Robert Smee

Craniofacial resection for paranasal sinus cancers.

Combined anterior craniofacial resection (CFR) has been in use for more than 25 years. The advent of the free revascularized tissue transfer flap in l980 permitted safe resection of tumors that had spread beyond the confines of the paranasal sinuses with immediate reconstruction of the sino‐orbital cranial defect. The purpose of this study was to examine the outcomes and morbidity of a management policy of primary CFR and postoperative radiotherapy for paranasal sinus cancers infiltrating the skull base over a 21‐year period.

Does waiting time affect the outcome of larynx cancer treated by radiotherapy

AIM To determine the impact of waiting for radiotherapy on local control in early larynx cancer treated by radiotherapy alone. METHODS Records of patients with T1 and T2, N0-2 larynx cancer were examined at three radiotherapy centres. Waiting time was defined in three ways, (1) time from biopsy to radiotherapy, (2) time from presentation to radiation department to start of radiotherapy and (3) the minimum of (1) and (2). Time to relapse was the major end point. RESULTS There were 581 patients with a median follow-up of 6.8 years. Stage distribution was as follows: T1, 370; T2a, 106; T2b, 94; T2 unspecified, 11; N0, 563; N+, 18. Median times from biopsy, presentation and minimum time to treatment were 24, 16 and 15 days, respectively. Ninety percent of minimum waiting times were < or = 31 days. The median dose was 61 Gy in a median of 30 fractions over a median 46 days. Local recurrence occurred in 126 patients. The actuarial recurrence free rate at 5 years was 77% (SE 2%). In a multivariate analysis the significant predictors of relapse were higher T stage, longer treatment duration and increasing field area. Waiting time was not significantly associated with local relapse. CONCLUSION This study did not show longer waiting time to be a significant predictor of relapse in early larynx cancer. Other end-points which are relevant, such as quality of life, have not been examined. Longer treatment times were significantly associated with relapse.

OROPHARYNGEAL CANCER IN THE ELDERLY

PURPOSE The poor prognosis of elderly patients in many cancers may be due to less thorough investigation and less aggressive treatment because of the perception that radical treatment will be poorly tolerated and that elderly patients have a limited life expectancy. We wished to assess whether older age is associated with (a) less radical treatment, (b) poorer outcome, or (c) greater toxicity, after adjusting for other possible contributing factors. METHODS AND MATERIALS A retrospective study of patients with loco-regional oropharyngeal cancer treated between January 1980 and December 1985 was conducted. Patients were treated with radiotherapy, surgery, chemotherapy, or combinations. Cox regression was used to assess age effects while allowing for the influence of other factors. RESULTS Eighty-eight patients were treated radically and 16 palliatively. Treatment intent (radical or palliative) did not appear to be related to age, before (p = 0.42) or after adjusting for other factors (p = 0.34). In a selected group of 86 radically treated patients ages ranged from 33 to 85 (median 60). There were 35 loco-regional failures and 58 deaths (38 related to oropharyngeal cancer). Older patients were prescribed and received lower doses of radiation. However, older age was not related to the risk of loco-regional recurrence (p = 0.96) or shorter survival (p = 0.67), and was not associated with duration of treatment interruption or severity of toxicity after adjustment for prognostic factors. There was some suggestion of a higher risk of recurrence with increasing age for patients under 70 years but with a risk for patients over 70 at least equal to that of the youngest group. Elderly patients in our study may have been a selected group. CONCLUSION Older patients with loco-regional oropharyngeal cancer, or at least a subset of them, appear to be able to tolerate radical courses of radiotherapy, and to have similar outcomes as do younger patients.

Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer

BACKGROUND Despite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer. PATIENTS AND METHODS A total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression. RESULTS The prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes. CONCLUSIONS This study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV.

Role of radiotherapy in early glottic carcinoma

Early glottic carcinoma has a high local control prospect with radiotherapy. This review evaluates a single centers experience.

Human papillomavirus, smoking status and outcomes in tonsillar squamous cell carcinoma

It is now clear that the two separate entitles of tonsillar cancer, HPV induced and non‐HPV induced (smoking induced), have significantly different presenting stage and outcomes. A significant proportion of patients with human papillomavirus positive tonsillar cancer have had exposure to smoking. We examined the combined effect of human papillomavirus and smoking on the outcomes and determined whether smoking can modify the beneficial effect of human papillomavirus. A total of 403 patients from nine centers were followed up for recurrence or death for a median of 38 months. Determinants of the rate of loco‐regional recurrence, death from tonsillar cancer and overall survival were modeled using Cox regression. Smoking status was a significant predictor of overall survival (p = 0.04). There were nonstatistically significant trends favoring never smokers for loco‐regional recurrence and disease specific survival. In addition, there was no statistically significant interactions between smoking and human papillomavirus (p‐values for the interaction were 0.26 for loco‐regional recurrence, 0.97 for disease specific survival and 0.73 for overall survival). The effect of smoking on loco‐regional recurrence and disease specific survival outcomes was not statistically significant, nor was there significant evidence that the effect of smoking status on these outcomes was modified by HPV status. Irrespective of HPV status, however, smokers did have poorer overall survival than never‐smokers, presumably due to effects of smoking that are unrelated to the primary cancer.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy : A systematic review of randomised controlled trials

BACKGROUND Radiotherapy is a well-established treatment for some solid tumours. Hyperbaric oxygenation (HBO) may improve radiotherapeutic killing of hypoxic cancer cells, so the simultaneous administration of radiotherapy and HBO may reduce mortality and tumour recurrence. METHODS We performed a systematic search of the literature in September 2007 for randomised controlled trials, and made pooled analyses of pre-determined clinical outcomes. RESULTS Nineteen trials contributed to this review (2286 patients). There was a reduction in mortality for head and neck cancers at one and five years after therapy (at five years RR 0.82, P=0.03, NNT=5), and improved local tumour control at three months (RR 0.58, P=0.006, NNT=7). Any advantage is achieved at the cost of an increased rate of both severe radiation tissue injury (RR 2.35, P<0.0001, NNH=8) and the chance of seizures during therapy (RR 6.76, P=0.03, NNH=22). CONCLUSIONS There is some evidence that HBO improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the uterine cervix. These benefits may only occur with unusual fractionation schemes. HBO is associated with significant adverse effects including oxygen toxic seizures and severe radiation tissue injury. The methodological and reporting inadequacies of the studies included in this review demand a cautious interpretation. More research is needed for head, neck and uterine cervical cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other sites.

A single centre’s experience of stereotactic radiosurgery and radiotherapy for non-functioning pituitary adenomas with the Linear Accelerator (Linac)

Non-functioning pituitary adenomas are primarily a surgically managed pathology, but recurrence or regrowth is not uncommon. Previous large series have retrospectively validated the use of the Gamma Knife (GK) as an adjuvant treatment. To our knowledge, we present the largest case series to date with the Linear Accelerator (Linac) for the management of this pathology. In this study we review the clinical course of 118 patients, 51 of whom had stereotactic radiosurgery (SRS) and 67 who had fractionated stereotactic radiotherapy (FSRT); the discriminatory feature being proximity to the optic chiasm. For comparison purposes a population of 53 patients who had conventional radiotherapy (CRT) is included. The local control rates at 5 years for SRS, FRST and CRT were 100%, 93% and 87% respectively. Treatment-related morbidity was low. These data confirm that Linac SRS and FSRT are safe and effective for the treatment of non-functioning pituitary adenomas.

Malignancies of the external auditory canal and temporal bone: A review

Background: Malignancies of the external auditory canal and temporal bone are uncommon. A retrospective review was conducted of a large series treated at the Prince of Wales hospital between 1974 and 1995.

Split-course accelerated therapy in head and neck cancer: An analysis of toxicity

PURPOSE To retrospectively assess a protocol of split-course accelerated radiation therapy (SCAT) for selected head and neck cancers. METHODS AND MATERIALS SCAT consisted of 1.8 Gy per fraction administered twice daily with a minimum gap between fractions of 6 h. The treatment protocol prescribed an initial 16 fractions followed by a planned 5 to 12 day break, and then a further 20 to 22 fractions for a total dose ranging from 64.8 to 72 Gy delivered in 5 to 6 weeks. RESULTS Twenty-eight patients received SCAT for histologically confirmed head and neck cancer between January 1987 and August 1991. All patients were followed up until December 1, 1993. The mean potential follow-up time was 4.2 years (range: 2.9-6.2 years). All patients completed the treatment protocol. Thirteen tumors were laryngeal in origin, eight hypopharyngeal, four paranasal sinus, and three oropharyngeal. There were no Stage I, three Stage II, nine Stage III, and 12 Stage IV tumors. Four tumors were not staged (two paranasal sinus cancers and two surgical recurrences). Early and late toxicities were moderate to severe. Confluent mucositis was experienced by 27 of the 28 patients (96%). One patient required a prolonged midtreatment break of 24 days. Nine patients (32%) required narcotic analgesia for pain relief. Eleven patients (39%) required hospitalization for nasogastric feeding or pain control. The median length of hospital stay was 14 days (range 7-98 days). The actuarial rate of severe late toxicity at 3 years was 47% (standard error (SE) = 13%). A complete tumor response was achieved in 86% of patients. The actuarial local control rate at 3 years was 43% (SE = 11%) and the actuarial survival rate at 3 years was 25% (SE = 8%). CONCLUSION Given the encouraging complete response rate and local control for such advanced tumors, SCAT for locoregionally advanced tumors merits further investigation. However, because of the significant late toxicity observed, the total dose, interfraction interval, and fractionation technique used should be reconsidered.