Issues in Managing Hurthle Cell Carcinoma of Thyroid: A Case Report.

A 61-year-old woman noticed a right neck lump in October 2001. Fine needle aspiration showed follicular neoplasm, adenoma versus carcinoma. The ultrasound scan showed a solid mass of maximum dimension of 3.7 cm. She had a right thyroid lobectomy and isthmectomy in January 2002 (first surgery). The tissue specimen showed a 4.5 cm Hurthle cell carcinoma (HCC) with vascular invasion. There were no capsular invasion, extra-thyroidal extension, or margin involvement. A completion left lobectomy (second surgery) was performed two weeks later. Therefore the pathological stage is II (T3N0M0). She received adjuvant radioactive iodine ablation for residual thyroid tissue. By 2003, she developed local recurrence, which was resected (third surgery), followed by adjuvant external beam radiotherapy. Unfortunately, she developed further recurrence in the left main bronchus, as identified by Indium-111 Octreotide (Curium, Missouri, USA) and positron emission tomography-computed tomography PET-CT imaging in 2006. She underwent a left pneumonectomy (fourth surgery) in July 2006. In November 2007 she was found to have mediastinal recurrence which was treated with high-dose external beam radiotherapy. She initially responded but developed more local recurrence and a lung metastasis by 2011. She was treated with brivanib with ixabepilone, under a phase I clinical trial with mixed response. Her treatment was discontinued secondary to toxicity and she succumbed to her disease in 2012. This case report illustrates the natural history and clinical decision making for patients diagnosed with HCC of the thyroid. Specifically, we highlight the clinical issues surrounding the histopathological diagnosis, extent of surgical resection, radioiodine diagnostic imaging/ablative treatment, as well as external beam radiotherapy.

Low-serum GTA-446 anti-inflammatory fatty acid levels as a new risk factor for colon cancer.

Gastrointestinal tract acid-446 (GTA-446) is a long-chain polyunsaturated fatty acid present in the serum. A reduction of GTA-446 levels in colorectal cancer (CRC) patients has been reported previously. Our study compared GTA-446 levels in subjects diagnosed with CRC at the time of colonoscopy to the general population. Serum samples and pathology data were collected from 4,923 representative subjects undergoing colonoscopy and from 964 subjects from the general population. Serum GTA-446 levels were determined using a triple-quadrupole tandem mass spectrometry method. A low-serum GTA-446 level was based on the bottom tenth percentile of subjects with low risk based on age (40-49 years old) in the general population. Eighty-six percent of newly diagnosed CRC subjects (87% for stages 0-II and 85% for stages III-IV) showed low-serum GTA-446 levels. A significant increase in the CRC incidence rate with age was observed in subjects with low GTA-446 levels (p = 0.019), but not in subjects with normal levels (p = 0.86). The relative risk of CRC given a low GTA-446 level was the highest for subjects under age 50 (10.1, 95% confidence interval [C.I.] = 6.4-16.4 in the reference population, and 7.7, 95% C.I. = 4.4-14.1 in the colonoscopy population, both p < 0.0001), and declined with age thereafter. The CRC incidence rate in subjects undergoing colonoscopy with low GTA-446 levels was over six times higher than for subjects with normal GTA-446 levels and twice that of subjects with gastrointestinal symptoms. The results show that a low-serum GTA-446 level is a significant risk factor for CRC, and a sensitive predictor of early-stage disease.

Treatment outcomes in non-metastatic prostate cancer patients with ultra-high prostate-specific antigen.

PURPOSE: It is commonly believed that prostate cancer patients with very high prostate-specific antigen (PSA) levels are unlikely to benefit from definitive local treatment, and patients with very high PSA are often underrepresented in, or excluded from, randomized clinical trials. Consequently, little is known about their optimal treatment or prognosis. We performed a registry-based analysis of management and outcome in this population of patients. METHODS AND MATERIALS: Our provincial Cancer Registry was used to identify all men who were diagnosed with prostate cancer from 1990 to 2001. A retrospective chart review provided information on stage, Gleason score, PSA at diagnosis, and treatment. In this study, ultra-high PSA was defined as PSA of ≥ 50 ng/ml. For a more complete perspective, treatment outcomes of patients with PSA of 20 to 49.9 ng/ml were also studied. RESULTS: Of the 8378 men diagnosed with prostate cancer during this period, 6,449 had no known nodal or distant metastatic disease. The median follow-up of this group was 67.2 months (range, 0-192 months). A total of 1534 patients had PSA of ≥ 20 ng/ml. Among the 995 patients with PSA 20 to 49.9 ng/ml, 85 had radical prostatectomy (RP), and their 5- and 10-year cause-specific survivals (CSS) were 95% and 84%, respectively. The 497 patients treated with radiotherapy (RT) had 5- and 10-year CSS of 92% and 71%. For the 332 patients with PSA 50-99.9 ng/ml, RT was associated with 5- and 10-year CSS of 81% and 55%. For the 207 patients with PSA of ≥ 100 ng/ml, RT was associated with 5- and 10-year CSS of 80% and 54%. CONCLUSIONS: This is the largest series in the world on non metastatic cancer patients with ultra-high PSA at diagnosis. Even in the setting of a very high presenting PSA level, prostatectomy and radiotherapy are often associated with prolonged survival.

Second primary malignancies among women with uterine sarcoma.

OBJECTIVE: Uterine sarcomas (US) are rare malignancies with unclear aetiology. Studies on uterine sarcomas in the setting of second primary malignant tumours can provide clues to aetiology and identify side effects of different treatments. METHODS: A cohort of 8606 cases of US was extracted from the data from 13 cancer registries and followed for second primary cancers within the period 1943-2000. Standardized incidence ratios (SIRs) were calculated, and Poisson regression analyses were performed. RESULTS: There were 499 cancer cases observed after a first diagnosis of US (SIR 1.26, 95%CI 1.16-1.38). SIRs were elevated for cancers of the mouth and pharynx (2.16, 95%CI 1.15-3.69), colorectum (1.60, 95%CI 1.28-1.98), lung (1.73, 95%CI 1.27-2.29), breast (1.25, 95%CI 1.05-1.49), urinary bladder (1.74, 95%CI 1.02-2.79), kidney (2.00, 95%CI 1. 24-3.06), thyroid gland (2.74, 95%CI 1.42-4.79), and soft tissue sarcoma (5.23, 95%CI 2.51-9.62). The risk of breast cancer increased along with increasing age of US diagnosis (p trend 0.040). The risk of kidney cancer increased along with decreasing age of US diagnosis (p trend 0.004) and short time since the US diagnosis (p trend 0.018). CONCLUSIONS: Our study demonstrated increased risk of certain cancers following a diagnosis of US. The elevated risk for breast cancer may indicate shared hormonal aetiology, while the increased risk of colorectal and bladder cancers after US may be caused by radiation therapy of US. The clustering of smoking-related cancers after US is worth exploring in the future.

Second malignancies after childhood noncentral nervous system solid cancer: Results from 13 cancer registries.

Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adverse late effects, including second malignant neoplasm. The aim of our study was to assess the risk of specific second malignancies after a childhood NCNSSC. Diagnosis and follow-up data on 10,988 cases of NCNSSC in children (0-14 years) were obtained from 13 registries. Standardized incidence ratios (SIRs) with 95% confidence intervals (CI) and cumulative incidence of second malignancies were computed. We observed 175 second malignant neoplasms, yielding a SIR of 4.6, 95% CI: 3.9-5.3. When considering second cancers with at least 10 occurrences, highest relative risks were found for second malignant bone tumors (SIR = 26.4, 16.6-40.0), soft tissue sarcomas (SIR = 14.1, 6.7-25.8) and myeloid leukemia (SIR = 12.7, 6.3-22.8). Significant increased risks for all malignancies combined were observed after sympathetic nervous system tumors (SIR = 11.4, 5.2-21.6), retinoblastomas (SIR = 7.3, 5.4-9.8), renal tumors (SIR = 5.7, 3.8-8.0), malignant bone tumors (SIR = 5.6, 3.7-8.2), soft tissue sarcomas (SIR = 4.7, 3.2-6.8), germ-cell, trophoblastic and other gonadal neoplasms (SIR = 2.5, 1.1-4.9), carcinomas and other malignant epithelial neoplasms (SIR = 2.2, 1.4-3.3). The highest risk of a second malignancy of any type occurred 5 to 9 years after NCNSSC (SIR = 9.9, 6.8-13.9). The cumulative incidence of second malignancies 10 years after the first neoplasm was eight times higher among NCNSSC survivors than in the general population, with the absolute difference between observed and expected cumulative incidence still increasing after 50 years of follow-up. Children who survived a NCNSSC experience a large increased risk of developing a new malignancy, even many years after their initial diagnosis.

Use of non-steroidal anti-inflammatory drugs and prostate cancer risk: a population-based nested case-control study.

BACKGROUND: Despite strong laboratory evidence that non-steroidal anti-inflammatory drugs (NSAIDs) could prevent prostate cancer, epidemiological studies have so far reported conflicting results. Most studies were limited by lack of information on dosage and duration of use of the different classes of NSAIDs. METHODS: We conducted a nested case-control study using data from Saskatchewan Prescription Drug Plan (SPDP) and Cancer Registry to examine the effects of dose and duration of use of five classes of NSAIDs on prostate cancer risk. Cases (N = 9,007) were men aged ≥40 years diagnosed with prostatic carcinoma between 1985 and 2000, and were matched to four controls on age and duration of SPDP membership. Detailed histories of exposure to prescription NSAIDs and other drugs were obtained from the SPDP. RESULTS: Any use of propionates (e.g., ibuprofen, naproxen) was associated with a modest reduction in prostate cancer risk (Odds ratio = 0.90; 95%CI 0.84-0.95), whereas use of other NSAIDs was not. In particular, we did not observe the hypothesized inverse association with aspirin use (1.01; 0.95-1.07). There was no clear evidence of dose-response or duration-response relationships for any of the examined NSAID classes. CONCLUSIONS: Our findings suggest modest benefits of at least some NSAIDs in reducing prostate cancer risk.

High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries.

Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.

Comparison of treatment received versus long-standing guidelines for stage III colon and stage II/III rectal cancer patients diagnosed in Alberta, Saskatchewan, and Manitoba in 2004.

PURPOSE: Guideline-recommended treatment for stage II/III colorectal cancer includes postsurgical chemotherapy and/or radiation as standard of care. This study measures adherence to guidelines across 3 Canadian provinces and evaluates the relationship of patient characteristics with receiving standard care. PATIENTS AND METHODS: All surgically treated patients diagnosed in 2004 with stage III colon or stage II/III rectal cancer and residing in Alberta, Saskatchewan, or Manitoba were identified from provincial cancer registries. Sex, age at diagnosis, and area of residence were also obtained from the cancer registry. The primary outcome of interest was receipt of standard care: surgery followed by chemotherapy or radiation therapy (adjuvant therapy). chi2 tests and binary regression with log link assessed the relationship of patient demographic characteristics (age, sex, residence, cancer disease stage) with receipt of standard care. RESULTS: About half of the patients received adjuvant therapy. Patients with stage III rectal cancer were more likely to receive adjuvant treatment than stage II patients in Alberta and Saskatchewan. There was a large decrease in the percentage of patients who received adjuvant treatment with increasing age in all the provinces (P < .001), ranging from about 80% of those aged < 65 years to about 20% of those aged >or= 75 years for colon cancer patients and from about 70% to 30%, respectively, for rectal cancer patients. The decrease of adjuvant treatment with increasing age was most marked in Alberta. CONCLUSION: The percentage of patients receiving guideline-recommended treatment is low. Reasons for lack of adherence to guidelines need to be addressed.

Changes in case mix and treatment patterns in prostate cancer in Saskatchewan during the prostate specific antigen testing era.

BACKGROUND: The prostate specific antigen (PSA) test became available in Saskatchewan in 1990 as a part of the provincial health plan. The purpose of this population-based study was to describe the changes in case mix and treatment patterns for prostate cancer following its introduction. METHODS: The Saskatchewan Cancer Registry was used to identify all new cases of prostate cancer for the period 1985-2001. We reviewed over 10,000 charts to collect information on tumor characteristics, diagnostic methods, and first choice of treatment. This information was linked to the demographic and mortality data from the registry. RESULTS: The age-adjusted incidence of prostate cancer was influenced greatly by PSA testing volumes. Overall, the rate increased from 90.3 per 100,000 in 1985 to 151.3 per 100,000 in 2001. The increase was mostly organ-confined moderately differentiated cases. The incidence rate of metastatic disease dropped about 50% but only in the 70-79 and 80+ age groups. In 1985, 34% of cases were diagnosed by needle biopsy and 60.4% by TURP. In 2001, the values were 76.1% and 19.7%, respectively. More men now choose radical therapy as the first course of treatment, 81% during 1997-2001 compared to only 63.2% in the 1985-1989 period. Mortality rates remained stable in all age groups over these years. CONCLUSION: There have been dramatic changes in the case mix of prostate cancers diagnosed since the introduction of PSA testing in the population and significant changes in clinical management of this disease. Thus far, no changes have occurred in mortality rates in the population.

Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries.

The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a SPC. The present investigation is a multicenter study from 13 population-based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person-years of follow-up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person-years and the age-, sex- and calendar period-specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83-1.90) and the 20-year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20-year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking.

Analysis of health related quality of life (HRQoL) of patients with clinically localized prostate cancer, one year after treatment with external beam radiotherapy (EBRT) alone versus EBRT and high dose rate brachytherapy (HDRBT).

PURPOSE: Prostate cancer is the leading form of cancer diagnosed among North American men. Most patients present with localized disease, which can be effectively treated with a variety of different modalities. These are associated with widely different acute and late effects, which can be both physical and psychological in nature. HRQoL concerns are therefore important for these patients for selecting between the different treatment options. MATERIALS AND METHODS: One year after receiving radiotherapy for localised prostate cancer 117 patients with localized prostate cancer were invited to participate in a quality of life (QoL) self reported survey. 111 patients consented and participated in the survey, one year after completion of their treatment. 88 patients received EBRT and 23 received EBRT and HDRBT. QoL was compared in the two groups by using a modified version of Functional Assessment of Cancer Therapy-Prostate (FACT-P) survey instrument. RESULTS: One year after completion of treatment, there was no significant difference in overall QoL scores between the two groups of patients. For each component of the modified FACT-P survey, i.e. physical, social/family, emotional, and functional well-being; there were no statistically significant differences in the mean scores between the two groups. CONCLUSION: In prostate cancer patients treated with EBRT alone versus combined EBRT and HDRBT, there was no significant difference in the QoL scores at one year post-treatment.

Risk of second primary cancer among esophageal cancer patients: a pooled analysis of 13 cancer registries.

BACKGROUND: The objective of this study is to assess the risk of second primary cancers following a first primary esophageal cancer as well as the risk of esophageal cancer as a second primary, following first primary cancers of other sites. METHODS: The present investigation is a multicenter study of 13 population-based cancer registries in Europe, Australia, Canada, and Singapore. To assess excess occurrence of second cancers after esophageal cancers, we calculated standardized incidence ratios (SIR) by dividing the observed numbers of second cancers by the expected number of cancers calculated from the accumulated person-years and the age-, sex-, calendar period-, and registry-specific first primary cancer incidence rates. RESULTS: During the study period, 959 cases of second primary cancers occurred after an initial esophageal cancer, resulting in a SIR of 1.15 (95% confidence interval, 1.08-1.22). Second primary stomach cancers were associated with first primary esophageal adenocarcinomas (SIR, 2.13; 95% confidence interval, 1.26-3.37) and second primary cancers of the oral cavity and pharynx (6.68; 5.33-8.26), stomach (1.53; 1.14-2.01), larynx (3.24; 1.88-5.18), lung (1.55; 1.28-1.87), kidney (1.88; 1.18-2.85), and thyroid (2.92; 1.18-6.02) were associated with first primary squamous cell carcinomas of the esophagus. An excess of esophageal cancer as a second primary were observed following first primary cancers of the aerodigestive tract, female breast, cervix, testis, bladder, Hodgkin's lymphoma, and non-Hodgkin lymphoma. CONCLUSION: We observed associations of esophageal cancer with second primary head and neck cancers and lung cancer regardless of years of follow-up, which may suggest that common risk factors play a role in multiple tumor development.

Across-province standardization and comparative analysis of time-to-care intervals for cancer.

BACKGROUND: A set of consistent, standardized definitions of intervals and populations on which to report across provinces is needed to inform the Provincial/Territorial Deputy Ministries of Health on progress of the Ten-Year Plan to Strengthen Health Care. The objectives of this project were to: 1) identify a set of criteria and variables needed to create comparable measures of important time-to-cancer-care intervals that could be applied across provinces and 2) use the measures to compare time-to-care across participating provinces for lung and colorectal cancer patients diagnosed in 2004. METHODS: A broad-based group of stakeholders from each of the three participating cancer agencies was assembled to identify criteria for time-to-care intervals to standardize, evaluate possible intervals and their corresponding start and end time points, and finalize the selection of intervals to pursue. Inclusion/exclusion criteria were identified for the patient population and the selected time points to reduce potential selection bias. The provincial 2004 colorectal and lung cancer data were used to illustrate across-province comparisons for the selected time-to-care intervals. RESULTS: Criteria identified as critical for time-to-care intervals and corresponding start and end points were: 1) relevant to patients, 2) relevant to clinical care, 3) unequivocally defined, and 4) currently captured consistently across cancer agencies. Time from diagnosis to first radiation or chemotherapy treatment and the smaller components, time from diagnosis to first consult with an oncologist and time from first consult to first radiation or chemotherapy treatment, were the only intervals that met all four criteria. Timeliness of care for the intervals evaluated was similar between the provinces for lung cancer patients but significant differences were found for colorectal cancer patients. CONCLUSION: We identified criteria important for selecting time-to-care intervals and appropriate inclusion criteria that were robust across the agencies that did not result in an overly selective sample of patients to be compared. Comparisons of data across three provinces of the selected time-to-care intervals identified several important differences related to treatment and access that require further attention. Expanding this collaboration across Canada would facilitate improvement of and equitable access to quality cancer care at a national level.

Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation.

BACKGROUND: Skin cancers are known to be associated with sun exposure, whereas sunlight through the production of vitamin D may protect against some cancers. The aim of this study was to assess whether patients with skin cancer have an altered risk of developing other cancers. METHODS: The study cohort consisted of 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer extracted from 13 cancer registries. 10,886 melanoma and 35,620 non-melanoma skin cancer cases had second cancers. The observed numbers (O) of 46 types of second primary cancer after skin melanoma, basal cell carcinoma or non-basal cell carcinoma, and of skin cancers following non-skin cancers were compared to the expected numbers (E) derived from the age, sex and calendar period specific cancer incidence rates in each of the cancer registries (O/E=SIR, standardised incidence ratios). Rates from cancer registries classified to sunny countries (Australia, Singapore and Spain) and less sunny countries (Canada, Denmark, Finland, Iceland, Norway, Scotland, Slovenia and Sweden) were compared to each other. RESULTS: SIR of all second solid primary cancers (except skin and lip) after skin melanoma were significantly lower for the sunny countries (SIR(S)=1.03; 95% CI 0.99-1.08) than in the less sunny countries (SIR(L)=1.14; 95%CI 1.11-1.17). The difference was more obvious after non-melanoma skin cancers: after basal cell carcinoma SIR(S)/SIR(L)=0.65 (95%CI=0.58-0.72); after non-basal cell carcinoma SIR(S)/SIR(L)=0.58 (95%CI=0.50-0.67). In sunny countries, the risk of second primary cancer after non-melanoma skin cancers was lower for most of the cancers except for lip, mouth and non-Hodgkin lymphoma. CONCLUSIONS: Vitamin D production in the skin seems to decrease the risk of several solid cancers (especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder and kidney cancers). The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma, which is consistent with earlier reports that non-melanoma skin cancers reflect cumulative sun exposure, whereas melanoma is more related to sunburn.

Risk of second malignant neoplasms after childhood leukemia and lymphoma: an international study.

BACKGROUND: Survivors of childhood leukemia and lymphoma experience high risks of second malignant neoplasms. We quantified such risk using a large dataset from 13 population-based cancer registries. METHODS: The registries provided individual data on cases of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma occurring in children aged 0-14 years and on subsequent second malignant neoplasms for different time periods from 1943 to 2000. Risks of second malignant neoplasms were assessed through standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs), using the incidence rates in the general populations covered by the registries as a reference. Cumulative absolute risks were also calculated. RESULTS: A total of 133 second malignant neoplasms were observed in 16,540 patients (12,731 leukemias, 1246 Hodgkin lymphomas, and 2563 non-Hodgkin lymphomas) after an average follow-up of 6.5 years. The most frequent second malignancies after leukemia were brain cancer (19 cases, SIR = 8.52, 95% CI = 5.13 to 13.3), non-Hodgkin lymphoma (nine cases, SIR = 9.41, 95% CI = 4.30 to 17.9), and thyroid cancer (nine cases, SIR = 18.8, 95% CI = 8.60 to 35.7); the most frequent after Hodgkin lymphoma were thyroid cancer (nine cases, SIR = 52.5, 95% CI = 24.0 to 99.6), breast cancer (six cases, SIR = 20.9, 95% CI = 7.66 to 45.4), and neoplasms of skin (non-melanoma) (six cases, SIR = 34.0, 95% CI = 12.5 to 74.0); and the most frequent after non-Hodgkin lymphoma were thyroid cancer (six cases, SIR = 40.4, 95% CI = 14.8 to 88.0) and brain cancer (four cases, SIR = 6.97, 95% CI = 1.90 to 17.9). Cumulative incidence of any second malignant neoplasm was 2.43% (95% CI = 1.09 to 3.78), 12.7% (95% CI = 8.29 to 17.2), and 2.50% (95% CI = 1.04 to 3.96) within 30 years from diagnosis of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma, respectively. CONCLUSIONS: This population-based study provides, to our knowledge, the most precise and up-to-date estimates for relative and absolute risks of second malignant neoplasms after childhood leukemia and lymphoma.

Second primary malignancies in females with primary fallopian tube cancer.

Primary fallopian tube cancer (PFTC) is a rare disease, and its aetiological factors are poorly understood. Studies on PFTC in the setting of 2nd primary malignant neoplasms can provide clues on aetiology and also define the possible side effects of different treatment modalities for PFTC. A cohort of 2,084 cases with first PFTC was extracted from the data from 13 cancer registries from Europe, Canada, Australia and Singapore and followed for second primary cancers within the period 1943-2000. Standardized incidence ratios (SIRs) were calculated and Poisson regression analyses were done to find out the RRs related to age at, period of and time since the PFTC diagnosis. There were 118 cancer cases observed after first PFTC (SIR 1.4, 95%CI 1.1-1.6). Elevated SIRs were seen for colorectal cancer (1.7, 95%CI 1.0-2.6), for breast cancer (1.5, 95%CI 1.1-2.2), for bladder cancer (2.8, 95%CI 1.0-6.0), for lung cancer (1.8, 95% CI 0.9-3.2) and for nonlymphoid leukaemia (3.7, 95%CI 1.0-9.4). Significant risk increases were detected for colorectal cancer during the 2nd to 5th year after the first PFTC diagnosis, for breast cancer in follow-up 10+ and for nonlymphoid leukaemia during the 2nd to 10th year. The clustering of cancers of the lung and bladder in PFTC patients may suggest shared smoking aetiology. The excess of colorectal and breast cancers after PFTC may indicate a genetic aetiology.

Second primary cancers in patients with nasopharyngeal carcinoma: a pooled analysis of 13 cancer registries.

OBJECTIVE: To study the risk of second primary cancers in nasopharyngeal carcinoma (NPC) patients and the risk of NPC as second primary cancer. METHODS: We used data from the cancer registries from Singapore and from 12 low-incidence areas, including a total of 8,947 first occurring NPC cases, and 167 second occurring cases. We calculated standardized incidence ratios (SIRs) by comparing the second cancer incidence in NPC patients to the first primary cancer incidence in non-cancer population. We also calculated SIRs of second NPC after other primaries. RESULTS: In Singapore, the risk of cancers of the lung (SIR=0.42), stomach (SIR=0.41), and colon (SIR=0.23) was significantly decreased after NPC, whereas that of cancer of the tongue (SIR=11.1) was significantly increased. In Australia, Canada, and Europe, the risk of non-Hodgkin's lymphoma (NHL) (SIR=3.06), tongue cancer (SIR=5.29), brain cancer (SIR=3.89), myeloid leukemia (SIR=3.85), and non-melanoma skin cancer (NMSC) (SIR=3.47) was significantly increased after NPC. Incidences of second occurring NPCs following various primary cancers were not significantly altered compared to the incidence of first occurring NPCs. CONCLUSIONS: Immune suppression (NHL, NMSC), shared genetic factors (lung cancer, NHL, myeloid leukemia), and shared environmental risk factors (tongue and brain cancers) might explain the associations. Except for NHL, there was no evidence of association with other Epstein-Barr virus-related cancers.

Associations between ocular melanoma and other primary cancers: an international population-based study.

Ocular melanoma is a rare neoplasm with a poorly understood etiology, especially concerning its link with ultraviolet-light exposure. Studying the risk of second primary cancers may help to formulate causal hypotheses. We used data from 13 cancer registries, including 10,396 first occurring ocular melanoma cases, and 404 second occurring cases. To compare the second cancer incidence in ocular melanoma patients to that in noncancer population, we calculated standardized incidence ratios (SIRs) of 32 types of cancer. We also calculated SIRs of second ocular melanoma after other primaries. Ocular melanoma patients had significantly increased risk of cutaneous melanoma (SIR = 2.38, 95% CI 1.77-3.14), multiple myeloma (SIR = 2.00, 1.29-2.95), and of liver (SIR = 3.89, 2.66-5.49), kidney (SIR = 1.70, 1.22-2.31), pancreas (SIR = 1.58, 1.16-2.11), prostate (SIR = 1.31, 1.11-1.54), and stomach (SIR = 1.33, 1.03-1.68) cancers. Risks of cutaneous melanoma were highly variable between registries and were mainly increased in females, in younger patients, in first years following diagnosis, and for patients diagnosed after 1980. The risk of ocular melanoma was significantly increased only after prostate cancer (SIR = 1.41, 1.08-1.82). Risk of cutaneous melanoma after ocular melanoma had epidemiological patterns, similar to cutaneous melanoma screening in the general population. The increased risk of cutaneous melanoma would be largely due to greater skin cancer surveillance in ocular melanoma patients, and not to common etiological factors. The high SIR found for liver cancer may be explained by misclassification bias. Common etiological factors may be involved in ocular and prostate cancers.

Second malignancies among survivors of germ-cell testicular cancer: a pooled analysis between 13 cancer registries.

We investigated the risk of second malignancies among 29,511 survivors of germ-cell testicular cancer recorded in 13 cancer registries. Standardized incidence ratios (SIRs) were estimated comparing the observed numbers of second malignancies with the expected numbers obtained from sex-, age-, period- and population-specific incidence rates. Seminomas and nonseminomas, the 2 main histological groups of testicular cancer, were analyzed separately. During a median follow-up period of 8.3 years (0-35 years), we observed 1,811 second tumors, with a corresponding SIR of 1.65 (95% confidence interval (CI): 1.57-1.73). Statistically significant increased risks were found for fifteen cancer types, including SIRs of 2.0 or higher for cancers of the stomach, gallbladder and bile ducts, pancreas, bladder, kidney, thyroid, and for soft-tissue sarcoma, nonmelanoma skin cancer and myeloid leukemia. The SIR for myeloid leukemia was 2.39 (95% CI: 1.41-3.77) after seminomas, and 6.77 (95% CI: 4.14-10.5) after nonseminomas. It increased to 37.9 (95% CI: 18.9-67.8; based on 11 observed cases of leukemia) among nonseminoma patients diagnosed since 1990. SIRs for most solid cancers increased with follow-up duration, whereas they did not change with year of testicular cancer diagnosis. Among subjects diagnosed before 1980, 20 year survivors of seminoma had a cumulative risk of solid cancer of 9.6% (95% CI: 8.7-10.5%) vs. 6.5% expected, whereas 20 years survivors of nonseminoma had a risk of 5.0% (95% CI: 4.2-6.0%) vs. 3.1% expected. In conclusion, survivors of testicular cancers have an increased risk of several second primaries, where the effect of the treatment seems to play a major role.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with limited stage small cell lung cancer.

A few series in the literature were published before 1987 on syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer (SCLC). This study examines the outcome in more recent era. From 1981-1998, there were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244 were of limited stage (LS). A chart review and statistical analyses were performed using Mann-Whitney test, chi-square test and Kaplan-Meier method. Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of 230 LS patients without SIADH. There were more patients with poorer performance status (ECOG 2-4) in group A than B (28.6% versus 7.8%, P=0.03). Otherwise, sex, age at diagnosis, nodal spread, pleural effusion, bronchial obstruction, superior vena cava obstruction, performance status, weight loss, and lactic dehydrogenase at presentation, were comparable between the two groups. Treatments given, e.g., extent of surgical resection (if performed, whether complete/incomplete), total number of chemotherapy cycles, radiotherapy doses, were comparable (P>0.05). The response to chemo-radiation was not significantly different (P=0.7). Five-year overall survival (8% versus 19%, P=0.08), and cause-specific survival (16% versus 20%, P=0.13) showed that group A patients had a worse outcome, though of borderline significance. Symptoms related to SIADH included: weakness, 4 patients; tiredness, 3; change in level of consciousness, 1; seizure, 1. The range of lowest sodium level was 110-129. Two patients also had paraneoplastic myopathy. SIADH resolved in 12 patients at 1.6-44.7 weeks (median: 4.3). Among the 14 patients who initially presented with SIADH and recurred later, 10 had recurrence of SIADH at the time of tumor recurrence. Serum sodium was useful for post-treatment surveillance in SCLC patients who presented with SIADH, with 71% (10/14) developing SIADH again at the time of recurrence. SIADH is a poor prognostic factor for LS SCLC.