Second primary malignancies in patients with neuroendocrine tumors

Purpose

An association between neuroendocrine tumors (NETs) and second primary malignancies (SPMs) has been reported. We have examined the incidence and etiology of SPMs in patients with NETs included in the Neuroendocrine Tumor Association of Andalusia (ATNEA) Registry.

Methods

Data on 111 patients were collected. Sex, age, NET site, chromogranin A levels, neuropeptide secretion and disease stage were compared between NETs with and without SPMs.

Results

SPMs were present in 21 patients (18.9 %): five colorectal tumors, four non-small-cell lung cancers, three gastric cancers, two tumors in the small intestine, one hepatocarcinoma, two ovarian tumors, one breast adenocarcinoma, one hypernephroma, one bladder cancer, and one neuroblastoma. SPMs were present in 18 % of patients with a gastrointestinal NET and 22 % of those with a non-gastrointestinal NET. SPMs were found in 23 % of patients with elevated levels of serum chromogranin A, compared to 17 % of patients with normal levels, and in 22 % of patients with functional tumors, compared to 11 % of those with non-functional tumors. Finally, SPMs were observed in 24 % of patients with a local or locoregional tumor but in only 13 % of those with a metastatic tumor. No other differences between patients with and without SPMs were observed.

Conclusions

The percentage of patients with SPMs in the ATNEA Registry is similar to those reported in other series. In our registry, patients with functional NETs and local/locoregional tumors have higher probability of SPMs. The low number of patients, selection bias and other etiologic factors of SPMs may have influenced our results.     

Multiple primary malignancies in patients with sporadic pancreatic endocrine tumors

BACKGROUND: To investigate the appearance of multiple primary malignancies in patients with sporadic neuroendocrine pancreatic tumors (NEPTs). METHODS: One hundred forty-five patients with NEPTs were treated at the Department of Surgery, Philipps-University Marburg. Multiple primary malignancies included tumors that were not considered to be a metastasis, invasion, or recurrence of NEPTs. Data on sex, age at diagnosis of cancer, follow-up time after diagnosis, and death rate were collected. RESULTS: Of 115 patients with sporadic NEPTs, 15 (13.0%) patients were identified with at least one malignant tumor, other than a NEPT. The median age at diagnosis of the associated tumor(s) was 57 years (range, 10-72 years). Two of the 15 patients had insulinomas, 5 had gastrinomas and 8 had non-functioning NEPTs, respectively. The risk of developing multiple cancers was the highest for patients with gastrinoma (21.7%), followed by patients with non-functioning NFPTs (20.5%). CONCLUSIONS: In patients with NEPTs multiple primary malignancies are found more frequently than in the general population. The etiology of the increased risk of other primaries is not clearly defined, but it may be the result of accumulated growth stimulation by the secreted hormones or a genetic alteration that leads to tumorogenesis in these patients.     

Lymphocyte subpopulations in patients with multiple primary tumors

BACKGROUND: Cancer patients with single tumors live longer today due to earlier detection and improved treatment methods. For this reason, the authors see more patients who develop a second primary tumor. The etiology of the second tumor can be the same as the first, whether treatment-induced or unknown. The prognoses of these patients usually depend on the behavior of the second tumor. METHODS: The authors investigated the lymphocyte subset in 88 of the more than 750 patients listed in the tumor registry at their treatment center who had at least one carcinoma of the breast or colon and a second primary of the same or another site. Mononuclear cells were obtained from heparinized blood by the standard fractionation Hypaque gradient centrifugation technique. Helper and suppressor cells were identified by using three murine monoclonal antibodies: CD3 for mature T lymphocytes, CD4 for helper inducer cells, and CD8 for suppressor cytotoxic cells. T-cell subset distribution was evaluated with flow cytometry. RESULTS: Most values of CD3, CD4, and CD4/CD8 were lower in patients than in healthy controls. The values of CD4 and CD4/CD8 were lower in patients who had a second tumor in the colon rather than in the breast. CONCLUSIONS: As tumors in patients with a second primary sometimes recur or the patient develops a third primary, the authors are prospectively following their patients to see whether those with immunosuppression have a greater tendency to develop recurrent disease or a third primary.     

合并甲状腺癌的多原发性癌的临床及病理特征分析

  目的  分析合并甲状腺癌的多原发性癌患者的临床及病理特征。  方法  回顾性分析2007年10月至2017年3月云南省肿瘤医院确诊的4 861例甲状腺癌患者,从中筛选出290例（5.97%）合并其他恶性肿瘤的多原发癌患者,分析其临床及病理特征。  结果  筛选出290例甲状腺癌患者,其中7例（2.4%）为三原发性恶性肿瘤,283例（97.6%）为双原发性恶性肿瘤。以肿瘤发生时间分类:83例（28.6%）为同时性多原发性癌,207例（71.4%）为异时性多原发性癌。248例（85.5%）患者以其他恶性肿瘤为首发,甲状腺癌为后发现。本研究以女性256例（88.3%）、年龄≥45岁191例（65.9%）、甲状腺乳头状癌281例（96.9%）多见。甲状腺癌最常合并的原发癌是乳腺癌44.5%（129/290）,其次是宫颈癌、肺癌、结直肠癌等。  结论  年龄≥45岁女性恶性肿瘤患者,尤其是乳腺癌患者,在随访复查过程中建议进行甲状腺癌筛查。      

Second primary malignancies among patients with soft tissue tumors in Sweden

Survival from soft tissue tumors (STTs) has been improved because of the successful treatment. One of the late sequelae in STT survivors is the development of a second malignancy. The present study aimed at quantifying risks for second malignancies in patients with STTs, and risks for second STTs after other primary malignancies. Adjusted standardized incidence ratios (SIRs), calculated from the Swedish Family-Cancer Database, were used as a measure of risk. Among 6,671 primary STT patients, a total of 650 second malignancies occurred. Besides second STTs, other cancer sites with an increased SIR were the nervous system, endocrine glands, skin (melanoma and squamous cell carcinoma) and prostate; the risk for non-Hodgkin lymphoma (NHL) was also increased. The overall risk of second malignancies decreased in the following order: fibrosarocma (1.63) > myxosarcoma (1.48) > leiomyosarcoma (1.44) > liposarcoma (1.21). An increased risk of second STTs after primary cancers of the bone, ovary, nervous system, cervix, thyroid gland, skin, endometrium, breast, upper aerodigestive tract, and after Hodgkin disease, NHL and leukemia was also noted. This study showed that the incidence of second primary malignancies in patients with STTs was increased, but the SIRs varied among specific cancer sites. Besides therapeutic effects, the associations between STTs and bone and nervous system tumors suggested that cancer syndromes, such as neurofibromatosis type 1 and Li-Fraumeni syndrome, may partly explain the excesses. The associations of STTs with cancers of the skin (squamous cell carcinoma and melanoma) and with NHL may be related to immunodeficiency.     

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.     

卵巢少见原发肿瘤的临床特点及 MRI 征象对比

目的：探讨几种卵巢原发少见肿瘤的临床及 MRI 特点,提高该类病变的诊断准确率。方法：回顾性研究45例经手术病理证实的卵巢少见原发肿瘤的临床及术前 MRI 资料。结果：45例卵巢肿瘤患者48处肿块,单侧病灶42例,双侧病灶共3例,包括卵巢子宫内膜样腺癌12例,透明细胞癌6例,颗粒细胞瘤8例,卵泡膜细胞瘤10例,纤维瘤9例;患者多数见于围绝经期及绝经后女性,临床表现多样,上皮样肿瘤可见 CA125升高及部分 CEA 升高,颗粒细胞瘤及卵泡膜细胞瘤可出现雌激素增高及相关依赖症状,纤维瘤症状轻微;MRI 平扫卵巢肿块多为囊实性,实性肿块次之,但病灶内成分及信号存在差异,增强扫描强化特点及 DWI 信号各异,有助于提高诊断率。结论：几种卵巢少见肿瘤的临床表现及 MRI 征象具有一定的差异性,综合应用对肿瘤的定性诊断有重要的临床价值。     

Non-AIDS-defining malignancies in HIV patients: clinical features and perspectives

Eventhough the advent of highly active antiretroviral therapy (HAART) has dramatically improved patient outcome and provided a significant shrinking of the cases and severity of opportunistic infections, AIDS malignancies have become responsible of a new vexing challenge in HIV patient care and cure. Indeed, malignant tumors currently rank among the leading cause of morbidity and mortality in patients infected with HIV. In addition to the AIDS-malignancies, non-AIDS defining tumors have a higher incidence than the general population such as Hodgkin disease, lung cancer, cutaneaous cancer and anal cancer. These malignant tumors are generally characterized by a more aggressive behaviour at diagnosis and a poorer outcome compared with the same tumors in the general population. Although recent therapeutic advances have been made in chemotherapy, combinations with antiretroviral agents, for many of these malignancies the pronostic remains poor and there is a deeply lack of current therapeutic guidelines for these cancer patients care and cure. These recommendations might be the fruit of a new networking between HIV specialists and oncologists and of an improving knowledge of the pathogenesis and clinical features of these AIDS non-defining tumors.     

Longitudinal study of smoking patterns in relation to the development of smoking-related secondary primary tumors in patients with upper aerodigestive tract malignancies

BACKGROUND: The authors set out to assess the correlation between smoking-related second primary tumor (SPT) development and cigarette smoking habits after diagnosis and definitive treatment in patients with early-stage head and neck squamous cell carcinoma who were enrolled in a placebo-controlled randomized chemoprevention trial of 13-cis-retinoic acid. METHODS: Longitudinal data collected for 10 years after the index diagnosis are presented for 1190 patients. Cox proportional hazards regression models were used to examine the effects of changes in smoking behavior on smoking-related SPT development. RESULTS: One-third of all patients who quit smoking within 12 months before randomization experienced recurrence, compared with 6.9% and 10.4% of all never-smokers and former smokers, respectively. Approximately 16% of all current smokers stopped smoking, and nearly 22% of current smokers developed SPTs, compared with 14.5%, 13.2%, and 8.8% of all recent smokers, former smokers, and never-smokers, respectively. The probability of developing a smoking-related SPT was highest among patients who were current smokers at randomization. These patients, regardless of whether they ceased smoking during follow-up, were nearly three times more likely than patients who had never smoked to develop a smoking-related SPT. In contrast, former smokers and recent quitters who continued to abstain from smoking during follow-up were approximately 1.5 times more likely to develop an SPT compared with patients who had never smoked. CONCLUSIONS: Patients who continue to smoke after the successful treatment of their index head and neck malignancies have a substantially higher risk of developing smoking-related SPTs.     

Gastrointestinal carcinoid tumors and second primary malignancies

The development of second primary malignancies (SPM) in patients with gastrointestinal carcinoid tumors is a well-described phenomenon, with reported rates as high as 55%. There is a predilection for gastrointestinal and genitourinary adenocarcinomas, but a variety of other malignancies have been reported as well. The etiology of this malignant predisposition may be rooted in the tumorigenic properties of the various neuroendocrine peptides elaborated and secreted by neuroendocrine cells. Peptides such as secretin, gastrin, bombesin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) are believed to promote the growth of tumor cells. As many as 30 peptides and amines identified in neuroendocrine cells may have similar properties. This review of the literature on carcinoid-associated second primary malignancies is accompanied by a case report of metastatic carcinoid identified during surgical exploration for a perforating colon adenocarcinoma.     

Therapy of synchronous multiple primary malignancies

The data on 526 patients treated for primary multiple synchronous malignancies were evaluated. The total number of detected tumors was 1,069; concomitant pathology was identified in 377 out of 490 (76.9 +/- 1.9%). Removal of all synchronous tumors was considered radical--and palliative or symptomatic when, whatever the modality, two or at least one tumor was treated. Most of primary multiple synchronous tumors were removed radically (56.4 +/- 2.3%). The best results were obtained when combined therapy was used for early-stage tumors while surgical treatment of advanced cancer was complemented with radiochemotherapy. Radical treatment was contraindicated in 30.3 +/- 3.8% because of concomitant pathology.     

Thyroid cancer and multiple primary malignancies in Israel

The exact risk of multiple primary neoplasms in patients with thyroid cancer is difficult to ascertain from the data available in the literature. Three thousand seventy-two patients with thyroid cancer, listed in the Israel Cancer Registry during a 16-year time span, were studied to determine the true incidence of another primary cancer. Ninety-two cases were reported as having an additional primary cancer. The prevalence of multiple primary malignancies was 3%. The frequency was higher among patients of European rather than of Asian or African origin. The second primary cancers in order of decreasing frequency were of the breast, lung, colorectum, head and neck, and lymphoma/myeloma. Most of the deaths were due to the additional cancer. The 5-year survival rate was highest for head and neck and lowest for lung cancer patients. These results emphasize the need for greater awareness of the possibility of developing additional cancers, and indicate the need to incorporate strategies for the prevention, early detection, and treatment of multiple primary neoplasms.     

Incidence of multiple primary malignancies in a cohort of adult patients with soft tissue sarcoma

OBJECTIVE: Some studies to date have suggested the development of multiple primary malignancies in patients with soft tissue sarcoma. The current study was performed to quantify the risk of development of multiple primary malignancies in adult patients with soft tissue sarcoma. METHODS: A total of 406 consecutive patients who were diagnosed with soft tissue sarcoma were identified in the study analysis. The cumulative incidence of multiple malignancies was calculated by comparing Kaplan-Meier curves and log-rank tests from each histological type. A Cox proportional hazards model was used to estimate the influence on the hazard ratio (HR) of each variable. RESULTS: A total of 35 patients with soft tissue sarcoma (9%), having preceding (n = 15) and subsequent (n = 20) malignancies other than soft tissue sarcoma were documented. The 5- and 10-year estimated cumulative incidence of multiple primary malignancies were 7.6 and 12.3%, respectively. The hazard risk of multiple primary malignancies adjusted for potential confounding variables was significantly associated with age at diagnosis (HR = 1.51, P = 0.0019). The risk of multiple primary malignancies was also increased in patients with myxofibrosarcoma adjusted by the potential confounding variables (HR = 2.34, P = 0.048). The 5- and 10-year estimated cumulative incidence of multiple primary malignancies in patients with myxofibrosarcoma were both 16.9%. CONCLUSION: The results of our study confirm that the risk of multiple malignancies appears to be impacted by age at the time of diagnosis of the first tumor and by the histological type of myxofibrosarcoma.     

Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor

Background: We sought to investigate the characteristics and survival rate of patients with gastrointestinal stromal tumor (GIST) associated with other primary malignancies.Patients and methods: A total of 783 patients with GIST were identified from 1995 to 2007. Additional primaries included tumors not considered metastasis, invasion, or recurrence of GIST, nor non-melanoma skin cancer. Data on gender, age at diagnosis, follow-up time after diagnosis, and death were collected.Results: Of the 783 patients with GIST, 153(20%) were identified with at least one additional primary. Patients with additional primaries were more often men (M : F 1.5 versus 1.3) and older (66 versus 53 years). More patients had another cancer diagnosed before (134) than after (52) GIST. Primaries observed before GIST were cancers of the prostate (25), breast (12), esophagus (9), and kidney (7) and melanoma (6). Lung (5) and kidney (5) primaries were the most frequent after GIST. The 5-year survival was 68% for patients with primaries before GIST, 61% for patients with primaries after GIST, 58% for patients with GIST only, and 49% for patients with two or more primaries in addition to GIST (P = 0.002).Conclusions: Approximately 20% of patients with GIST develop other cancers. Inferior median 5-year survival was observed in patients with GIST with two or more other cancers. The etiology and clinical implications of other malignancies in patients with GIST should be investigated.     

Second malignancies in patients with multiple myeloma.

Seven patients with multiple myeloma who developed a second neoplasm are presented. There were four patients with acute leukemia and three patients with non-hematologic neoplasms. The patients with acute leukemia were among the longest survivors (median duration approximately 72 months) and the response to anti-leukemic therapy in these patients was generally poor. Of the three patients with non=hematologic neoplasms, one patient was observed with simultaneous renal cell carcinoma and the other two patients developed adenocarcinoma of the colon and lung subsequently. In addition, two patients with mammary carcinoma who subsequently developed multiple myeloma were included. Literature was reviewed and the possibility that multiple myeloma itself might be a risk factor for the development of other malignancies was discussed.     

Clinical features and outcomes of patients with stage I multiple primary lung cancers

The number of patients with multiple primary lung cancers (MPLC) is rising. We studied the clinical features and factors related to outcomes of MPLC patients using the database of surgically resected lung cancer (LC) cases compiled by the Japanese Joint Committee of Lung Cancer Registry. From the 18 978 registered cases, 9689 patients with clinical stage I non-small-cell lung cancer who achieved complete resection were extracted. Tumors were defined as synchronous MPLC when multiple LC was simultaneously resected or treatment was carried out within 2 years after the initial surgery; metachronous MPLC was defined as second LC treated more than 2 years after the initial surgery. Of these cases, 579 (6.0%) were synchronous MPLC and 477 (5.0%) metachronous MPLC, with 51 overlapping cases. Female sex, nonsmoker, low consolidation-tumor ratio (CTR), and adenocarcinoma were significantly more frequent in the synchronous MPLC group, whereas patients with metachronous MPLC had higher frequencies of male sex, smoker, chronic obstructive pulmonary disease (COPD), and nonadenocarcinoma. There was no significant difference in survival rate between patients with and without synchronous or metachronous MPLC. Age, gender, CTR for second LC, and histological combination of primary and second LC were prognostic indicators for both types of MPLC. Logistic regression analysis showed that female sex, history of malignant disease other than LC, and COPD were risk factors for MPLC incidence. The present findings could have major implications regarding MPLC diagnosis and identification of independent prognostic factors, and provide valuable information for postoperative management of patients with MPLC.     

肺癌和肺外器官恶性肿瘤组成的多原发癌281例临床分析

背景与目的:随着肿瘤诊断水平的提高,肺及肺外器官多原发癌的发现逐渐增多,而其临床特征和预后尚未完全明了。本研究回顾性分析肺及肺外器官恶性肿瘤组成的多原发癌临床特征、吸烟影响、肺癌与肺外器官恶性肿瘤间关系及预后。方法:收集本院1990年1月至2000年12月收治的发生于肺及肺外器官的多原发癌患者资料281例:115例首发器官为肺,继发器官为肺或肺外器官(A组);166例首发器官为肺外器官,继发器官为肺(B组)。分析两组患者的临床特征及预后。结果:A、B两组性别比无差异(P=0.51)。诊断第一原发癌时患者中位年龄A、B两组间有显著性差异(62.5岁vs.54.5岁,P=0.02);但诊断重复癌时患者中位年龄两组无显著性差异(64.5岁vs.63.5岁,P=0.08)。第一原发癌与重复癌的时间间隔,A组与B组有显著性差异(36.0个月vs.49.0个月,P<0.001)。A组中Ⅰ～Ⅱ期肺癌占83.9%,B组占63.7%,A组肺癌病理分期较B组早(P<0.01)。从第一原发癌确诊算起,A、B两组中位生存时间分别为69.0个月和87.5个月,5年生存率分别为59.0%和70.0%,B组优于A组(P<0.001)。从重复癌确诊算起,A、B两组中位生存时间分别为25.0个月和28.0个月,5年生存率分别为10.5%和13.5%,两者无显著性差异(P=0.92)。重复癌多见部位依次是肺第二原发癌、上呼吸道、乳腺、食道、结直肠、胃、宫颈。吸烟是引起肺及上呼吸道多原发癌危险因素。结论:发生于肺及肺外器官的多原发癌中,肺外恶性肿瘤可发生在多个脏器,其中肺第二原发癌和上呼吸道恶性肿瘤发生率较高,吸烟是其潜在的危险因素。首发器官为肺外器官的多原发癌患者,与首发器官为肺的患者相比,患第一原发癌时其年龄较小,预后较好,出现重复癌间隔时间较长。     

Risk factors for double primary malignancies and their clinical implications in patients with sporadic gastric cancer

Aims

We carried out a large scale study to identify the risk factors for double primary malignancy (DPM) development in gastric cancer patients and to evaluate the clinical implications for these patients.

Methods

A total of 2593 patients who underwent gastrectomy for primary gastric cancer from January 2005 to November 2010 were reviewed with regard to DPM. We compared the clinicopathological characteristics, risk factors for developing DPM, and prognosis between the DPM(+) group and the DPM(−) group.

Results

Of the 2593 patients, 152 (5.9%) were diagnosed with DPM. The most common accompanying malignancies were colorectal, lung and thyroid. Multivariate analysis indicated that age (p = 0.016) and MSI status (p = 0.002) were associated with a higher frequency of DPM. 30.3% of patients were diagnosed with DPM within 1 year around perioperative period and 53.3% of patients had DPM detected during 5 years of post-operative follow up periods. Although there was no significant difference in overall survival between the DPM(+) and DPM(−) group, DPM(+) patients had a worse prognosis than DPM(−) patients in stage I gastric cancer.

Conclusions

Gastric cancer patients over the age of 60 or with a MSI-high status had an increased risk for developing DPM. Further, in stage I gastric cancer, the presence of DPM was associated with a worse prognosis. Therefore, careful pre- and postoperative surveillance is especially important in these patients.     

Metachronous multiple primary tumors of the female genitals. Role of radiotherapy in secondary tumorigenesis

According to the Center's register, primary multiple tumors were detected in 584 patients (5%) (metachronous--413 (70.7%); synchronous--138 (23.6%) in 1960-1998. In 4.8%, both types were hormonally-dependent; familial cancer was identified in 10.8%. Out of 298 patients treated with radiation, 41 (13.8%) developed tumors in the area of exposure. Excessive dosage due to taking repeat courses for relapse was received by 10 (24.4%). Thirty patients (10.1%) had malignancies outside the exposed area, in distant organs. Such factors as total over dosage due to repeat courses, extensive exposure of the bone marrow and idiosyncrasy to radiotherapy were mainly responsible for secondary tumorigenesis both in and outside zone of exposure.