Conventional external beam volumes for cervical cancer: Are they adequate?

Cervical cancer is one of the important cancers not just from the epidemiology point of view but also from the radiocurability point of view. The curability rates are maintained for a considerable number of patients even in locally advanced disease. This curability in moderately radio-sensitive squamous cell carcinoma with large tumor burden is possible due to various anatomic and physiological factors which help us to deliver high doses to the tumor. The anatomical factors include stepwise local and regional spread of disease, presence of vaginal cavity which permits intracavitary brachytherapy in a particular geometric fashion so that a high lateral dose throw to the parametrium can be achieved with sharp fall anterior-posteriorly to spare rectum and bladder, and considerable distance, and ability to separate rectum and bladder away from cervix. The physiological factors include high-radiation tolerance of uterus, cervix, and vagina in decreasing order.

Locally advanced patients are not suitable for upfront localized brachytherapy treatment at presentation. The external bean radiation treatment is of paramount importance in these patients and is required to be used in combination with brachytherapy. It not only shrinks the central tumor to appropriate size for brachytherapy, but also addresses the regional macroscopic and microscopic disease to appropriate doses. The regional disease definition in pelvis has been based on various surgical and radiological series (lymphangiography) documenting pattern of spread and radiotherapy series documenting relapse pattern.[123] Previously, these regions were defined radiologically on x-ray based on bony landmarks which are convenient and suitable for radiotherapy planning, a technology available at those times. More than availability and convenience, this system provided standard technique of treatment across the world so that outcomes can be compared and modifications can be generated from a standard platform. Also, the clinical outcomes in various series do not show significant relapses in these regions in isolation as compared to central and in field recurrences (70%).[4]

Although it was previously known that there are individual variations like confluence of major vessels (IVC/aorta along which the lymphatics and nodes are situated) into common iliac at 5th lumbar vertebrae, this is seen in 13% patients only.[5] So, anatomically if we intend to treat common iliac nodes adequately, we need to reach at least till the formation of inferior vena cava. This information is available from previous intra-operative and lymphangiography series.[345] But this was conventionally ignored because of unreported gain from chasing vascular divisions, while at the same time it will increase the volume of normal tissue irradiated and normal tissue toxicities. Most importantly, normal tissues including small bowel and bone marrow may compromise the overall treatment tolerance with acute and late toxicity adversely affecting treatment efficacy and outcomes. This is even more important when concurrent chemotherapy is added to improve the outcomes.[6]

With the advent of sophisticated imaging modalities defining better anatomy details like ultra-small super paramagnetic iron-oxide-based Magnetic Resonance Imaging (MRI), lymph nodal regions can be mapped along the vessels and so adequate volumes delineation margins and guidelines have been defined by various authors[78] and are almost similar to what was achieved in historic times.[35] But again relevance of these increased margins and borders in terms of better loco-regional controls is yet to be demonstrated in the literature. At the same time, the increased risk of toxicity with increased volume of irradiation has to borne in mind. Similarly with MR imaging, the gross tumor definitions and positions during fractionated course of external radiation have questioned the conventional borders and margins, especially the anterio-posterior borders due to variable ante-versions and ante-flexions at uterus and bladder-rectum movements.

The two studies in this journal by Goswami et al.[9] and Gulia et al.[10] adequately demonstrate that if modern guidelines based on sophisticated imaging anatomical definitions are followed as compared to conventional bony landmarks; there is definite improvement in coverage of target volumes at the cost of more normal tissue radiation exposure. Being dosimetric studies they would count on more clinical outcome data in future for relevance of more generalized applicability of contouring-based individualized treatments than conventional. The offset by increased risk of toxicities can be tackled after better dosimetric correlation with toxicities or successful implementation of emerging radiation technologies, such as IMRT and IGRT. Recently, the knowledge regarding improved contouring guidelines for normal tissues and use of conformal techniques like IMRT and correlation of toxicity data with DVH parameters is fast accumulating, especially for bowel and bone marrow.[11] Such comparisons are not new and numerous previous studies have shown theoretical as well as to a certain extent clinical advantageous implications of use of IMRT and IGRT in the treatment of cervical cancer.[121314]

Also, with improvement in brachytherapy techniques like MR image-based treatments, it has been demonstrated in several series that local control can be significantly improved.[15] This is more likely to change the relapse pattern in these patients, and then, probably the less important regional or geographical misses and distant relapse in today's date will be a major issue. In such times, better target definitions with conformal techniques would probably be more important as cited in the two studies presented in this journal.[910] At that time, these dosimetric studies can serve as an important benchmark to guide directions for target volumes modifications and organs at risk constraints for external beam radiotherapy treatments. Also addition of more potent concurrent chemotherapy regimens will be looked for.[6] But the minimization of normal tissue toxicity for such intensive treatments would be of more significance than tumor target approach alone in such times.

Till then, in most of the developing countries, the challenge will be to provide optimal radiotherapy treatment with optimal brachytherapy technique and compliance to concurrent cisplatin-based chemotherapy.[16]