multiple primary cancers, including 26 oral cancers. Surgeries and radiotherapy were performed in 57 (90.5%) and 6 (9.5%) cases, respectively. The 5-year overall survival and disease-specific survival rates were 74.6 and 78.8%, respectively. Conclusion Our study confirms that buccal SCC may develop in older adult Japanese patients, especially in women who have never smoked or drank. These patients could be at risk for second primary malignancy.

Second primary malignancies in patients with lymphoma in Denmark after high-dose chemotherapy and autologous haematopoietic stem-cell transplantation: a population-based, retrospective cohort study

Second primary malignancies (SPMs) are known complications after chemotherapy, but the risk is not well characterised for patients with lymphoma treated with high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the rate of SPMs in this population relative to matched control individuals from the general population. In this retrospective, population-based cohort study, patients aged 18 years or older with an aggressive lymphoma who received high-dose chemotherapy and autologous HSCT in Denmark between Jan 1, 2001, and Dec 31, 2017, were included from the Danish Lymphoma Registry and matched (1:5) to control individuals from the general population on birth year and sex via the Danish Civil Registration System. Patients were eligible if they had a registered date of autologous HSCT and patients with primary CNS lymphoma were excluded. Exclusion criteria for both patients and matched control individuals were HIV infection, organ transplantation, or other malignancies before inclusion. The key endpoint was the incidence of SPMs assessed in all study participants. The effect of treatment on SPMs was also investigated in patients who were followed up from first lymphoma diagnosis, with high-dose chemotherapy and autologous HSCT as a time-dependent exposure. Of 910 patients with lymphoma assessed, 803 were included (537 [67%] were male and 266 [33%] were female); 4015 matched control individuals were included (2685 [67%] were male and 1330 [33%] were female). Ethnicity data were not available. Median follow-up was 7·76 years (IQR 4·77-11·73). The SPM rate was higher among patients receiving high-dose chemotherapy and autologous HSCT than matched control individuals (adjusted hazard ratio [HR] 2·35, 95% CI 1·93-2·87, p<0·0001). Patients receiving high-dose chemotherapy and autologous HSCT had a higher rate of non-melanoma skin cancer (2·94, 2·10-4·11, p<0·0001) and of myelodysplastic syndrome or acute myeloid leukaemia (AML; 41·13, 15·77-107·30, p<0·0001) than matched control individuals, but there was no significant difference in the rate of solid tumours (1·21, 0·89-1·64, p=0·24). The cumulative risk of SPMs at 10 years was 20% (95% CI 17-23) in patients compared with 14% (13-15) in matched control individuals. High-dose chemotherapy and autologous HSCT was associated with an increased risk of SPMs when analysed as a time-dependent exposure from first lymphoma diagnosis (adjusted HR 1·58, 95% CI 1·14-2·17, p=0·0054). High-dose chemotherapy and autologous HSCT was associated with an increased risk of non-melanoma skin cancer and myelodysplastic syndrome or AML but not with increased risk of solid tumours in patients treated for lymphoma. These findings are relevant for future individualised risk-benefit assessments when choosing between high-dose chemotherapy and autologous HSCT and chimeric antigen receptor T-cell therapy in this setting. Danish Cancer Society.

P-468 Risk of secondary primary malignancies after multiple myeloma in the novel therapy era: a nationwide case-control cohort study

P-468 Risk of secondary primary malignancies after multiple myeloma in the novel therapy era: a nationwide case-control cohort study

Outcome of Second Primary Malignancies Developing in Multiple Myeloma Patients.

There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs. 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger (p = 0.05) and more frequently had a prior AutoHCT (p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, p = 0.037) predicted longer OS. With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.

Nomograms constructed for predicting diagnosis and prognosis in cervical cancer patients with second primary malignancies: a SEER database analysis.

Cervical cancer (CC) patients are more likely to develop second primary malignancies (SPMs) than general population. With the advancement in cancer therapy, CC patients are achieving long-term survival, leading SPMs to our attention. Our study aims to establish diagnostic and prognostic nomograms for CC patients with second primary malignancies (CCSPMs) to help make personalized follow-up plans and treatments. Data of CCSPMs between 2000 and 2019 was extracted from SEER. The proportions and the median interval time of CCSPM onset were calculated. 11 related clinical characteristics, including age, race, marital status, grade, FIGO stage, radiotherapy, chemotherapy, and surgery, were further explore. Logistic and Cox regressions were employed to predict risk factors for CCSPMs diagnosis. Finally, two nomograms were developed to predict the probability occurrence and prognosis of CCSPMs, respectively. For diagnostic nomogram construction, 59,178 CC patients were randomly divided into training (n = 41,426) and validation cohorts (n = 17,752). For prognostic nomogram construction, 3527 CCSPMs patients were randomly divided into training (n = 2469) and validation cohorts (n = 1058). The diagnostic nomogram consisting of above 11 independent risk factors (all P < 0.05), had high accuracy (AUCtraining = 0.851 and AUCvalidating = 0.845). The prognostic nomogram integrated with eight independent prognostic factors such as treatments, FIGO stage and TNM stage performed well in predicting 5-year OS (AUCtraining = 0.835 and AUCvalidating = 0.837). Our diagnostic and prognostic nomograms could facilitate clinicians to quantify individual SPMs risk and survival probabilities and optimize the surveillance recommendations and personalized clinical decision-making.

Changing trends in the risk factors for second primary malignancies after autologous stem cell transplantation for multiple myeloma before and after the introduction of proteasome inhibitors and immunomodulatory drugs.

The incidence of second primary malignancies (SPM) in long-term survivors of multiple myeloma (MM) is increasing because of increased life expectancy. We retrospectively analyzed the risk factors for SPM in patients with MM after autologous stem cell transplantation (ASCT) before and after the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs). In total, 2,340 patients newly diagnosed with MM who underwent ASCT between 1995 and 2016 were enrolled in this study. Forty-three patients developed SPM (29 solid, 12 hematological, and 2 unknown tumors), with cumulative incidence rates of 0.8% and 2.5% at 24 and 60 months, respectively. The cumulative incidence rates of hematological and solid SPM at 60 months were 0.8% and 1.8%, respectively. The overall survival (OS) rate at 60 months after ASCT was 62.9% and the OS rates after the diagnosis of SPM at 24 months were 72.2% for hematological SPM and 70.9% for solid SPM. Multivariate analysis revealed that the use of IMiDs (P=0.024) and radiation (P=0.002) were significant independent risk factors for SPM. The probabilities of developing SPM and death due to other causes (mainly MM) at 60 months were 2.5% and 36.5%, respectively, indicating that the risk of SPM was lower than that of death from MM. Furthermore, SPM between the pre-novel and novel agent eras (ASCT between 2007 and 2016) groups significantly increased (1.9% vs. 4.3% at 60 months; P=0.022). The early occurrence of SPM after ASCT should be monitored cautiously.