Overestimated risk of second primary malignancies in ovarian cancer patients

Registry-based cohort studies have established an increased risk of developing second primary malignancies (SPM) in patients with a primary ovarian cancer. In order to examine the accuracy of cancer registration with emphasis on registration of SPM, 344 women with ovarian cancer and 379 subsequent SPM, registered between 1958 and 1992 in the Stockholm-Gotland Cancer Registry (SGCR), a division of the Swedish Cancer Registry (SCR), were investigated. Complete records including pathology reports were examined and an additional histopathological evaluation was conducted for a sample of the group. The results revealed that 28 diagnoses of SPM were incorrectly registered (14 cases were misdiagnosed SPM of the gastrointestinal tract, mainly colon and rectum) and 34 women (with 38 SPM) were incorrectly registered with ovarian cancer. Recalculations of the risk of a subsequent cancer were performed on the basis of these findings and the results suggest an overestimation of the risk of developing SPM. Inferences of these findings to other primary sites of multiple malignancies should be made with caution and further studies are needed.     

Second primary malignancies in thyroid cancer patients

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected.     

Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers

Although radiation is considered a risk factor for thyroid cancer, the potential relationship between radiation therapy and the risk of second primary cancer among patients with first primary thyroid cancer has not been evaluated. We identified 26,639 patients with first primary thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2000. Information on radiation therapy as well as second primary cancers was recorded in SEER. The proportional hazards model was utilized to estimate adjusted risk ratios (RRs) and their 95% confidence intervals (CIs) to assess the potential association between radiation therapy for thyroid cancer and the risk of second primary cancers. With 270,674.33 person-years of follow-up, 1,896 (7.1%) of the 26,639 patients with first primary thyroid cancer developed second primary cancers. Among the second primaries, 35 occurred in the thyroid. No obvious association was observed between radiation therapy and the overall risk of second primary cancer after ten years of follow-up (RR=1.07, 95% CI=0.88-1.30). However, an increased risk was seen for several cancers, including upper digestive system cancers (RR=1.66, 95% CI=1.07-2.57) and myeloid malignancies (RR=3.26, 95% CI=1.39-7.67). Radiation therapy was associated with reduced second cancer risks for thyroid cancer (RR=0.18, 95% CI=0.04-0.76). Beam radiation might be important to the digestive system, radioactive implants might be associated with the male genital system, radioisotopes might have an effect on myeloid malignancies, and combined beam radiation with radioactive implants or radioisotopes might be related to the increased risk of respiratory system cancers. This study suggests that radiation therapy for patients with first primary thyroid cancer might be associated with an increased risk of developing a second primary cancer in the upper digestive system and second primary myeloid malignancies. Radiation therapy for adult patients with thyroid cancer might be associated with a reduced risk of second primary thyroid cancer.     

Breast cancer risk factors and second primary malignancies among women with breast cancer

Purpose To examine the association between breast cancer risk factors and second primary cancers (independent diagnoses occurring at least 12 months after the initial breast cancer diagnosis) among breast cancer survivors. Methods In this population-based study, cancer outcomes among breast cancer survivors first diagnosed during 1987–2000 were investigated. Invasive breast cancer cases were identified from the statewide tumor registry and interviewed regarding their pre-diagnosis risk factors, including reproductive and lifestyle characteristics, approximately 1 year after diagnosis. Data on second primary cancers (not recurrences) and deaths were obtained by linkage with tumor registry reports and death certificates through December 31, 2002. Hazard ratios (HR) were estimated using proportional hazards regression stratified by age and adjusted for stage and other factors. Results Among the 10,953 breast cancer cases, 10.8% experienced a second cancer diagnosis within an average of 7 years (including 488 breast, 132 colorectal, 113 endometrial, and 36 ovarian cancers). Risk of a second primary breast cancer increased according to low parity (P = 0.002), older age at menopause (P = 0.08), greater body mass index (P = 0.003) and adult weight gain (P = 0.02), and a family history of breast cancer-particularly among women with 2 or more first-degree affected relatives (HR = 1.8, 95% CI: 1.1–2.9). Reduced risk of colorectal cancer after breast cancer was observed in relation to older ages at menarche (P = 0.05), younger age at menopause (P = 0.04), postmenopausal hormone use (HR = 0.4, 95% CI: 0.3–0.7), normal body mass index (P = 0.07), and infrequent alcohol consumption (P = 0.01). Second endometrial cancer risk was associated with increasing body mass index (P < 0.01) and adult weight gain (P = 0.03). Risk of second ovarian cancer appeared related to recent alcohol intake and family history of breast cancer. Women who reported consuming any alcohol appeared to have a 55% reduction in ovarian cancer risk (95% CI: 0.2–1.0) compared to non-drinkers, while having 2 or more first-degree relatives with breast cancer was associated with an increased risk of ovarian cancer (HR = 4.3, 95% CI: 1.3–14.6). Conclusion This study suggests that family history of breast cancer as well as potentially modifiable characteristics including body weight, alcohol intake, and postmenopausal hormone use may be associated with risk of a second cancer diagnosis among breast cancer cases.     

Risk of second malignancies among survivors of pediatric thyroid cancer

Background

Thyroid carcinoma is a very rare tumor in the pediatric age group, accounting for only 1.5–3% of childhood carcinomas in the United States and Europe. We aimed to identify the risk of a second malignancy among pediatric thyroid cancer survivors.

Methods

The cohort analysis consisted of pediatric cancer patients aged less than 20 years, diagnosed with a primary thyroid cancer, identified by site code ICD-0-3: C739, and reported to the SEER 9 database between 1973 and 2013. They were followed up until December 31, 2013; the end of the study period, or up to death if earlier.

Results

Out of 1769 patients diagnosed primarily with thyroid carcinoma, 42 patients had a total of 45 incidences of subsequent malignancies. The mean age of patients at the initial diagnosis of thyroid cancer was 16 years. Females (90.5%) had a significantly higher incidence of second malignancies (SM) than males (9.5%). The overall Standardized Incidence Ratio (SIR) of SM in the study patients was higher than expected (SIR?=?1.48). Some specific sites showed significantly higher incidences: the salivary glands (SIR?=?33.95), the gum and other parts of the mouth [excluding the lips, tongue, salivary glands and floor of the mouth] (SIR?=?24.53)*** and the kidneys (SIR?=?5.72). The overall risk of SM in patients who had received radioactive iodine was higher than expected (SIR?=?4.41). The cumulative incidence of SM after treatment of thyroid cancer in children increases steadily over 40 years (11.92%).

Conclusions

Race, gender, histological subtypes, and radioactive iodine are potentially significant prognostic factors for the development of SM among pediatric thyroid cancer survivors. Identification of underlying mechanisms that raise the risk of SM is important for both treatment and follow-up strategies.

     

Prognostic factors in well-differentiated thyroid cancer

The differentiated thyroid carcinomas are malignant neoplasms most of them following an indolent course with infrequent metastases and long survival. However, a few cases behave in an aggressive fashion and, despite every attempt to treat, cause the death of the patient. Numerous investigations have been carried out to define the markers which affect the prognostic course of these tumors. There are three types of prognostic markers: clinicopathological, pathological (morphological) and biological. The first group include: age, sex, size of the tumor, multifocality, vascular and extrathyroidal invasion, grading and metastases. The second category collects some morphological features like tumor subtype, association with autoimmune thyroid diseases and ploidy. The last group features the oncogenes (RET and RET/PTC rearrangements). The accurate evaluation of all the previous prognostic markers is the basis of the treatment schemes discussed in the last section.     

Multiple primary malignancies in patients with prostate cancer: increased risk of secondary malignancies after radiotherapy

Background

New treatment strategies for prostate cancer have recently been developed, but multiple malignancies remain a major concern. The aim of this study was to evaluate the characteristics of multiple malignancies and to analyze the risk of secondary malignancies after radiotherapy for prostate cancer.

Methods

From 2000 to 2011, 150 patients with prostate cancer were treated with curative radiotherapy in our department. Patient age range was 54–92 years (median, 70 years), and the follow-up period was 4–142 months (median, 48 months). The incidence of multiple primary cancers was compared with the estimated incidence.

Results

A total of 147 patients (98 %) survived more than 12 months (12–142 months; median, 48 months); 20/150 patients (13 %) died within 10 years. Cause of death was recurrent prostate cancer in 11 patients, other primary malignancies in 7 patients, and cardiovascular disease in 2 patients. Multiple primary cancers were present in 26 of 150 patients (17 %), including 16 subsequent malignancies (11 %) with latent periods of 13–83 months (median, 43 months). The subsequent non-prostate malignancies were lung cancer in 4 patients, urinary bladder or ureter cancer in 4, stomach cancer in 3, malignant lymphoma in 2, and other in 3. Analysis of the observed incidence of secondary malignancies compared with the estimated incidence in the general population revealed a higher incidence of ureter cancer and malignant lymphoma.

Conclusion

Close attention should be paid to secondary malignancies after radiotherapy for prostate cancer, including malignancies occurring within 5 years, which could be attributable to radiotherapy.     

The risk of second cancer (SC) in patients treated for testicular seminoma

The exact risk of second cancer (S.C.) following treatment of testicular seminoma is not well determined in most series. At our institution, 122 patients with pure seminoma were treated by orchidectomy followed by radiation therapy from 1951 to 1986. Six were lost to follow-up. For the 116 remaining patients, the overall 5-, 10-, 15- and 20-year survival probability was 95%, 90%, 87%, and 84%, respectively. Eleven patients developed 12 second cancers, with a cumulative risk of 7%, 16%, and 16% at 10, 15, and 20 years, respectively. Overall, the risk of second cancer was increased (O/E = 1.97, p = 0.023). There were 3 controlateral seminoma (O/E = 50, p = 0.001), 2 transitional carcinoma of the bladder (O/E = 6.9, p = 0.035), 2 non-Hodgkin's lymphoma (N.S.), 1 acute myeloblastic leukemia, 1 chronic lymphocytic leukemia, 1 intracranial dysgerminoma, 1 rectal and 1 lung adenocarcinoma. Four tumors developed within the previously irradiated field (O/E = 2.2, N.S.). Excluding second seminoma, the overall risk of second cancer was not significant (O/E = 1.33). Five of the 11 patients with second cancer are currently alive without recurrent cancer. We conclude that patients treated for seminoma have an increased risk of second cancer but the overall prognosis remains excellent. The potential factors responsible for second cancer, including irradiation, are discussed.     

Long-term results in patients affected by testicular seminoma treated with radiotherapy: risk of second malignancies

AIMS: To report clinical results in patients with testicular seminoma treated with postoperative radiotherapy with regard to survival, acute and late toxicity, and risk of second malignancy. MATERIALS AND METHODS: 176 stage I-Il testicular seminoma patients treated with radiotherapy from 1964 to 1994 at the Radiotherapy Division of Pisa University, using 60Co or Linac, were analyzed retrospectively. The follow-up ranged from 0.13 to 32.37 years, with a median of 12.1 years. The observed numbers of second malignancies were compared with those expected, taking into account age, sex, and incidence rates from the Tuscany Tumor Registry. RESULTS: Overall and specific survival at 10-15 years were 89-82% and 93-92%, respectively. Multivariate analysis revealed a significantly better survival in patients younger than 50 years and in those treated with Linac. Severe late sequelae occurred in 8% of the patients. Sixteen second malignancies were observed (14 solid tumors and 2 leukemias); median latency was 13 years (range, 3-27) and the observed/expected ratio 1.4 (P not significant). Solid cancers were localized in the bladder (2), kidney (2), skin (2), stomach (1), prostate (1), lung (1), larynx (1), uvea (1) and contralateral testicle (1); 1 patient presented an intestinal carcinoid and 1 a metastasis from an unknown primary. The risk of a second malignancy was higher in the patient group receiving less than 4000 cGy (observed/expected, 2.8; P = 0.015). CONCLUSIONS: The study confirmed the high cure rate in stage I-II seminomas after postoperative radiotherapy. Incidence of a second malignancy was higher than expected, but the difference was not statistically significant.     

Family history of cancer and risk of second malignancies in young cancer patients in Trieste, Italy

We carried out a cohort study in the Italian province of Trieste (2001 population, 242,000) to ascertain whether the risk of a subsequent primary cancer among 265 individuals diagnosed with a first malignancy at ages up to 25 years between 1971 and 1993 differed from that in the general population and to evaluate the effect of cancer family history, quantified by the family risk index (FRI), on the occurrence of second primaries. During the follow-up (median duration = 10 years; 25th-75th percentile = 2-16), 15 cohort members developed a second cancer vs. 1.60 expected for a standardized incidence ratio (SIR) of 9.4 (p < 0.0001). The overall SIR fell to 4.7 (p = 0.004) after excluding the 8 patients with well-known cancer-predisposing conditions (SIR = 300.0; p < 0.0001) and the 50 with a positive family history (FRI >/= 1.0) of malignant tumors (SIR = 20.0; p < 0.0001). Among 114 patients treated with radiotherapy and chemotherapy for their first neoplasms and not affected by predisposing disorders, 23 with a positive family history of cancer showed a 6.4-fold excess risk of second primaries (p = 0.008) compared with 91 with a negative history (FRI < 1.0). It is imperative that clinicians carefully and regularly evaluate cancer family history of young patients with malignancies. This would enable them to identify possible individual and familial features in patients at higher risk of multiple primaries and to adopt more suitable preventive and therapeutic measures.     

Primary treatment of well-differentiated thyroid cancer

Operations for well-differentiated thyroid carcinoma should be individualized on the basis of the pathologic variety and clinically demonstrated extent of carcinoma. Although precise studies have not been carried out specifically to provide treatment plans for various clinical situations, experience does provide management policies to follow currently. The basic operation is thyroid lobectomy. This appears adequate for minimal carcinoma, small (under 1.5 cm diameter) carcinoma, and low grade encapsulated follicular carcinomas of the thyroid. Extent of operation for other clinical patterns of well-differentiated thyroid carcinoma is individualized to permit control of the disease in the neck. If well-differentiated carcinoma is recognized only postoperatively, a decision for reoperation can relate to evidence of multicentricity. Improvements in autotransplantation of parathyroid tissue and diagnostic needle biopsy have permitted improvements in therapy in recent years.     

Contralateral breast cancer and other second malignancies in patients treated by breast-conserving therapy with radiation

Metachronous contralateral breast cancers and other second malignancies were evaluated in 2,850 patients treated between 1960 and 1981 primarily with radiotherapy (RT) either alone or following breast-conserving surgery. One hundred eighty-four contralateral cancers were observed in 22,491 patient-years of observation (818 per 10(5) patient-years), with a cumulative probability of 4.5% at 5, 7.9% at 10, and 11% at 15 and 20 years. Compared to patients with unilateral tumors, those destined to develop contralateral cancers were younger (mean age 51.9 vs 56.6) and more often gave a family history of breast cancer. Contralateral breast cancers were more frequent for more extensive tumors (T3 10% vs T1-26%; with inflammatory signs 10.6% without 6%), and in patients with ipsilateral local recurrence (with 9.1%, without 5.6%). Patients with contralateral cancers had a significantly less favorable survival experience (15-year actuarial survival after primary therapy 42%) than patients without contralateral cancer (15-year survival 65.5%). In early stage patients treated with conservative surgery and RT, contralateral cancer was not prognostically more favorable than ipsilateral breast recurrence. Among 72 other second malignancies (320 per 10(5) patient-years) were 2 soft tissue sarcomas in the irradiated area. This corresponds to an incidence of 21 cases per 10(5) patient-years for survivors beyond the fifth year. The possible influence of RT on contralateral cancers and other second malignancies is discussed.     

Increased risk of second malignancies after in situ breast carcinoma in a population-based registry

Among 1276 primary breast carcinoma in situ (BCIS) patients diagnosed in 1972-2002 in the Southern Netherlands, 11% developed a second cancer. Breast carcinoma in situ patients exhibited a two-fold increased risk of second cancer (standardised incidence ratios (SIR): 2.1, 95% confidence interval (CI): 1.7-2.5). The risk was highest for a second breast cancer (SIR: 3.4, 95% CI: 2.6-4.3; AER: 66 patients per 10,000 per year) followed by skin cancer (SIR: 1.7, 95% CI: 1.1-2.6; AER: 17 patients per 10,000 per year). The increased risk of second breast cancer was similar for the ipsilateral (SIR: 1.9, 95% CI: 1.3-2.7) and contralateral (SIR: 2.0, 95% CI: 1.4-2.8) breast. Risk of second cancer was independent of age at diagnosis, type of initial therapy, histologic type of BCIS and period of diagnosis. Standardised incidence ratios of second cancer after BCIS (SIR: 2.3, 95% CI: 1.8-2.8) resembled that after invasive breast cancer (SIR: 2.2, 95% CI: 2.1-2.4). Surveillance should be directed towards second (ipsi- and contra-lateral) breast cancer.     

Management of locally invasive well-differentiated thyroid cancer

Thyroid carcinoma invasion of the aerodigestive tract and recurrent laryngeal nerve (RLN) are important factors with increase in morbidity and mortality. Primary treatment is surgery; the decision about the extent of surgery is difficult, because preserving function is as essential as removal of the tumor. This article discusses the literature relating to the assessment of disease, surgical management, and adjuvant therapy for invasive thyroid cancer of the aerodigestive tract and RLN and makes suggestions based on the authors' experience.     

Anaplastic thyroid cancer and primary thyroid lymphoma: a review of these rare thyroid malignancies

BACKGROUND: To review the current literature on the treatment of anaplastic thyroid cancer (ATC) and thyroid lymphoma (TL). RESULTS: Both anaplastic carcinoma (ATC) and TL represent rare forms of thyroid cancer. ATC behaves in a highly aggressive manner, resulting in significant morbidity and mortality. Multimodality therapy consisting of both radiotherapy (RT) and chemotherapy is essential in obtaining local/regional control. Although ATC has been relatively chemo resistant, newer agents such like taxotere show promise. The role of surgery in the treatment of ATC continues to evolve, presently it should be reserved for patients who have shown an initial response to multimodality therapy and in patients in whom a complete macroscopic resection can be achieved with minimal morbidity. The successful treatment of TL currently lies in accurately diagnosing the histological subtype. Both large B-cell and mixed lymphomas are best treated with multimodality therapy consisting of CHOP combined with hyper-fractioned RT. MALT lymphomas with there more indolent course may be amenable to single modality RT or total thyroidectomy if diagnosed at an early stage IE. DISCUSSION: Although both ATC and TL are rare, it is important for surgeons to be aware of the need for multimodality therapy when treating these patients and to understand the limited role surgery plays in diagnosis and treatment.