Dear Editor,
We appreciate the opportunity to review the response of Dr. Cellini and colleagues to our manuscript “Recommendations on the use of radiation therapy in managing patients with gastrointestinal malignancies in the era of COVID-19” [1]. We agree with Dr. Cellini that preoperative chemoradiation, and not preoperative chemotherapy, is and should remain the standard of care in the management of esophageal cancer, of either histology. As Dr. Cellini and colleagues point out, while there are no randomized studies directly comparing preoperative chemotherapy to preoperative chemoradiation, the results of two meta-analyses indicate the superiority of the combined modality approach [2], [3], and this is reflected in national guidelines [4].
First, we should clarify that we did not suggest replacing preoperative chemoradiation with preoperative chemotherapy, rather, we suggested the possibility of induction chemotherapy preceding preoperative chemoradiation. Second, it should be noted that we acknowledge that this was a controversial recommendation based on limited, but highly promising, data [5], [6], [7].
Some cancer centers hit particularly hard by the COVID-19 pandemic have tried to minimize in-person clinic visits for patients to reduce exposure to the virus, thus leading many radiation oncology departments to delay daily radiation therapy for as long as it is safe to do so. Under these dire circumstances, we feel that the available data is sufficient to support delaying preoperative chemoradiation through the use of induction chemotherapy for patients with esophageal adenocarcinoma. Moreover, this approach has been shown to be safe and effective in patients with adenocarcinoma of the gastroesophageal junction [8].
In sum, we agree that neoadjuvant chemoradiation should remain the standard of care in the management of resectable esophageal cancer until more data becomes available to support induction chemotherapy followed by chemoradiation. For centers strained for resources in the COVID-19 era, induction chemotherapy as a means of delaying daily radiation therapy until after the peak of the pandemic is a reasonable approach.
Footnotes
The Editors of the Journal, the Publisher and the European Society for Radiotherapy and Oncology (ESTRO) cannot take responsibility for the statements or opinions expressed by the authors of these articles. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. For more information see the editorial “Radiotherapy & Oncology during the COVID-19 pandemic”, Vol. 146, 2020.
References
- 1.Tchelebi L.T., Haustermans K., Scorsetti M., Hosni A., Huguet F., Hawkins M.A., et al. Recommendations for the use of radiation therapy in managing patients with gastrointestinal malignancies in the era of COVID-19. Radiother Oncol. 2020;148:194–200. doi: 10.1016/j.radonc.2020.04.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ronellenfitsch U., Schwarzbach M., Hofheinz R., Kienle P., Kieser M., Slanger T.E., et al. Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer. 2013;49:3149–3158. doi: 10.1016/j.ejca.2013.05.029. [DOI] [PubMed] [Google Scholar]
- 3.Sjoquist K.M., Burmeister B.H., Smithers B.M., Zalcberg J.R., Simes R.J., Barbour A., et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–692. doi: 10.1016/s1470-2045(11)70142-5. [DOI] [PubMed] [Google Scholar]
- 4.Jin J., Liu S., Zhu Y., Wang W., Wang X., Wang J., et al. The updated results for the phase 3 study of 5×5 Gy followed by chemotherapy in locally advanced rectal cancer (STELLAR trial) Int J Radiat Oncol Biol Phys. 2017;99:E157. doi: 10.1016/j.ijrobp.2017.06.976. [DOI] [Google Scholar]
- 5.Goodman K.A., Hall N., Bekaii-Saab T.S., Ou F.-S., Twohy E., Meyers M.O., et al. Survival outcomes from CALGB 80803 (Alliance): a randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer. J Clin Oncol. 2018;36 doi: 10.1200/JCO.2018.36.15_suppl.4012. 4012-4012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Meluch A.A., Greco F.A., Gray J.R., Thomas M., Sutton V.M., Davis J.L., et al. Preoperative therapy with concurrent paclitaxel/carboplatin/infusional 5-FU and radiation therapy in locoregional esophageal cancer: final results of a Minnie Pearl Cancer Research Network phase II trial. Cancer J. 2003;9:251–260. doi: 10.1097/00130404-200307000-00007. [DOI] [PubMed] [Google Scholar]
- 7.Chiarion-Sileni V., Innocente R., Cavina R., Ruol A., Corti L., Pigozzo J., et al. Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer. Cancer Chemother Pharmacol. 2009;63:1111–1119. doi: 10.1007/s00280-008-0834-3. [DOI] [PubMed] [Google Scholar]
- 8.Stahl M., Walz M.K., Stuschke M., Lehmann N., Meyer H.J., Riera-Knorrenschild J., et al. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009;27:851–856. doi: 10.1200/jco.2008.17.0506. [DOI] [PubMed] [Google Scholar]