Risk Of Second Primary Malignancies Research Articles

Association between radiation therapy for primary endometrial cancer and risk of second primary malignancies: a retrospective cohort study

Our objective was to evaluate the association of adjuvant radiation therapy (RT) to subsequent second primary malignancies (SPMs) in endometrial cancer survivors. Patients with endometrial cancer as their first malignancy were identified from 8 registries of the Surveillance, Epidemiology, and End Results (SEER) database. SPMs were defined as any type of primary malignancy that occurred more than 12 months after the diagnosis of endometrial cancer. Fine-Gray competing risk regression and Poisson regression were used to evaluate the radiotherapy-associated risk (RR) for SPMs. The Kaplan-Meier method was applied to assess the survival outcomes of endometrial cancer patients. Of 62,108 endometrial cancer patients,16,846 patients (27.12%) were in the RT group, and 45,262 patients (72.88%) were in the no-RT group. During the 30-year follow-up period, the cumulative incidence of SPMs was 20.9% and 19.7% in each group, respectively. In both multivariable competing risk regression analysis and Poisson regression analysis, adjuvant RT was found to be associated with a higher risk of developing colon and rectum cancer (adjusted hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.12–1.50; P < 0.001; adjusted RR, 1.29; 95% CI, 1.11–1.49; P < 0.001), lung and bronchus cancer (adjusted HR, 1.27; 95% CI, 1.08–1.50; P = 0.004; adjusted RR, 1.26; 95% CI, 1.07–1.49; P = 0.005), vulva cancer (adjusted HR, 1.72; 95% CI, 1.04–2.85; P = 0.036; adjusted RR, 1.74; 95% CI, 1.03–2.88; P = 0.035), urinary bladder cancer (adjusted HR, 1.86; 95% CI, 1.41–2.46; P < 0.001; adjusted RR, 1.85; 95% CI, 1.40–2.44; P < 0.001), and non-Hodgkin lymphoma (adjusted HR, 1.37; 95% CI, 1.06–1.77; P = 0.016; adjusted RR, 1.37; 95% CI, 1.05–1.76; P = 0.017). However, a slightly decreased risk of breast cancer was observed in patients who underwent adjuvant RT (adjusted HR, 0.89; 95% CI, 0.80–0.98; P = 0.021; adjusted RR, 0.88; 95% CI, 0.80–0.98; P = 0.020). The RR for colon and rectum cancer decreased with age and elevated with increasing latency since endometrial cancer diagnosis, and the RR for urinary bladder cancer showed a similar tendency with latency. SPMs can significantly impair the survival outcomes of primary endometrial cancer survivors. Our findings suggest that adjuvant RT for endometrial cancer patients increases the risk of non-Hodgkin lymphoma and several types of solid cancer. Long-term surveillance of these patients should be recommended for detecting SPMs.

Is radiotherapy still the optimal initial choice for patients with early-stage low-grade follicular lymphoma in the modern era? A population-based study.

Despite radiotherapy (RT) is recognized as preferred initial therapy for early-stage low-grade follicular lymphoma (FL) by many international practice guidelines, the medical oncologist has improperly underutilized RT, and diverse management strategies, including systemic therapy (ST), combined modality (CM) and watch and wait (WW), are still used. Except survival outcomes, previous studies concerned little about the treatment-related toxicity, which is also important factor in choosing initial management strategy, especially second primary malignancies (SPMs). The aim of this study was to compare the overall survival (OS) and the SPMs risk between different management strategies, which can provide guidance for the choice of optimal initial management strategy. Data was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Finally, A total 10,900 patients were identified, in which 930 cases developed SPMs. The use of radiotherapy (RT) has remained consistently low, with a utilization rate of around 20%, while most patients have received watchful waiting (WW) and systemic therapy (ST). In the rituximab era, multivariate analysis indicated that RT exhibited significantly superior OS and did not increase SPMs risk in comparison with ST and WW. At the same time, although there were no significant differences in OS between CM and RT, RT had significantly lower SPMs risk in comparison with CM. The use of RT improved the OS and did not increase the SPMs risk in comparison with other management strategies. Considering the low application rate of RT, oncologists should emphasize and increase the use of RT as an initial management strategy in patients with early-stage low-grade FL.

A nomogram for overall survival of second primary cancers following upper-tract urothelial carcinoma: a SEER population-based study.

With improving prognosis in upper-tract urothelial carcinoma (UTUC), an increasing number of second primary malignancies (SPMs) are being identified. However, there is limited research on SPMs following UTUC. This study aims to evaluate the risk of SPMs in UTUC patients and create a nomogram to predict their survival rates. Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database, we assessed the risk of SPMs among UTUC patients. Additionally, we developed and validated an overall survival (OS) nomogram for SPM patients post-UTUC diagnosis. The prevalence of SPMs among UTUC patients was 30.23%, with solid tumors being the most prevalent type of second malignancy, constituting 95.30% of all SPMs. The overall risk of SPMs was significantly elevated across all subgroups. Univariate and multivariate Cox regression analyses identified age, race, gender, UTUC SEER historic stage, surgery, SPM site, histologic type, grade, and SEER historic stage as independent prognostic factors for SPM OS. Subsequently, we developed a nomogram for predicting SPM OS. The C-index for the training and validation sets were 0.72 [95% confidence interval (CI): 0.70-0.74] and 0.71 (95% CI: 0.67-0.75), respectively. The area under the curve (AUC) demonstrated good performance of our model in predicting the 3-year (0.73 and 0.737) and 5-year (0.723 and 0.733) OS of SPMs in both sets. This study represents the first comprehensive analysis of SPM incidence in UTUC patients and introduces a nomogram for predicting SPM prognosis.

Association between radiotherapy and the risk of second primary malignancies in breast cancer patients with different estrogen receptor statuses.

Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses. We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(-) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups. Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(-) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50-70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20-30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(-) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50. Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.

Analyzing risk factors for second malignancies in early gastric carcinoma from the SEER database

This retrospective study analyzed a large population of gastric cancer (GC) patients treated between 2010 and 2015 to investigate the clinical features and predictive risk factors for developing secondary primary malignancies (SPMs). The cumulative incidence of SPM was assessed using Kaplan–Meier analysis. Competing risk analyses adjusted for mortality were conducted using stratified Cox proportional hazard regression models and multivariate analyses to identify independent predictors of SPM. A total of 3289 out of 167,747 GC patients were included in the analytic cohort, with 155 patients diagnosed with SPM. Patients whose histologic type other than adenocarcinomas (AC) and signet ring cell carcinoma (SRCC) emerged as an independent risk factor for developing SPM (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.146–4.465, P = 0.019) in multivariate Cox regression analysis. The surgical method, including biopsy/local excision (HR 2.3, [CI] 1.291–4.095, P = 0.005) and subtotal/total resection ([HR] 1.947, [CI] 1.028–3.687, P = 0.041), chemotherapy ([HR] 1.527, [CI] 1.006–2.316, P = 0.047), and histologic type ([HR] 2.318, [CI] 1.193–4.504, P = 0.013)), were identified as independent risk factors in the competitive risk model. Subgroup analyses, stratified by chemotherapy, revealed an increased risk of SPM among older patients. Furthermore, a nomogram was developed and internally validated to predict the cumulative incidence of SPM in GC patients (C-index = 0.73 for 72 months). These findings suggested that in specific histologic types of GC, the lymph node infiltration region missed after local surgical resection, and concomitant chemotherapy would have an increased risk of SPM for cancer survivors.

Second primary malignancy for early-stage head and neck squamous cell carcinoma by SEER17 registries.

Investigating treatment modalities' association with second primary malignancy risk in early-stage head and neck squamous cell carcinoma (HNSCC). Data of 5-year survivors of early-stage (stages I-II, seventh TNM staging manual) HNSCC from 2000 to 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio and excess absolute risk were used to assess second primary malignancy (SPM) development externally. Relative risk was estimated to compare SPM risk within groups. Fine-Gray's model estimated cumulative incidence of second primary malignancy. Overall, 8957 5-year survivors with early-stage HNSCC were enrolled. Patients receiving definitive radiotherapy had poorer survival than surgery patients. Surgery correlated with lower risk of second primary malignancy (RR = 0.89, 95% CI 0.80-0.99), especially for oropharyngeal squamous cell carcinoma (RR = 0.56, 95% CI 0.39-0.82). Differences in the risk of second primary malignancy among subgroups based on clinical characteristics were not significant. Treatment modalities did not significantly affect risk of second primary malignancy within each subgroup. Surgery led to better survival and lower risk of second primary malignancy compared to definitive radiotherapy in 5-year survivors. Incidence and sites of second primary malignancy varied by primary sites, emphasizing targeted long-term surveillance's importance.

Levothyroxine Dosage and the Increased Risk of Second Primary Malignancy in Thyroid Cancer Survivors

Levothyroxine Dosage and the Increased Risk of Second Primary Malignancy in Thyroid Cancer Survivors

Stage-adapted treatment of HIV-associated Hodgkin lymphoma: Long-term results of a prospective, multicenter study.

Results of a prospective study of stage-adapted treatment of humanimmunodeficiency virus (HIV)-associated Hodgkin lymphoma (HIV-HL) showed a 2-year overall survival (OS) of 90.7% with no significant difference between early favorable (EF), early unfavorable (EU), and advanced HL. Patients with EF HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy involved field (IF) radiation, those with EU HIV-HL received four cycles of ABVD or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) baseline + 30 Gy IF, and six to eight cycles of BEACOPP baseline were administered in advanced disease. The objective of the present analysis is to determine long-term outcomes of HIV-HL. Of 108 patients, 23 (21%) had EF HL, 14 (13%) had EU HL, and 71 (66%) had advanced-stage HL. After a median follow-up of 9.14 (range, 0-12.9) years, there were five primary refractory HL patients (5%) and 11 relapses (10%), of which seven were late relapses (>2 years). A second primary malignancy (SPM) occurred in 10 patients after a median of 7.3 years (range, 1.5-10.7) from HL diagnosis. The 10-year OS for patients with EF, EU, and advanced HL was 95.7%, 84.6%, and 76.1%, respectively. By multivariate analysis, Center for Disease Control and Prevention category C (hazard ratio [HR]3.00, 95% confidence interval [CI]:1.16-7.74, p = 0.023) and achievement of complete remission were significant for OS (HR 0.03, 95% CI: 0.01-0.08, p = 2.45 × 10-9). In conclusion, a stage-adapted treatment approach for HIV-HL is highly effective with long-term survival rates similar to those reported in HIV-uninfected HL. However, the risk for late relapse and SPM is significant.

Maintenance therapy after Autologous Stem Cell Transplantation in Multiple Myeloma – currents and perspectives

MM is non-curable cancer that arises from plasma cells and is the second most common type of blood cancer. Drug-refractory relapses are inevitable, making it essential to sustain long-lasting remissions as part of therapy. Lenalidomide maintenance until progression is a standard of care for transplant-eligible newly-diagnosed patients. However, poor outcomes of high-risk patients and the risk of secondary primary malignancies associated with maintenance underline the need for novel approaches. Significant changes in frontline treatment maintenance are expected, with the increasing importance of minimal residual disease monitoring and the development of novel drug combinations for maintenance. This article explores current standards and prospects for maintaining response after upfront in ASCT in MM.

Effect of maintenance therapy (MT) on real-world outcomes (RWO) of patients (pts) with newly diagnosed multiple myeloma (NDMM) post stem cell transplant (SCT).

7562 Background: SCT followed by MT is the standard of care for pts with transplant-eligible (TE) NDMM. Five randomized clinical trials (RCTs) comparing lenalidomide MT versus no MT showed improved progression free survival (PFS), but no overall survival (OS) benefit except for one by McCarthy et al. that allowed pt crossover between treatment arms. Use of MT has also been associated with an increased risk of second primary malignancies and an inferior quality of life. We report RWO post SCT with and without MT in TE NDMM. Methods: We performed a multi-center, retrospective, observational study using the de-identified COTA real-world database derived from the EMRs of US centers. Pts with NDMM from 1/1/2012 to 1/1/23 were included in the study. Kaplan-Meier method was used to evaluate time to next treatment (TTNT), OS, follow-up time (reverse OS endpoint), and report log-rank test p-values. TTNT was defined in two ways: time from SCT to the earliest of initiation of next line of therapy (LOT) or death (TTNT1) and the time from 2nd LOT post-SCT to the earliest of initiation of next LOT or death (TTNT2). A propensity score (PS) matched analysis was used to compare study cohorts and report hazard ratios (HRs) using the Cox proportional hazards method. High risk cytogenetic abnormalities (HRCA) were defined as pts with 17p(-), t(4;14), t(14;16), t(14;20) and 1q+. Results: 1928 ptsmet the study criteria: 957 pts received SCT with MT (M) and 971 pts received no MT (NM). Median age at Dx was 61 y, 57% were male, 70% were White, and 31.2% had HRCA with a median follow-up of 64 months (mos) (95% CI: 61.6, 66.7). In the M vs NM arms, 29.6% and 32.7% pts had HRCA, respectively. Median TTNT1 for M vs NM was 51 vs 36 months (mos), (p&lt;0.001), respectively. Median TTNT2 for M vs NM was 11.7 vs 21.6 mos, (p&lt;0.001), respectively. Median OS for M vs NM was 108.8 mos vs 126.3 mos, (p=0.08), respectively. In the PS model, the NM group had significantly lower hazard of TTNT2 and OS events (HRs 0.65 and 0.85, p&lt;0.001 and p=0.08, respectively). Conclusions: Our study demonstrates improved TTNT2 outcomes with the NM approach. M therapy did not have an impact on OS in this cohort. Both results indicate an absence of long-term benefit with the use of M therapy. OS is a difficult primary outcome to achieve in MM RCTs where survival may have to be collected for decades. Thus, our large study of RWO with long-term follow-up is valuable. [Table: see text]

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 nonsmall cell lung cancer and risk of second primary malignancies: comparative study.

The most common form of therapy for nonsmall 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. The authors aimed to quantify the risks of SPM associated with PORT treatment for young‑onset NSCLC in early stage. The authors 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 [relative risks (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 60-69 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.

Incidence of Second Primary Malignancies Following Thyroid Cancer Treatment with Radioactive Iodine

Background: Thyroid cancer is the most common endocrine malignancy, with an increasing incidence globally and in Oman. The standard treatment for differentiated thyroid cancer (DTC) involves radioactive iodine (RAI). However, previous studies have suggested that RAI treatment may increase the risk of second primary malignancies (SPM). Despite the high incidence of thyroid cancer in Oman, to our knowledge, there are no published reports on the association between RAI treatment and the risk of SPM in Oman.

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.