Delayed Radiation Toxicity after Focal or Whole Brain Radiotherapy for Low-Grade Glioma

To evaluate the influence of radiation volume and other risk factors for the development of delayed radiation toxicity in patients treated for low-grade glioma, a retrospective analysis of 41 adult patients treated with focal or whole brain radiotherapy (WBRT) was performed. For all patients CT and MRI scans were revised to quantify brain atrophy and white matter lesions. Medical data were reviewed concerning baseline and tumor characteristics, treatment, survival, signs and symptoms of clinical encephalopathy and cardiovascular risk factors. In patients treated with WBRT an increased risk was found for brain atrophy (RR 3.1), white matter lesions (RR 3.8) and clinical encephalopathy (RR 4.2). An increased risk of atrophy (RR 2.2) and white matter lesions (RR 2.9) was also found in patients aged over 40 years. Furthermore, brain atrophy and white matter lesions were more severe in patients treated with WBRT and in older patients. In conclusion, both the incidence and the severity of abnormalities is greater in patients treated with WBRT and in older patients.     

Delayed, transient encephalopathy after marrow transplantation: case reports and MRI findings in four patients

Summary Subacute encephalopathy developed in four patients within one to two months after undergoing high-dose chemotherapy and bone marrow transplantation or peripheral blood progenitor (stem) cell transplantation for breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. None of the patients had previously known neurologic disorders, central nervous tumor or infection. Two patients presented with generalized tonic, clonic seizures, and two with confusion and lethargy. In all patients lumbar puncture and CT scans of the brain were normal, while magnetic resonance imaging (MRI) demonstrated multifocal predominantly white matter lesions. Phenytoin therapy was given to the two patients with seizures and all four patients improved without specific therapeutic intervention. Repeat MRIs became normal within three months. We report a delayed and transient encephalopathy which appears to be a unique complication of high-dose cytotoxic chemotherapy. The corresponding brain lesions may not be appreciated on CT scans, suggesting an expanded role for MRI studies in patients who develop neurologic findings while undergoing high-dose cytotoxic therapy.     

鼻咽癌放射治疗后脑脊髓损伤的临床和影像学诊断

目的　探讨鼻咽癌患者放射治疗后脑脊髓放射性损伤的临床和影像学诊断。方法　对 32例鼻咽癌放射治疗脑脊髓放射性损伤患者的临床表现、CT及MRI表现进行回顾性分析。结果　 32例中共发现 4 5个损伤病灶 ,颞叶 30个 (占脑损伤病灶的 70 % ) ,脑干 13个 ,颈段脊髓 2个。其中 6例放射性颞叶损伤无临床症状。CT对颞叶放射性损伤的检出率为 87% ,对脑干损伤的检出率仅 2 9%。放射性颞叶损伤在CT图象上主要表现为指状低密度。MRI检查T1WI图象上放射性脑脊髓损伤均表现为低或等信号 ,T2 WI图象上为高信号或混合信号 ,颞叶损伤可伴有周围指状分布水肿信号 ,86 %病灶有增强效应 ,中间有不增强区。结论　放射性脑脊髓损伤的临床表现无特征性 ,亦可无症状 ,CT及MRI表现具有一定的特征性 ,结合病史可做出诊断。MRI在诊断脑干、脊膜损伤上优于CT。     

Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States)

Objective: This study evaluated the joint effects of tobacco smoking and alcohol consumption on the risk of second primary tumors (SPT) in patients with early-stage head and neck squamous cell carcinoma (HNSCC). Methods: Data are presented for 1181 patients enrolled in a placebo-controlled chemoprevention trial of 13-cis-retinoic acid. Nearly 17% of patients presented with a SPT. The log rank test and Cox proportional hazards model were used to examine risk factors for SPT development. Results: After adjusting for the time from the index diagnosis to randomization, age at diagnosis, stage, and site of the primary cancer, the factors that emerged as simultaneous predictors of SPT development were continued smoking and alcohol intake after the index diagnosis. Increased SPT risk was associated with older age (RR = 2.1; 95% CI 1.5–2.8); stage II diagnosis (RR = 1.5; 95% CI 1.1–2.1); index diagnosis of pharyngeal cancer (RR = 1.6; 95% CI 1.1–2.5); current smoking at registration (RR = 2.1; 95% CI 1.3–3.6) and continued alcohol consumption post-diagnosis (RR = 1.3; 95% CI 1.0–1.7). Conclusion: Important associations exist between SPT development and continued smoking and alcohol consumption after treatment for HNSCC.     

Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States)

Objectives: The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics. Methods: Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models. Results: 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9–1.0); prostate (RR = 1.0, 95% CI = 0.9–1.1); colon (RR = 0.9, 95% CI = 0.7–1.2); or lung (RR = 0.9, 95% CI = 0.7–1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7–1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8–1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7–1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6–1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3–0.8). Conclusions: The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.     

Late radiation injury following hyperfractionated craniospinal radiotherapy for primitive neuroectodermal tumor

PURPOSE: To document the late radiographic change following hyperfractionated craniospinal radiotherapy for primitive neuroectodermal tumor. METHODS AND MATERIALS: We reviewed long-term MRI scans on 21 patients with standard risk and high risk primitive neuroectodermal tumor treated with hyperfractionated radiotherapy following surgical resection. High risk patients also received adjuvant chemotherapy. Long-term scans were defined as scan obtained at least 1 year from diagnosis. Clinical follow-up data was available on all patients. RESULTS: Twelve of 21 patients had MRI evidence of necrosis, telangiectasia, white matter changes, basal ganglia change, or cerebral atrophy consistent with radiation injury. No patient required treatment for the radiographic change. CONCLUSIONS: Slightly over half of the patients had evidence of long-term radiation effect following craniospinal axis radiotherapy. However, no patient had frank clinical symptoms related to the radiographic findings.     

Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance

Cyclin D1 plays an important role in the regulation of the G1 phase in the cell cycle. In mammary epithelial cells the expression of cyclin D1 is regulated through the oestrogen receptor and via ErbB2 signalling. Here we investigated the prognostic significance of cyclin D1 among 230 breast cancer patients randomised for tamoxifen, CMF chemotherapy and radiotherapy. The importance of combined cyclin D1 and ErbB2 overexpression was also analysed. Immunohistochemical analysis of the cyclin D1 expression resulted in 69 (29.8%) weakly positive, 107 (46.5%) moderately positive and 54 (23.7%) strongly positive cases. The prognostic importance of ErbB2 was significantly greater for patients whose tumours overexpressed cyclin D1 than for other patients (p = 0.026). In the former group, ErbB2 overexpression was strongly associated with increased risk of recurrence (RR = 4.7; 95% CI, 2.1–10.4) and breast cancer death (RR = 5.4; 95% CI, 2.3–12.6). This result is in accordance with experimental studies demonstrating a link between cyclin D1 and ErbB2 in oncogenesis. Among oestrogen receptor positive patients, those with moderate cyclin D1 expression significantly did benefit from tamoxifen treatment (RR = 0.42; 95% CI, 0.21–0.82) whereas those with weak or strong expression did not. Therefore cyclin D1 might be a predictive marker for tamoxifen resistance.     

Magnetic resonance imaging identifies multifocal and multicentric disease in breast cancer patients who are eligible for partial breast irradiation

BACKGROUND: In this retrospective study, the authors hypothesized that magnetic resonance imaging (MRI) would alter partial breast irradiation (PBI) eligibility by identifying cancers outside the PBI volume compared with mammography alone. METHODS: Since 2002, MRI was used nonselectively at the authors' institution for the staging of patients with nonmetastatic breast cancer. Of 450 consecutive patients with invasive breast cancer, 110 patients who were eligible for PBI were identified by using criteria outlined by National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Oncology Group trial 0413 based on mammography, ultrasonography, and initial pathology. In that trial, patients were randomized (stage I/II invasive cancers that measured 相似文献   

Dementia Following Treatment of Brain Tumors with Radiotherapy Administered Alone or in Combination with Nitrosourea-based Chemotherapy: A Clinical and Pathological Study

A retrospective clinical and pathological study of 4 patients who developed the syndrome of radiation induced dementia was performed. All patients fulfilled the following criteria: (1) a history of supratentorial irradiation; (2) no evidence of symptomatic recurrent tumor; (3) no other cause of progressive cerebral dysfunction and dementia.The clinical picture consisted of a progressive subcortical dementia occurring 3–12 months after a course of cerebral radiotherapy. Examination revealed early bilateral corticospinal tract involvement in all patients and dopa-resistant Parkinsonian syndrome in two. On CT scan and MRI of the brain, the main features consisted of progressive enlargement of the ventricles associated with a diffuse hypodensity/hyperintensity of the white matter best seen on T2 weighted images on MRI. The course was progressive over 8–48 months in 3 patients while one patient had stabilization of his condition for about 28 years. Treatment with corticosteroids or shunting did not produce sustained improvement and all patients eventually died. Pathological examination revealed diffuse white matter pallor with sparing of the arcuate fibers in all patients. Despite a common pattern on gross examination, microscopic studies revealed a variety of lesions that took two basic forms: (1) a diffuse axonal and myelin loss in the white matter associated with tissue necrosis, particularly multiple small foci of necrosis disseminated in the white matter which appeared different from the usual radionecrosis; (2) diffuse spongiosis of the white matter characterized by the presence of vacuoles that displaced the normally-stained myelin sheets and axons.Despite a rather stereotyped clinical and radiological course, the pathological substratum of radiation-induced dementia is not uniform. Whether the different types of white matter lesions represent the spectrum of a single pathological process or indicate that the pathogenesis of this syndrome is multifactorial with different target cells, remains to be seen.     

The effect of dietary exposures on recurrence and mortality in early stage breast cancer

We studied the effect of diet and body weight on recurrence and death in 472 women diagnosed with early-stage breast cancer in 1982–1984. From Cox proportional hazards regression models we found that the strongest effects were observed in premenopausal women. For example, after accounting for disease stage and age, reported baseline consumption (times/day) of butter, margarine, and lard (risk ratio (RR)=1.67; 95% confidence interval (CI)=1.17–2.39) and beer (drinks/day) (RR=1.58; 95% CI=1.15–2.17) increased the risk of recurrence. There also appeared to be an increased risk associated with consumption of red meat, liver, and bacon, corresponding to about a doubling of risk for each time per day that foods in this category were consumed (RR=1.93; 95% CI=0.89–4.15). Relative body weight increased risk at the rate of 9% (RR=1.09; 95% CI=1.02–1.17) for each kg/m2 (equivalent to about 5.8 pounds for a woman 54 tall). For death, the results were similar, but relative weight was more strongly associated, increasing risk by 12% per kg/m2 (RR=1.12; 95% CI=1.03–1.22).     

Tubal sterilization and risk of breast cancer mortality in US women

Objective: To investigate the hypothesis that tubal sterilization is associated with a reduced risk of breast cancer. Methods: We examined this hypothesis in a large prospective study of US adults. After 14 years of mortality follow-up, 3837 deaths from breast cancer were observed in a cohort of 619,199 women who were cancer-free at study entry in 1982. Results: Cox proportional hazards models (adjusted for multiple breast cancer risk factors) showed a significant inverse association between tubal sterilization and breast cancer mortality (adjusted rate ratio (RR) = 0.82, 95% confidence interval (CI) 0.70–0.96). Women who were sterilized before age 35 had a lower risk (adjusted RR = 0.69, 95% CI 0.53–0.88) than women who were sterilized at 35 years of age or older (adjusted RR = 0.92, 95% CI 0.75–1.13). Also, sterilizations performed before 1975 resulted in a lower risk (RR = 0.75, 95% CI 0.62–0.91) than those performed during or after 1975 (RR = 0.98, 95% CI 0.74–1.29), possibly reflecting the likelihood of greater tissue damage with earlier procedures. Conclusions: These results suggest that tubal sterilization may lower subsequent risk of breast cancer, especially among women who are sterilized at a relatively young age. Additional studies are needed to confirm or refute these findings.     

Risk of second malignancy after Hodgkin's disease in a collaborative British cohort: the relation to age at treatment.

PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin's disease in relation to age at treatment and other factors. PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin's disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete. RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3. 3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radiotherapy (RR = 2.9; 95% CI, 1.9 to 4.1); breast cancer risk was increased only after radiotherapy without chemotherapy (RR = 2.5; 95% CI, 1.4 to 4.0); and leukemia risk was significantly increased after chemotherapy (RR = 31.6; 95% CI, 19.7 to 47.6) and mixed-modality treatment (RR = 38.1; 95% CI, 24.6 to 55. 9). These risks were generally greater after treatment at younger ages: for patients treated at ages younger than 25 years, there were RRs of 18.7 (95% CI, 5.8 to 43.5) for gastrointestinal cancer after mixed-modality treatment, 14.4 (95% CI, 5.7 to 29.3) for breast cancer after radiotherapy, and 85.2 (95% CI, 45.3 to 145.7) for leukemia after chemotherapy (with or without radiotherapy). CONCLUSION: Age at treatment has a major effect on risk of second malignancy after Hodgkin's disease. Although absolute excess risks are greater for older patients, RRs of several important malignancies are much greater for patients who are treated when young. The increased risk of gastrointestinal cancers may relate particularly to mixed-modality treatment, and that of lung cancer to chemotherapy as well as radiotherapy; there are also well-known increased risks of breast cancer from radiotherapy and leukemia from chemotherapy. The roles of specific chemotherapeutic agents in the etiology of solid cancers after Hodgkin's disease require detailed investigation.     

Significant Efficacy of Additional Concurrent Chemotherapy with Radiotherapy for Postoperative Cervical Cancer with Risk Factors a Systematic Review and Meta-analysis

Background Whether concurrent chemotherapy treatment is superior to radiotherapy alone as an adjuvant regimen for postoperative cervical carcinoma with risk factors remains controversial. Materials and Methods A literature search strategy examined Pubmed, Embase, the Cochrane Library, the China National Knowledge Internet Web, the Chinese Biomedical Database and the Wanfang Database. Article reference lists and scienti c meeting abstracts were also screened. Controlled trials comparing concurrent chemoradiotherapy versus radiotherapy alone in postoperative cervical cancer were included. The methodological quality of non- randomized controlled trials was evaluated using the Newcastle-Ottawa Scale. Randomized controlled studies were evaluated with the Cochrane handbook. A meta-analysis was performed with RevMan 5.3. Results A total of 1,073 patients from 11 clinical trials were analysed, with 582 patients in the concurrent chemoradiotherapy group and 491 patients in the radiotherapy group. Hazard ratios (HR) of 0.47 (95% CI 0.31-0.72) and 0.50 (95% CI 0.35-0.72) were observed for overall survival and progression-free survival, indicating a bene t from the additional use of concurrent chemotherapy. Subgroup analyses demonstrated that cervical cancer with high risk factors signi cantly bene tted from concurrent chemotherapy when examining overall survival (HR 0.44, 95% CI 0.28-0.67) and progression-free survival (HR 0.48, 95% CI 0.33-0.70), but patients with intermediate risk factors showed no bene t from concurrent chemotherapy in overall survival (HR 1.72, 95% CI 0.28-10.41) and progression-free survival (HR 1.09, 95% CI 0.19-6.14). No signi cant differences were observed for grade 3-4 anaemia (risk ratio (RR) 3.87, 95% CI 0.69-21.84), grade 3-4 thrombocytopenia (RR 3.04, 95% CI 0.88- 10.58), grade 3-4 vomiting or nausea (RR 1.71, 95% CI 0.27-10.96), or grade 3-4 diarrhoea (RR 1.40, 95% CI 0.69-2.83). Signi cant differences were observed for grade 3-4 neutropenia in favour of the radiotherapy group (RR 7.23, 95% CI 3.94-13.26). Conclusions In conclusion, concurrent chemoradiotherapy improves survival in postoperative cervical cancer with high risk factors but not in those with intermediate risk factors.     

Hormone replacement therapy is not associated with an increased risk of leukemia (United States)

Objective Recent studies have reported an increased risk of certain cancers associated with hormone replacement therapy (HRT), possibly due to stimulation of estrogen receptors. Since estrogen receptors are expressed on certain hematopoietic cells, it is possible that HRT use may also increase the risk of leukemia.Methods A cohort of 37,172 post-menopausal Iowa women ages 55–69 years with no history of prior cancer was linked annually to the population-based state cancer registry through 2001. In addition to other self-reported cancer risk factors, participants were asked about current and former use of HRT in 1986 and on four subsequent follow-up questionnaires. A total of 201 cases of leukemia were identified over 16 years of follow-up including 74 acute myeloid leukemias (AMLs) and 87 chronic lymphocytic leukemias (CLLs).Results Compared to never users of HRT at study baseline, current [multivariate relative risk (RR), 1.09; 95% confidence interval (CI) 0.70–1.71)] and former users (RR=0.82, 95% CI=0.59–1.15) were at no increased risk of developing leukemia. For AML, current users also had no increased risk (RR=0.83, 95% CI=0.37–1.84) and there was a suggestion that former users had a slightly decreased risk (RR=0.66, 95% CI=0.37–1.17). For CLL, all RRs were around unity.Conclusion We conclude that HRT is unlikely to be an appreciable risk factor for leukemia.     

Subsequent primary cancers in relation to treatment of ovarian cancer

The incidence of subsequent primary cancers was assessed in relation to treatment for a cohort of 7,203 patients from the Birmingham and West Midlands Cancer Registry diagnosed between 1957 and 1976. The total of 213 cancers observed one or more years after treatment for ovarian cancer (mean follow-up = 6.5 person-years) represented a significant excess (observed (O) = 213, expected (E) = 140.07, relative risk (RR) = 1.5, 95% CI 1.3-1.7, P less than 0.001). Among patients whose treatment included chemotherapy (CT), with or without radiotherapy (RT), the risk of acute and non-lymphocytic leukaemia (A + NLL) was significantly increased (O = 5, E = 0.18, RR = 27.8, 95% CI 9.0-64.8, P less than 0.001). The relative risks of A + NLL following RT without CT (RR = 4.5) and after other treatments (RR = 2.9) were not significantly in excess of 1.0. Significant excesses of subsequent cancers were observed at several sites: breast (RR = 1.7, 95% CI 1.3-2.2), lung (RR = 2.0, 95% CI 1.3-3.4), colon and rectum (RR = 1.6, 95% CI 1.1-2.3), urinary system (RR = 1.9, 95% CI 0.9-3.7), nervous system (RR = 3.3, 95% CI 1.2-7.3) and connective tissue (RR = 6.7, 95% CI 1.8-17.1) but the relationship with type of treatment was not so clearly defined as that for leukaemia. Although the treatment groups were broad and based on routinely collected data, they can enhance the use of cohort analyses for exploratory and monitoring purposes.     

Cancer incidence among male Swedish veterinarians and other workers of the veterinary industry: a record-linkage study

Objective: To investigate the risk of cancer among veterinarians in a large record-linkage study from Sweden. Methods: We used the nationwide, Swedish Cancer Environment Registry III, which links the Cancer Register data for 1971–1989 to the national population censuses from 1960 and 1970, to compare the incidence of cancer among male veterinarians to that of the remaining part of the active population using multivariable Poisson regression models and standardized incidence ratios. One thousand one hundred and seventy eight men classified as veterinarians or workers in the veterinary industry at either census were identified. Results: Veterinarians in the veterinary industry experienced increased risk of esophageal (relative risk (RR) 3.78, 95% confidence interval (CI) 1.42–10.09), colon (RR: 2.36, 95% CI: 1.42–3.91), pancreatic (RR: 2.10, 95% CI: 0.94–4.68) and brain (RR: 2.51, 95% CI: 1.04–6.03) cancers as well as melanoma of the skin (RR: 2.77, 95% CI: 1.24–6.17). Similar excess risks were observed when veterinarians were compared with individuals of similar socio-economic status. Conclusion: The increased risks of esophageal, colon, pancreatic and brain cancers as well as melanoma observed among veterinarians did not seem to be explained by the high socio-economic status of this occupational group. Therefore, it is possible that some of these results reflect the carcinogenicity of occupational exposures, including animal viruses, solar or ionizing radiations and anesthetics.     

Benefit of radiotherapy on survival in resectable gastric carcinoma: a meta-analysis

We aimed to perform a meta-analysis to assess the impact of radiotherapy (RT) on both 3- and 5-year survival in patients with resectable gastric cancer. Relevant studies were identified by using PubMed, Embase and the Cochrane Controlled Trials Register through May 2013. We included randomized clinical trials (RCTs) that compared survival of surgery combined with RT (preoperative and/or postoperative) to surgery alone or surgery plus chemotherapy. Meta-analysis was performed using risk ratios (RRs). Both fixed- and random-effects models were used to calculate the summary risk estimates. Fourteen RCTs involving 2,853 participants were included in this meta-analysis. The addition of RT significantly increased the 3-year (RR 1.19; 95 % confidence interval (CI) 1.05–1.35) and 5-year survival (RR 1.25; 95 % CI 1.12–1.40). A significant advantage was also observed in subgroup analysis of preoperative RT for both 3-year (RR 1.56; 95 % CI 1.19–2.05) and 5-year overall survival (RR 1.40; 95 % CI 1.13–1.73). There was no evidence that preoperative RT increased postoperative mortality (RR 0.85; 95 % CI 0.42–1.72). Surgery combined with RT or chemoradiotherapy compared to surgery alone improved the 3-year (RR 1.18; 95 % CI 1.01–1.38) and 5-year survival rate (RR 1.38; 95 % CI 1.18–1.61). Although the quality of the studies was variable, the data were consistent, and no substantial publication bias was observed. In patients with resectable gastric carcinoma, adjuvant RT significantly increased the 3-year and 5-year survival. Preoperative RT is safe and definitely improves overall survival. Available evidence is insufficient to determine the benefit of postoperative RT after an extended lymphadenectomy and radical resection.     

Employment as butcher and cancer risk in a record-linkage study from Sweden

Objective: To investigate the risk of cancer among butchers and other meat workers in a large record-linkage study from Sweden. Methods: The Swedish Cancer Environment Register III contains nationwide data on cancer incidence during 1971–1989 for all residents, by occupation and industry of employment as reported at the 1960 and 1970 censuses. We identified 25,049 men classified as butchers or meat workers at either census. We used as a comparison group the remaining part of the active male population, after exclusion of workers with direct contact with animals. Results: Butchers in the meat industry had a slight increase in the risk of cancer (relative risk [RR] 1.1, 95% confidence interval [CI] 1.0–1.3), which was due to an increased risk of cancers of the oral cavity and pharynx (RR 1.6, 95% CI 1.0–2.7), stomach (RR 1.6, 95% CI 1.1–2.7), larynx (RR 1.4, 95% CI 0.6–3.4), and lung (RR 1.4, 95% CI 1.1–1.9). The risk of stomach cancer was highest during the first 5 years of the study, and among butchers from urban areas. No temporal or geographic variations were seen for lung cancer risk, with elevations restricted to squamous cell carcinoma. An increased risk of stomach, laryngeal and lung cancers was present in butchers and meat workers outside the meat industry. There was no clear indication of an increased risk of other neoplasms. Conclusions: The increased risk of oral, laryngeal, lung and stomach cancers among Swedish butchers may be at least partly due to confounding by tobacco smoking, alcohol drinking, and other lifestyle factors. However, exposures in the meat industry (e.g., viruses, nitrosamines, polycyclic aromatic hydrocarbons) may contribute the elevated cancer risks.     

Impact of chemotherapy dose-density on radiotherapy dose-intensity after breast conserving surgery

Purpose:To evaluate if chemotherapy (CT) dose-intensificationjeopardizes radiotherapy (RT) dose-intensity (DI). Patients and methods:From 1992 to 1997, 247 stage I–IIbreast cancer patients, treated with conserving surgery, were treated at theNational Cancer Institute of Genoa in a randomized study comparing the sameCEF regimen delivered every two weeks (CEF14) or three weeks (CEF21). RT wasapplied to the residual breast at a total dose of 50 Gy in five weeks.Allowance was made for treatment at 2.3 Gy per fraction in order to compensatefor gaps (hypofractionation). Radiotherapy DI was expressed as the averagetotal dose received each week, i.e., weekly dose-rate (WDR). Theeffect of various tumour, treatment and patient-related factors on theendpoint (a delivered WDR of RT < 9.5 Gy) was investigated by univariateanalysis. Factors found to have P-value 0.20 were entered inmultivariate analysis. Results:All but three patients (244 of 247, 98.8%)received a cumulative total dose of RT within ±10% of thatplanned. Moreover, most of them (197 of 247, 79.8%) received an averageWDR of 9.5 Gy/wk. With univariate analysis the probability of WDR < 9.5Gy/wk significantly correlated with age, menopausal status, concomitantadministration of RT and CT, and white blood cell toxicity. Moreover, apositive effect on WDR was found in patients treated at 2.3 Gy per fraction.The type of treatment (CEF14 vs. CEF21) did not affect the probability of WDR< 9.5 Gy/wk. With multivariate analysis, age (55 vs. >55 years, RR= 3.99, 95% CI: 1.89–8.42, P= 0.0003), RT fractionation(conventional vs. hypofractionation, RR = 0.32, 95% CI:0.15–0.68, P= 0.017) and WBC toxicity (none vs. some, RR =1.54, 95% CI: 1.06–2.22,P = 0.027) wereindependent predictors of WDR < 9.5 Gy. Regarding the CT-RT overlap,patients receiving more than two cycles of chemotherapy during radiotherapyhad an increased risk of RT delay compared to other patients (RR = 3.74,95% CI: 1.44–9.48, P= 0.0063). Conclusions:There is no evidence of a direct effect of CTdose-density on dose-intensity of RT. However, the concomitant use of CT andRT reduces the possibility of giving a full dose-intensity of RT.     

Prognostic significance of etiological risk factors in early breast cancer

Several risk factors for the etiology of breastcancer have also been correlated with the prognosisof breast cancer. However, the published studies haveyielded conflicting results.Women under 71 years of age with stageI, II, or III breast cancer were eligiblefor inclusion in a clinical study. 866 patientswith breast cancer entered the study, of whom463 had positive lymph nodes.Survival was analysed using Cox's proportional hazards model.Age at menarche, parity, age at menopause andfamily history were not consistently related to survival.Young age at first full-term pregnancy was relatedto decreased survival (adjusted relative risk (RR): 1.69,95% confidence intervals (95% CI): 1.04–2.68), but itcannot be excluded that this result was dueto chance alone. Use of oral contraceptives wasnot correlated with survival (RR: 1.10, 95% CI:0.80–1.51) nor was family history (RR: 0.93, 95%CI: 0.66–1.30).This study provided little support for the hypothesisthat risk factors for breast cancer are relatedto survival.