Time to Surgery Following Short-Course Radiotherapy in Rectal Cancer and its Impact on Postoperative Outcomes. A Population-Based Study Across the English National Health Service, 2009-2014.

AIMS: Preoperative short-course radiotherapy (SCRT) is an important treatment option for rectal cancer. The length of time between completing SCRT and surgery may influence postoperative outcomes, but the evidence available to determine the optimal interval is limited and often conflicting. MATERIALS AND METHODS: Information was extracted from a colorectal cancer data repository (CORECT-R) on all surgically treated rectal cancer patients who received SCRT in the English National Health Service between April 2009 and December 2014. The time from radiotherapy to surgery was described across the population. Thirty-day postoperative mortality, returns to theatre, length of stay and 1-year survival were investigated in relation to the interval between radiotherapy and surgery. RESULTS: Within the cohort of 3469 patients, the time to surgery was 0-7 days for 76% of patients, 8-14 days for 19% of patients and 15-27 days for 5% of patients. There was a clear variation in relation to different patient characteristics. There was, however, no evidence of differences in postoperative outcomes in relation to interval length. CONCLUSIONS: This study suggests that the time interval between SCRT and surgery does not influence postoperative outcomes up to a year after surgery. The study provides population-level, real-world evidence to complement that from clinical trials.

One millimetre is the safe cut-off for magnetic resonance imaging prediction of surgical margin status in rectal cancer.

BACKGROUND: A pathologically involved margin in rectal cancer is defined as tumour within 1 mm of the surgical resection margin. There is no standard definition of a predicted safe margin on magnetic resonance imaging (MRI). The aim of this study was to assess which cut-off (1, 2 or 5 mm) was the best predictor of local recurrence based on preoperative MRI assessment of the circumferential resection margin (CRM). METHODS: Data were collected prospectively on the distance between the tumour and mesorectal fascia for patients with documented radiological margin status in the MERCURY study. Positive margin and local recurrence rates were compared for MRI distances from the tumour to the mesorectal fascia of 1 mm or less, more than 1 mm up to 2 mm, more than 2 mm up to 5 mm, and more than 5 mm. The Cox proportional hazard regression method was used to determine the effect of level of margin involvement on time to local recurrence. RESULTS: Univariable analysis showed that, relative to a distance measured by MRI of more than 5 mm, the hazard ratio (HR) for local recurrence was 3·90 (95 per cent confidence interval 1·99 to 7·63; P < 0·001) for a margin of 1 mm or less, 0·81 (0·36 to 1·85; P = 0·620) for a margin of more than 1 mm up to 2 mm, and 0·33 (0·10 to 1·08; P = 0·067) for a margin greater than 2 mm up to 5 mm. Multivariable analysis of the effect of MRI distance to the mesorectal fascia and preoperative treatment on local recurrence showed that a margin of 1 mm or less remained significant regardless of preoperative treatment (HR 3·72, 1·43 to 9·71; P = 0·007). CONCLUSION: For preoperative staging of rectal cancer, the best cut-off distance for predicting CRM involvement using MRI is 1 mm. Using a cut-off greater than this does not appear to identify patients at higher risk of local recurrence.

Tarsal metastases in a patient with rectal cancer.

Bone metastases from colorectal cancer are uncommon and usually present late in the natural history of metastatic disease. This case report describes a 48-year-old man who developed an unusual distribution of bony metastases with multifocal osteolytic tarsal metastases 50 months after excision of a rectal carcinoma. An open biopsy was required to establish the diagnosis, exclude osteomyelitis and allow palliative radiotherapy to be given.

Stereotactic multiple arc radiotherapy. I. Vascular malformations of the brain: an analysis of the first 108 patients.

Between March 1989 and December 1993, 101 patients with inoperable arteriovenous malformations (AVMs) and seven patients with inoperable angiographically occult malformations (AOVMs) have been treated with stereotactic multiple arc radiotherapy (SMART). All patients (excluding one patient with a brain stem AOVM) were treated with a uniform dose of 1750 cGy prescribed to the 90% isodose. Fifty-two patients with AVMs have had follow-up angiographic studies performed 11-42 months after SMART. The complete angiographic obliteration rates were 75-77% for AVMs < 10 cm3 and 40-75% for AVMs > 10 cm3, when studied 18-30 months after SMART. Four patients re-bled prior to complete obliteration representing an actuarial 2-year incidence of re-bleeding of 5.1%. Seven patients developed a new neurological deficit after SMART after a median latent interval of 17 months (range 6-32). The actuarial 2-year incidence of neurological complications was 1.8% for lesions < 10 cm3. The actuarial 2-year incidence of neurological complications was 16% for lesions > 10 cm3 (10.5% for persisting deficit). Of seven patients with AOVM six have shown a reduction in size and degree of contrast enhancement, but in no patient has there been complete resolution shown by CT. Five patients with AOVMs developed symptomatic neurological deterioration at a median of 6 months after SMART (range 5-9). When viewed in the context of the natural history of conservatively managed inoperable AVMs, this series has demonstrated that our highly specialized irradiation technique is a safe and effective treatment for many patients.

Treatment of advanced carcinoma of the vulva with chemoradiotherapy - can exenterative surgery be avoided?

Thirty-seven patients with advanced FIGO stage (17 stage III, 20 stage IV) carcinoma of the vulva whose extent of disease would have required extenterative surgery were treated with chemoradiotherapy (CRT). Radiotherapy was given as a split course (2500 cGy mid-plane dose in 10 daily fractions, repeated 1 month later) to the first seven patients. Subsequently radiotherapy was given as a continuous course (4500 cGy mid-plane dose in 20-25 daily fractions). Chemotherapy included mitomycin c as an intravenous bolus and 5 fluorouracil as a continuous intra-venous infusion over 4-5 days, with variations in timing and dose according to the type of radiotherapy course. Fifteen (47%) complete and 11 (34%) partial responses were seen at 3 months after completion of treatment. Of the 15 patients with complete response, 10 remained disease-free for a median of 24 months (range 6-36 months). The median sur-vival for complete and partial responding patients was 15 and 11 months, respectively (range 2-37 months). Acute toxicity included moist perineal desquamation, diarrhea and myelosupression. One death secondary to neutropaenic sepsis occurred in the split course group. WHO grade 3 radiation enteritis occurred in one patient (14%) in the split course and two patients (6%) in the continuous CRT groups. Using CRT, very high response rates have been obtained with relatively low toxicity. There is a useful role for CRT in the treatment of patients with locally advanced recurrent disease although its place in the management of extensive primary disease requires further evaluation.

Intracranial germ cell tumours: I. Experience with platinum based chemotherapy and implications for curative chemoradiotherapy.

The results of treatment with platinum based combination chemotherapy in ten patients with intracranial germ cell tumours (GCT) are presented. Two patients, treated for relapse within the central nervous system (CNS), attained partial responses of short duration. One patient with systemic relapse was successfully salvaged with chemotherapy. Seven patients received primary chemotherapy, six of whom received a 'CNS friendly' regimen consisting of vincristine, etoposide, carboplatin (VEJ) prior to craniospinal axis (CSA) irradiation. Three complete and three partial responses, and one patient with stable disease, were seen prior to irradiation. All seven patients are alive and remain disease-free at a median time of 12 months after treatment. Current treatment policy for germinomas attaining complete response to two courses of VEJ is a lowered CSA dose prescription, while non-germinomatous germ cell tumours (NGGCT) receive standard total dose CSA irradiation.

Intracranial germ cell tumours: II. The application of a partial transmission block technique to reduce late morbidity.

Craniospinal axis (CSA) irradiation may be associated with significant late sequelae. The recognition of the influence of dose per fraction on late sequelae and the radiosensitivity of germ cell tumours (GCT) led to the adoption of a partial transmission block (PTB) technique for patients with intracranial GCTs. The PTB allows a dose differential between the whole cranium (prophylactic area) and the primary site (high-dose area) throughout the CSA prescription. The PTB technique has been used in four patients, two with germinoma and two with non-germinomatous germ cell tumours (NGGCT). All patients received two courses of primary chemotherapy with at least a partial response prior to CSA irradiation with the PTB and a three-field boost to the primary site. There was no prolongation in the overall treatment time. The use of this 'CNS friendly' radiotherapy technique was straightforward and the potential benefit in reducing late sequelae is discussed using two isoeffect methods.

Variation in mantle technique: implications for establishing priorities for quality assurance in clinical trials.

74 European and American radiotherapists responded to a questionnaire investigating the treatment of a patient with stage IIA non-bulky Hodgkin's disease by mantle irradiation. A consensus was present for the dose aims to involved and uninvolved lymph nodes and the acceptable incidence of late normal tissue effects. There was less agreement as to the total dose and dose per fraction required to maintain normal tissue toxicity within the agreed acceptable incidence. Variation was found in the radiation technique employed, the amount of spinal cord shielding used, the prescription point, modifications if irradiation was given after chemotherapy, and the routine recording of dose and dose per fraction to the normal tissue at risk. This descriptive survey confirms the need for well designed quality assurance programmes and indicates the areas of particular uncertainty that currently exist.