Size does matter: can we reduce the radiotherapy field size for selected cases of anal canal cancer undergoing chemoradiation?

AIMS: Chemoradiation is the standard of care for the treatment of anal canal cancer, with surgery reserved for salvage. For tumours with uninvolved inguinal nodes, it is standard to irradiate the inguinal nodes prophylactically, resulting in large field sizes, which contribute to acute and late toxicity. The aim of this single-centre retrospective study was to determine if, in selected cases, prophylactic inguinal nodal irradiation could be avoided. MATERIALS AND METHODS: Between August 1998 and August 2004, 30 patients with biopsy-proven squamous cell anal canal cancer were treated with chemoradiation using one phase of treatment throughout. A three-field beam arrangement was used without attempting to treat the draining inguinal lymph nodes prophylactically. The radiotherapy dose prescribed was 50Gy in 25 daily fractions over 5 weeks. Concomitant chemotherapy was delivered with the radiation using mitomycin-C 7-12mg/m(2) on day 1 and protracted venous infusional 5-fluorouracil 200mg/m(2)/day throughout radiotherapy. RESULTS: All patients had clinically and radiologically uninvolved inguinal and pelvic nodes and all had primary lesions that were T3 or less. The median age at diagnosis was 65 years (range 41-84). The median follow-up was 41 months (range 24-113). The mean posterior field size was 14x15cm and the mean lateral field size was 12x15cm. All patients achieved a complete response. Ninety-four per cent of patients (28/30) were alive and disease free. The two patients who died did so of unrelated causes and were disease free at death. Four patients relapsed and all were salvaged with surgery; two for local disease requiring abdominoperineal resection, one with an inguinal nodal relapse requiring inguinofemoral block dissection and one for metastatic disease to the liver who underwent liver resection. CONCLUSIONS: This single-centre retrospective study supports the treatment for selected cases of anal canal cancer with smaller than standard radiation fields, avoiding prophylactic inguinal nodal irradiation. Hopefully this will translate into reduced acute and late toxicity. In future studies we would suggest that consideration is given as to whether omission of prophylactic inguinal nodal irradiation for early stage tumours should be explored.

Targeted therapy in colorectal carcinoma: more than a theory.

OBJECTIVE: The aim of this review was to examine clinical trial data reporting the use of targeted therapies in colorectal cancer. METHOD: Candidate trials were identified by a comprehensive literature search. RESULTS: The data on the use of targeted therapies; usually combined with chemotherapy in the treatment of colorectal cancer is accumulating rapidly. These new agents will increasingly become incorporated into standard treatment schedules. CONCLUSION: Targeted therapy has moved rapidly from the laboratory to the clinic and is opening up potentially new and exciting areas for the development of the systemic treatment of colorectal cancer.

The role of positron emission tomography in the management of colorectal cancer.

Positron emission tomography (PET) is a functional imaging modality that has made the transition from the research environment to the clinical environment over the last 10 years. Its major role is in the field of oncology where it is being used increasingly in the management of several tumour types including colorectal cancer. This review aims to outline the current and future role of PET scanning in the field of colorectal cancer.

Peri-operative radiotherapy for rectal cancer: the case for a selective pre-operative approach - the third way.

Peri-operative radiotherapy has been used widely in addition to surgery in an attempt to reduce local recurrence (LR) following surgical resection of rectal cancer. Currently different groups follow different approaches with some routinely administering one weeks pre-operative radiotherapy to all cases of operable mobile cancer with others favouring postoperative chemoradiotherapy for selected high risk groups. In this review we bring together the changes in surgery, pathology and imaging that have occurred in recent years and together with the data from recent randomized pre-operative radiotherapy trials propose a logical and optimal way of managing rectal cancer. This third way is selective and pre-operative and should ensure a low rate of LR with radiotherapy reserved for those cases that need it.

Successful chemoradiotherapy for anal cancer despite previous radical radiotherapy for gynaecological malignancy.

Repeat radical irradiation of the pelvis is generally not undertaken because of concerns regarding normal tissue damage; in particular to small bowel, bladder and bone. Two patients with carcinoma of the anal canal are presented who had previously been treated by radical pelvic radiotherapy for gynaecological malignancy. Both were re-treated with radical radiotherapy to the pelvis with concomitant chemotherapy. A complete remission of anal cancer was achieved in both patients with minimal acute and late toxicities.

Management of Merkel cell carcinoma.

Merkel cell carcinoma is an uncommon cutaneous malignancy. Although it is rare, Merkel cell carcinoma has been described as the most malignant primary skin tumor. It is therefore important that once diagnosed, Merkel cell carcinoma is treated appropriately. The aim of this short review is to provide a summary of the available literature to guide clinicians in the future management of such patients. Inevitably in such a rare disease, there are no randomized trials of therapy. The treatment of individual patients will rely on opinion as much as the 'evidence'.

Fluorodeoxyglucose positron emission tomography in the evaluation of germ cell tumours at relapse.

Differentiation of active disease from fibrosis/mature teratoma in patients with residual masses or identifying of sites of recurrence in patients with raised markers following treatment of their testicular cancer remains a problem.(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management in these patients. We performed a retrospective study of the use of FDG-PET in detecting residual/recurrent testicular carcinoma in 55 patients (seventy FDG-PET scans). Forty-seven scans were for the assessment of residual masses (18 had raised markers) and 23 scans were for the investigation of raised markers in the presence of normal CT scans. True positive results were based on positive histology or clinical follow-up. FDG-PET had a positive predictive value (PPV) of 96% and a negative predictive value (NPV) of 90% in patients with residual masses. This PPV was equivalent to that of markers (94%) but FDG-PET had the advantage of identifying the site of that recurrence. The NPV was higher than that of markers. In patients with raised markers alone the PPV of FDG-PET was 92% but the NPV was only 50%. However, subsequent FDG-PET imaging was frequently the first imaging modality to identify the site of disease. FDG-PET effected a management change in 57% of cases. FDG-PET scanning detected viable tumour in residual masses and identified sites of disease in suspected recurrence.

Fluorodeoxyglucose PET in the initial staging of germ cell tumours.

Testicular cancer is a rare tumour with the potential for cure at diagnosis. It is important, however, to identify those patients with metastases at presentation so as to ensure that the optimum treatment strategy is employed. Many criteria have been used to try to place patients into high- or low-risk groups, with variable success. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management. Here we report on a retrospective study of the use of FDG-PET in the detection of metastatic testicular carcinoma at diagnosis. Thirty-one patients [13 with seminoma and 18 with non-seminomatous germ cell tumours (13 teratomas, 5 mixed)] were staged by FDG-PET scanning. The imaging was performed using a Siemens ECAT 951 scanner. All results were assessed on the basis of histology or clinical follow-up. FDG-PET scan identified metastatic disease in ten and was negative in 16; there were no false-positives and five false-negatives. There were six patients in whom FDG-PET was negative and computed tomography was regarded as suspicious but follow-up was inconclusive. The positive predictive value was 100%. The negative predictive value was 76% or 91%, depending on whether the aforementioned six cases were regarded as true-negatives or false-negatives. It may be concluded that FDG-PET is capable of detecting metastatic disease at diagnosis that is not identified by other imaging techniques. These preliminary results are sufficient to suggest that a large prospective study should be performed to evaluate the role of FDG-PET in primary staging of disease.

Gestational choriocarcinoma metastatic to the brain treated successfully by stereotactic radiosurgery and chemotherapy.

Metastatic gestational choriocarcinoma not uncommonly affects the central nervous system. If possible, the initial management of these metastases is surgical excision prior to chemotherapy, since these lesions are haemorrhagic. We report a patient with choriocarcinoma metastatic to the brain in whom surgery was potentially hazardous. Treatment was successfully given with stereotactic radiosurgery followed by chemotherapy.

Palliation of symptomatic adrenal gland metastases by radiotherapy.

Whilst adrenal metastases are common in patients with metastatic disease, they are rarely symptomatic. We present a series of seven patients with painful adrenal metastases who were seen in one centre over an 18-month period. All responded to palliative radiotherapy with a reduction in pain.

Iodine seeds in the treatment of slowly proliferating tumours in the head and neck region.

Locally recurrent/persistent disease is a major cause of morbidity and mortality in patients suffering from tumours arising in the head and neck region. Iodine-125, with its long half-life of 60 days, is particularly suited for the treatment of slowly proliferating tumours (e.g. adenoidcystic carcinomas) of this site. We report our experience with 18 patients using iodine-125 seeds, placed at the time of surgery in patients with such tumours. Eleven of the patients were treated for recurrent disease following previous radical treatment. Disease free survival was 89% at 2 years and 53% at 5 years after treatment. These results are encouraging in a group of patients in whom achieving and maintaining local control can be extremely difficult.

An audit of the use of agreed treatment protocols at a major centre for cancer treatment.

The treatment that a patient with cancer receives may vary considerably, depending on where and by whom the treatment is given. Agreement on treatment protocols for patients undergoing cancer treatment is clearly a desirable aim. Within departments this will result in greater uniformity of treatment, lead to greater safety, facilitate the evaluation of treatment strategies, and improve cost effectiveness. We have examined prospectively the extent to which treatment protocols are being adhered to within a major cancer treatment centre. One hundred newly registered cancer patients were studied. The results are encouraging, with complete adherence to protocol for 84. Of the 16 occurrences of deviation from a protocol this was unavoidable for three and of minor importance for five, being relatively small changes in radiotherapy dose reflecting particular clinical situations. Thus, eight deviations represented serious departures from the protocols by the responsible clinicians. This study has shown that in a major cancer treatment centre the development of agreed treatment protocols is both feasible and practical.

The early changes in salivary gland function during and after radiotherapy given for head and neck cancer.

The salivary gland function of 47 patients treated by radical radiotherapy (CHART or conventionally fractionated treatment) for head and neck cancer has been studied before, during and for up to 12 weeks from the start of treatment. Pronounced falls in salivary flow and pH are seen once radiotherapy has commenced, particularly when both parotid glands are included in the treatment volume. The initial rate of reduction in flow reflects the rate of delivery of treatment. The parotid glands show the greatest sensitivity to radiotherapy compared with the other salivary glands and reduction in salivary flow is dependent on both dose and the proportion of the gland included in the treatment volume. These early changes in salivary gland function are as marked for patients receiving either CHART or conventionally fractionated treatment, so differing from the late changes which have been shown to be less evident after CHART.

Pneumothorax as a complication of tumour response to chemotherapy.

A patient with extensive pulmonary involvement by disseminated adenocarcinoma is presented. Response to chemotherapy resulted in the direct rupture of necrotic tumour tissue into the pleural cavity leading to a pneumothorax. The condition failed to improve with chest drainage and suction, necessitating surgical intervention. The development of the pneumothorax proved to be a fatal complication of treatment.

Weekly cisplatinum concomitant with radical radiotherapy in the treatment of advanced head and neck cancer.

A total of 36 patients with advanced head and neck cancer were treated with radical radiotherapy and weekly concomitant cisplatinum chemotherapy. Rapid tumour response of both primary tumours and nodes was notable and an initial complete response rate of 75% was obtained. The disease free survival was 64% at 1 year and 52% at 2 years. The protocol proved feasible with little increase in toxicity from the addition of chemotherapy. Considering the advanced stage of the tumours treated the initial results are promising and this approach would seem to warrant further investigation.

Impaired salivary gland function after radiotherapy compounded by commonly prescribed medications.

Impaired salivary gland function can be a major cause of late morbidity following the treatment of head and neck cancer with radiotherapy. A large number of commonly prescribed medications can also reduce salivary gland function. We report three patients with already impaired salivary gland function following successful radiotherapy in whom additional prescribed medication led to an increased reduction in salivary flow, thus further impairing the quality of life of these patients. Stopping the medication resulted in subjective and objective improvement in salivary gland function.

Tumour proliferation assessed by combined histological and flow cytometric analysis: implications for therapy in squamous cell carcinoma in the head and neck.

The two techniques of flow cytometry analysis (FCM) and immunohistochemical localisation of bromodeoxyuridine (BrdUrd) incorporation after in vivo administration, were combined to study proliferation in squamous cell carcinoma of the head and neck region. Care was taken in this study to ensure that similar material was processed using both techniques such that comparisons could be made. FCM underestimated the labelling index (LI) in tumours classified as diploid compared to the histological evaluation of the tumour cells within those tumours (4.6% vs 17.1%). However, in aneuploid tumours, the FCM LI (10.7%) was similar to that obtained from histology (13.5%). Indeed, proliferation assessed by the combination of histology LI and FCM duration of S-phase (Ts) indicated that diploid tumours had a shorter median potential doubling time (Tpot) of 2.1 days compared to aneuploid (2.8 days). Despite the heterogeneity of proliferation evident histologically within the specimens, there was not a wide variation in the results of FCM analysis when multiple samples from resections were studied. Using FCM data alone, 46% of the tumours showed a Tpot of less than 5 days. When the Ts from the FCM data was combined with the average histological LI, 84% were less than 5 days and with the maximum LI, 99% were within this time interval. Compared with previous estimates, the proportion of tumours possessing proliferative characteristics which may indicate the need for acceleration of treatment seems to be much larger.