Occurrence Of Second Primary Malignancies Research Articles

Prognosis and clinicopathological features of patients with early-onset and late-onset colorectal cancer with second primary malignancies.

The risk of developing a second primary malignancy differs among colorectal cancer patients in different age groups. This study aimed to investigate the differences in prognosis and clinicopathological features of patients with early-onset colorectal cancer and late-onset colorectal cancer who developed second primary malignancies. The study included 15489 patients who underwent surgery for colorectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2018. Data pertaining to these patients were derived from the database. A total of 680 (4.5%) patients subsequently developed a second primary malignancy. Considering death as a competing event, the 10-year cumulative risk of second primary malignancy for early-onset colorectal cancer was 5.3%, compared with 7.3% for late-onset colorectal cancer. Cox analysis showed that late-onset colorectal cancer, colon cancer, smaller tumor size, and fewer tumor nodules without residual lymph node structure, chemotherapy, and radiotherapy were independent risk factors for second primary malignancy. In our patient cohort, early-onset colorectal cancer was associated with better prognosis compared to late-onset colorectal cancer, for both overall survival and second primary malignancy-free survival. In addition, there was insufficient evidence that early-onset colorectal cancer also affected prognosis after the occurrence of second primary malignancies. The risk of early-onset colorectal cancer subsequently developing second primary malignancy was significantly lower than late-onset colorectal cancer, and the second primary malignancies of early-onset colorectal cancer were more likely to be colorectal cancer. Overall survival and second primary malignancy-free survival of early-onset colorectal cancer were consistently better than late-onset colorectal cancer.

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.

Melanoma as Subsequent Primary Malignancy in Hematologic Cancer Survivors-A Literature Review.

The occurrence of second primary malignancies is becoming increasingly important among cancer survivors. Melanoma, an aggressive neoplasm originating from the melanocytes, is responsible for most skin cancer-related deaths. This review aims to explore the risk of melanoma occurrence as a second primary cancer after the most common subtypes of hematologic neoplasia, a malignant disease originating from myeloid or lymphocytic cell lineages. Chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) are among the most associated subtypes with melanoma development. We also discuss the underlying hypotheses that may explain the associations between these malignancies and the impact of melanoma on survival. The review emphasizes the importance of increasing awareness of melanoma risk in hematologic cancer survivors, as it can lead to prompt recognition, improved skin surveillance, and better survival outcomes.

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.

Incidence of second primary malignancies in patients with multiple myeloma receiving anti-CD38 monoclonal antibodies: A systematic review and meta-analysis

Anti-CD38 monoclonal antibodies (mAbs) are commonly used for treating newly diagnosed and relapsed/refractory (r/r) multiple myeloma (MM). However, concerns have been raised about the occurrence of second primary malignancies (SPMs) in patients receiving anti-CD38 mAbs. Assessing the safety data for rare adverse events like SPMs is challenging because individual clinical trials are typically focused on the primary endpoint. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) published between January 2005 and April 2022, including patients with newly diagnosed or r/r MM. Our aim was to compare SPM rate with the use of anti-CD38 mAb-based regimens with other anti-myeloma regimens. After a median follow-up of 35.3 months (range: 8.2–56.2), we found that exposure to anti-CD38 mAbs was associated with an increased risk of developing SPMs compared to the control group (6.8% vs. 5.2%; Peto odds ratio [OR]: 1.53 [95% confidence interval (CI): 1.20–1.95]; I2= 0%, p-value for heterogeneity= 0.44). This increased risk was primarily driven by non-melanoma cutaneous cancers (92 vs. 47; Peto OR: 1.77 [95% CI: 1.25–2.51]; I2 = 0%, p-value for heterogeneity = 0.54). However, there was no significant difference in the incidence of solid tumors (including malignant melanoma) (OR: 1.28 [95% CI: 0.85–1.95]) or hematologic SPMs (OR: 1.86; [95% CI: 0.81–4.27]). In conclusion, the use of anti-CD38 mAb-based combination regimens is associated with a higher risk of non-invasive cutaneous SPMs, but not solid tumors or hematologic SPMs. The increased occurrence of non-invasive cutaneous SPMs may be due to enhanced monitoring resulting from longer treatment duration with anti-CD38 mAbs.

Incidence of second primary malignancies in women with different stages of breast cancer.

Breast cancer (BC) is the most common cancer in women worldwide. Because of the extended survival of patients with BC, the occurrence of second primary malignancies (SPMs) after BC is an important issue. We identified female patients with BC in the Breast Cancer Health Database of Taiwan, which includes four cancer registry datasets between 2002 and 2014 from Taiwan Cancer Registry. We compared the incidence of SPM between patients who received chemotherapy and/or radiotherapy with those who did not. Stratified analyses were performed according to the American Joint Committee on Cancer (AJCC) stage. The Cox regression model was used to identify the risk factors for SPM and evaluate their effects. We enrolled 85,947 eligible patients with BC, and 2,656 (3.09%) patients developed SPM. The median duration of SPM was 2.70 (1.14-5.14) years. Radiotherapy was administered in 40,946 (47.64%) patients, and chemotherapy was administered in 52,120 (60.64%). The most common SPMs were digestive tract cancers (876, 31.89%). The risk factors for SPM included the AJCC stage, chemotherapy, radiotherapy, age, and underlying comorbidities. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in any stage. In contrast, after adjusting for other risk factors, patients at stage III/IV who received both therapies had lower risks of SPM compared with those who did not (p = 0.047). The risk of SPM was different across BC stages. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in women with BC.

Dual primary malignancies in gynaecological cancers

Abstract The occurrence of second primary malignancy (SPM) in a diagnosed case of a cancer patient and also in a cancer survivor is not very uncommon. We report the occurrence of double malignancies in 9 patients with gynaecological cancers. Three patients had gynaecological index malignancy (1 endometrium and 2 cervix); 7 had second malignancy as gynaecological (3 endometrium, 2 ovary, 1 each cervix and vulva). Three had synchronous, 6 had metachronous malignancies; 1 patient had multiple gynaecological malignancies. Primary index malignancies were treated with radical intent (n=8), except for one patient with gallbladder cancer with liver metastases and simultaneous ovarian cancer was treated by palliative chemotherapy. Second primary tumours were managed with radical intent in six and palliative intent in three patients.

Clinical characteristics of second primary malignancies among first primary malignancy survivors: A single-center study, 2005-2020.

The cancer survivor population is growing due to advances in detection and treatment. For improved long-term patient management, it is critical to examine the clinical characteristics and outcomes of second primary malignancies (SPMs). An SPM is defined as a second distinct pathological diagnosis, with the same or different origin as the first primary malignancy (FPM). In the present retrospective study, categorical clinical variables were compared between subgroups and the impact on overall survival was evaluated. A total of 1,188 patients with an FPM were included, of which 102 experienced an SPM (8.59%). When compared with the patients who did not develop an SPM, patients with an SPM were significantly older at first diagnosis, had a higher pathological stage and higher rates of biliary tract disease and thyroid disease. In addition, patients with an SPM were more likely to have received postoperative chemotherapy (28.43 vs. 12.16%, P<0.0001) and to be long-term consumers of cigarettes and alcohol (25.00 vs. 8.95%, P<0.05). In addition, an increase in the number of regimens received but not in the number of courses of chemotherapy was associated with a reduction in the time interval to SPM development. Non-small cell lung cancer (NSCLC) was the most common type of FPM (18.27%). In patients with NSCLC the occurrence of SPMs was relatively low (5.07%) and the SPM-associated mortality rate was 2.30%. Breast cancer was the second common type of FPM (12.09%). Patients with breast cancer had a relatively high likelihood of developing an SPM (9.30%), for which family history of malignancy and postoperative chemotherapy were identified as potential risk factors. Patients with stomach cancer were the most vulnerable to SPM (17.95%) and patients with digestive tract cancer had the longest time interval between the FPM and SPM development. In addition, thyroid adenoma was identified as a potential risk factor for SCLC. The findings of the present study may provide valuable guidance for the short- and long-term monitoring of FPM survivors.

Analysis and prediction of second primary malignancy in patients with breast cancer.

Second primary malignancy (SPM) is common in breast cancer (BC). The present study aimed to profile the characteristics of BC with SPM and to identify patients at high risk of SPM. Clinical and outcome data of BC cases were retrieved from the SEER database. Principal component analysis and a random forest model were utilized to create a model for predicting the occurrence of SPMs. Of the 286,047 BC cases analyzed, 9.32% developed SPMs. Approximately 70% of BCs that developed SPMs were ductal carcinoma and 71% of BCs that developed SPMs were human epidermal growth factor receptor 2 (HER2)-/hormone receptor (HR)+. The overall survival (OS) of the SPM cohort was significantly worse (hazard ratio: 1.49; 95% CI: 1.44-1.53; log-rank P<0.001). After adjusting for metastasis status, SPM was still a poor prognostic factor (hazard ratio: 1.71; 95% CI: 1.70-1.82; log-rank P<0.001). Of note, 50.5% of the SPMs occurred in the breast and the OS of the breast SPM group was significantly better than that of the other single-organ SPM group (hazard ratio: 0.46; 95% CI: 0.45-0.49; log-rank P<0.001) and the multiple-organ SPM group (hazard ratio: 0.44; 95% CI: 0.39-0.50; log-rank P<0.001). A random forest model created from clinical features predicted SPM with a positive predictive value of 32.3% and negative predictive value of 90.7% in the testing set. Thus, SPM occurs in nearly 1/10 of BC survivors and its existence and occurrence site significantly influence OS. SPM may be partly predicted from clinical features. In addition, it was indicated that postmenopausal elderly patients with a HER2-/HR+ molecular subtype should be more watchful and undergo screenings for SPMs.

Risk of second primary malignancies among appendiceal cancer survivors in the United States.

e15514 Background: Appendiceal cancer (AC) survival rates have improved over the last decade. The risk of second primary malignancy (SPM) in AC survivors has become an important concern. Therefore, this study aimed to estimate the risk of SPM in patients with primary AC. Methods: We performed a retrospective cohort study of patients ≥18 years of age diagnosed with AC between 2000-2016 using data extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. The study endpoint was the occurrence of SPM diagnosed after two months of the index AC. We calculated the standardized incidence ratio (SIR) with 95% confidence intervals (CI) for SPM in AC survivors by using the SEER software. Results: Of 9578 patients with AC, 598 (6.2%) developed a SPM. The overall risk of SPM for all sites was significantly increased in AC patients (SIR = 1.46, 95% CI 1.34-1.58). The highest risk of developing a SPM was seen in ages &lt; 60 years, females, and Asian/Pacific Islanders, respectively (SIR = 1.84, 95% CI 1.64-2.07; SIR = 1.55, 95% CI 1.38-1.74; SIR = 1.72, 95% CI 1.12-2.52). The SPM sites associated with increased incidences included the small intestine, followed by the appendix, splenic flexure of the colon, and peritoneum/omentum/mesentery. There was an increased risk of developing non-Hodgkin lymphoma, but no elevated risk with developing second leukemias. Surgery and chemotherapy were associated with an increased incidence risk of SPM, respectively (SIR = 1.45, 95% CI 1.33-1.57; SIR = 1.47, 95% CI 1.25-1.71). Conclusions: AC survivors have an increased incidence of developing SPM, most notably in the small intestine, which suggests a pathophysiological process affecting derivatives of similar embryological origin. Long-term surveillance for SPM is recommended for AC survivors, especially those at high risk.[Table: see text]

Second primary malignancy in stage I and II breast cancer survivor: A United States population-based study.

e12579 Background: In United States, breast cancer accounts for over 260,000 cases each year and is responsible for over 40,000 deaths. Survival primarily depends on the stage at time of diagnosis. 5-year survival among early breast cancer is more than 50%. It is known that patients with cancer undergoing treatment have a significant risk of developing a second primary malignancy (SPM); we aimed to focus our study at the incidence of various SPM among patients surviving stage I and II breast cancer, which can help in their targeted surveillance. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to select adult patients (18 and above) diagnosed with stage I and II breast cancer as their first malignancy between January 2000 and December 2015. This is one of the largest cancer registries worldwide. SPM is metachronous cancer which develops six months after an index localized breast cancer diagnosis based on Warren and Gates criteria. Multiple primary standardized incidence ratios (MP-SIR) and absolute excess risk (AER) for an occurrence of SPM were obtained utilizing SEER. SIR is observed to expected incidence ratio (O/E) of SPM and AER, it is an actual number of excess SPMs in patients with early breast cancer per 10,000 person-years at risk. Statistical significance was defined as a p-value ≤ 0.05. Results: We localized 513,408 patients with a diagnosis of stage I and II breast cancer from 2000 - 2015. Patients were followed for a median duration of 8.92 years (range 0.5 to 15.92). Of these patients, 81.5% were white. About 8.6% (43938) of patients developed 47708 primary malignancies. These malignancies were significantly higher than the general population with O/E ratio of 1.15 and AER of 17.12. The median age of diagnosis of SPM was 69.8 years (range 22.8 – 105.08 years). The average latency to develop SPM was 5.28 years (range 0.5 – 15.92 years). Among solid tumors, a statistically significant increased risk was observed with salivary gland, tongue, gastric, colon, lung cancer, and genitourinary cancers. Among hematological malignancies, statistically significant risk was seen for ALL, AML and CML. The risk of hepatobiliary, CNS cancers and lymphoma were significantly lower among our cohort included in current study. The SPM was found significantly increased after the latency of 24 months, and the risk of SPM was greater across all age groups. Conclusions: Due to robust breast cancer screening strategies, a significantly higher proportion of the patients are diagnosed early in the course of the disease which tends to be curative and this group of patients has better survival rates. Our study recognizes that the risk of certain SPM is higher in stage I and II breast cancer survivals compared to general population; and they would benefit from guidelines that can identify cancer with increased risk in these patients population.

Second primary malignancies after ovarian cancer: A SEER-based analysis (1975–2016)

ObjectiveTo investigate the risk of occurrence of second primary malignancies (SPMs) in survivors of ovarian cancer (OC) using large data from the Surveillance, Epidemiology, and End Results (SEER) database. Materials and methodsMultiple primaries standardized incidence ratios (MP-SIRs) to calculate the risk of developing second primary malignancies after a diagnosis of ovarian cancer. ResultsOf our included 59,880 women with OC, 3972 cases (6.6%) developed 4495 s primary malignancies over an average follow-up period of 114.39 (±102.66) months. Overall, the risk of occurrence of second primary malignancies after a diagnosis of OC was greater than what would be expected for a reference US population (SIR = 1.05, 95%CI = 1.02–1.08, p-value < 0.05). The occurrence of second myeloid malignancies and second thyroid cancer were most notable across our latency periods. Among the most significant second primary malignancies by latency were malignancies of the appendix (SIR = 14.04, 95%CI = 5.65–28.93, p-value <0.05) at 2–11 months, the small intestine (SIR = 3.15, 95%CI = 1.76–5.2, p-value <0.05) at 12–59 months, and the urinary bladder (SIR = 1.63, 95%CI = 1.3–2.02, p-value <0.05) after 10 years of an OC diagnosis. ConclusionWomen with OC are at significant risk for the development of second primary malignancies across all sites, as compared to a reference US population, and may benefit from second primary malignancies site-specific screening post-diagnosis.

Incidence of Non-Melanoma Skin Cancers in Patients with Chronic Lymphocytic Leukaemia: A Retrospective Study in a Bay of Plenty, New Zealand Population

Background/Aims: Chronic lymphocytic leukaemia (CLL) incurs an increased risk of developing second primary malignancies (SPMs). The pathogenesis underpinning this increased SPM risk is attributable to synergism between genetic aberrations, chronic immune suppression / dysfunction and CLL treatments. Specifically, CLL associated skin cancer is a well-documented phenomenon, with common malignancies such as squamous (SCC) and basal cell (BCC) carcinomas occurring at higher frequencies in CLL patients and are often of a more aggressive phenotype. The incidence of non-melanoma skin cancers (NMSCs) among New Zealand CLL patients is unknown, as NMSCs are not required to be reported to the New Zealand Cancer Registry. Accordingly, this study aimed to analyse the incidence of NMSC in CLL patients from the Bay of Plenty region of New Zealand.Methods: We conducted a retrospective analysis of 213 CLL patients, who were referred to Bay of Plenty District Health Board (BOPDHB) between 2015 and 2020, for the occurrence of SPMs. Clinical notes were reviewed for the demographics of sex, age at time of CLL diagnosis, CLL treatments received and occurrence and type of NMSCs. A control group of 76 patients referred to BOPDHB haematology, for anaemia or thrombocytopenia, of which the cause subsequently remained unknown and was not associated with lymphoproliferative disease, was reviewed for primary malignancy (PM), occurrence and type. NMSC incidence was also compared to a local data, on overall NMSC incidence in the general Bay of Plenty population, in 2015.Results: The predominant SPM types occurring in this CLL patient group were NMSCs. A total of 249 and 170 histological diagnoses of SCC and BCC were made in our group of CLL patients, respectively. Of the 213 CLL patients, 48.8% had a diagnosis of at least one NMSC, with median time between CLL and NMSC diagnosis of 5 years (range, -6 to 19 years). CLL patients that were diagnosed with NMSC developed a mean number of 3.93 ± 2.94 separate lesions, compared to 2.6 ± 1.7 lesions in our control population. Note: comparison of NMSC incidence data between CLL group and Bay of Plenty populationConclusion: Patients with CLL are at increased risk of developing multiple NMSC lesions. Therefore, we believe CLL patients should be assessed by dermatologists or general practitioners for whole-body skin examination, 6 monthly following their CLL diagnosis. This strategy promotes early diagnosis, and patient education on importance of sun protection strategies to reduce NMSC risk. This is essential to the ongoing care of CLL patients in a NZ context, given the increased incidence of NMSC associated with CLL, in combination with the high levels of UV exposure and skin damage among the NZ general population. This study also highlights how NMSC disease burden is likely to be significantly underestimated due to a lack of data collection on these malignancies by the New Zealand Cancer Registry. DisclosuresNo relevant conflicts of interest to declare.

Occurrence of Second Primary Malignancies in Patients With Primary Optic Nerve Gliomas: A Surveillance, Epidemiology, and End Results Analysis.

Advanced understanding of screening and therapeutic modalities acts as provision for increased survival in patients diagnosed with optic nerve gliomas. Secondary primary malignancies (SPMs) in patients diagnosed with primary optic nerve glioma (OPG) are currently an uncharacterized frontier. This US national database analysis highlights the incidences of SPMs in patients diagnosed with primary OPG. Standardized incidence ratios (SIR) and excess absolute risk (EAR) for SPMs were calculated using the SEER-specific multiple outcome analysis. 95% SIR confidence intervals were calculated with statistical significance achieved at p<0.05. SPMs originating from soft tissues (including the heart) (SIR=33.23, CI=6.85-97.11; EAR=5.07), breast (SIR=4.99, CI=1.36-12.77; EAR=5.57), female breast (SIR=5.03, CI=1.37-12.89; EAR=5.58), brain (SIR=105.38, CI=65.23-161.08; EAR=36.23), cranial nerves (SIR=103.29, CI=12.51-373.12; EAR=3.45), non-lymphocytic leukemia (SIR=15.05, CI=1.82-54.37; EAR=3.25), myeloid and monocytic leukemia (SIR=16.26, CI=1.97-58.75; EAR=3.27), and Kaposi's sarcoma (SIR=79.88, CI=2.02-445.08; EAR=1.72) demonstrated significantly increased SIR. Overall, the values for cumulative SPM (SIR=6.04, CI=4.33-8.19; EAR=59.60) highlight the overall significance in incidence of SPM in patients diagnosed with OPG. Clinical decision-making should reconcile enhanced propensities for development of SPM.

Second primary malignancies associated with radiation therapy in cervical cancer patients diagnosed between 1975 and 2011: a population-based competing-risk study.

BackgroundCervical cancer is a major health threat for women. Radiotherapy plays an important role in the treatment of cervical cancer. However, its overall benefit has been questioned due to the risk of second primary malignancies.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to search for cervical cancer patients diagnosed between January 1975 and November 2011. Factors that could possibly affect the occurrence of second primary malignancies included the year of diagnosis, gender, ethnicity, histologic type, SEER cancer stage, histology, grade, and whether surgery, chemotherapy, or radiotherapy were used. Age-adjusted and propensity scoring matching (PSM)—adjusted competing-risk analysis was applied for analysis.ResultsOf the 23,112 patients identified through SEER, 14,800 (64.0%) received radiotherapy. Second malignancies were diagnosed in 2,545 (11.0%) cases. PSM-adjusted competing analysis revealed that patients receiving radiotherapy had a significantly higher risk of developing a second cancer in the colon, rectum and anus [hazard ratio (HR): 1.43; 95% confidence interval (CI): 1.09–1.87; P=0.01], lung and bronchus (HR: 1.41; 95% CI: 1.13–1.76; P=0.002), corpus uteri (HR: 3.71; 95% CI: 1.71–8.06; P<0.001), ovary (HR: 2.79; 95% CI: 1.38–5.64; P=0.004), and urinary bladder (HR: 2.18; 95% CI: 1.35–3.54; P=0.002). However, radiotherapy significantly lowered the risk of second cancers in the female breast (HR: 0.67; 95% CI: 0.52–0.86; P=0.002). Age-adjusted competing-risk analysis showed generally consistent results.ConclusionsRadiotherapy increased the risk of second cancers among cervical cancer patients. Those who underwent radiotherapy had a significantly higher risk of developing a second cancer in the colon, rectum and anus, lung and bronchus, corpus uteri, ovary, and urinary bladder.

The Impact of Diabetes Mellitus on the Second Primary Malignancies in Colorectal Cancer Patients

IntroductionAll colorectal cancer (CRC) survivors have an increased risk of developing second primary malignancies (SPMs). The association between diabetes mellitus (DM) and the risk of cancer is well known. However, the role of DM and its therapy in the development of SPMs in CRC patients is not well described.MethodsIn this single-institutional retrospective analysis we identified 1,174 colorectal carcinoma patients, median follow-up 10.1 years, (median age 63 years, 724 men). All patients over 18 years with histologically confirmed CRC who were admitted in the period 1.1. 2003- 31.12.2013 and followed-up till 31.12. 2018 at the Masaryk Memorial Cancer Institute (MMCI) were screened for eligibility. The exclusion criteria were CRC diagnosed at autopsy, lost to follow-up and high risk of development of SPMs due to hereditary cancer syndrome. Tumours are considered multiple primary malignancies if arising in different sites and/or are of a different histology or morphology group. Comparisons of the basic characteristics between the patients with SPM and the patients without SPM were performed as well as comparison of the occurrence of SPMs by the site of diagnosis between the DM and non-DM cohorts and survival analyses.ResultsA SPM was diagnosed in 234 (20%) patients, DM in 183 (15%) patients. DM was diagnosed in 22.6% of those with SPM vs. in 13.8% of those without SPM (p=0.001). The most common types of SPMs in DM patients were other CRC, kidney, lung, bladder and nonmelanoma skin cancer, but only carcinoma of the liver and bile duct tracts was significantly more common than in the group without DM. Although breast cancer was the second most common in the group with DM, its incidence was lower than in the group without DM, as well as prostate cancer. A significantly higher incidence of SPMs was found in older CRC patients (≥ 65 years) and in those with lower stage colon cancer and DM. No significant difference in DM treatment between those with and without a SPM was observed including analysis of type of insulin.ConclusionCRC patients with diabetes mellitus, especially those with older age, and early stages of colon cancer, should be screened for second primary malignancies more often than the standard population. Patients without DM have longer survival. According to the occurrence of the most common second malignancies, a clinical examination, blood count, and ultrasound of the abdomen is appropriate, together with standard breast and colorectal cancer screening, and lung cancer screening under certain conditions, and should be recommended in CRC survivors especially in patients with intercurrent DM, however the necessary frequency of screening remains unclear.

Second primary malignancy in myelofibrosis patients treated with ruxolitinib.

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22-4·60, P=0·01] and thrombocytosis>400×109 /l at RUX start (HR:1·98, 95%CI: 1·10-4·60, P=0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24-7·92, P=0·02) and duration of hydroxycarbamide and RUX therapy>5years (HR: 3·20, 95%CI: 1·17-8·75, P=0·02 and HR: 2·93, 95%CI: 1·39-6·17, P=0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11-5·25, P=0·03), platelet>400×109 /l (HR: 3·30, 95%CI: 1·67-6·50, P=0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48-8·14, P=0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.

Risk of second primary malignancies among patients with carcinoid of the lung

ObjectivesLittle is known about the etiology of pulmonary carcinoids (PC). Associations with other types of cancer may identify shared risk factors but results from earlier studies were inconclusive. The aim of the present study was to explore the association between PC and other primary malignancies for identifying risk factors. MethodsA query of the nationwide Netherlands Cancer Registry generated data about patients diagnosed with PC from 1989 to 2018. The occurrence of second primary malignancies was evaluated separately for year 1 and years 2−30. The expected numbers of second primary malignancies were calculated using incidence reference tables, controlling for age, gender and period. Confidence intervals (95 % CI) for the ratio between observed and expected numbers (SIR: standardized incidence ratio) were calculated using Poisson distributions. ResultsIn a total of 2933 patients with PC, 425 consecutive primary malignancies were observed in 376 patients. Concomitant diagnoses in the first year mainly comprised lung (n = 59) and renal cancer (n = 14). Metachronous malignancies beyond the first year were most common for breast (n = 50), colorectal (n = 41), prostate (n = 32), and lung cancer (n = 29). Beyond year 1, the overall risk of second primary cancer in patients with PC was similar to the risk within the general population (n = 256, SIR = 1.12, 95 % CI 0.99–1.27). Increased risks were observed for soft tissue sarcoma (n = 5, SIR = 3.52, 95 % CI 1.14–8.22) and GEPNET (n = 4, SIR = 4.30, 95 % CI 1.17–11.01). ConclusionsConcomitant diagnosis of PC with other cancers is common, reflecting surveillance diagnostics. Apart from MEN-1 family history, no shared risk factors could be identified.

Spectrum of Second Primary Malignancies in Pediatric and Adult Langerhans Cell Histiocytosis Cases

Introduction: Langerhans cell histiocytosis (LCH) is a rare MAPK-ERK pathway driven histiocytic neoplasm that occurs in pediatric as well as adult population. Despite improvement in clinical outcomes, there is some data to suggest an increased propensity to develop second primary malignancies (SPMs) in LCH patients. However, population-based studies analyzing the incidence and spectrum of SPMs in pediatric and adult LCH patients are lacking. In this study, we utilized the Surveillance, Epidemiology and End Results (SEER) database to examine the various SPMs occurring among pediatric and adult LCH cases. Methods: We used the November 2018 submission of the SEER 18 registry, which covers ~27.8% of the US population based on the 2010 census, as our database. We used the SEER*Stat version 8.3.6 statistical software to analyze data. We identified cases diagnosed with LCH as their first primary malignancy between 2000 and 2016 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) codes, including LCH NOS (not otherwise specified) (9751/1), LCH (9751/3), LCH, unifocal (9752/1), LCH, multifocal (9753/3), LCH, disseminated, borderline (9754/1) and Disseminated LCH (9754/3). These cases were followed for 180+months, and the standardized incidence ratio (SIR) or relative risk and absolute excess risk (AER) were calculated. We examined the differences in occurrence of SPMs among the pediatric (Age &amp;lt;18 years) and adult population (Age ≥18 years). Additionally, we evaluated the concurrent and prior cancers in LCH patients as an exploratory objective. Results: The study included 1392 cases with LCH (Table 1), with median age at diagnosis 8 years (range newborn - 86 years). Out of these cases, 1205 (87%) were diagnosed as LCH and 186 (13%) as disseminated LCH. 936 cases (67%) were diagnosed at age &amp;lt;18 years (pediatric LCH), while 456 cases (33%) were diagnosed at age ≥18 years (adult LCH). The overall age-adjusted incidence rate for LCH was found to be 1 per 1,000,000. The incidence rate was 2.6 per 1,000,000 in pediatric LCH group and 0.4 per 1,000,000 in the adult LCH group. Out of the entire cohort, 20 (1.4%) cases developed a total of 21 SPMs [SIR 2.07; 95% Confidence Interval (CI): 1.28-3.16]. Median latency period to development of SPMs was 28 months. The pediatric LCH group had an overall higher risk of developing SPMs [SIR 6.42, 95%CI 2.08-14.97] than the general population, especially for hematologic malignancies [SIR 18.76, 95%CI 6.09-43.78], mainly, nodal Hodgkin lymphoma [SIR 60.93, 95%CI 7.38-220.12] and extranodal non-Hodgkin lymphoma [SIR 60.88, 95%CI 1.54-339.2]. No solid tumors were seen in this group. The adult LCH group did not have an overall increased risk of developing SPMs than the general population [SIR 1.71, 95%CI 0.98-2.77], except for Acute Lymphocytic Leukemia (ALL) [SIR 66.29, 95%CI 1.68-369.36] especially 60-119 months from diagnosis of LCH and miscellaneous cancers [SIR 11.43, 95%CI 2.36-33.39] especially 12-59 months after diagnosis of LCH. 62.5% of SPMs that developed in the adult LCH group were solid tumors, however, the overall risk for developing solid tumors was not higher than the general population [SIR 1.2, 95%CI 0.58-2.2], except for carcinoma in-situ of vulva [SIR 62.72, 95%CI 1.59-349.45] 2-11 months from diagnosis of LCH. Overall, tumors of the respiratory system (21%), female breast (13%) and prostate (9%) were the most common malignancies occurring prior to development of LCH whereas tumors of the respiratory system (28%), non-Hodgkin lymphoma (20%) and endocrine system (13%) occurred concurrent to LCH. Conclusion: To our knowledge, this is the first comprehensive population-based study assessing the incidence of SPMs in pediatric and adult LCH. Our study shows that the incidence of LCH is higher in the pediatric age group compared to adults. We found an increased risk for hematologic malignancies, specifically for Hodgkin and non-Hodgkin lymphoma in pediatric LCH compared to the general population. Among adult LCH, however, the risk was higher for development of ALL and carcinoma in-situ of vulva when compared to the general population. Our results may help guide survivorship and surveillance strategies among LCH patients. More studies are needed to understand the molecular underpinning leading to increased SPM formation in LCH patients. Disclosures No relevant conflicts of interest to declare.

Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: Data from a retrospective multi-centric study

BackgroundPatients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population. AimThis study aimed to analyze the occurrence of second primary malignancies. MethodsA retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included. ResultsBetween 2000 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5- and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms. ConclusionIn NEN patients the prevalence of second primary malignancies was not negligible, suggesting a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy.