Development Of New Malignancies Research Articles

Cancer in patients with heart failure: Incidence, risk factors and prognostic impact

AimsTo assess the incidence of cancer diagnosis and cancer-related mortality in patients with heart failure (HF). MethodsObservational study based in a prospective cohort of patients with HF referred to a specialized Spanish clinic between 2010 and 2019. The observed incidence of malignancies (excluding non-melanoma skin cancer) was compared to that expected for the general Spanish population according to the Global Cancer Observatory. ResultsWe studied 1909 consecutive patients with HF. Over a median follow-up of 4.07 years, 165 new cases of malignancy were diagnosed. Observed age-standardized incidence rates of cancer were 861 (95% CI 618.4–2159.4) cases per 100,000 patients-years in men and 728.5 (95% CI 451.1–4308.7) cases per 100,000 patients-years in women; while age-standardized incidence rates of cancer expected for the general Spanish population were 479.4 cases per 100,000 patients-years in men (risk ratio = 1.80) and 295.5 cases per 100,000 patients-years in women (risk ratio = 2.46). Both a history of pre-existing malignancy at baseline and the development of new malignancies during follow-up were associated with reduced survival. Observed age-standardized cancer-related mortality was 344.1 (95% CI 202.1–1675) deaths per 100,000 patient-years in men and 217.0 (95% CI 32.8–3949.3) deaths per 100,000 patient-years in women; while age-standardized cancer-related mortality expected for the general Spanish population was 201.4 deaths per 100,000 patients-years in men (risk ratio = 1.71) and 96.2 deaths per 100,000 patients-years in women (risk ratio = 2.26). ConclusionPatients with HF showed higher incidence rates of cancer diagnosis and cancer-related mortality than those expected for the general population.

Risk Factors for the Development of Cutaneous Melanoma after Allogeneic Hematopoietic Cell Transplantation

IntroductionAdvances in clinical practice for allogeneic hematopoietic cell transplantation (HCT), a potentially curative treatment most frequently indicated for hematologic malignancies, have led to substantial improvements in prognosis. HCT survivors are at risk for a number of post-transplant complications, including the development of new malignancies. Although cutaneous melanoma risk is known to be increased after HCT, no previous study has comprehensively investigated risk factors in order to identify patients at highest risk for melanoma development. The purpose of this study was to identify risk factors for developing melanoma after allogeneic HCT, specifically evaluating the relationship between melanoma and conditioning regimens as well as factors associated with immunosuppression and immune dysfunction.MethodsWe conducted a nested case-control study of melanoma within a cohort of 21,590 patients receiving a first allogeneic HCT during 1985-2012, as reported to the Center for International Blood and Marrow Transplant Research. Data on patient and transplant characteristics derived from standardized reports pre-HCT, 100 days and 6 months post-HCT, and annually thereafter or until death. The cohort was restricted to non-Hispanic Caucasians because melanoma is rare among other racial/ethnic groups. Among cases with a melanoma diagnosis reported by transplant centers (N=140), 82 (59%) were confirmed by pathology report review. Four controls were matched to each case on age at HCT (±3 years), sex, primary disease, and time since HCT (without a melanoma diagnosis). Conditional logistic regression was utilized to assess risk factors associated with melanoma development after allogeneic HCT. Multivariable models were adjusted for ambient ultraviolet radiation (UVR), estimated based on residence at the time of HCT, because of the known association between UVR and melanoma. Exploratory analyses were conducted to assess melanoma risk by age and time to melanoma development.ResultsAmong the 140 melanoma cases, the median age at HCT was 46 years (range, 1-73 years), 56% were male, and median time from HCT to melanoma was 4 years (range <1-24 years). Patients were most frequently transplanted for chronic myeloid leukemia (24%) followed by acute myeloid leukemia (18%), acute lymphoblastic leukemia (18%), and non-Hodgkin lymphoma (12%). Multivariable analysis showed that melanoma risk was statistically significantly increased among HCT survivors who received myeloablative conditioning regimens with total body irradiation [odds ratio (OR), 95% confidence interval (95%CI): 1.8, 1.0-3.2] or reduced intensity conditioning regimens containing melphalan (OR, 95%CI: 2.6, 1.1-6.0) or fludarabine (OR, 95%CI: 2.7, 1.0-7.3) compared with those receiving a busulfan-containing myeloablative conditioning regimen; acute graft-versus-host disease (GvHD) with stage 2+ skin involvement (OR, 95%CI: 1.9, 1.2-3.1) versus no acute GvHD; chronic GvHD without skin involvement (OR, 95%CI: 1.9, 1.0-3.6) versus no chronic GvHD; and occurrence of keratinocytic carcinoma (OR, 95%CI: 2.4, 1.2-4.8; median time from keratinocyte carcinoma to melanoma: cases=3.5 years, controls=2.8 years). In exploratory analyses of these factors by patient subgroup, melanoma risks associated with acute GvHD stage 2+ skin involvement were especially increased among individuals of younger age at HCT (age<40 years: OR, 95%CI: 3.2, 1.4-7.4) but not among those of older age at HCT. In the multivariable model, no significant associations were observed with other patient and transplant characteristics, including graft source and ex-vivo or in-vivo T-cell depletion.ConclusionIn the largest study to date of melanoma risk factors following allogeneic HCT, we report novel associations with specific conditioning regimens, occurrence of acute and chronic GvHD, and occurrence of keratinocyte carcinoma. Our results emphasize the importance of adherence to current surveillance guidelines for HCT recipients, specifically routine skin examination, heightened skin cancer awareness, and photoprotection recommendations, particularly for those survivors at highest risk. DisclosuresNo relevant conflicts of interest to declare.

Impact of smoking on multiple primary cancers survival: a retrospective analysis

According to available literature, active tobacco smoking enhances the risks of recurrence and development of new primary malignancies. Smoking also shortens the survival period for patients with a diagnosed neoplastic disease. Medical records of 1622 patients hospitalized at the Center for Pulmonary Diseases from January 2013 till March 2017 were retrospectively analyzed, out of which 741 cases with a diagnosis of at least one primary cancer were selected, including 111 patients with multiple primary malignancies. Survival time, the impact of smoking on cancer development and the influence of smoking cessation on the prognosis of the development of new malignancies were analyzed. The incidence of multiple primary malignancies in the population of cancer patients amounted to 14.98%. In the group of smokers, those who ceased smoking developed the second primary malignancy later as compared to those who did not: the period between the first and the new cancer was 11.55 years (SD 7.24) for those who quit smoking, whereas for those who continued to smoke after their first cancer diagnosis it was 6.10 years (SD 8.62) (p = 0.005). It was revealed that patients who had never smoked lived longer than those who had continued to smoke (p = 0.004) and that those who had ceased smoking had a longer survival time than those who had not (p = 0.027). Ceasing smoking after the first cancer diagnosis prolongs the time before a new malignancy develops and is diagnosed, as well as the total survival time after the first cancer diagnosis.

Association between multiple cutaneous melanoma and other primary neoplasms

The risk of a subsequent cancer is an important issue for patients with melanoma. The development of a second primary cancer in patients with a solitary melanoma has been discussed in several studies. However, to our knowledge, the incidence of second primary cancer (SPC) in patients with multiple primary melanoma (MPM) has not been thoroughly investigated. To quantify the incidence of SPC in patients with MPM, with the aim of possibly developing further preventive measures. In a retrospective study, 76 patients with MPM were identified from 2155 patients being followed up at our unit. Of the 76 patients, 12 (16%) developed another neoplasm, with 59% of them having nonmelanoma skin cancer (NMSC), and 41% other noncutaneous cancers. By contrast, only 8% of those with single primary melanoma had other neoplasms (21% of whom had NMSC). Patients with MPM, especially men with skin phototype II, have a significantly increased incidence of developing SPC, particularly NMSC. Thus, careful monitoring is essential not only to detect recurrence of the original cancer or development of another primary melanoma, but also development of new malignancies of different types, particularly NMSC.

Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.

Persistent cigarette smoking and other tobacco use after a tobacco-related cancer diagnosis.

People who continue to smoke after a cancer diagnosis have an increased risk for recurrences or development of new malignancies. These risks may be even higher among tobacco-related cancer survivors (TRCS). We describe tobacco use behaviors among TRCS, other cancer survivors, and people without a history of cancer. We used 2009 Behavioral Risk Factor Surveillance System data to describe demographic characteristics, smoking history, current smoking prevalence, and smokeless tobacco use among TRCS, other cancer survivors, and people without a history of cancer (cigarette smoking and smokeless tobacco use were calculated after adjusting for age, sex, race, and insurance status). Tobacco-related cancers were defined as lung/bronchial, pharyngeal, laryngeal, esophageal, stomach, pancreatic, kidney/renal, urinary bladder, cervical, and acute myeloid leukemia. A total of 20 % of all cancer survivors were TRCS. TRCS were primarily female (68 %) and white (78 %). Smoking prevalence was higher among TRCS (27 %) compared with other cancer survivors (16 %) and respondents without a history of cancer (18 %). Smokeless tobacco use was higher among respondents without a history of cancer (4 %) compared with TRCS (3 %) and other cancer survivors (3 %). The self-reported smoking prevalence among TRCS is higher than among other cancer survivors and people without a history of cancer. Targeted smoking prevention and cessation interventions are needed for cancer survivors, especially those diagnosed with a tobacco-related cancer. We recommend all cancer survivors be made aware of the health risks associated with smoking after a cancer diagnosis, and smoking cessation services be offered to those who currently smoke. We provide the first population-based report on demographic characteristics and tobacco use behaviors among self-reported tobacco-related cancer survivors.

Cancer Survivors in the United States: A Review of the Literature and a Call to Action

Background: The number of cancer survivors in the U.S. has increased from 3 million in 1971, when the National Cancer Act was enacted, to over 12 million today. Over 70% of children affected by cancer survive more than 10 years, and most are cured. Most cancer survivors are adults, with two-thirds of them 65 years of age or older and two-thirds alive at five years. The most common cancer diagnoses among survivors include breast, prostate and colorectal cancers. This review was conducted to better appreciate the challenges associated with cancer survivors and the opportunities healthcare providers have in making a difference for these patients.Methods: Comprehensive review of literature based on PubMed searches on topics related to cancer survivorship, and associated physical, cognitive, socio-economic, sexual/behavioral and legal issues.Results: At least 50% of cancer survivors suffer from late treatment-related side effects, often including physical, psychosocial, cognitive and sexual abnormalities, as well as concerns regarding recurrence and/or the development of new malignancies. Many are chronic in nature and some are severe and even life-threatening. Survivors also face issues involving lack of appropriate health maintenance counseling, increased unemployment rate and workplace discrimination.Conclusions: Advances in the diagnosis and treatment of cancer will lead to more survivors and better quality of life. However, tools to recognize potentially serious long-lasting side effects of cancer therapy earlier in order to treat and/or prevent them must be developed. It is incumbent upon our health care delivery systems to make meeting these patients' needs a priority.

Parascapular free flaps in skin malignancies

This study was a retrospective review of a case series of nine patients, aged 40 to 83 years, presenting to the head and neck cancer department at Wake Forest Baptist Medical Center, with a diagnosis of head and neck cutaneous squamous cell carcinoma (SCC), requiring reconstruction after surgical resection. In this group of patients, parascapular fasciocutaneous free flaps proved to be a safe, reliable, and cosmetically effective choice for reconstruction of head and neck skin cancer defects. Choosing donor tissue from a relatively non-sun exposed area can prevent potential development of new malignancies that may arise from donor sites using sun-exposed skin. We discuss the benefits and versatility of the parascapular fasciocutaneous free flap and our experience in using this flap to reconstruct complex surgical defects.

Abstract B90: Smoking prevalence among tobacco-related cancer survivors in the United States, BRFSS 2009

Abstract Introduction: Cancer survivors who continue to smoke are at increased risk for primary cancer recurrences or development of new malignancies. Risks may be even higher among Tobacco Related Cancer Survivors (TRCS). We provide a national report on smoking behavior among TRCS. Methods: Tobacco-related cancers (lung/bronchial, pharyngeal, esophageal, stomach, pancreatic, kidney/renal, urinary bladder, cervical and leukemia) are defined according to the 2004 report of the Surgeon General on The Health Consequences of Smoking. Data from the 2009 Behavioral Risk Factor Surveillance System (BRFSS) were used to describe demographic characteristics and tobacco use behaviors reported by TRCS, other cancer survivors and the non cancer BRFSS cohort. Self reported prevalence percentages and confidence intervals were calculated using SAS version 9.2 (SAS Institute, Inc, Cary, North Carolina). Results: Overall, 10% of BRFSS respondents reported being diagnosed with cancer. Approximately 17% of all cancer survivors were diagnosed with a tobacco related cancer. Survivors in this group were primarily white (85.4%) and female (71.9%). Approximately 8.8% of TRCS were Hispanic. TRCS report a substantially higher proportion of current and past tobacco use. Among TRCS, 68% (95%CI 66.0-69.0) reported a history of smoking and 27.1% (95%CI 25.4-28.9) reported currently smoking; among other cancer survivors, 45.7% (95%CI 45.4-45.9) reported a history of smoking and 27.6% (95%CI 27.3-27.9) reported currently smoking. Conclusion: When compared to other cancer survivors, persons diagnosed with tobacco related cancers have higher past and current smoking rates. Smoking cessation interventions should target TRCS, and increased surveillance of smoking behaviors is needed in this population. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B90.

Increased DNA damage in hematopoietic cells of mice with graft-versus-host disease

Patients who received hematopoietic cell transplants have an increased risk for a new malignancy. In addition to genotoxic regimens such as radiotherapy and chemotherapy, graft-versus-host disease (GVHD) is a risk factor for development of new malignancies in long-term survivors. To understand mechanisms underlying this malignant transformation, we evaluated genomic damage in several murine models of GVHD by enumerating reticulocytes containing micronuclei (MN) in the blood after semi-allogeneic (parent-into-F1) hematopoietic cell transplantation. On day 40 after transplantation, MN frequencies were significantly increased in unirradiated (C57BL6 × DBA/2) F1 (BDF1) and (BALB/c × C57BL6) F1 (CBF1) mice that received cells from C57BL6 (B6) donors. MN frequencies were not significantly increased in F1 mice that received cells from DBA/2 or BALB/c donors. Serum levels of tumor necrosis factor-α (TNF-α) were higher after transplantation with B6 donors than with DBA/2 or BALB/c donors. The results indicate that GVHD, without irradiation, can induce genomic damage associated with inflammatory reactions manifested by increased TNF-α levels.

Choice of Calcineurin Inhibitor and Development of New Malignancies in Liver Transplant Recipients

Purpose: The goal was to examine whether the choice of calcineurin inhibitor is associated with the development of new malignancies in liver transplant patients. We also examined demographic and clinical variables associated with new malignancy development. Methods: Data was obtained from The United Network for Organ Sharing (UNOS) on all liver transplants done from 1987–2005. To be included, patients must: 1) have been transplanted from 1995–2005, 2) be ≥ 18 years old at the time of transplant, 3) not have a history of malignancy or be found to have malignancy at the time of transplant, 4) not have received an organ from a donor with a history of malignancy, 5) have been discharged from the hospital on either cyclosporine (CSA) or tacrolimus, and 6) not have been diagnosed with a “new” malignancy within the first 6 months post-transplant. Unadjusted hazard rates (HR) for each variable were obtained by entering them individually into a Cox proportional hazards (CPH) model. Statistically significant variables, as well as basic demographic variables, were then used to build a multivariate CPH model. Results: 37,331 patients met criteria for inclusion. 24,433 (65%) were on tacrolimus and 12,898 (35%) were on CSA at discharge. There were 1,392 (3.7%) new malignancies (934 in the tacrolimus group and 458 in the CSA group). The most common non-cutaneous malignancies were non-Hodgkin's lymphoma (171 cases), lung cancer (158 cases), and colorectal cancer (51 cases). After multivariate adjustment, there was no statistically significant difference in the hazard rate for developing a new malignancy for tacrolimus compared to CSA (HR 0.96, 95% CI: 0.84–1.09). Older age, male gender, and Caucasian race were independently associated with an increased hazard rate of malignancy. Clinical factors independently associated with a statistically significantly increased hazard rate for malignancy included alcohol-induced liver disease (HR 1.28, 95% CI: 1.13–1.46) or primary sclerosing cholangitis (HR 1.42, 95% CI: 1.20–1.68), and use of mycophenolate mofetil (HR 1.15, 95% CI: 1.02–1.29). Conclusions: There is no significant difference in the hazard rate for developing a post-transplant malignancy among liver transplant patients receiving either a tacrolimus or CSA-based immunosuppressant regimen. After controlling for demographic variables, transplantation for alcohol-induced liver disease or primary sclerosing cholangitis and use of mycophenolate mofetil are associated with an increased hazard for new malignancy.

New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors.

To determine the incidence and risk factors for the development of new malignancies occurring after stem-cell transplantation (SCT). Between January 1, 1974, and March 31, 2001, 3,372 patients underwent SCT at the University of Minnesota. From these transplants, 147 posttransplant malignancies (PTMs) were identified in 137 patients. Excluding nonmelanoma skin cancers (n = 19) and carcinoma-in-situ (n = 5), the remaining 123 cases represented an 8.1-fold (95% confidence interval [CI], 6.7 to 9.6) increased risk of a PTM, an excess risk of 102.7 cases/10,000 persons/yr (age and sex adjusted). This includes a significantly elevated risk for developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML; standardized incidence ratio [SIR] = 300; 95% CI, 210 to 406), non-Hodgkin's lymphoma including posttransplant lymphoproliferative disorder (PTLD; SIR = 54.3; 95% CI, 39.5 to 41.1), Hodgkin's disease (SIR = 14.8; 95% CI, 3.9 to 32.9), or solid tumors overall (SIR = 2.8; CI, 2.0 to 3.7) and in specific for melanoma, brain, and oral cavity tumors. The cumulative incidence for the development of any PTM was 6.9% (95% CI, 5.2 to 8.6) at 20 years post-SCT. For PTLD (n = 43), the cumulative incidence plateaued at 1.4% (95% CI, 1.0 to 1.8) by 10 years post-SCT. For MDS or AML, the cumulative incidence plateaued at 1.4% (95% CI, 0.9 to 1.9) by 10 years post-SCT. The cumulative incidence of developing a solid tumor did not plateau and was 3.8% (95% CI, 2.2 to 5.4) at 20 years post-SCT. These data reveal that the risk of PTMs, especially solid tumors, continues to increase even 20 years after transplant, necessitating long-term close follow-up for these patients.

Persistence of chromosome aberrations in peripheral lymphocytes from Hodgkin's lymphoma remission patients

Purpose : To analyse spontaneous and in vitro bleomycin-induced chromosome aberrations in peripheral lymphocytes taken from Hodgkin's disease patients after prolonged (up to 31 years) remission periods, and to consider these data from the point of view of the carcinogenic potential of anticancer therapy. Materials and methods : Conventional analysis of chromosome preparations stained with azure-eosin. Results : The mean frequency and patterns of both spontaneous and induced aberrations in remission patients were significantly different from comparison groups (healthy donors and primary Hodgkin's disease patients). Individual values were characterized with high variation and did not show correlation with post-therapy time. New cancer cases diagnosed in remission patients were more frequent in subjects with high chromosome sensitivity to in vitro bleomycin challenge than in patients whose sensitivity to bleomycin was at a control level. Conclusions : The results are interpreted as suggesting that the tumorigenic potential of radiochemotherapy is mediated via induction of genetic instability in exposed cells. Long after the therapy, the instability may become an initiating event in the development of new malignancies in affected tissues, whereas the instability induced in haemopoietic stem cells may reveal itself in peripheral lymphocytes derived from formerly exposed precursors.

Second malignant neoplasms associated with immunosuppressive medications.

Previous studies have shown that immunosuppressive therapy permits the growth and spread of inadvertently transplanted malignant cells in man, and, in addition, is associated with a 5 to 6% incidence of de novo cancers in organ homograft recipients who were apparently free of cancer before and at the time of transplantation. In the present report two further groups of patients were studied. There was a 4% incidence of new tumors in 101 organ homograft recipient- who had had pre-existing cancers. The immunosuppressive effects of cancer chemotherapeutic agents may have been responsible for the development of 166 new malignancies in 160 patients who received treatment for 161 neoplasms. This does not contraindicate the use of chemotherapy in patients with advanced or widespread neoplasms, as the occasional development of new malignancies is far outweighed by the many months or years of control of the original tumors.