Dose-response of anal cancer
Clinical target volumes in anal cancer: Calculating what dose was likely to have been delivered in the UK ACT II trial protocol

https://doi.org/10.1016/j.radonc.2012.03.007Get rights and content

Abstract

Purpose

Preliminary results of the UK Anal Cancer Trial (ACT) II trial in squamous cell carcinoma of the anus (SCCA) are promising, but 2-D planning with parallel–opposed fields provoked significant toxicity. We calculated likely doses delivered in the ACT II protocol to the planning target volume (PTV), nodal clinical target volumes (n-CTV) and organs at risk (OARs).

Methods and Materials

Original planning CT datasets of 33 consecutive patients with SCCA, included in the ACT II trial or treated to an identical protocol, enabled dose to the primary tumour, involved nodal PTV’s, uninvolved nodal CTVs (inguino-femoral and pelvic lymph nodes) and femoral heads to be retrospectively calculated.

Results

The mean dose delivered to primary PTV was 51.37 ± 1.68 Gy (95% CI), with a maximum dose (Dmax) of 54.63 ± 2.68 Gy (95% CI). Involved inguinal nodes received a mean 51.41 ± 3.08 Gy, Dmax 54.17 ± 2.84 Gy (95% CI). Clinically uninvolved nCTVs received a mean 36.53 ± 3.38 Gy (inguinal nodes) and 34.15 ± 5.59 Gy (external/internal iliac nodes). Femoral heads received a Dmax of 47.32 ± 3.45 (95% CI). Conclusion: Calculating the likely doses delivered in ACT II from chemoradiation to PTV, n-CTV and OARs facilitates specification of nodal doses and constraints for 3D-conformal/IMRT planning and allows rational dose-escalation for T3/T4 tumours, and potential dose-reduction for T1/T2 tumours.

Section snippets

Radiotherapy treatment planning

The ACT II protocol aimed to deliver 50.4 Gy to the primary tumour, and palpable regional lymph nodes or those nodes involved by imaging criteria or positive on biopsy, over five and a half weeks using a two-phase technique. If the regional lymph nodes were not palpably or radiologically enlarged they were intended to receive a dose of 30.6 Gy. Both phases of treatment were planned simultaneously with a CT dataset acquired prior to radiotherapy treatment.

The phase I dose was 30.6 Gy in 17

Patient and tumour characteristics

The median age was 63 years (range 38–84) with 11 males, and 22 females. Clinical staging included T1(5), T2(16), T3(7) and T4(5) and nine patients (27%) had clinically palpable or radiologically positive lymphadenopathy. The tumour site was canal in 23, anal margin in eight, and both sites in two patients. Median number of treatment days was 38 (range 38–45) with no intended treatment breaks. All 33 patients received concurrent chemotherapy. During this period, eight patients were treated

Discussion

To design a future phase III trial with appropriate doses to CTVs, we needed to calculate the doses received in the ACT II trial by both gross tumour volume and subclinical areas. However we also needed to decide a suitable prescribed planning dose to the PTV and an appropriate PTV margin expansion for 3D conformal planning. We could find no meta-analyses or systematic reviews in anal cancer to offer guidance on the optimal total dose or target definition. In addition no dose–response curves

Conclusion

The patients in our study had either been treated in the ACT II trial or planned to an identical protocol. Their stage distribution is similar. They are therefore likely to represent the population of patients with anal cancer within the whole trial, and be applicable to patients in any future trial. Our calculated doses are likely to represent doses delivered within the ACT II trial.

Dose-escalation of radiation may improve local control, particularly for cT3/T4 patients. The dose actually

Conflict of interest notification

There are no potential or actual conflicts of interest.

References (27)

Cited by (14)

  • Treatment of the Primary Tumor in Anal Canal Cancers

    2017, Surgical Oncology Clinics of North America
    Citation Excerpt :

    Inclusion of the common iliac nodes, and full coverage of the entire internal iliac nodal system, by setting the upper CTV border at or above the sacral promontory1,2 remains controversial. In ACT II the superior aspect of the initial anterior-posterior/posterior-anterior field was defined as 2 cm above the inferior aspect of the sacroiliac (SI) joints, usually at the S1/S2 interface; with beam divergence, the estimated dose to the common iliac nodes was small.45 Very few isolated recurrences are observed above this field in the ACT II dataset.4

  • Tumour- and treatment-related colostomy rates following mitomycin C or cisplatin chemoradiation with or without maintenance chemotherapy in squamous cell carcinoma of the anus in the ACT II trial

    2014, Annals of Oncology
    Citation Excerpt :

    We attribute this to the continuous CRT schedule with no planned treatment breaks used in ACT II. In ACT I, only 40 out of 577 patients had a colostomy formed to ameliorate late effects [3], and in ACT II, this figure fell to 15 out of 940, reflecting the fact that estimated doses to the anorectal sphincter in ACT II are low [23]. The consistency of dose received in ACT II—98% of patients received 51.4 Gy to the anal sphincter with an IQR for duration of treatment 38–39 days—indicates that the data presented are robust and unique.

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