Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.

BACKGROUND: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. METHODS: We explored the predictive value of referral guidelines (Kernick and NICE 2005) for brain imaging where a tumour is suspected, in a population-based patient group referred for direct access CT of the head. A consensus panel reviewed whether non-tumour findings were clinically important or whether further investigation was necessary. RESULTS: Over a 5-year period, 3257 head scans were performed; 318 scans were excluded according to pre-specified criteria. 53 patients (1.8%) were reported to have intracranial tumours, of which 42 were significant (diagnostic yield of 1.43%). There were no false negative CT scans for tumour. With symptom-based referral guidelines primary care doctors can identify patients with a 3% positive predictive value (PPV). 559 patients had non-tumour findings, 31% of which were deemed clinically significant. In 34% of these 559 patients, referral for further imaging and/or specialist assessment from primary care was still thought warranted. CONCLUSION: Existing referral guidelines are insufficient to stratify patients adequately based on their symptoms, according to the likelihood that a tumour will be found on brain imaging. Identification of non-tumour findings may be significant for patients and earlier specialist input into interpretation of these images may be beneficial. Improving guidelines to better identify patients at risk of a brain tumour should be a priority, to improve speed of diagnosis, and reduce unnecessary imaging and costs. Future guidelines may incorporate groups of symptoms, clinical signs and tests to improve the predictive value.

Methods to induce labour: a systematic review, network meta-analysis and cost-effectiveness analysis.

OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of labour induction methods. METHODS: We conducted a systematic review of randomised trials comparing interventions for third-trimester labour induction (search date: March 2014). Network meta-analysis was possible for six of nine prespecified key outcomes: vaginal delivery within 24 hours (VD24), caesarean section, uterine hyperstimulation, neonatal intensive care unit (NICU) admissions, instrumental delivery and infant Apgar scores. We developed a decision-tree model from a UK NHS perspective and calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit, and cost-effectiveness acceptability curves. MAIN RESULTS: In all, 611 studies comparing 31 active interventions were included. Intravenous oxytocin with amniotomy and vaginal misoprostol (≥50 µg) were most likely to achieve VD24. Titrated low-dose oral misoprostol achieved the lowest odds of caesarean section, but there was considerable uncertainty in ranking estimates. Vaginal (≥50 µg) and buccal/sublingual misoprostol were most likely to increase uterine hyperstimulation with high uncertainty in ranking estimates. Compared with placebo, extra-amniotic prostaglandin E2 reduced NICU admissions. There were insufficient data to conduct analyses for maternal and neonatal mortality and serious morbidity or maternal satisfaction. Conclusions were robust after exclusion of studies at high risk of bias. Due to poor reporting of VD24, the cost-effectiveness analysis compared a subset of 20 interventions. There was considerable uncertainty in estimates, but buccal/sublingual and titrated (low-dose) misoprostol showed the highest probability of being most cost-effective. CONCLUSIONS: Future trials should be designed and powered to detect a method that is more cost-effective than low-dose titrated oral misoprostol. TWEETABLE ABSTRACT: New study ranks methods to induce labour in pregnant women on effectiveness and cost.

Age as a prognostic factor in carcinoma of the cervix.

The influence of age on prognosis for carcinoma of the cervix was evaluated for a population of 218 patients treated at Loma Linda University between 1972 and 1982. Treatment methods were consistent over this time interval and were tailored according to age and extent of disease. Minimum follow-up is 5 years. The age groups were less than 35, 35-55, 55-75, and greater than or equal to 75. There was a significantly higher percentage of stages IIB and III in the older (greater than 55) age groups. The age groups were subdivided by stage for analysis of local-regional and distant failures. No significant age differences in local-regional or distant failures were found. Actuarial analysis of disease-free survival demonstrated no significant difference by age group. Age could not be verified as a prognostic factor in this study population.

Randomized trial of the addition of cis-platin (DDP) and/or BCG to cyclophosphamide (CTX) chemotherapy for ovarian carcinoma.

A prospective randomized trial has compared cyclophosphamide (CTX) with CTX plus cis-diamminodichloroplatinum (DDP) as the initial chemotherapy for advanced ovarian carcinoma. A secondary randomization compared the addition of BCG treatment to either chemotherapy. The addition of DDP had no measurable impact on survival, but a small survival trend favoring BCG-treated patients was noted (P less than 0.08). Toxicity from BCG treatment was insignificant, but the addition of DDP increased both early nausea and vomiting and later hematologic toxicity. There were three long-term complete remission patients, and these all came from the group of six patients with pretreatment residual disease less than 2 cm. A univariate analysis of pretreatment prognostic factors indicated significantly better prognosis (P less than 0.02) for patients with no palpable tumor, platelet count less than 400,000/mm3, residual tumor less than 2 cm, resting pulse less than 91/min. and LDH less than 250 U/L. The authors conclude that for patients with large (greater than 2 cm) residual disease, there is no compelling evidence that initial combination therapy is superior to aggressive single alkylating agent treatment.

Radical hysterectomy for recurrent carcinoma of the uterine cervix after radiotherapy.

Patients with small recurrent cervical carcinomas following radiation therapy may be salvaged with radical hysterectomy rather than exenteration. Between 1953 and 1993, 50 patients underwent radical hysterectomy for persistent (n = 18) or recurrent (n = 32) cervical cancer after primary radiotherapy. The mean age of the cohort was 44 years (range, 23-70). Histologic types were squamous in 46, adenocarcinoma in 3, and adenosquamous in 1. Of 37 patients with staged disease, 24 had stage IB/IIA, 7 had stage IIB, 2 had stage IIIA, and 2 had stage IIIB. Combination radiotherapy, consisting of 40-45 Gy external-beam radiation plus brachytherapy (mean 6980 mg/hr), was performed in 32 patients (64%). In the 32 patients with recurrent lesions, the median interval from definitive radiotherapy to radical hysterectomy was 16 months (4-301), with 19 of these patients (60%) presenting within the first 24 months. Patients with persistent carcinomas underwent radical hysterectomy after a median observation interval of 2 months (1-4). A class II or III radical hysterectomy was performed in 39 (78%) cases. Pelvic and para-aortic lymph node samplings were performed in 39 patients (78%), including 33 (66%) who underwent complete pelvic lymphadenectomy. Among those sampled, 5 (13%) had metastatic nodal disease. All 5 patients died of disease at a median 13 months after surgery. Severe postoperative complications occurred in 21 patients (42%). The most common site of injury was the urinary tract, with 14 patients (28%) developing vesicovaginal or rectovaginal fistulae, 11 (22%) developing ureteral injuries, and 10 (20%) developing severe long-term bladder dysfunction. There was one postoperative death from sepsis among the entire population. Patients with abnormal preoperative intravenous pyelograms (P < 0.05), patients with recurrent presurgical lesions (P < 0.05), and patients with postoperative pelvic cellulitis (P < 0.01) were more likely to develop fistulae. The 5- and 10-year actuarial survival rates for all cases was 72 and 60%, respectively. Tumor size at radical hysterectomy was significantly associated with survival. Five-year actuarial survival in 12 of 44 patients (27%) with identifiable lesion diameters less than 2 cm was 90% compared with 64% in patients with larger lesions (P < 0.01). Prolonged disease-free survival occurred in 26 of 50 patients (52%) who had known disease status at follow-up, whereas recurrence after radical hysterectomy was seen in 24 patients (48%).(ABSTRACT TRUNCATED AT 400 WORDS)

Concurrent radiation therapy and chemotherapy in the treatment of primary squamous cell carcinoma of the vulva.

BACKGROUND: Interest in combined modality treatment and in quality of life issues may affect the choice of radical vulvectomy as the treatment of choice in many vulvar carcinomas. To evaluate the potential role of combined radiation and chemotherapy with or without local excision as primary treatment for squamous cell carcinoma of the vulva, the outccomes of 19 patients with this disease treated with combination therapy were reviewed. METHODS: Nineteen patients were treated between September 1987 and October 1992. Fifteen patients had American Joint Committee on Cancer Stage III disease; 4 had Stage II. All had clinically negative inguinal lymph nodes with the exception of two patients who had positive ipsilateral inguinal nodes that were removed before treatment. The patients received 45-50 Gy to the pelvis and inguinal nodes with concurrent chemotherapy that consisted of 5-fluorouracil given as a 96-hour continuous infusion (1000 mg/m2/d) during weeks 1 and 5 of radiation. A single dose of mitomycin-C (10 mg/m2) during the first day of chemotherapy has been used since November 1991. Ten patients were boosted with implants or electrons and 6 others underwent local excision. RESULTS: The median follow-up was 34 months. Responses were determined clinically 1 month after completion of the radiation and chemotherapy. Clinically, complete responses were obtained in 10 patients (53%), partial responses in 7 (37%), and no response in 1; 1 patient progressed during treatment. The combined modality therapy (radiation/chemotherapy/with or without wide local excision) resulted in a local control rate of 74% (14/19). All five treatment failures occurred within 6 months of treatment. Four of these patients were rendered disease free by radical vulvectomy and/or exenteration, for an overall local control rate of 95% (18/19). CONCLUSION: Concurrent radiation therapy and chemotherapy with local excision performed as needed, appears to be a reasonable alternative to radical vulvectomy in patients with primary squamous cell carcinoma of the vulva. Radical surgery remains a viable option for patients in whom primary therapy has failed.