Treatment of early carcinoma of the vocal cords by radiotherapy

A total of 145 patients with early carcinoma of the vocal cords (T_1,2N₀) were treated by radiotherapy from 1979 to 1989. Survival and local control data were available for 135 and 127 patients, respectively. The respective 5 and 10 year results for overall survival were 75 and 68%. The 5 and 10 year probabilities of local control by radiotherapy were 89 and 86%, respectively, for T₁ tumours and 70% at both time intervals for T₂ tumours. Tumour recurrence following radiotherapy was documented in 18 of 127 patients. Tumour stage predicted significantly for local control, with recurrence rates for T₁ and T₂ tumours of 11 and 27%, respectively (P= 0.02). There was a higher proportion of recurrences for total radiation doses ≦ 6200 cGy (17%) compared with >6200 cGy (8%), but the difference was not statistically significant. Increasing duration of treatment was related significantly to increased recurrence for T₂ (P= 0.01), but not T₁, tumours. Most recurrences (60%) were salvaged successfully by laryngectomy. Three patients required laryngectomy for laryngeal oedema without recurrent tumour; all had been treated using a large field size (7 × 6 cm). There were 20 metachronous tumours, including five lung and two head and neck tumours. These results are similar to previous reports and confirm that radiotherapy is very effective for early glottic cancer, with high local control rates and effective salvage if local recurrences are recognized early.     

Impact of radiotherapy on laryngeal cancer survival: a population-based study of 13,808 US patients

BACKGROUND:

Radiotherapy with its advantage of organ preservation has been used to treat laryngeal cancer (LC) for several decades. However, the impact of radiation on overall survival (OS) in a large population‐based study has not been evaluated to date.

METHODS:

The authors analyzed all patients who had localized and/or regional glottic and supraglottic cancer in the Surveillance, Epidemiology, and End Results Program by comparing treatment trends and OS for the periods 1988 to 1993, 1994 to 1999, and 2000 to 2006. Kaplan‐Meier and logistic regression analyses were conducted to evaluate OS and the influence of patient demographics on treatment received.

RESULTS:

Among 13,808 patients with LC, radiotherapy use increased over the 3 periods for localized glottic cancer (LGC) (94%, 97%, and 98% during 1988‐1993, 1994‐1999, and 2000‐2006, respectively; P < .001); for regional glottic cancer (RGC) (53%, 66%, and 75%, respectively; P < .001), for localized supraglottic cancer (LSGC) (61%, 83%, and 94%, respectively), and for regional supraglottic cancer (RSGC) (43%, 55%, and 78%, respectively; P < .001). No significant decrease in 5‐year OS was observed during the 3 periods (LGC: 73%, 76%, and 78%, respectively; RGC: 57%, 51%, and 56%, respectively; LSGC: 33%, 35%, and 39%, respectively; and RSGC: 36%, 36%, and 43%, respectively). Blacks were significantly less likely to receive radiotherapy than whites (odds ratio: LGC, 0.42; RGC, 0.76; RSGC, 0.68; all P < .05). Those in the lowest tertile of median household income, compared with highest tertile, received radiotherapy less frequently (odds ratio: LGC, 0.42; RGC, 0.57; RSGC, 0.57; all P < .001).

CONCLUSIONS:

The current results indicated that the increased use of radiation with its advantage of speech preservation had no adverse impact on the survival of patients with LC. Black race and low income status had significant, inverse relations with the receipt of radiotherapy. Cancer 2012;. © 2011 American Cancer Society.     

T1N0/T2N0 glottic carcinoma: A comparison of two fractionation schedules

The aim of this paper is the retrospective comparison of accelerated/hypofractionated radiotherapy regimen (AHFX) with standard fractionation regimen (SFX) for patients with early glottic carcinoma. One hundred and forty‐five patients with T₁–T₂ glottic cancer between 1986 and 1998 were eligible. Before 1992, patients received 60–66 Gy in 30–33 fractions over 6–6.5 weeks (SFX) with ⁶⁰Co and 6‐MV beams. After 1992, patients received 52.5–55 Gy in 20 fractions over 4 weeks (AHFX) using 6‐MV beams. The end‐points were overall survival, laryngectomy‐free survival (LFS), loco‐regional control and toxicity. One hundred and two were stage T₁N₀; 43 were stage T₂N₀. Median follow up was 4.9 years. The 5‐year overall survival was 78%. Five‐year loco‐regional control in T₁N₀ patients was higher in AHFX than in SFX group (95 vs 75%, P = 0.002). Loco‐regional control in T₂N₀ patients was similar for AHFX and SFX (81 vs 80%, P = 0.813). Overall LFS was 88%. T₁N₀ AHFX patients had 5‐year LFS of 95% compared with 75% for SFX (P = 0.003). For T₂N₀ AHFX patients, overall LFS was 92% compared with 80% for the SFX group (P = 0.291). No grade 4 or 5 late toxicity occurred. One AHFX patient developed grade 3 toxicity; two of 51 SFX patients developed grade 2 toxicity versus five of 94 AHFX patients. AHFX using 6‐MV beams for treatment of early glottic cancer resulted in equivalent LFS and toxicity when compared with SFX.     

Planned preoperative radiation therapy for advanced laryngeal carcinoma

One hundred ten patients with predominantly advanced laryngeal carcinoma were treated in the period 1969–1978 with planned preoperative radiation therapy followed by surgery. Site distribution was: 63 supraglottic, 26 glottic, 15 transglottic and 6 subglottic. There were 4 Stage II patients, 66 Stage III and 40 Stage IV. Preoperative radiation therapy consisted of Telecobalt irradiation to a total dose of 25 Gy given to a target volume encompassing the larynx and regional neck nodes, given in 5 equal daily fractions of 5 Gy in 5 consecutive days. Surgery was performed 2 days later. Total laryngectomy was performed on 48 patients, total laryngectomy with neck dissection on 55 patients, supraglottic laryngectomy on 5 and supraglottic laryngectomy with neck dissection on 2 patients. Crude actuarial 5 and 10 year survival probability for the whole group is 71 and 61%, respectively. The corrected 5 and 10 year survival is 75%. For patients with T₃T₄N₀ tumors 5 and 10 year survival probability is: crude 65 and 58%, and corrected 70% respectively. For T₃T₄N , crude: 75 and 60% and corrected: 78%.Of 110 patients, one died postoperative, three died of intercurrent disease, five died as a result of second malignancy, and 23 died of their larynx carcinoma: $\text{12}\text{23}$ because of locoregional failure, and $\text{11}\text{23}$ because of distant metastasis. We concluded that short intensive preoperative radiation therapy and surgery offer a high cure rate in the treatment of advanced resectable laryngeal carcinoma. The merits of this technique are outlined in the text.     

Carcinoma-in-situ of the glottic larynx: results of treatment with radiation therapy

Purpose: Carcinoma-in-situ (CIS) of the vocal cords frequently progresses to invasive disease if untreated. Treatment approaches include vocal cord stripping, radiation therapy (RT), and laser excision. The purpose of this analysis was to assess the efficacy and safety of a standard RT regimen in the treatment of this condition.Methods and Materials: Between January 1980 and December 1994, 67 patients (52 men, 15 women; median age, 65 years) with glottic CIS were treated with RT. The standard RT regimen was 51 Gy in 20 fractions given over 4 weeks (99% of patients). Prior to receiving RT, 21 patients (31%) had undergone 1 or 2 vocal cord stripping procedures, and 1 had been treated with laser.Results: With a median follow-up of 6.5 years, 1 patient developed invasive glottic cancer, giving a 5-year actuarial local control rate of 98%. This patient recurred 14 months after treatment and was salvaged with laryngectomy. He is currently free of disease 2 years after surgery. There were no serious acute or late treatment complications. Sixteen patients (24%) developed subsequent malignancies, 8 of these being in the upper aerodigestive tract, although none were in the radiation field.Conclusions: Moderate-dose radiation therapy is an effective treatment for glottic CIS. It is well tolerated, produces no serious acute or long-term side effects, with an excellent cure rate.     

The epidemiology of laryngeal cancer in a country on the esophageal cancer belt

Objective

Laryngeal cancer is one of the most common malignant neoplasms of the head and neck and occurs predominantly in males. Squamous cell carcinomas arising in the glottic region are the most common of all laryngeal cancers and more prevalent than the supraglottic ones. But this pattern is reverse in some countries. This study was done to investigate the epidemiologic aspect of this subject in Iran.

Study design

Cross-sectional study

Subjects and methods

During a ten-year period from 1997 to 2007, all patients referred to two tertiary referral hospitals with a diagnosis of laryngeal cancer were enrolled in this study.

Results

Laryngeal cancer was diagnosed in a total of 453 patients and confirmed histologically. The average patient age was 59.92 years. Men outnumbered women (9.5:1). Four hundred patients (88.5%) were tobacco smokers. The primary location of the tumor was supraglottic in 221 (49%) cases, followed by glottic in 163 (36.2%), transglottic (the tumor involved all regions of the larynx and the origin was unspecified) in 60 (13.3%), and subglottic in 7 (1.6%).

Conclusion

In our series, although we excluded transglottic tumors, the supraglottic tumor was dominant and the ratio of supraglottic to glottic tumors was 1.36. This is compatible with results from countries with a reverse ratio.     

Effects of dexmedetomidine on immune response in patients undergoing radical and reconstructive surgery for oral cancer

Oral cancer is one of the most common malignancies in the world. The present study aimed to investigate the effects of dexmedetomidine on immune response in patients undergoing radical and reconstructive surgery for oral cancer. Patients were randomly divided into the dexmedetomidine and control groups. Within 15 min before anesthesia induction, dexmedetomidine was infused with a 0.5 µg·kg⁻¹ loading dose followed by a maintenance dose of 0.4 µg·kg⁻¹·h⁻¹ to the end of operation in the dexmedetomidine group, whereas the same volume of saline was administered in the control group. Blood samples were obtained at five time-points: 30 min Before induction (T₀), 1 h after induction (T₁), end of the operation (T₂) and 24 (T₃) and 48 h (T₄) after the operation. The T lymphocyte subsets (including CD3⁺, CD4⁺ and CD8⁺ cells) and CD4⁺/CD8⁺ ratio, B lymphocytes, dendritic cells and myeloid-derived suppressor cells (MDSCs) were analyzed by flow cytometry. All immunological indicators, except CD8⁺ cells, significantly decreased between the two groups at T_1–3 compared with T₀ (P<0.05). The percentages of CD3⁺, CD4⁺, dendritic cells and the CD4⁺/CD8⁺ ratios were significantly higher at T_2–4 and the percentages of MDSCs were significantly lower at T_2–4 in the dexmedetomidine group compared with the control group (all P<0.05). These findings suggested that dexmedetomidine can attenuate immunosuppression in patients undergoing radical and reconstructive surgery for oral cancer.     

Results of definitive radiotherapy in T1 and T2 glottic carcinoma: Institute of Rotary Cancer Hospital experience

Early glottic carcinomas (T₁ and T₂) constitute only 2% of all laryngeal cancers in our data. Seventy patients were seen between 1985 and 1992. All patients were treated by cobalt-60 small field radiotherapy using a beam directed shell. The total dose delivered was 60–65 Gy in 31 patients and 66–70 Gy in 39 patients. The follow-up period ranged from 5 to 126 months, with a mean follow up of 37 months overall and 55 months in the surgical salvage group. Radiation therapy controlled disease in 71% (50 of 70) of patients overall; 75% with T₁ and 67% with T₂ lesions. Total laryngectomy as salvage surgery was performed in 70% (14 of 20) of patients whose disease recurred. Ultimate control including surgical salvage occurred in 64 (91%) of 70 patients in the present study. The actuarial 5 year survival was 83 and 80% in T₁ and T₂ tumours, respectively (statistically insignificant). This report supports the policy of definitive irradiation, reserving surgical salvage for radiation failures in early laryngeal cancers.     

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.     

Prediction of local control in early glottic carcinoma using the maximum standardised uptake value

Purpose

This retrospective study aimed to determine whether the maximum standardised uptake value (SUV_max) can predict local tumour control in early glottic cancer (Tis, T1, and T2).

Radiotherapy for Laryngeal Cancer in Patients under 50 Years Old

Fifty-nine cases of laryngeal cancer treated by radiotherapyat the National Cancer Center Hospital between 1962 and 1990were analyzed retrospectively. All the patients were less than50 years old. The median total dose of the radiation deliveredto the primary tumor site was 70 Gy. The overall 5-yr survivalrate and 5-yr local control rate were 88% and 72%, respectively.Five (8.5%) of the 59 patients developed late recurrence morethan five yr after initial treatment, but subsequent salvageoperations were successful for disease control; three patientshad T1 glottic cancer, one had T2-3 glottic cancer and one hadT3N1 supraglottic cancer. Since the local control rate and the5-yr survival rate after radiotherapy are satisfactory, radiotherapy,which allows both functional and esthetic conservation, hasan important role in the treatment of laryngeal cancer in adultsunder 50 yr of age.     

Duration of symptoms, stage at diagnosis and relative survival in colon and rectal cancer

In colorectal cancer, the relation between duration of symptoms and stage at presentation and prognosis is not yet settled. All 1263 patients treated for colorectal cancer at Levanger Hospital, 1980–2004, and 2892 patients treated in Norway during 2004 were included. The association between symptom duration as an explanatory variable and tumour stage as a dependent variable was analysed using a proportional odds logistic regression model. Known duration of symptoms was divided into four categories: <1 week, 1–8 weeks, 2–6 months and >6 months. There was an inverse relationship between symptom duration and colon cancer TNM-stage, OR = 0.73 (95% CI 0.63–0.84), p < 0.001 (Levanger Hospital) and 0.84 (0.75–0.95), p = 0.004 (Norway 2004), where the OR is per category of symptom duration. Duration of symptoms were also inversely associated with T-stage, N-stage and M-stage in colon cancer. These relationships were not found for rectal cancer. In colon cancer the relative five-year survival for the four intervals of symptom duration was 44%, 39%, 54% and 66%, p < 0.001, in Levanger, 1980–2004, and four-year survival was 46%, 62%, 75% and 74%, p < 0.001, in Norway 2004, respectively. For rectal cancer survival was not dependent on symptom duration. In a multivariate analysis of relative survival of patients with colon cancer, duration of symptoms was associated with survival independent of tumour differentiation and TNM-stage. Increasing duration of symptoms was positively associated with less advanced disease and better survival in colon cancer, but not in rectal cancer.     

Tumour purine nucleotides and cell proliferation in response to exercise in rats

Voluntary physical exercise can delay the onset of anorexia and cachexia in tumour-bearing rats. A substrate deviation in the host which has been hypothesised as tumour burden is reduced despite an increase in food intake. Therefore, we determined the levels of purine nucleotides, the energy charge and the cell division rate in tumours from exercising animals in the postexercise period. Tumour content of purine nucleotides was analysed by HPLC. Tumour cell kinetics was studied by flow cytometry after incorporation of bromodeoxyuridine (BrdU) into DNA. Exercising animals demonstrated a 34.4% reduction in tumour volume (P < 0.05) but a 1.31-fold increase in energy charge in tumour tissue (P < 0.05). Labelling index (LI), DNA synthesis time (T_s) and potential doubling time (T_pot) were not significantly altered. These results suggest that the influence on tumour growth is closely related to the exercise period.     

TRAIL-R1 polymorphisms and cancer susceptibility: An evidence-based meta-analysis

Published data on the association between tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1 or DR4) polymorphisms rs20575 (C626G), rs2230229 (A1322G) and rs20576 (A683C) and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of nine studies, among which eight articles including 2941 cases and 3358 controls described C626G genotypes, three articles including 736 cases and 668 controls described A1322G genotypes and three studies totalling 1550 cases and 2257 controls described A683C genotypes were involved in this meta-analysis. Overall, all three polymorphisms were associated with cancer susceptibility. For C626G polymorphism, there was no association between C626G polymorphism and the risk of cancer in all genetic models when all the eligible studies were pooled into the meta-analysis. In the subgroup analysis by source of controls, statistically significantly reduced cancer risks were found among groups with population-based controls for CG versus CC (OR = 0.77, 95% CI:0.65–0.91, P_{heterogeneity} = 0.007) and dominant model (OR = 0.84, 95% CI:0.72–0.99, P_{heterogeneity} = 0.409). For A1322G polymorphism, we found it was associated with a significantly elevated cancer risk of all cancer types in different genetic models (homozygote comparison: OR = 2.80, 95% CI:1.16–6.76, P_{heterogeneity} = 0.905; dominant model comparison: OR = 1.57, 95% CI:1.02–2.41, P_{heterogeneity} = 0.167; and recessive model comparison: OR = 1.22, 95% CI:0.94–1.60, P_{heterogeneity} = 0.535). Similar results were obtained from A683C polymorphism (homozygote comparison: OR = 3.21, 95% CI:1.26–8.20, P_{heterogeneity} = 0.012; dominant model comparison: OR = 1.61, 95% CI: 1.09–2.36, P_{heterogeneity} = 0.000; and recessive model comparison: OR = 2.79, 95% CI: 1.17–6.68, P_{heterogeneity} = 0.025). In summary, this meta-analysis suggests that TRAIL-R1 C626G polymorphism is marginally associated with cancer susceptibility, and both TRAIL-R1 A1322G G allele and A683C C allele are associated with increased risk for cancer.     

Modification of N staging systems for penile cancer: a more precise prediction of prognosis

Background:

The tumour-node-metastasis (TNM) classification is the most widely used tool for penile cancer. However, the current system is based on few studies and has been unchanged since 2009. We determined whether a modified pathological N staging system that incorporates the laterality and number of lymph node metastases (LNMs) increases the accuracy of the results in predicting survival compared with the 7th edition of the pathological N staging system of the American Joint Committee on Cancer (AJCC) for penile cancer.

Methods:

The clinical and histopathologic data from 111 patients with penile cancer with LNMs were analysed. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the impact of the clinical and pathological factors on disease-specific survival of these patients. The predictive accuracy was further assessed using the concordance index.

Results:

According to the 7th edition of the pathological N classification, the 3-year disease-specific survival (DSS) rates for patients with pN1, pN2, and pN3 disease are 89.6%, 65.9%, and 33.6%, respectively (P_N1–N2=0.030, P_N2–N3<0.001, P<0.001). Under the modified pathological N category criteria, the 3-year DSS rates for pN1, pN2, and pN3 patients were 90.7%, 60.5%, and 31.4%, respectively (P_N1–N2=0.005, P_N2–N3=0.004, P<0.001). In separate multivariate Cox regression models, only modified N stages (hazard ratio: 4.877, 10.895; P=0.018, P<0.001) exhibited independent effects on the outcome. The accuracy of the modified pathological N category was significantly increased.

Conclusions:

The modified pathological N staging system is a better reflection of the prognosis of patients with penile cancer. Our study should contribute to the improvement of prognostic stratification and systemic treatment to avoid overtreatment of patients.     

Vitamin D receptor gene polymorphism(s) and breast cancer risk in north Indians

Background: Vitamin D (1,25-dihydroxyVitamin D₃) has shown experimentally anticarcinogenic effects and is thought to protect against breast cancer. The actions of Vitamin D are mediated via the Vitamin D receptor (VDR), and the polymorphisms at 3′UTR region of this gene are associated with the risk and progression of breast carcinoma. The current study is an attempt to examine the association of these variations with breast cancer risk in north Indians. Methods: A total of 160 cases and 140 control subjects were studied for the polymorphisms at 3′ end of the VDR gene. A polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method and fragment analysis was performed to determine ApaI and TaqI polymorphisms and variable length poly-A microsatellite repeats. Linkage disequilibrium (LD) was calculated for each pair of polymorphisms. Unadjusted and adjusted odds ratios for breast cancer with genotypes comprising the polymorphic sites were calculated to understand their role towards breast cancer susceptibility. Results: Patient's with long poly-A repeat showed a significant association with disease (χ² = 9.52, df = 2, P ≤ 0.01). Compared to subjects having two S alleles (SS), odds ratios (and 95% CI) were 0.75 (0.45–1.23) and 2.49 (1.18–5.27) for subjects having genotypes SL and LL, respectively. Among matched pairs (age), the poly-A LL genotype was found significantly associated with increased risk of breast cancer among early-onset cases (P = 0.02). The unconditional logistic regression analysis demonstrated a significant association between grade and LL genotype [(unadjusted odds ratio (95% CI): 4.45 (1.87, 10.63); adjusted odds ratio: 4.66 (1.88, 11.53)]. No significant association was observed for the VDR ApaI (χ² = 1.00, df = 2, P = 0.60) and TaqI polymorphism (χ² = 0.35, df = 2, P = 0.83). Although, strong LD was not observed among these polymorphic sites, it denies the total equilibrium at the same time. Based on haplotype distribution, the most common one observed among cases and controls was ATS while, genotype AATTLL had shown a significant association with the breast cancer risk (P = 0.02). Conclusions: The results indicate that the VDR poly-A polymorphism is significantly associated with breast cancer risk in north Indians especially with early onset disease. Although, ApaI and TaqI did not show any significant association with the disease when analyzed in isolation, but TaqI might modulate the risk associated with L alleles. Further, understanding the functional role of these variants residing on the VDR haplotype associated with disease susceptibility may suggest novel approaches for breast cancer prevention and therapy.     

Incorporating biologic measurements (SF2, CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy

To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF₂) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. Measurements of SF₂ and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp_α,ρ). Regression analysis was performed to assess the prognostic power of tcp_α,ρ vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF₂ and CFE measurements alone. In a univariate regression analysis of 44 patients, tcp_α,ρ was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF₂ alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp_α,ρ emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp_α,ρ, CFE was still a significant independent prognostic factor for local control, whereas SF₂ was not. The sensitivities of tcp_α,ρ and SF₂ as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. A Poisson tcp model incorporating individual SF₂, CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.     

Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer

Previous studies have suggested that hyperinsulinaemia and other components of metabolic syndrome are risk factors for clinical prostate cancer. This prospective study tested the hypothesis that hyperinsulinaemia and other components of metabolic syndrome are risk factors for lethal clinical prostate cancer. The clinical, haemodynamic, anthropometric, metabolic and insulin profile at baseline in men who had died from clinical prostate cancer during follow-up was compared with the profile of men who were still alive at follow-up. If the hypothesis is true, men with an unfavourable prognosis would have a higher profile at baseline than those with a favourable prognosis. A total of 320 patients in whom clinical prostate cancer, stages T2–3, had been diagnosed were consecutively included in the study during 1995–2003. Height, body weight, waist measurement, hip measurement and blood pressure were determined. Body mass index and waist/hip ratio (WHR) were calculated. Blood samples were collected to determine triglycerides, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, uric acid, alanine aminotransferase and fasting plasma insulin level. The prostate gland volume was measured using transrectal ultrasound. The annual benign prostatic hyperplasia (BPH) growth rate was calculated. The diagnosis of prostate cancer was established using transrectal ultrasound-guided automatic needle biopsy of the prostate gland. All patients with clinical prostate cancer were followed up until their death or until the study was terminated on 31 December 2003. At follow-up, 54 patients had died from prostate cancer and 219 were still alive. The results showed that the men who died of clinical prostate cancer during the follow-up period were older (P < 0.001), had a larger prostate gland volume (P < 0.001), a faster BPH growth rate (P < 0.001), a higher prevalence of type 2 diabetes (P < 0.035) and treated hypertension (P < 0.023), a higher stage (P < 0.001) and grade (P = 0.028) of clinical prostate cancer, a higher prostate-specific antigen (PSA) level (P < 0.001) and a higher PSA density (P < 0.001) at baseline than men still alive with clinical prostate cancer at follow-up. These men also had a lower HDL-cholesterol level (P = 0.027), a higher fasting plasma insulin level (P = 0.004), a higher WHR (P = 0.097) of borderline significance and a higher uric acid level (P = 0.079) of borderline significance. Eliminating the effect on mortality of higher stage and grade of the clinical prostate cancer and PSA at baseline, the following statistically significant correlations remained: a higher fasting plasma insulin level (P = 0.010) and a lower HDL-cholesterol level of borderline significance (P = 0.065). In conclusion, hyperinsulinaemia and five other previously established components of metabolic syndrome are shown to be prospective risk factors for deaths that can be ascribed to prostate cancer. These findings confirm previous study, which indicate that prostate cancer is a component of metabolic syndrome. Moreover, these data indicate that hyperinsulinaemia and other metabolic disorders precede deaths caused by prostate cancer. Thus, our data support the hypothesis that hyperinsulinaemia is a promoter of clinical prostate cancer. Furthermore, our data suggest that the insulin level could be used as a marker of prostate cancer prognosis and tumour aggressiveness, regardless of the patient’s prostate cancer stage, cancer grade and PSA level.     

Experience of symptoms indicative of gynaecological cancers in UK women

Background:

Gynaecological cancers account for ∼12% of female cancer incidence in the United Kingdom. Encouraging prompt help-seeking for potential symptoms could help improve outcomes. However, before developing help-seeking interventions, it is important to estimate the number of women with symptoms potentially indicative of a gynaecological cancer to help estimate the impact of such interventions on primary care.

Methods:

As part of a face-to-face, population-based survey, women aged ⩾16 (n=911) were shown a list of symptoms potentially indicative of a gynaecological cancer and were asked to indicate any experienced in the last 3 months. Those who reported symptoms were asked about their responses to one randomly selected index symptom.

Results:

Just under half (44%) of the respondents reported a symptom, with 35% reporting a frequent and/or severe symptom. Younger (P<0.001), lower socioeconomic status (P<0.01) and non-White women (P<0.05) were significantly more likely to report symptoms. Few (14%) respondents were both older (⩾45 years) and had a frequent and/or severe symptom. Of these women, 38% had seen a GP.

Conclusion:

Symptoms that potentially indicate a gynaecological cancer, even if limited to those that are frequent and/or severe, appear to be common. Consequently, encouraging prompt help-seeking may increase the burden on primary care. However, targeting those at increased risk (older women with frequent or severe symptoms) should avoid unmanageable increases in primary care consultations for gynaecological conditions.     

Childhood cancer and factors related to prolonged diagnostic intervals: a Danish population-based study

Background:

Early diagnosis of childhood cancer provides hope for better prognoses. Shorter diagnostic intervals (DI) in primary care require better knowledge of the association between presenting symptoms, interpretation of symptoms and the wording of the referral letter.

Methods:

A Danish nationwide population-based study. Data on 550 children aged <15 years with an incident cancer diagnosis (January 2007–December 2010) were collected through questionnaires to parents (response rate=69%) and general practitioners (GPs) (response rate=87%). The DI from the first presentation in general practice until diagnosis was categorised as short or long based on quartiles. Associations between variables and long DIs were assessed using logistic regression.

Results:

The GPs interpreted symptoms as ‘vague'' in 25.4%, ‘serious'' in 50.0% and ‘alarm'' in 19.0% of cases. Symptom interpretation varied by cancer type (P<0.001) and was associated with the DI (P<0.001). Vomiting was associated with a shorter DI for central nervous system (CNS) tumours, and pain with a longer DI for leukaemia. Referral letter wording was associated with DI (P<0.001); the shortest DIs were observed when cancer suspicion was raised in the letter.

Conclusion:

The GPs play an important role in recognising early signs of childhood cancer as their symptom interpretation and referral wording have a profound impact on the diagnostic process.