Preoperative carboplatin and paclitaxel-based chemoradiotherapy for esophageal carcinoma: results of a modified CROSS regimen utilizing radiation doses greater than 41.4 Gy

Abstract

Trimodality therapy for resectable esophageal and gastroesophageal junction cancers utilizing preoperative radiotherapy with concurrent carboplatin and paclitaxel-based chemotherapy is being increasingly utilized secondary to the results of the phase III CROSS trial. However, there is a paucity of reports of this regimen as a component of chemoradiotherapy in North America. We aim to report on our clinical experience using a modified CROSS regimen with higher radiotherapy doses. Patients with advanced (cT2-cT4 or node positive) esophageal or gastroesophageal junction carcinoma who received preoperative carboplatin/paclitaxel-based chemoradiotherapy with radiation doses of greater than 41.4 Gray (Gy) followed by esophagectomy were identified from an institutional database. Patient, imaging, treatment, and tumor response characteristics were analyzed. Twenty-four patients were analyzed. All but one tumor had adenocarcinoma histology. The median radiation dose was 50.4 Gy. Pathologic complete response was achieved in 29% of patients, with all receiving 50.4 Gy. Three early postoperative deaths were seen, due in part to acute respiratory distress syndrome and all three patients received 50-50.4 Gy. With a median follow-up of 9.4 months (23 days-2 years), median survival was 24 months. Trimodality therapy utilizing concurrent carboplatin/paclitaxel with North American radiotherapy doses appeared to have similar pathologic complete response rates compared with the CROSS trial, but may be associated with higher toxicity. Although the sample size is small and further follow-up is necessary, radiation doses greater than 41.4 Gy may not be warranted secondary to a potentially increased risk of severe radiation-induced acute lung injury.

Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base

“…However, if these values are ascribed to surgery, it is possible that patients in the HD (having higher T stage and node positive disease) required more extensive surgeries and hence a greater likelihood of complications. This is consistent with a retrospective single-institution report of HD therapy being associated with more acute adverse effects and potentially suboptimal surgical conditions (23). Nevertheless, in light of studies demonstrating that advanced RT techniques may decrease adverse and postoperative events, further work must assess whether a decrease in dose has additive effects as well (24)(25)(26)(27)(28).…”

Modification of preoperative radiochemotherapy for esophageal cancer (CROSS protocol) is safe and efficient with no impact on surgical morbidity

“…The dosage used in this study (46 Gy) was comparable with the dose used in the NEOSCOPE phase II trial (45 Gy) [18]. Interestingly, contrary to other reports, we did not observe increased morbidity using a higher dosage of radiation [19]. This may be explained by a considerable difference in dosage of radiation (50.4 Gy vs. 46 Gy in this publication) [19].…”

Neoadjuvant chemoradiotherapy with concurrent cisplatin/5-fluorouracil is associated with increased pathologic complete response and improved survival compared to carboplatin/paclitaxel in patients with locally advanced esophageal cancer

“…Finally, the higher doses of radiation used at our institution (50.4 Gy) compared to the published CROSS regimen of (41.4 Gy) may also contribute to increased toxicity and decreased survival. 17 It is worth mentioning that the tolerability profile of carboplatin/paclitaxel is generally considered to be superior to that of cisplatin/5-fluorouracil in terms of side effects and patient experience. While direct dosing and tolerability data could not be expressly collected in this study due to the disparate locations across a wide geographical area where our patients received their chemotherapy, other authors have demonstrated this to be the case.…”

“…Despite recent advancements, esophageal cancer remains a prevalent and deadly malignancy with an urgent need for further refined treatment strategies. Future studies evaluating the efficacy of various neoadjuvant approaches, such as the currently enrolling PROTECT trial, 16 as well as evaluation of different radiation doses and modalities 17 will be an integral part of improving outcomes of this highly morbid disease. Such research is vital to further elucidate the role of alternate neoadjuvant chemotherapy regimens in esophageal cancer.…”