Prescriptions of analgesics during complete disease trajectories in patients who are diagnosed with and die from cancer within the five-year period 2005-2009.

BACKGROUND: Even though validation studies of the WHO analgesic ladder have indicated that the simple approach of the analgesic ladder can provide adequate pain control in most patients, prevalence studies have documented a high prevalence of pain in cancer patients. Little is known about how analgesics are actually prescribed for cancer pain. The aim of the study was to study prescriptions of analgesics during the entire disease trajectory in patients dying from cancer within five years of diagnosis. METHODS: Complete national data from the Norwegian Cancer Registry, the Norwegian Prescription Database, the Cause of Death Registry and Statistics Norway were used to study prescriptions of analgesics in a complete study population of all patients dying from cancer within five years of diagnosis in Norway from 2005 to 2009. RESULTS: Of a total of 10,977 subjects who received prescriptions for analgesics between diagnosis and death, 56% started analgesic treatment at step I of the analgesic ladder, 29% started at step II and 14% started at step III. Of the patients starting at step I, 28% continued to step II, 37% bypassed step II and moved directly to step III whereas the remaining 35% remained at step I. Approximately 60% received one or more dispensed prescription of a step III analgesic during the disease trajectory, whereas nearly 20% remained at step I and 20% at step II respectively. CONCLUSION: The study indicates that clinicians seem to individually tailor analgesic treatment instead of applying the stepwise approach in the WHO analgesic ladder. SIGNIFICANCE: Complete national data covering the complete disease trajectory in cancer patients dying within five years of diagnosis. The majority of patients do not receive treatment in concordance with the stepwise approach suggested by the WHO analgesic ladder.

Increased stomach cancer risk following radiotherapy for testicular cancer.

BACKGROUND: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse. METHODS: In a cohort of 22,269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression. RESULTS: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend<0.001), with an OR of 20.5 (3.7-114.3) for ⩾50.0 Gy compared with <10 Gy. Radiation-related risks remained elevated ⩾20 years after exposure (P<0.001). Risk after any chemotherapy was not elevated (OR=1.1; 95% CI 0.5-2.5; 14 cases and 23 controls). CONCLUSIONS: Radiotherapy for TC involving parts of the stomach increased gastric cancer risk for several decades, with the highest risks after stomach doses of ⩾30 Gy. Clinicians should be aware of these excesses when previously irradiated TC survivors present with gastrointestinal symptoms and when any radiotherapy is considered in newly diagnosed TC patients.

Pancreatic cancer risk after treatment of Hodgkin lymphoma.

BACKGROUND: Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents. PATIENTS AND METHODS: We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls. RESULTS: Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide. CONCLUSION: Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks.

Body mass index and the risk of meningioma, glioma and schwannoma in a large prospective cohort study (The HUNT Study).

BACKGROUND: Obesity increases the risk for a number of solid malignant tumours. However, it is not clear whether body mass index (BMI) and height are associated with the risk of primary tumours of the central nervous system (CNS). METHODS: In a large population study (The Nord-Trøndelag Health Study (HUNT Study)) of 74 242 participants in Norway, weight and height were measured. During follow-up, incident CNS tumours were identified by individual linkage to the Norwegian Cancer Registry. Sex- and age-adjusted and multivariable Cox regression analyses were used to evaluate BMI and height in relation to the risk of meningioma, glioma and schwannoma. RESULTS: A total of 138 meningiomas, 148 gliomas and 39 schwannomas occurred during 23.5 years (median, range 0-25) of follow-up. In obese women (BMI ≥ 30 kg m(-2)), meningioma risk was 67% higher (hazard ratio (HR)=1.68, 95% confidence interval (CI): 0.97-2.92, P-trend=0.05) than in the reference group (BMI 20-24.9 kg m(-2)), whereas no association with obesity was observed in males. There was no association of BMI with glioma risk, but there was a negative association of overweight/obesity (BMI ≥ 25 kg m(-2)) with the risk of schwannoma (HR=0.48, 95% CI: 0.23-0.99). However, the schwannoma analysis was based on small numbers. Height was not associated with the risk for any tumour subgroup. CONCLUSION: These results suggest that BMI is positively associated with meningioma risk in women, and possibly, inversely associated with schwannoma risk.

Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007: a population-based study.

BACKGROUND: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. METHODS: We analysed the data on 257,362 women diagnosed with breast cancer during 2000-7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis. RESULTS: Age-standardised 3-year net survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42-45% elsewhere. Women in the UK had low survival for TNM stage III-IV disease compared with other countries. CONCLUSION: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.

Risk of treatment-related esophageal cancer among breast cancer survivors.

BACKGROUND: Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. DESIGN: Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. RESULTS: The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). CONCLUSIONS: Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.

Craniotomy for brain metastases: a consecutive series of 316 patients.

OBJECTIVE: To assess the incidence of craniotomy for brain metastases, overall survival (OS), surgical mortality, and prognostic factors in a large, contemporary, consecutive series from a well-defined catchment area. MATERIAL AND METHODS: All patients ≥ 18 years who underwent craniotomies for intracranial metastases at Oslo University Hospital, Rikshospitalet and Ullevål, between 2005 and June 30, 2009 were included (n = 316). Patients were identified from our prospectively collected database and a thorough review of all charts to validate the entered data was performed. RESULTS: The annual incidence of first-time craniotomy for a brain metastasis was 2.6/100,000 inhabitants. Patient age ranged from 25 to 87 years (median 64 years). The 30-day mortality rate was 3.8%. Median OS was 9.2 months. Recursive partitioning analysis was class I in 19.6%, class II in 59.2%, and class III in 21.2% with median OS of 16.2, 8.9, and 5.6 months, respectively (P < 0.001). Lung cancer and melanoma were associated with a higher risk (>1% per year) of developing brain metastases. Significant negative prognostic factors were age ≥ 65, a poor performance score, unstable extracranial disease, presence of extracranial metastases, multiplicity, metastasis in eloquent area, and no post-operative radiotherapy. CONCLUSIONS: In this population study, the annual incidence of a first-time craniotomy for a brain metastasis was 2.6/100,000, the 30-day mortality rate was 3.8%, and median OS was 9.2 months. The well-known prognostic factors were confirmed.

Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data.

BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. METHODS: Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995-2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985-2005. FINDINGS: Relative survival improved during 1995-2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2-6% at 1 year and by 2-3% at 5 years. INTERPRETATION: Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. FUNDING: Department of Health, England; and Cancer Research UK.

Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme.

OBJECTIVES: To study overall survival (OS), prognostic factors, and repeated surgery in glioblastoma multiforme (GBM). MATERIAL AND METHODS: Retrospective study of 516 consecutive adult patients who underwent primary surgery for a GBM in year 2003-2008. RESULTS: Median age at primary surgery was 63.7 years (range 18.0-88.0). Median OS was 9.9 months. Age > 60 years, poor preoperative ECOG score, bilateral tumor, biopsy rather than resection, and no temozolomide chemoradiotherapy were negative risk factors. Repeat surgery was performed in 65 patients (13%). Median time between first and second surgery was 7 months. Indications for second surgery were increasing neurological deficits (35.4%), raised ICP (33.8%), asymptomatic but reoperated because of tumor progression verified on MRI (20.0%), and epileptic seizures (11%). Patients who underwent repeated surgery had longer OS; 18.4 months vs 8.6 months (P < 0.001). CONCLUSIONS: OS for adult GBM patients was 9.9 months. Negative prognostic factors were increasing age, poor neurological function, bilateral tumor involvement, biopsy instead of resection, and RT alone compared to temozolomide chemoradiotherapy. Our rate of repeated surgery for GBM was 13% and the main indications for second surgery were raised ICP and increasing neurological deficits. In a carefully selected group of patients, repeat surgery significantly prolongs OS.

A population-based study of spinal metastatic disease in South-East Norway.

AIMS: Spinal metastatic disease (SMD) is a serious complication of cancer. To our knowledge, only one population-based study of metastatic spinal cord compression (MSCC) has been carried out. The purpose of the present study was to describe population-based incidences of SMD that required local treatment, such as radiotherapy, surgery or vertebroplasty, including patients with or without cord compression, and to characterise the neurological status of these patients. MATERIALS AND METHODS: During 18 months, all patients with SMD who received local treatment in the South-Eastern Health Region of Norway (population 2.6 million inhabitants) were identified and their medical records were reviewed. RESULTS: In total, 1002 patients were included; 83% had multiple lesions in the spine; 39% had SMD at the time of the primary cancer diagnosis. At the start of local treatment, 31% had MSCC and 11% were not able to walk. The prevalence of MSCC at the time of cancer diagnosis was 0.36%. The annual incidences per 100,000 inhabitants were 26.0 for SMD and 8.1 for MSCC. CONCLUSION: Population-based incidences of SMD requiring local treatment have been reported for the first time. The prevalence of MSCC at the time of cancer diagnosis was higher than previously reported. A more precise definition of MSCC and more population-based studies are needed to reduce selection bias when comparing different studies.

Intracranial tumor surgery in patients >70 years of age: is clinical practice worthwhile or futile?

OBJECTIVES: To study survival and functional outcome after intracranial tumor surgery in elderly patients. MATERIALS AND METHODS: This is a retrospective study of 289 consecutive patients of age > or =70 years, who underwent primary surgery (resection or biopsy) in the time period 2003-2007 for an intracranial tumor (87 astrocytomas, 79 meningiomas, 62 brain metastases, 33 pituitary adenomas and 28 other tumors). RESULTS: The surgical mortality was 2.8%. Overall survival at 6 months, 1, 2 and 5 years was 73%, 57%, 46% and 38% respectively. Histology, pre-operative Eastern Cooperative Oncology Group (ECOG) performance score and resection, as opposed to biopsy, were significantly associated with survival. Gender, age and American Association of Anaesthetists (ASA) score were not significantly related to survival. One-year survival after surgery for astrocytoma, meningioma, brain metastases and pituitary adenoma were 24%, 94%, 31% and 96% respectively. More than 85% of the patients who were alive 6 months after surgery had a stable or improved ECOG score compared with their pre-operative score. CONCLUSIONS: Surgery for intracranial tumors in selected elderly patients is worthwhile, not futile. Age alone should not be used as a selection criterion for treatment.

Incidence of primary cutaneous T-cell lymphoma in Norway.

BACKGROUND: Studies from different countries have reported an increased incidence of primary cutaneous lymphomas over the last decades. OBJECTIVES: To estimate the incidence rates of primary cutaneous T-cell lymphoma (CTCL) and mycosis fungoides (MF)/Sézary syndrome (SS) in Norway, and to compare these rates with those reported from other countries. METHODS: Data from the Cancer Registry of Norway on non-Hodgkin lymphomas during the period 1980-2003 were analysed. RESULTS: In total, 337 cases of CTCL were reported to the Cancer Registry during the study period, of which 262 cases were classified as MF/SS. The incidence rate of CTCL increased significantly (P(trend) < 0.001) from 0.16 (95% confidence interval, CI 0.11-0.20) per 100,000 person-years in 1980-84 to 0.29 (95% CI 0.22-0.36) per 100,000 person-years in 2000-2003. The incidence of MF/SS also increased during the same period (P(trend) = 0.05) from 0.15 (95% CI 0.10-0.19) per 100,000 person-years to 0.18 (95% CI 0.13-0.24) per 100,000 person-years. CONCLUSIONS: The incidence of both CTCL and MF/SS increased in Norway during the period 1980-2003.

Prevalence of Norwegian patients diagnosed with childhood cancer, their working ability and need of health insurance benefits.

The object of this study was in a population-based material to investigate the prevalence of patients diagnosed with childhood cancer, and compared to the general population to assess working ability, yearly income and need for health insurance benefits in patients surviving at least five years after treatment for childhood CNS tumours or hematological malignancies. During the period January 1, 1970 to December 31, 2002 the prevalence in the Norwegian population of patients diagnosed with any childhood cancer increased from 12.2 (473/3 888 305) to 65.1 (2944/4 524 066) per 100 000 population. The proportion of survivors in need of any health insurance benefit was for CNS tumours 47.1% and for hematological malignancies 21.0%. The proportion in the age group 16-67 receiving disability pension for CNS tumours was 94/454 (20.7%) compared to 21/575 (3.7%) for patients treated for hematological malignancies (p < 0.001). Of patients given radiotherapy 25/70 (35.7%) received disability pension, compared to 90/959 (9.4%) in unirradiated patients, p < 0.001. Yearly income and working ability was particularly low for CNS tumour survivors. This study illustrates loss of working capability associated with pediatric cancer and treatment and long-term requirement of health insurance benefits.

Trends in incidence of brain and central nervous system tumors in Norway, 1970-1999.

The aim of this study was to investigate trends in the incidence of childhood and adult brain and central nervous system (CNS) tumors in Norway from 1970 through 1999. In this period, a total of 14,641 patients were diagnosed with a primary benign or malignant neoplasm of the brain and CNS. Age-adjusted incidence rates were reported together with results of loglinear regression and an age-period-cohort model based on the Poisson regression model. In children (<15 years), the proportion of brain and CNS tumors was 28.2% (1,042/3,697) of all new cancer cases compared with 2.8% in adults (13,599/492,237). The overall rate of brain and CNS tumors increased during the study period from 6.49 to 12.02 cases per 100,000 person-years. A trend of leveling off in incidence of most tumor categories during the study period was indicated with a possible continuing increase in the period 1995-1999, especially in the age group 0-4 years and in patients aged 60 years or more. Age and period together provided a satisfactory model in patients being <60 years of age and less completeness of diagnosis was found in males compared with females, possibly due to the distribution in males of more aggressive tumors.

Cause of death and long-term survival in patients with neuro-epithelial brain tumours: a population-based study.

Long-term survivors of neuro-epithelial brain tumours have a higher death rate compared with the general population and the aims of this study were to investigate the causes of death and analyse long-term survival using population-based material. A total of 6209 patients were registered in the period of 1970-1993 with a primary intracranial neuro-epithelial tumour in the The Norwegian Cancer Registry. In a pilot study, a high level of agreement with regard to the cause of death was found between clinical data and the registered cause of death. Underlying causes of death in the whole population were therefore analysed. Most deaths were caused by the primary neuro-epithelial brain tumour within 10 years of diagnosis. Although the numbers were small, the proportion of patients dying from other cancers, vascular disease, infections and accidents continued to rise with time. Survival was computed using the Kaplan-Meier method. For children, survival at 5, 10 and 15 years significantly improved from the time period of 1970-1981 to 1982-1993 (47.9, 43.6 and 43.3% versus 63.8, 59.8 and 59.8%, respectively, P <0.0001). Similar improvements in survival at 5, 10 and 15 years were observed for young adults aged 15-49 years (32.7, 21.3 and 16.5% versus 50.1, 37.5 and 33.1%, for the same time periods, P<0.0001). No such improvement for those aged 50 years and over was observed (corresponding figures of 6.6, 3.8 and 2.8% versus 7.7, 4.8 and 3.4%). Prognosis for those with childhood medulloblastomas improved significantly, as did the prognosis of younger adults with low-grade gliomas and unbiopsied/ unclassifiable grade gliomas.

Intracavity fractionated balloon brachytherapy in glioblastoma.

In order to reduce hospitalisation time for patients receiving postoperative radiotherapy a phase I-II study of intracavity balloon brachytherapy was instituted. An indwelling balloon catheter was implanted during the closing phase of the initial operation. Starting on the second or third postoperative day the catheter was afterloaded with a high dose rate isotope via a remotely controlled afterloading system. The treatment consisted of 10-12 fractions over a period of 5-6 days, with each treatment session requiring approximately 15 minutes. No external beam radiation was given. Forty-four newly diagnosed patients were treated. A total dose of either 60 Gy (33 patients) or 72 Gy (11 patients) was given. The overall median survival was 11.7 months, (range 2.7-50.9). The treatment was well tolerated and none of the applicators were removed prematurely. The total median hospital stay for this group of patients was significantly reduced compared to more conventional protocols. This study indicates that intracavity high dose rate balloon brachytherapy can achieve survival rates equivalent to those of conventional radiotherapy and is both cost and time efficient.

Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer.

BACKGROUND: In phase II studies, irinotecan is active in metastatic colorectal cancer, but the overall benefit has not been assessed in a randomised clinical trial. METHODS: Patients with proven metastatic colorectal cancer, which had progressed within 6 months of treatment with fluorouracil, were randomly assigned either 300-350 mg/m2 irinotecan every 3 weeks with supportive care or supportive care alone, in a 2:1 ratio. FINDINGS: 189 patients were allocated irinotecan and supportive care and 90 supportive care alone. The mean age of the participants was 58.8 years; 181 (65%) were men and 98 (35%) were women. WHO performance status was 0 in 79 (42%) patients, 1 in 77 (41%) patients, and 2 in 32 (17%) patients. Tumour-related symptoms were present in 134 (71%) patients and weight loss of more than 5% was seen in 15 (8%) patients. With a median follow-up of 13 months, the overall survival was significantly better in the irinotecan group (p=0.0001), with 36.2% 1-year survival in the irinotecan group versus 13.8% in the supportive-care group. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (p=0.001). Survival without performance-status deterioration (p=0.0001), without weight loss of more than 5% (p=0.018), and pain-free survival (p=0.003) were significantly better in the patients given irinotecan. In a quality-of-life analysis, all significant differences, except on diarrhoea score, were in favour of the irinotecan group. INTERPRETATION: Our study shows that despite the side-effects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour-related symptoms, and a better quality of life when treated with irinotecan than with supportive care alone.