PTC CLINIC
Information for Healthcare Professionals

Carcinoma of the Anus – Treatment Strategy

Concomitant chemoradiotherapy is a standard modality of anal cancer treatment. The disease has
a high cure rate, thanks to the combination of a large volume irradiated, concomitant chemotherapy and the total dose of radiation. However, the risk of early and late side effects is high. More than one third of patients develop acute toxicity of grade 3 or 4.

Currently, patients with carcinoma of the anus are treated with the IMRT technique. A disadvantage of this technique still consists in a high burden to the skin and subcutaneous tissues, the bladder, rectosigmoid colon and loops of the small intestine. Another disadvantage is the high integral dose of radiation delivered using this technique. This results in a high degree of acute toxicity of the treatment, especially acute skin reactions, acute gastrointestinal and genitourinary toxicity, and also hematologic toxicity due to the effects of concomitant chemotherapy. Late side effects are related mainly to fibrotisation of the perianal region, groins and other adjacent tissues. It involves dysfunction of the pelvic floor and sphincters, vaginal stenosis, deformation and dysfunction of external genitalia and obstruction in the groin area.

Indications of Proton Radiotherapy Under the PTC Protocols Are as Follows:

• Invasive squamous cell carcinoma of the anus.
• Invasive squamous cell carcinoma of the anus after excision biopsy (non-radical procedure).

Use of Proton Therapy in the Treatment of Anal Carcinoma

Treatment of anal tumors has been gradually introduced in proton centers worldwide. The reason is the chance to reduce the integral dose in the entire pelvic area, i.e. the radiation burden to the skin, subcutaneous tissues, bladder, genitalia, rectosigmoid colon and small intestine. Dosimetry studies have been published. The possibility of reducing toxicity is significant especially in those constellations where the toxicity is a long-term limitation, and where the development of IMRT photon radiotherapy techniques brought only a minor improvement and in some cases even an increase in the integral dose as compared to the previous 3 DCRT techniques.

Strategy in Radiation Therapy: 

Anal tumors are treated with irradiation of 2 volumes using the SIB technique (simultaneous integrated boost) at 2 dose levels:

• The volume of electively irradiated regional lymph nodes in the following groups: perirectal, presacral, external, internal and common iliac, inguinal. This volume of drainage regional lymph nodes creates a large concavity in the central pelvis.
• The volume of the primary tumor with a margin and the volume of macroscopically visible involvement of the lymph nodes with a margin.

The requirements for dose distribution with this technique and the geometric constellation can be optimally managed during proton radiation dosimetry. It offers a significant reduction of doses to the critical structures of the pelvis. This includes mainly reduction of doses to the following structures:

• Urinary bladder
• Small intestine
• Skin and subcutaneous tissue
• Vagina
• Penile bulb
• Bone marrow of pelvis

Figure 1: Example of irradiation plan and dose distribution in the pelvis during proton and photon irradiation. It is clear that a significantly lower or zero dose is applied to healthy tissue during proton radiotherapy.

Table 1: Specification of doses to the individual structures/organs.

Dosimetry Results; Advantages

Proton radiotherapy clearly provides a significant benefit for the required doses and irradiated volumes in terms of average organ doses and doses to the designated quantiles according to the required dose constraints. Organ doses can be reduced to less than a half. (Peak doses in the organs are usually given by the usual inclusion of a part of the organ in the irradiated volume, which, for the singular intestine, is a phenomenon compensated by its variable position).

Clinical Manifestation of Proton Therapy Benefits

In the patients that have been treated so far at PTC Prague, we observed the following advantages compared to our own experience with photon radiation:

• Proton radiotherapy is carried out on an outpatient basis.
• It is possible to administer standard concomitant chemotherapy with CDDP+FU on outpatient basis.
• Hematologic toxicity was rare, probably due to a genetically based intolerance of 5-FU.
• The extent of mucosal and skin reactions is smaller and sharply demarcated.
• No need of opiate analgesia.
• Acute adverse reactions are fully reversible.
• Typical chronic adverse reactions have not developed.
• Complete regression has always been achieved, as expected.

Advantages of Proton Radiotherapy Versus Conventional Photon Therapy

• When comparing conventional and proton RT, a clear profit is seen in reducing the burden of healthy tissues and adherence to the prescribed dose in the target volume at 2 levels.
• For anal tumors, the advantage of improved conformity and lower integral dose outside the irradiated volume can be used during proton radiation. Biology of anal tumors does not require the advantage of dose escalation. The SIB radiation technique uses, to a certain extent, the advantage of altered fractionation.
• If significant toxicity is a fundamental problem in the radiotherapy of anal carcinoma with a high curative potential and long-term survival of patients, the proton radiation therapy, with all its benefits, is an optimal solution.