|Year : 2021 | Volume
| Issue : 3 | Page : 538-540
Radiation therapy in esophageal cancer: Shifting paradigms
Department of Radiation Oncology, Max Institute of Cancer Care, Nanavati Hospital, Mumbai, Maharashtra, India
|Date of Submission||05-Sep-2021|
|Date of Decision||11-Sep-2021|
|Date of Acceptance||18-Sep-2021|
|Date of Web Publication||08-Oct-2021|
Department of Radiation Oncology, Max Institute of Cancer Care, Nanavati Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Talapatra K. Radiation therapy in esophageal cancer: Shifting paradigms. Cancer Res Stat Treat 2021;4:538-40
The esophagus is placed anatomically within a zone of complexity pertinent to structures and functions which poses various challenges to the radiation oncologist in appropriately planning radiotherapy for a patient of esophageal cancer.
In the last few years, radiation has found an important place in the treatment of esophageal cancer. The trend and the focus are also shifting from surgery only treatment to multimodality treatment. The Intergroup 0116 trial established the benefit of post-operative concurrent chemoradiation in patients with gastric and gastroesophageal junction tumors.
The CROSS protocol used a lower dose of radiotherapy with concurrent weekly carboplatin and paclitaxel. Between 2004 and 2008, this study randomly assigned 366 patients to receive either surgery alone or pre-operative chemoradiation with paclitaxel, carboplatin, and concurrent radiation to a dose of 41.4 Gy in 23 fractions. The majority of patients (75%) were diagnosed with adenocarcinoma. Chemoradiation was beneficial for patients with both squamous and adenocarcinoma (although the effect size was larger in squamous tumors, the R0 resection rates were greatly enhanced, and the incidence of pathologic complete response following chemoradiotherapy was 29%). At 5 years, the locoregional recurrence rate was 14% in patients who received neoadjuvant treatment, compared to 34% in individuals who underwent surgery alone.
In summary, these analyses convincingly suggest that concurrent chemoradiotherapy improves survival in patients with locally advanced, non-metastatic esophageal carcinoma, in both the surgically resectable and unresectable scenarios.
While contradicting evidence suggests that neoadjuvant chemotherapy alone may provide a survival benefit, a summary of the data from limited prospective studies comparing pre-operative chemoradiotherapy to chemotherapy alone indicates a benefit from the inclusion of radiation therapy.,
In the current issue, Dora et al. have made a commendable attempt at comparing two radiotherapy techniques, conformal and volumetric modulated arc therapy (VMAT) which is extremely pertinent in the modern era of radiotherapy. The study demonstrated a decrease in the cardiac doses in the VMAT technique which is an important finding. However, considering the retrospective nature of the study with a small number of patients, an assessment of the overall survival and disease-free survival outcomes may not be justifiable in the larger perspective.
Delineation is done on the planning fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) and includes all the available information (e.g., endoscopy, endoscopic ultrasound [EUS], endobronchial ultrasound [EBUS], diagnostic FDG-PET/CT, biopsy, magnetic resonance imaging [MRI], and ultrasound).
The gross tumor volume (GTV) should encompass the primary tumor (with the esophageal wall) as seen on the planning FDG-PET/CT scan and includes all the available information (e.g., endoscopy, EUS, diagnostic FDG-PET/CT, MRI, and fiducial markers). It includes the entire esophageal wall but does not include the peri-esophageal fat. The GTV must include the involved lymph nodes defined as pathological at any time before the radiation therapy. Lymph nodes that appear to be new on the planning FDG-PET/CT compared to the diagnostic FDG-PET/CT, suspected to be malignant lymph nodes, have to be included in GTVn. Fine-needle aspiration cytology (FNAC) is recommended in case of doubt and when it would have an impact on the delineation of the target volume.
The clinical target volume (CTV) is proposed to be oriented along the esophagus instead of being a simple geometric expansion.
The clinical target volume = GTVp + 1.0 cm radially and 3.0 cm craniocaudally along the esophageal wall. CTV is corrected for anatomy (muscles, bones, large vessels, and organs at risk [OARs]) if there is no invasion.
Proximal tumors: The CTV is proposed not to extend above the level of the cricoid cartilage unless there is gross disease at that level.
Lower esophagus and gastroesophageal junction: The CTV is restricted to 2.0 cm distal to the tumor.
The nodal CTV is proposed to include the grossly involved nodes with an expansion of 1.0 cm in all directions and the lymph node stations at that level. It involves the lymph node stations along the CTV primary as long as they are within 3.0 cm craniocaudally from the grossly involved primary tumor.
Nodal CTV is corrected for anatomy (muscles, bones, large vessels, and OARs) if there is no invasion.
The final CTV is sum of the primary and nodal CTV and is expanded to include potential gaps between the CTVs – esophagus and the lymph node station at that level are proposed to be included. If the distance of the gap is more than 3.0 cm, the decision to expand the CTV total or to irradiate two separate volumes is up to the treating physician.
An extensive elective nodal volume can be omitted, and only the involved lymph node stations are proposed to be additionally irradiated.
Various dosage schedules have been explored in the treatment of esophageal cancer. RTOG 85-01 proposed 50 Gy as the recommended dose with concomitant systemic therapy in the definitive setting., Given the high rate of persistence and local recurrence despite the use of concomitant chemotherapy, it was assumed that higher radiation doses might improve outcomes. This resulted in a phase III intergroup trial (INT 0123) in which the RTOG 85-01 chemoradiation dose (adjusted to 50.4 Gy from 50 Gy) was compared to a higher dose of 64.8 Gy employing the same concurrent chemotherapy regimen. 86% of the patients enrolled had squamous cell carcinoma. There was no difference in the 2-year survivals between the two arms in this trial. Moreover, 11 treatment-related deaths occurred in individuals assigned to the high dosage arm, compared to 2 in the standard-dose group. However, even the 11 deaths in the high-dose group occurred before the patients received a dosage of 50.4 Gy. The ARTDECO study randomized patients with medically inoperable or unresectable carcinoma of the esophagus. The study compared the dose of 50.4 Gy at 1.8 Gy/fraction over 5.5 weeks to the primary tumor and regional lymph nodes vs. the higher dose of 61.6 Gy to the primary tumor with concurrent paclitaxel and carboplatin administered as 6 weekly cycles. At a median follow-up of 50 months, the primary endpoint of local progression-free survival (LPFS) was not significantly different between the 2 arms.
Overall, the findings of RTOG 85-01, INT 0123, and ARTDECO study confirm 50.4 Gy in 28 fractions as the standard radiotherapy dose for definitive chemoradiation. Nonetheless, there is continued interest in increasing radiation doses to improve complete response rates and decrease local recurrence rates, especially for patients who are medically inoperable or who have cervical or more proximal tumors which would require a morbid laryngopharyngectomy surgery. Cervical tumors are substantially similar to hypopharyngeal malignancies, and despite a dearth of prospective randomized trials, modest retrospective, and prospective data indicate that higher radiation doses of 60 Gy or more are feasible in this circumstance.,,
The predominant failure pattern for esophageal squamous cell carcinoma is local in-field or distant failures. Regional nodal recurrence (out-of-field) is infrequent in the absence of elective node irradiation.
A high rate of nodal involvement characterizes esophageal cancer, and its pattern of spread is not always predictable. Skip nodal metastases are also frequently observed. Hence, the biological behavior of this disease makes it difficult to define in advance the extent of coverage of elective nodal irradiation. If distant lymph node areas are irradiated prophylactically, patients would then experience more severe radiation complications and have a poorer treatment tolerance. This forms the basis for omitting elective nodal irradiation in patients with esophageal squamous cell carcinoma.
The goal of radiation planning should always be minimizing esophageal toxicity, lung toxicity, and cardiotoxicity. It is pertinent to note that point doses are equally important as dose constraints relied on volume during radiotherapy plan analysis and approval. In the neoadjuvant chemoradiotherapy setting, the surgical anastomosis site is of paramount significance and hence must be taken into consideration.
The last decade has witnessed several advances in radiation techniques for the treatment of esophageal cancer. Incorporation of imaging tools such as PET/CT, 4D CT, and modern planning software has enhanced the scope for radiation oncologists to achieve critical goals in terms of target delineation, critical organ sparing, and dose delivery. Identification of biomarkers with respect to radiation would be the future goal, and there are exciting times ahead in the space of radiation treatment in esophageal malignancies.
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