Mutual Risks of Cutaneous Melanoma and Specific Lymphoid Neoplasms: Second Cancer Occurrence and Survival.
ABSTRACT: Background:It is unclear whether the established association between cutaneous melanoma (CM) and lymphoid neoplasms (LNs) differs across LN subtypes. This study quantifies risk for developing CM after specific LNs and, conversely, for developing specific LNs after CM, as well as assessing clinical impact. Methods:We identified a cohort of Caucasian adults (age 20-83 years) initially diagnosed with CM or LN, as reported to 17 US population-based cancer registries, 2000-2014. Standardized incidence ratios (SIRs) quantified second cancer risk. We assessed impact of second cancer development on risk of all-cause mortality using Cox regression. Results:Among 151 949 one-or-more-year survivors of first primary LN, second primary CM risk was statistically significantly elevated after chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR = 1.96, 95% confidence interval [CI] = 1.74 to 2.21), follicular lymphoma (SIR = 1.32, 95% CI = 1.09 to 1.58), and plasma cell neoplasms (SIR = 1.33, 95% CI = 1.07 to 1.63). Risks for these same subtypes were statistically significantly elevated among 148 336 survivors of first primary CM (SIR = 1.44, 95% CI = 1.25 to 1.66; SIR = 1.47, 95% CI = 1.21 to 1.77; SIR = 1.25, 95% CI = 1.06 to 1.47; respectively). Risk for CM was statistically significantly elevated after diffuse large B-cell lymphoma (SIR = 1.22, 95% CI = 1.02 to 1.45) and Hodgkin lymphoma (SIR = 1.75, 95% CI = 1.33 to 2.26), but the reciprocal relationship was not observed. There were no statistically significant associations between marginal zone lymphoma and CM. Among survivors of most LN subtypes, CM statistically significantly increased risk of death (hazard ratio [HR] range = 1.52, 95% CI = 1.25 to 1.85, to 2.46, 95% CI = 1.45 to 4.16). Among survivors of CM, LN statistically significantly increased risk of death (HR range = 1.75, 95% CI = 1.15 to 2.65, to 6.28, 95% CI = 5.00 to 7.88), with the highest risks observed for the most aggressive LN subtypes. Conclusions:Heterogeneous associations between CM and specific LN subtypes provide novel insights into the etiology of these malignancies, with the mutual association between CM and certain LN suggesting shared etiology. Development of second primary CM or LN substantially reduces overall survival.
Project description:Infectious agents have been identified in the etiology of certain non-Hodgkin lymphoma (NHL) subtypes and solid tumors. The impact of this shared etiology on risk for second cancers in NHL survivors has not been comprehensively studied. We used US population-based cancer registry data to quantify risk of solid malignancies associated with infectious etiology among 127 044 adult 1-year survivors of the 4 most common NHL subtypes diagnosed during 2000 to 2014 (mean follow-up, 4.5-5.2 years). Compared with the general population, elevated risks for liver, stomach, and anal cancers were observed among diffuse large B-cell lymphoma (DLBCL) survivors (standardized incidence ratio [SIR], 1.85; 95% confidence interval [CI], 1.46-2.31; SIR, 1.51; 95% CI, 1.16-1.94; SIR, 3.71; 95% CI, 2.52-5.27, respectively) and marginal zone lymphoma (MZL; SIR, 1.98; 95% CI, 1.34-2.83; SIR, 2.78; 95% CI, 2.02-3.74; SIR, 2.36; 95% CI, 1.02-4.64, respectively) but not follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. Anal cancer risk was particularly elevated among DLBCL survivors with HIV (SIR, 68.34; 95% CI, 37.36-114.66) vs those without (SIR, 2.09; 95% CI, 1.22-3.34). The observed patterns are consistent with shared associations between these cancers and hepatitis C virus, Helicobacter pylori, and HIV, respectively. In contrast, risks for cervical and oropharyngeal/tonsil cancers were not elevated among survivors of any NHL subtype, possibly because of the lack of NHL association with human papillomavirus or population-wide screening practices (for cervical cancer). In summary, patterns of elevated second cancer risk differed by NHL subtype. Our results suggest shared infectious etiology has implications for subsequent cancer risks among DLBCL and MZL survivors, which may help inform surveillance for these survivors.
Project description:Background:Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer. Methods:We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. Results:Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI?=?29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI?=?23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI?=?9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI?=?48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI?=?35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI?=?27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI?=?245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI?=?37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI?=?20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma. Conclusions:For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.
Project description:The occurrence of subsequent neoplasms has direct impact on the quantity and quality of life in cancer survivors. We have expanded our analysis of these events in the Childhood Cancer Survivor Study (CCSS) to better understand the occurrence of these events as the survivor population ages.The incidence of and risk for subsequent neoplasms occurring 5 years or more after the childhood cancer diagnosis were determined among 14,359 5-year survivors in the CCSS who were treated from 1970 through 1986 and who were at a median age of 30 years (range = 5-56 years) for this analysis. At 30 years after childhood cancer diagnosis, we calculated cumulative incidence at 30 years of subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess absolute risks (EARs) for invasive second malignant neoplasms, and relative risks for subsequent neoplasms by use of multivariable Poisson regression.Among 14,359 5-year survivors, 1402 subsequently developed 2703 neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma, and treatment with radiation therapy were associated with increased risk of subsequent neoplasm.As childhood cancer survivors progress through adulthood, risk of subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at greatest risk. There is no evidence of risk reduction with increasing duration of follow-up.
Project description:We analysed the risk of cutaneous malignant melanoma (CM) occurring in patients following a diagnosis of non-Hodgkin's lymphoma (NHL) or chronic lymphatic leukaemia (CLL), and of NHL or CLL subsequently developing in CM survivors. Cohorts of patients with CM, NHL or CLL (index cancer) diagnosed between 1975 and 1997 were identified from the Scottish national cancer registry and followed through the registry for subsequent CM, NHL or CLL. The standardised incidence ratio (SIR) for each cancer was calculated and overall risk, risk in relation to gender and age at diagnosis of the index cancers and time from diagnosis of the index cancer to the diagnosis of the second malignancy were measured. There were 9385 CM patients, 4016 CLL patients and 13 857 NHL patients identified with an index cancer with 56 195, 14 450 and 44 999 person-years of follow-up, respectively. There was an increased risk of both CLL and NHL following a diagnosis of CM (SIR 2.3 and 1.5, respectively) and of CM following a diagnosis of CLL and NHL (SIR 2.3 and 2.1, respectively). The risk was statistically significantly increased for CLL developing in CM patients and for CM occurring in NHL survivors (P<0.05). This study supports an association between CM, CLL and NHL developing in the same patient. Immunosuppression, exposure to ultraviolet radiation and genetic factors may lead to a host environment that is conducive to the development of these malignancies.
Project description:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10?000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2?g?m-2 was associated with a 3.3-fold higher CRC risk (95%CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2?g?m-2 procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (Padditivity=0.004).Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.
Project description:The risk of lymph node positivity (LN+) in rectal cancer is a parameter that impacts therapeutic recommendations. We aimed to quantify the effect of younger age on LN+ in rectal cancer.Using the Surveillance, Epidemiology, and End Results (SEER) database, patients with rectal cancer diagnosed between 1988 and 2008 were identified. Patients were stage I-III, without preoperative radiotherapy, at least one lymph node examined, and a standard rectal cancer operation performed. The association of age and LN+ status was examined with logistic regression separately for each T stage, adjusting for multiple covariates. Poisson regression was used to evaluate age and number of positive lymph nodes (LNs). All statistical tests were two-sided.Fifty-six thousand seventy-six patients were identified, including 1194 (2.1%) patients age 20 to 39 years at diagnosis and 4199 (7.5%) patients age 40 to 49 years (defined as young). For each T stage, LN+ was inversely associated with age (all P < .001). For T1, T2, and T3, age remained predictive of LN+ status after adjustment for number of LNs examined and other covariates (P < .001 for each stage). Adjusted odds ratios (ORs) for LN+ for age 20 to 39 vs 60 to 69 were: T1: 1.97(95% confidence interval [CI] = 1.36 to 2.86); T2: 1.48 (95% CI = 1.13 to 1.95); T3: 1.30 (95% CI = 1.10 to 1.53). Young age was a statistically significant predictor of an increased number of LNs positive for stage T2 (P = .042) and T3 (P = .002).In this large national dataset, young age at diagnosis is associated with an increased risk of LN+. This finding merits further investigation and may ultimately impact treatment decision-making for young early-stage patients.
Project description:Background and aims:Lymphoma patients are frequently treated with cancer therapies that may increase the risk of adverse health outcomes later in life, including cardiovascular disease (CVD) mortality. We sought to investigate the long-term risk of CVD incidence in this survivor population relative to the general population to quantify this health burden. Methods:A systematic review and meta-analysis was conducted using EMBASE, MEDLINE, and CINAHL databases, from date of inception to November 2016, with additional searches completed through June 2018. Included reports were observational studies assessing CVD incidence in patients of either Hodgkin or non-Hodgkin lymphoma (HL, NHL) who survived for at least 5 years from the time of diagnosis or if the study had a median follow-up of 10 years. Meta-analyses were performed using random effects models, and subgroup analyses were conducted to determine the incidence of specific CVD subtypes (coronary heart disease, pericardial disease, valvular heart disease, myocardial disease, cardiac dysrhythmia, and cerebrovascular disease). Heterogeneity was assessed using I 2 statistics and prediction intervals. Results:Of the 7734 studies identified, 22 studies were included in this review, representing 32 438 HL and NHL survivors. Relative to the general population, lymphoma survivors had statistically significant two to threefold increases in the risk for nearly all subtypes of CVD examined. Lymphoma survivors appeared to be particularly susceptible to pericardial diseases (HL: 10.67, 95% confidence interval (CI), 7.75-14.69; NHL: 4.70, 95% CI, 2.08-10.61) and valvular diseases (HL: 13.10, 95% CI, 7.41-23.16; NHL: 3.76, 95% CI, 2.12-6.66). Although the 95% CIs were suggestive of increased risks, the 95% prediction intervals often included the null, reflecting the high heterogeneity of the estimates. Conclusion:Given the suggested increased risks of cardiovascular outcomes in lymphoma survivor populations relative to the general population, tailored screening and prevention programmes may be warranted to offset the future burden of disease.
Project description:We evaluated the association between hemodynamic parameters of chronic congestive heart failure (CHF) and mediastinal lymphadenopathy (MLA) in heart transplantation (HT) candidates and the effect of HT on MLA. We also described the results of lymph node (LN) biopsies of MLA in the patients.Patients who underwent HT evaluation over an 8-year period and had chest CT scans were evaluated retrospectively. Data collected included LN sizes pre-HT and post-HT, echocardiographic measurements, radionuclide-derived ejection fraction, and right-sided heart catheterization hemodynamics. MLA was defined as LNs > 1 cm in smallest dimension.Of 118 patients, 53 patients had MLA. MLA had weak statistically significant correlations with elevated mean pulmonary artery pressure (MPAP), mitral regurgitation (MR), tricuspid regurgitation (TR), right atrial pressure (RAP), and pulmonary capillary wedge pressure (PCWP). Thirty-six patients with MLA underwent HT, and nine of the 36 had post-HT chest CT scans. All nine patients showed a decrease in LN size post-HT (mean LN diameter pre-HT = 1.16 ± 0.137 cm, post-HT = 0.75 ± 0.32 cm). Seven of 53 patients with MLA underwent biopsies. Four had benign LNs, one had sarcoidosis, and two had lung cancer.MPAP, MR, TR, RAP, and PCWP had weak statistically significant correlations with MLA. HT led to regression of MLA in patients who underwent CT scans post-HT, implying that MLA is related to CHF. However, we also identified clinically important causes of MLA; therefore, biopsy should be considered if enlarged LNs fail to regress after maximal medical management of CHF.
Project description:Current methods of lymph node (LN) staging are controversial in predicting the survival of SBA. We aimed to develop an alternative LN-classification-based nomogram to individualize SBA prognosis.Based on the data from the Surveillance, Epidemiology, and End Results (SEER) database of patients diagnosed with SBA between 2004 and 2014, we identified the cut-off points for the number of LNs examined and the number found to be metastatic using the K-adaptive partitioning (KAPS) algorithm. Using metastatic LNs, a nomogram predicting the survival of SBA was derived, internally and externally validated, and measured by calibration curve, C-index, and decision curve analysis (DCA), and compared to the 8th TNM stage.A total of 1516 patients were included. The cut-off of 17 was the optimal examined LN number. For metastatic LN numbers, the cut-off points were 0, 2, and 8. The C-index for the nomogram was higher than the 8th TNM staging (internal: 0.734; 95% CI, 0.693 to 0.775 vs. 0.677; 95% CI, 0.652 to 0.702, P?<?0.001; external: 0.715; 95% CI, 0.674 to 0.756 vs. 0.648; 95% CI, 0.602 to 0.693, P?<?0.001). Also, the nomogram showed good calibration in internal and external validation and larger net benefit than TNM staging.We modified current N staging into a 4-level staging system based on the number of metastatic LNs: N0, no LN metastasis; N1, 1-2 metastatic LNs; N2, 3-8 metastatic LNs, and N3, >8 metastatic LNs and set the least examined LN number to 17. A nomogram based on this staging showed great clinical usability than TNM staging for predicting the survival of SBA patients.
Project description:BackgroundLymphadenectomy is an important part of surgical treatment for non-small cell lung cancer (NSCLC). However, the prognostic impact of lymph node (LN) dissection for patients with NSCLC ?1 and >1 to 2 cm who underwent sublobar resection is still unclear.MethodsA group of patients numbering 7,627 with NSCLC 2 cm or less who underwent sublobar resection were identified from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and November 2015. The overall survival (OS) and lung cancer-specific survival (LCSS) were evaluated among patients who had undergone dissection of ?4 LNs, 1 to 3 LNs or who had no-LN dissection; log-rank and Cox proportional-hazards regression analyses were used for the evaluation.ResultsPatients with NSCLC ?2 cm who underwent ?4 LNs dissection had better OS and LCSS compared with those who underwent dissection of 1 to 3 LNs or who had no-LN dissection after sublobar resection. Subgroup analysis showed that dissection of ?4 LNs had better OS and LCSS than those of 1 to 3 LNs dissection in NSCLC >1 to 2 cm, whereas had similar OS and LCSS in NSCLC ?1 cm. Multivariate Cox analysis showed that dissection of 1 to 3 LNs was not an independent risk factor of OS and LCSS than dissection of ?4 LNs in NSCLC ?1 cm after sublobar resection.ConclusionsThe extent of LN dissection is associated with the survival outcomes in patients with NSCLC ?2 cm after sublobar resection. Dissection of ?4 LNs should be recommended for NSCLC >1 to 2 cm, whereas surgeons can rely on surgical skills and patient profiles to decide ?4 LNs or 1 to 3 LNs dissection for NSCLC ?1 cm during sublobar resection.