Radiotherapy is a frequently utilized therapeutic modality in the treatment of esophageal cancer (EC). Even though extensive studies are carried out in radiotherapy for EC, the design of the clinical target volume and the radiation dose is not satisfactorily uniform. Radiotherapy acts as a double-edged sword on the immune system; it has both an immunostimulatory effect and an immunosuppressive effect. Radiation-induced lymphopenia and its potential association with tumor control and survival outcomes remain to be understood. The advent of immunotherapy has renewed the focus on preserving a pool of functioning lymphocytes in the circulation. In this review, we summarize the potential impact mechanisms of radiotherapy on peripheral blood lymphocytes and the prognostic role of radiation-induced lymphopenia in patients with EC. We also propose the concept of organs-at-risk of lymphopenia and discuss potential strategies to mitigate its effects on patients with EC. From an immunological perspective, we put forward the hypothesis that optimizing radiation modalities, radiation target volume schemes, and radiation doses could help to reduce radiation-induced lymphopenia risks and maximize the immunomodulatory role of radiotherapy. An optimized radiotherapy plan may further enhance the feasibility and effectiveness of combining immunotherapy with radiotherapy for EC.

Esophageal cancer (EC) is an extremely aggressive, lethal malignancy that is increasing in incidence worldwide. At present, definitive chemoradiotherapy is accepted as the standard treatment for locally advanced EC. The EC guidelines recommend a radiation dose of 50.4 Gy for definitive treatment, yet the outcomes for patients who have received standard-dose radiotherapy remain unsatisfactory. However, some studies indicate that a higher radiation dose could improve local tumor control, and may also confer survival benefits. Some studies, however, suggest that high-dose radiotherapy does not bring survival benefit. The available data show that most failures occurred in the gross target volume (especially in the primary tumor) after definitive chemoradiation. Based on those studies, we hypothesize that at least for some patients, more intense local therapy may lead to better local control and survival. The aim of this review is to evaluate the radiation dose, fractionation strategies, and predictive factors of response to therapy in functional imaging for definitive chemoradiotherapy in esophageal carcinoma, with an emphasis on seeking the predictive model of response to CRT and trying to individualize the radiation dose for EC patients.

Background To compare the dosimetric, normal tissue complication probability (NTCP), secondary cancer complication probabilities (SCCP), and excess absolute risk (EAR) differences of volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for left-sided breast cancer after mastectomy. Methods and materials Thirty patients with left-sided breast cancer treated with post-mastectomy radiation therapy (PMRT) were randomly enrolled in this study. Both IMRT and VMAT treatment plans were created for each patient. Planning target volume (PTV) doses for the chest wall and internal mammary nodes, PTV1, and PTV of the supraclavicular nodes, PTV2, of 50 Gy were prescribed in 25 fractions. The plans were evaluated based on PTV1 and PTV2 coverage, homogeneity index (HI), conformity index, conformity number (CN), dose to organs at risk, NTCP, SCCP, EAR, number of monitors units, and beam delivery time. Results VMAT resulted in more homogeneous chest wall coverage than did IMRT. The percent volume of PTV1 that received the prescribed dose of VMRT and IMRT was 95.9 ± 1.2% and 94.5 ± 1.6%, respectively (p < 0.001). The HI was 0.11 ± 0.01 for VMAT and 0.12 ± 0.02 for IMRT, respectively (p = 0.001). The VMAT plan had better conformity (CN: 0.84 ± 0.02 vs. 0.78 ± 0.04, p < 0.001) in PTV compared with IMRT. As opposed to IMRT plans, VMAT delivered a lower mean dose to the ipsilateral lung (11.5 Gy vs 12.6 Gy) and heart (5.2 Gy vs 6.0 Gy) and significantly reduced the V5, V10, V20, V30, and V40 of the ipsilateral lung and heart; only the differences in V5 of the ipsilateral lung did not reach statistical significance (p = 0.409). Although the volume of the ipsilateral lung and heart encompassed by the 2.5 Gy isodose line (V2.5) was increased by 6.7% and 7.7% (p < 0.001, p = 0.002), the NTCP was decreased by 0.8% and 0.6%, and SCCP and EAR were decreased by 1.9% and 0.1% for the ipsilateral lung. No significant differences were observed in the contralateral lung/breast V2.5, V5, V10, V20, mean dose, SCCP, and EAR. Finally, VMAT reduced the number of monitor units by 31.5% and the treatment time by 71.4%, as compared with IMRT. Conclusions Compared with IMRT, VMAT is the optimal technique for PMRT patients with left-sided breast cancer due to better target coverage, a lower dose delivered, NTCP, SCCP, and EAR to the ipsilateral lung and heart, similar doses delivered to the contralateral lung and breast, fewer monitor units and a shorter delivery time.