Risks of second primary cancer among patients with major histological types of lung cancers in both men and women.

BACKGROUND: Patterns of second primary cancers (SPCs) following first primary lung cancers (FPLCs) may provide aetiological insights into FPLC. METHODS: Cases of FPLCs in 13 cancer registries in Europe, Australia, Canada, and Singapore were followed up from the date of FPLC diagnosis to the date of SPC diagnosis, date of death, or end of follow-up. Standardised incidence ratios (SIRs) were calculated to estimate the magnitude of SPC development following squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC), and adenocarcinoma (ADC). RESULTS: Among SCC patients, male SIR=1.58 (95% confidence interval (CI)=1.50-1.66) and female SIR=2.31 (1.94-2.72) for smoking-related SPC. Among SCLC patients, the respective ratios were 1.39 (1.20-1.60) and 2.28 (1.73-2.95), and among ADC patients, they were 1.73 (1.57-1.90) and 2.24 (1.91-2.61). We also observed associations between first primary lung ADC and second primary breast cancer in women (SIR=1.25, 95% CI=1.05-1.48) and prostate cancer (1.56, 1.39-1.79) in men. CONCLUSION: The FPLC patients carried excess risks of smoking-related SPCs. An association between first primary lung ADC and second primary breast and ovarian cancer in women at younger age and prostate cancers in men may reflect an aetiological role of hormones in lung ADC.

Risk of second malignant neoplasms after childhood central nervous system malignant tumours: an international study.

PURPOSE: The aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study. METHODS: Individual data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943-2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed. RESULTS: We observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99) for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). CONCLUSION: This population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour.

Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases.

PURPOSE: To study the use of chemotherapy for Merkel cell carcinoma (MCC) of the skin. PATIENTS AND METHODS: Twenty-five cases of MCC were treated at the London Regional Cancer Center between 1987 and 1997. Thirteen cases treated with chemotherapy were reviewed with 191 cases from the literature. RESULTS: At presentation, 24 patients had localized skin lesions (stage I) and one had locoregional involvement (stage II). Among the nine cases with recurrent nodal disease, six had chemotherapy as a component of salvage treatment. They were all free of disease at a median of 19 months (range, 12 to 37 months). In contrast, two patients who had salvage radiotherapy alone died of disease. Overall survival (OS) and disease-free survival (DFS) were 59% and 43%, respectively, at two years. Median OS and DFS were 29 months (range, 1 to 133 months) and 9 months (range, 1 to 133 months), respectively. Nodal disease developed in 12 (50%) of 24 patients with stage I disease, and distant metastases developed in six (25%) of 24. Including those from the literature, there were 204 cases treated with chemotherapy. Cyclophosphamide/doxorubicin (or epirubicin)/vincristine combination +/- prednisone was the most commonly used chemotherapy regimen (47 cases), with an overall response rate of 75.7% (35.1% complete, 35. 1% partial, and 5.4% minor responses). Etoposide/cisplatin (or carboplatin) was the next most commonly used regimen (27 cases), with an overall response rate of 60% (36% complete and 24% partial responses). The difference in response rate was not statistically significant (P =.19). Among the 204 cases, there were seven (3.4%) toxic deaths. CONCLUSION: Chemoradiation for locally recurrent or advanced disease may be an option for patients with a good performance status.

Radiation treatment for cervical esophagus: patterns of practice study in Canada, 1996.

PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat esophageal cancers, using a trans-Canada survey, completed at the end of 1996. METHODS AND MATERIALS: One of 3 case presentations of different stages of cervical esophageal cancer was randomly assigned and sent to participating radiation oncologists by mail. Respondents were asked to fill in questionnaires regarding treatment techniques and to outline target volumes for the boost phase of radiotherapy. Radiation oncologists from 26 of 27 (96%) of all Canadian centers participated. RESULTS: High-energy X-rays (>/= 10 MV) were employed by 68% of the respondents in part of the treatment course. The majority (83%) of the radiation oncologists used at least two phases of treatment. Very few, 10 of 59 (17%), responses started with multifield treatment. The most frequently used prescription dose was 60 Gy/30 fractions/6 weeks, given with concurrent chemotherapy. Dose prescriptions were to the isocenter in 39 of 48 (81%) or to a particular isodose line in 9 of 48 (19%) of respondents. CONCLUSION: There was a variety of radiation treatment techniques in this trans-Canada survey. The majority of the patients had combined cisplatin-based chemoradiation. The isocenter was not used consistently as a dose prescription point.

Pelvic fractures following irradiation of endometrial and vaginal cancers-a case series and review of literature.

PURPOSE: To review the induction of pelvic fractures as a result of radiation therapy and to assess their management. MATERIALS AND METHODS: The charts of patients with endometrial and vaginal cancers irradiated between 1991 and 1995 were reviewed. All patients were treated with megavoltage machines, energy ranging from cobalt to 25 MV photons. RESULTS: We treated 336 patients, with a median follow-up duration of 28.9 months (range 0-73.3). Sixteen patients had symptomatic pelvic fractures. The 5-year actuarial incidence of symptomatic pelvic fracture was 2.1%. All patients had pain as the first symptom. The median time of onset was 11 months (range 4-46). Imaging studies of 37.5% (6/16) were initially interpreted to be recurrent malignancy. All patients were managed conservatively and nine patients showed radiological evidence of healing over a median time of 13 months (range 2-34). Six patients had specific drug treatment including provera, premarin, calcium supplements, or pamidronate. Of these, five healed. For the ten patients who did not have any specific treatment, only four showed signs of healing at the time of last follow-up. There was a trend toward earlier healing with specific drug treatment (P=0.11). CONCLUSIONS: Fractures can easily be mistaken for metastatic lesions (37.5% in this series) which might be treated with further irradiation. Although not statistically significant, there was a trend towards early healing with drug therapy. More studies are required to generate quantitative data for dose-response relationships and to evaluate the effect of drug therapy on the healing of such fractures.

Management issues in chordoma: a case series.

This study presents a combined case series of chordomas from two Canadian institutes. Twenty-seven patients were identified for the period 1954-1998. Management issues with regard to diagnostic pitfalls, selection of charged particle treatment and retreatment of recurrences are discussed. The diagnosis of early stage chordoma requires a high index of suspicion. One patient in the series presented with hoarseness and is described in detail. The diagnosis was made coincidentally by a computed tomographic scan of the head, performed after a motor vehicle accident. The planning of both surgery and radiotherapy was optimized by using magnetic resonance imaging. A review of the literature supports the use of a combined surgical and radiotherapeutic approach.

A population-based study of cervix cancer: incidence, management and outcome in the Canadian province of Saskatchewan.

AIMS: To document the incidence, management and outcome of uterine cervix cancer in the Canadian province of Saskatchewan. To compare provincial results of low dose rate (LDR) and high dose rate (HDR) brachytherapy in this population. MATERIALS AND METHODS: We carried out a retrospective population-based cohort study of all uterine cervix cancer cases in Saskatchewan diagnosed between 1985 and 2001. We used data from the provincial cancer registry for incident cases, the provincial death registry for vital status information and chart reviews for treatment and toxicity information. RESULTS: In total, 714 cases of uterine cervix cancer were identified. Stage distribution was IA 22.7%, IB 31.8%, II 19.1%, III 18.4%, IV 6.8%; 81.2% were squamous cell carcinoma, 13.4% adenocarcinoma, 1.5% adenosquamous, 0.9% small cell and 3.1% other. The annual crude incidence rate of uterine cervix cancer in Saskatchewan ranged from 6.5 to 12.3% between 1985 and 2001. The 5-year cause-specific survival rate ranged from 100% for stage IA1 to 22% for stage IV. One hundred and seven patients were treated with LDR and 37 with HDR with similar stage distribution. The 5-year cause-specific survival rate was 56% for HDR and 67% for LDR (P = 0.72). For 43 patients managed with external beam radiotherapy alone, outcome was poor for stage IIB to IIIB. The most common acute toxicities of radiation treatment were diarrhoea (60%) and abdominal cramps (12.5%). The common chronic toxicities were vaginal stenosis (5.5%) and small bowel obstruction (4%). CONCLUSIONS: Our population-level outcomes are in keeping with published observed results and provide some of the first Canadian population-level data on HDR and LDR outcomes. We found no significant different in cause-specific survival between patients managed with HDR and LDR, although interpretation is limited by patient numbers. Our results for external beam radiotherapy alone emphasise the vital role brachytherapy plays in the management of cervical cancer.

Second primary cancers among 109 000 cases of non-Hodgkin's lymphoma.

An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43-51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkin's lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL.

Prostate cancer in Saskatchewan Canada, before and during the PSA era.

OBJECTIVES: The purpose of this study was to describe changes in the incidence of prostate cancer and in survival of diagnosed cases, as well as prostate cancer-specific mortality, during a period spanning the introduction of prostate specific antigen (PSA) testing in Saskatchewan in 1990. METHODS: All cases of neoplasms of the prostate (ICD-O = C61.9) diagnosed in Saskatchewan from 1970 to 1997 inclusive, were identified in the Saskatchewan Cancer Registry. A subgroup of adenocarcinomas was defined for further study. Age-adjusted and age-specific incidence rates, and actuarial and relative survival were calculated according to time period of diagnosis. Age-adjusted and age-specific mortality rates from prostate cancer were also calculated for each time period, using Vital Statistics data. RESULTS: The age-adjusted incidence of prostate cancer was 60.5 per 10(5) in 1970, rising gradually to 101.5 per 10(5) in 1989. In 1990, incidence rose much more sharply, reaching a peak of 163.1 per 10(5) in 1993, after which it began to fall. This sharp increase coincided with the introduction and increasing use of the PSA test in the province. Relative survival of prostate cancer patients was stable from the late 1970s through the 1980s, then improved markedly in the 1990-94 period. After the introduction of the PSA test, the relative risk of death for prostate cancer patients was only about 60% of what it had been throughout the previous 15 years. Prostate cancer-specific death rates did not change from the early 1980s to the end of the study period. CONCLUSIONS: The above data are consistent with earlier diagnosis of prostate cancer due to PSA screening. Because mortality has not yet changed, it is premature to recommend widespread screening of asymptomatic men.

Merkel cell carcinoma of the skin.

BACKGROUND: Neuroendocrine/Merkel cell carcinoma (MCC) of the skin is an uncommon tumour. Currently, there are only limited data available on the natural history, prognostic factors, and patient management of MCC. OBJECTIVES: To review our experience and build the largest database from the literature. METHODS: Twenty-eight cases from the London Regional Cancer Center were combined with 633 cases obtained from the literature searched in English, French, German, and Chinese for the years 1966 to 1998. The database included age, sex, initial disease status at presentation to the clinic, site of primary, any coexisting disease, any previous irradiation, sizes of primary/nodal/distant metastases, management details, and final disease status. A new modified staging system was used: stage Ia (primary disease only, size > 2 cm), stage Ib (primary disease only, size > 2 cm); stage II (regional nodal disease), and stage III (beyond regional nodes and/or distant disease). RESULTS: Age > 65 years, male sex, size of primary > 2 cm, truncal site, nodal/distant disease at presentation, and duration of disease before presentation (< or =3 months) were poor prognostic factors. Surgery was the initial treatment of choice and it significantly improved overall survival (p =.004). CONCLUSIONS: We identified poor prognostic factors that may necessitate more aggressive treatment. The suggested staging system, incorporating primary tumour size, accurately predicted outcomes.

Medical radiologic technologist review: effects on a population-based breast cancer screening program.

PURPOSE: To evaluate the effects of medical radiologic technologist review of mammograms in a population-based breast cancer screening program. MATERIALS AND METHODS: A technologist review pilot project was incorporated into the Regina, Saskatchewan, Canada, reading center. Technologists received special training in mammographic interpretation. They reviewed all 27,863 mammograms obtained at the center from July 1995 to September 1996 that were reviewed by a radiologist and selected cases for second blind reading by another radiologist. When the two radiologists' readings were in agreement, the report was sent. When the readings differed, a third opinion was obtained from the program's consulting radiologist. Changes in the number of mammograms interpreted as abnormal and the number of cancers detected were assessed. RESULTS: The technologist review was responsible for the detection of nine cancers missed at the first radiologist's interpretation. Technologists were very discriminating; only 391 cases (1.4%) were sent for double reading. The positive predictive value of screening did not change significantly (7.5% without review, 8.1% with review; P > .20). CONCLUSION: A substantial number of cancers were found with the technologist review. The number of mammograms interpreted as abnormal was reduced slightly. The technologist review proved to be a cost-effective alternative to double reading by two radiologists.

Gastroschisis: A sixteen-year review.

PURPOSE: The aim of this study was to examine the incidence of gastroschisis in Saskatchewan over a 16-year period and identify risk factors associated with mortality. METHODS: Information was obtained by retrospective review of all infant charts at the only 2 provincial neonatal intensive care centers from January 1985 through December 2000. Factors recorded were gestational age, birth weight, gender, Apgar score, time to operation, method of closure, time to attain full feedings, presence of sepsis, and length of hospital stay. Live birth data for the province was obtained, and the incidence per 10,000 live births for 3 time intervals was calculated. Analysis was performed with mortality as the dependent variable. RESULTS: Seventy-one infants were identified. Overall survival rate was 93% (66 of 71). During the 3 time intervals examined, the incidence of gastroschisis per 10,000 live births increased from 1.85 in 1985 to 1990 to 3.66 in 1991 to 1995 to 4.06 in 1996 to 2000. The analysis found that intestinal atresia P =.009, OR = 18.3 (95%CI: 2.457-136) and intestinal necrosis P =.050, OR = 10.33 (95%CI: 1.32-80.68) were significantly associated with mortality. CONCLUSIONS: The incidence of gastroschisis is increasing. Intestinal atresia and the development of intestinal necrosis were associated with poor outcome. Patients who had these complications all had short bowel, and full feedings could not be established. They required continuation of total parenteral nutrition and experienced episodes of sepsis.