How Histopathologic Tumor Extent and Patterns of Recurrence Data Inform the Development of Radiation Therapy Treatment Volumes in Solid Malignancies

doi:10.1016/j.semradonc.2018.02.007

Seminars in Radiation Oncology

Volume 28, Issue 3, July 2018, Pages 218-237

https://doi.org/10.1016/j.semradonc.2018.02.007 Get rights and content

The ability to deliver highly conformal radiation therapy using intensity-modulated radiation therapy and particle therapy provides for new opportunities to improve patient outcomes by reducing treatment-related morbidities following radiation therapy. By reducing the volume of normal tissue exposed to radiation therapy (RT), while also allowing for the opportunity to escalate the dose of RT delivered to the tumor, use of conformal RT delivery should also provide the possibility of expanding the therapeutic index of radiotherapy. However, the ability to safely and confidently deliver conformal RT is largely dependent on our ability to clearly define the clinical target volume for radiation therapy, which requires an in-depth knowledge of histopathologic extent of different tumor types, as well as patterns of recurrence data. In this article, we provide a comprehensive review of the histopathologic and radiographic data that provide the basis for evidence-based guidelines for clinical tumor volume delineation.

Introduction

The ability to effectively utilize radiation therapy (RT) depends critically on the availability of radiographic studies that can guide the delineation of the volumetric extent of disease. Advances in diagnostic imaging have allowed for improved delineation of the gross tumor extent, defined volumetrically as the gross tumor volume (GTV).Unfortunately, limitations still exist primarily in the inability to radiographically identify microscopic areas of disease that would not be identified with advanced imaging modalities. As a result, our knowledge of appropriate clinical tumor volume (CTV) margins has, in large, part been informed by surgical pathologic data as well as by analyzing patterns of recurrence and tumor spread. We aim to provide a comprehensive review of the current knowledge that informs modern day CTV margins for various solid malignancies.

Section snippets

High-Grade Glioma

There are currently 2 methods utilized in the contouring of high-grade gliomas (HGG): a single phase vs a 2-phase scheme. For example, the EORTC promotes a single-phase scheme where the GTV encompasses the T1-enhancing tumor mass and the resection cavity with a wide 3 cm margin for the CTV. Recently published guidelines from ESTRO-ACROP recommend a single CTV composed of the resection cavity and areas of T1-enhancement with a 2 cm margin.¹ For secondary glioblastoma, they recommend the inclusion

Oral Tongue

Oral cavity cancer accounts for a large proportion of head and neck cancers overall, with a significant increase noted over the past 2 decades⁴⁹ principally affecting young white females.50, 51 Lip and oral cavity tumors are predominantly managed with surgery, with the use of RT based on surgical, pathologic, and clinical risk factors. Given that oral tongue primaries represent the most common subsite in this cohort, our discussion will focus on CTV delineation for oral tongue cases.

Conventional Fractionated Radiotherapy

Definitive chemoradiotherapy (CRT) is generally indicated for locally advanced, stage IIIA-B disease but can also be utilized for stage II patients not eligible for surgery or stereotactic body radiation therapy (SBRT). Target volume delineation for NSCLC cases should be based on the information obtained from radiographic imaging studies such as CT chest or PET/CT scans, as well as from comprehensive mediastinal evaluations. In addition, 4-dimensional CT scans are regularly utilized for

Preoperative and Definitive

The role of preoperative or definitive RT in the management of esophageal carcinoma has been well established based on multiple randomized trials. Our current margin recommendations for CTV volumes derive primarily from clinical and pathologic series. Initially, the GTV for the gross primary should be delineated using diagnostic imaging and tumor extent as obtained from the EGD/EUS. For squamous cell histology, Gao et al¹⁴² prospectively analyzed the microscopic submucosal distance of spread

Definitive

With an estimated 161,000 new cases of prostate cancer (PC) in the U.S. in 2017, PC continues to remain the leading cancer diagnosis in males. RT is excellent management option for PC. Prospective trials have demonstrated the superiority of IMRT over 3-dimensional conformal (3D-CRT) techniques for the treatment of PC.173, 174 However, the advent of IMRT necessitated recommendations on appropriate target volume delineation. The recommended CTV volumes for PC vary depending on risk stratification

Pelvic Region

The CTV for whole-pelvic radiotherapy when treating locally advanced cervical cancer with definitive CRT includes the entire uterus with cervix, parametrial tissues including ovaries, entire mesorectum if uterosacral ligament is involved, upper vagina (longer length depending on degree of vaginal involvement), and regional nodes.²⁰³ Modern surgical series evaluating cervical cancer patients in whom positive lymph nodes were identified during radical abdominal hysterectomy or those undergoing