Relative Risk Of Second Cancers Research Articles

Previous Malignancy as a Risk Factor for the Second Solid Cancer in a Cohort of Nuclear Workers

This paper describes the results of epidemiological analysis of a cohort of nuclear workers hired at the main facilities of “Mayak” Production Association located in the city of Ozyorsk in Southern Urals of the Russian Federation. Previous malignancy as a risk factor for second cancer in a cohort of 22,373 workers occupationally exposed to ionizing radiation has been analyzed in a retrospective study with more than 60 years of follow-up. Information on main radiation and non-radiation risk factors (attained age, sex, tobacco smoking), as well as the dose of exposure to occupational ionizing radiation has been obtained for the analysis using the data from cancer register as well as other main population registries created in Epidemiological Laboratory of Southern Urals Biophysics Institute. Poisson’s regression realized in the “Amfit” module of “Epicure” statistical package has been applied for risk analysis. Excess relative risk per 1 Gy of absorbed dose of external gamma radiation and internal alpha radiation has been calculated using linear model. Among the 2,471 cancer cases accumulated in the study cohort to the end of follow-up 6.4% of second cancer cases have been diagnosed among workers occupationally exposed to protracted external gamma- and internal alpha radiation. The relative risk of second cancer (except for non-melanoma skin cancer) among nuclear workers with previously diagnosed cancer was about 4 times higher after a decade compared with those cancer patients who had single cancer only. The results showed that previous malignancy along with main non-radiation factors is statistically significant carcinogenic risk factor among nuclear workers exposed to protracted occupational radiation. Doi: 10.28991/SciMedJ-2021-0301-2 Full Text: PDF

Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models?

In the era of modern radiation therapy, the compromise between the reductions in deterministic radiation-induced toxicities through highly conformal devices may be impacting the stochastic risk of second malignancies. We reviewed the clinical literature and evolving theoretical models evaluating the impact of intensity-modulated radiation therapy (IMRT) on the risk of second cancers, as a consequence of the increase in volumes of normal tissues receiving low doses. The risk increase (if any) is not as high as theoretical models have predicted in adults. Moreover, the increase in out-of-field radiation doses with IMRT could be counterbalanced by the decrease in volumes receiving high doses. Clinical studies with short follow-up have not corroborated the hypothesis that IMRT would drastically increase the incidence of second cancers. In children, the risk of radiation-induced carcinogenesis increases from low doses and consequently the relative risk of second cancers after IMRT could be higher than in adults, justifying current developments of proton therapy with priority given to this population. Although only longer follow-up will allow a true assessment of the real impact of these modern techniques on radiation-induced carcinogenesis, a comprehensive risk-adapted strategy will help minimize the probability of second cancers.

Risk-optimized proton therapy to minimize radiogenic second cancers

Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment planning utilized a combination of a commercial treatment planning system and an in-house risk-optimization algorithm. When normal-tissue dose constraints were incorporated in treatment planning, the risk model that incorporated the effects of fractionation, initiation, inactivation, repopulation and promotion selected a combination of anterior and lateral beams, which lowered the relative risk by 21% for the bladder and 30% for the rectum compared to the lateral-opposed beam arrangement. Other results were found for other risk models.

Second primary tumors in cancer patients: A retrospective analysis based on institutional tumor registry.

1595 Background: The relative risk of developing a second tumor by site of primary tumor or gender is still unclear. Methods: We retrospectively analyzed data of 24,224 consecutive patients admitted to the European Institute of Oncology between 2000 and 2006 for a first primary invasive tumor. All the data were extracted from the institutional Tumor Registry. All tumors were registered and indexed within the same patient’s record. We limited the analysis to the patients who were diagnosed and received at least one treatment in IEO for their first primary tumor. Follow-up was based on the last registered patient’s control visit. Cumulative incidence was compared across different subgroups by means of the Gray test. The observed cases of second metachronous primary tumors was compared with the number of cancers we expected from the general Italian population. We used the standardized incidence ratio (SIR), defined as the ratio of the number of second cancers observed to the number of second cancers expected, to estimate the relative risk of second cancers, and we calculated 95% confidence intervals (95% CIs) by applying the Wilson and Hilferty approximation for chi-square percentiles. Results: In this population the 5-year cumulative incidence of a second tumor on the average population was 5.0%, SIR (CI 95%) was 1.3 (1.2-1.4). The Table reports details on observed versus expected second metachronous primary tumors by first tumor site. Conclusions: Cancer patients have a higher risk of a second primary tumor than general population. [Table: see text]

Region of Treatment in Radiotherapy and Second Malignancies in Breast Cancer Patients

A cohort study was conducted based on clinical records for 5248 women treated for breast cancer in Florence (Italy), with continuous follow up from 1965 to 1994. The subjects were categorised into groups such as no radiation treatment; breast dose only; and radiation doses in one, two, three or four of the following fields: namely internal mammary chain, supraclavicular nodes, axillary lymph nodes and chest wall. The Cox proportional hazards model for ungrouped survival data was used to estimate the relative risk for second cancer after radiotherapy delivered to different regions. The relative risk for all second cancers combined was statistically significantly raised if the internal mammary chain and supraclavicular nodes were irradiated. However, we found that the relative risk of the second malignancies could be reduced if all the locoregional lymph nodes (the internal mammary chain, supraclacicular nodes, axillary nodes) and chest wall are irradiated at the same time. If this finding can be verified by other large cohort studies or randomized clinical trials, it may have implications in clinical practice when deciding upon the targeted areas for radiotherapy; partial radiation treatment of the locoregional lymph nodes could raise the risk of second malignancies and should ideally be avoided.

Simultaneous Presentation of Hairy Cell Leukemia and Metastatic Signet Ring Carcinoma of the Stomach Diagnosed by Bone Marrow Biopsy

Hairy cell leukemia (HCL) is a rare chronic B-cell disorder with an increased risk of second tumors. The relative risk of second cancers reported in various series of HCL patients ranged from 0.95 to 4.33, but simultaneous presentation of HCL and other epithelial malignancies is very rare. To our knowledge, we present the first case of the coexistence of signet ring carcinoma of the stomach and HCL. We report a case of the simultaneous presentation of HCL and metastasis of the primary signet ring cell carcinoma of the stomach to the bone marrow and skin. A bone marrow biopsy was performed on a patient with pancytopenia. A histologic examination with immunostaining of the bone marrow specimen showed the presence of signet ring carcinoma cells in addition to HCL. As a consequence, our patient underwent further diagnostic procedures including endo-gastro-duodenoscopy with biopsy of gastric tumor mass, which established the diagnosis of gastric signet ring cell carcinoma.

Second malignancies in breast cancer patients following radiotherapy: a study in Florence, Italy.

IntroductionPatients diagnosed with breast cancer are often treated with surgery followed by radiation therapy. In this paper, we evaluate the effect that radiotherapy may have had on the subsequent risk of second malignancies, including the possible influences of age at treatment and menopausal status.MethodsIn order to evaluate the long-term consequences of radiotherapy, a cohort study was conducted based on clinical records for 5,248 women treated for breast cancer in Florence (Italy), with continuous follow-up from 1965 to 1994. The Cox proportional hazards model for ungrouped survival data was used to estimate the relative risk for second cancer after radiotherapy.ResultsThis study indicated an increased relative risk of all second cancers combined following radiotherapy (1.22, 95% CI: 0.88 to 1.69). The increased relative risk appeared five or more years after radiotherapy and appeared to be highest amongst women treated after the menopause (1.61, 95% CI: 1.13 to 2.29). Increased relative risks were observed specifically for leukaemia (8.13, 95% CI: 0.96 to 69.1) and other solid cancers (1.84, 95% CI: 1.06 to 3.16), excluding contralateral breast cancer. For contralateral breast cancer, no raised relative risk was observed during the period more than five years after radiotherapy.ConclusionsThe study indicated a raised risk of second malignancies associated with radiotherapy for breast cancer, particularly for women treated after the menopause.

Long-Term Survival and Risk of Second Cancers After Radiotherapy for Cervical Cancer

To evaluate the risk of second cancers after cervical cancer treated with radiotherapy for Asian populations. We reviewed 2,167 patients with cervical cancer undergoing radiotherapy between 1961 and 1986. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (12%). Relative risk (RR), absolute excess risk (AR), and cumulative risk of second cancer were calculated using the Japanese disease expectancy table. For 1,031 patients, the impact of smoking habit on the increasing risk of second cancer was also evaluated. The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among the 2,167 patients, 1,063 (49%) survived more than 10 years. Second cancers were observed in 210 patients, representing a significant 1.2-fold risk (95% confidence interval [CI], 1.1-1.4) of developing second cancer compared with the general population, 1.6% excess risk per person per decade of follow-up, and elevating cumulative risk up to 23.8% (95% CI, 20.3-27.3) at 30 years after radiotherapy. The RR of second cancer was 1.6-fold for patients with the smoking habit and 1.4-fold for those without. Small but significant increased risk of second cancer was observed among Japanese women with cervical cancer mainly treated with high-dose rate brachytherapy. Considering the fact that about half of the patients survived more than 10 years, the benefit of radiotherapy outweighs the risk of developing second cancer.

Risk of a second malignant neoplasm among 5‐year survivors of cancer in childhood and adolescence in British Columbia, Canada

We examined second malignancies, a recognized late effect of therapy among survivors of childhood and adolescent cancer, among a recent, population-based cohort of 2,322 5-year survivors diagnosed before 20 years of age in British Columbia (BC), Canada between 1970 and 1995. Survivors and second malignancies were identified from the BC Cancer Registry. Risk of second malignancy was evaluated using standardized incidence ratios (SIRs), absolute excess risk (AER), and cumulative risk. The effect of demographic, temporal, and disease-related characteristics on risk was assessed. Fifty-five second malignancies were observed after 26,071 person-years of follow-up. Relative rate of developing a second malignancy among survivors was 5 times higher than expected (SIR = 5.0, 95% CI, 3.8-6.5), and absolute excess risk was 1.7 deaths per 1,000 person-years. Cumulative incidence of a second malignancy was 5.1% at 25 years after diagnosis of the first cancer. SIRs and absolute excess risk of subsequent cancer was higher among females (SIR = 5.9, 95% CI, 4.5-8.3 and AER = 2.66). While relative risk of second cancer was higher for those diagnosed before 10 years of age (SIR = 10.6, 95% CI, 7.1-16.0), absolute excess risk was slightly higher for those diagnosed after 10 years of age. SIRs were significantly elevated for all follow-up periods, but absolute excess risk of a second cancer was highest among patients surviving more than 15 years. Increased risk of a subsequent neoplasm is evident among childhood cancer survivors diagnosed in more recent periods than has been previously reported, continues years after diagnosis, and varies according to several risk factors. Continued surveillance is essential to quantify and characterize long-term and changing risks for appropriate follow-up.

Multiple primary cancers in families with Li-Fraumeni syndrome.

Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, sarcomas, and other cancers in children and young adults. Members of families with this syndrome also develop multiple primary cancers, but the frequency is unknown. To approach this issue, we quantified the incidence of second and third primary cancers in individuals from 24 Li-Fraumeni kindreds originally diagnosed with cancer during the period from 1968 through 1986. The relative risk (RR) of subsequent cancers and 95% confidence intervals (CIs) were calculated by use of population-based incidence data from the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative probability (+/- standard error) of subsequent cancers. Among 200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while four (2%) eventually developed a fourth cancer. Overall, the RR of occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer occurrence of 57% (+/- 10%) at 30 years after diagnosis of a first cancer. RRs of second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of Li-Fraumeni syndrome. Compared with the general population, members of Li-Fraumeni syndrome families have an exceptionally high risk of developing multiple primary cancers. The excess risk of additional primary cancers is mainly for cancers that are characteristic of Li-Fraumeni syndrome, with the highest risk observed for survivors of childhood cancers. Cancer survivors in these families should be closely monitored for early manifestations of new cancers.

Leukaemias and cancers following iodine-131 administration for thyroid cancer

We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).

Second malignancy in hairy cell leukaemia: no evidence of increased incidence after treatment with interferon alpha.

The last decade has seen a dramatic improvement in prognosis of hairy cell leukaemia (HCL) but concern has emerged with regard to the incidence of second malignancy. A recent report found an 18.8% incidence of second cancers and suggested a possible role for alpha-interferon (IFN) in their pathogenesis. We reviewed our larger series of 200 patients with HCL. We found second malignancies in 8 cases (4.0%), all but one of whom had received IFN. However, when compared to age- and sex- matched population data this represents no increase in relative risk of second cancer in patients with HCL and provides no evidence of a role for IFN in the pathogenesis of these second malignancies.

Risk of second primary cancer after Hodgkin's disease in patients in the British National Lymphoma Investigation: relationships to host factors, histology and stage of Hodgkin's disease, and splenectomy.

The risks of second primary cancer were analysed in 2846 patients with Hodgkin's disease treated within the British National Lymphoma Investigation during 1970-87. The relative risk (RR) of leukaemia was significantly greater in women (RR = 30.1; 95% confidence limits (CL) 13.0-59.5) than in men (RR = 10.9; 95% CL 4.7-21.5), and showed a significant trend of greater risk with younger age at first treatment (P < 0.001). The relative risk of solid cancers was similar between the sexes, but again significantly greater at young than at older ages of first treatment (P < 0.01). Non-Hodgkin's lymphoma relative risks, although not related to sex or age, were significantly related to histology of the original Hodgkin's disease, and were greatest after lymphocyte predominant Hodgkin's disease (RR = 55.6; 95% CL 18.0-129.7). The relative risk of second cancers did not vary significantly according to whether or not splenectomy had been performed. Leukaemia risk was non-significantly greater after splenectomy than with no splenectomy, which accorded with previous evidence of a modest increased risk associated with this operation. If the greater relative risk of solid second cancers after treatment at young than at older ages persists with longer follow-up, the incidence rates of these second primaries in patients treated young for Hodgkin's disease will become very substantial as they age. This emphasises the need to maintain long-term follow-up surveillance of young Hodgkin's disease patients apparently cured of their disease, and to continue to develop new less carcinogenic treatment regimens.

Increased risk of second cancers in managing Hodgkins disease: the 20-year Leiden experience.

Between January 1969 and December 1988, 482 patients were treated for Hodgkin's disease at the Leiden University Hospital. All cases were routinely recorded in the Hospital Information System, which has an active annual follow-up. Of all patients, 57% remained relapse free. According to the kinds of treatment they received, the following major categories were established: radiotherapy only (28.2%), chemotherapy only (20.1%), only initial combination of radiotherapy and chemotherapy (34.2%), all other combinations of radio- and chemotherapy (15.4%), or not registered (2.1%). Twenty-seven second cancers were observed; six leukemias, five non-Hodgkin lymphomas, and 16 solid tumors. Of all solid tumors only nine occurred in relapse-free patients. The overall relative risk of second cancers increased with the duration of follow-up. Using general population incidence rates to calculate expected numbers, the risk for developing leukemia, non-Hodgkin lymphoma, and solid tumors was increased 36-fold, 31-fold, and 2.4-fold, respectively. The cumulative risk of developing a second cancer 10 years after diagnosis of Hodgkin's disease was 7% for both the radiotherapy-only and the initial combination of radio- and chemotherapy group. It was 16% and 17% for the chemotherapy-only and the other combinations of radio- and chemotherapy group, respectively. Multivariate analysis (using the Cox regression model) show an increased risk of second cancers (RR = 0.7) when a relapse of Hodgkin's disease resulting in increasing cumulative therapy occurred. Age at diagnosis of Hodgkin's disease was an important determinant for the risk of non-Hodgkin lymphoma and solid tumors. Cumulative chemotherapy intensity was an important factor in increasing leukemic risk in a dose-response fashion. Apart from this, the stage of Hodgkin's disease, although closely related to the kind of therapy, seemed to have an independent effect on leukemic risk.