Neoadjuvant Radiotherapy

There are many reasons for advocating pre-operative RT of advanced rectal cancers:

• reduction of local recurrence rate (better local control),

• reduction of tumour cells' spread via pelvis in the course of surgery,

• reduction of cases of residual disease (microscopic disease),

• reduction of tumour stage (increasing the chance for sphincter-preserving surgery),

• reduction of tumour size and infiltration,

• lower morbidity in comparison to post-operative RT (especially connected with small bowel). Other biological conditions supporting the role of pre-operative RT include higher level of oxygenising of tissues and sensitivity of tumour tissues to irradiation (no effect of ischaemic bed). The specific anatomical shape of mesorectum in pelvis results in a small circumferential margin when LAR is performed, which results in concerns about oncological clearance. Pre-operative RT improves this situation. The number of local recurrences is statistically lower with the use of pre-operative RT. In some cases the LAR is virtually possible because of RT.

In 1997, a Swedish trial showed a positive influence of pre-operative RT on life expectancy [55]. Unfortunately, no other trials have confirmed this conclusion. On the other hand there is a revolutionary paper describing 71 (28%) out of 260 patients with complete clinical response to pre-operative chemoradiotherapy who were not treated surgically [56].

It must be emphasised that precise estimation of tumor stage is the key to qualification for pre-opera-tive RT. If the tumor is described as T1 or T2, surgery alone is standard. T3 tumors, short course pre-oper-ative RT is advocated. Short course of RT comprises of total dose of 25 Gy, 5 Gy per fraction for 5 days and is given before consecutive surgery which follows i week after radiation. In case of T4 tumors, long course pre-operative RT should be introduced. The patient is irradiated 5 days/week for 5 weeks to the total dose of 45-50.4 Gy with 1.8 Gy per single fraction. It is mainly combined with 5-FU chemotherapy with (first and last week of irradiation). The surgery is performed 4-7 weeks after irradiation.

In the Uppsala trial in Sweden, adjuvant and neoadjuvant therapy were compared directly. The study revealed a significantly lower rate of local recurrence after the neoadjuvant mode of irradiation (12 vs. 21%) [57].

Although some authors suggest that in selected cases a sphincter-preserving operation could be performed because of the downstaging result of long course pre-operative RT [58], there is general agreement that the operation policy should not be changed after neoadjuvant therapy.

Beside the fact that more and more data are being gathered in favour of the pre-operative mode of irradiation, post-operative radiochemotherapy is still acceptable. It should be performed if post-operative pathological assessment reveals symptoms of cancer advancement. It is conducted in the following manner: radiation to the total dose of 45-50.4 Gy with 1.8 Gy per single fraction. The patient is irradiated 5 days/week for 5 weeks. It is combined with chemotherapy with 5 FU (6 courses, one week each; first and last week of radiation is combined with 3rd and 4th course of chemotherapy).

Talking about RT, we must remember about morbidity. Colitis, cystitis, wound healing problems and small bowel obstruction are the most frequent side effects of radiation. As LAR is performed more and more frequently, LAR syndrome is one of the most frequent side effects of RT is which is worsened by RT (15% LAR alone vs. 30% LAR plus RT) [59, 60]. The goal is that both neoadjuvant courses seem to result in less frequent complications than post-operative RT [59, 61]. This provides another argument in favour of pre-operative RT.

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