Good response of stage IV melanoma to high­dose radiation therapy combined with immunotherapy: A case report.

Patients with advanced malignant melanoma (MM) often do not receive satisfactory treatment. The present study reports the case of a 51-year-old female patient with stage IV MM of unknown primary. After undergoing immune checkpoint inhibitor therapy, the patient received multiple doses of hypofractionated radiotherapy (HFRT) for the left inguinal lymph node and single-fraction high-dose-rate brachytherapy for the left and right lung metastases. After combination treatment, the patient experienced almost complete remission of the inguinal target area, significant relief of pain and discomfort and an improved quality of life. The time of lung radiotherapy lesion control was 8 months. Meanwhile, the observed lesions (observation lesions 1, 2, 3 and 5) adjacent to the target lesion received lower doses of scattering (0.9-1.8 Gy) and the time of control for these lung observation lesions was 9 months. In addition, restarting targeted therapy after cessation of other treatments due to myelosuppression resulted in a progression-free survival time of 6 months. Nevertheless, the patient developed new metastases in the brain and abdomen. The present case report demonstrates that high-dose radiotherapy combined with immunotherapy may be effective for local lesions and that multiple doses of HFRT may be superior to single-fraction high-dose-rate brachytherapy for certain patients. Low-dose scattering also shows improvement for local lesions. Furthermore, restarting targeted therapy may be effective in the presence of target sites. Thus, the present case report provides a possible therapeutic option for the treatment of advanced melanoma.

The value of a multimodal approach combining radical surgery and intraoperative radiotherapy in the recurrence treatment of gynecological malignancies - analysis of a large patient cohort in a tertiary care center.

BACKGROUND: Recurrent and locally advanced gynecological malignancies have a poor prognosis. In particularly, pelvic local recurrence after previous radiotherapy and/or positive resection margins during surgical treatment for recurrent disease result in low survival rates. Consequently, locoregional control is of utmost importance in this cohort of patients. The aim of this study was to analyze treatment outcomes and determine prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for recurrent and locally advanced gynecological malignancies. METHODS: 40 patients who underwent surgical treatment and IORT between 2010 and 2022 were eligible for inclusion. The median follow-up time was 22 months. The outcomes measured were locoregional control (LRC), overall survival (OS), and survival without distant metastases (DMFS). The Cox proportional hazards model was used for univariate and multivariate analysis to assess the impact of patient variables and treatment factors on the endpoints mentioned. The following variables were analyzed: age at surgical treatment and IORT and initial diagnosis (< 65 vs. ≥65 years, each), disease-free interval (DFI) between initial diagnosis and first recurrence, DFI to surgical treatment and IORT, grading, histology, IORT dose (≤ 13 vs. >13 Gy) and technique (high dose radiotherapy (HDR) vs. IORT using electrons, (IOERT)). Survival curves were generated using the Kaplan-Meier method. RESULTS: The mean IORT dose was 13.8 Gy (range 10-18 Gy). Cervical carcinoma was most frequently found in 27.5% of patients followed by endometrial carcinoma and vulvar carcinoma in 25% respectively. The final histopathologic results after surgery with IORT showed no residual tumour in 24 patients (60%), microscopic residual disease in 5 patients (12.5%), resection status could not be evaluated in three patients (7.5%) and the resection status was unknown in eight patients (20%). Subsequently, 27.5% of patients also received adjuvant radiotherapy of the local recurrence bed. However, after IORT, 65% of the women suffered a recurrence. Of these, the recurrences were localized: in-field 32.5%, out-of-field 22.5% and margin-of-field 12.5%. The 3- and 5-year OS was 69% and 55% respectively. The 3- and 5-year LRC was 56% respectively. The 3- and 5-year DMFS was 66% and 49%. Whereas the comparison between groups by IORT dose level (≤ 13 vs. >13 Gy) showed a non-significant trend in favor of the higher dose only for OS (p = 0.094), but not in LRC and DMFS (p > 0.05). OS and DMFS, but not LRC, differed significantly between the HDR-IORT and IOERT groups (p = 0.06 and p = 0.03,) in favor of the HDR-IORT technique. For HDR-IORT technique a trend towards superior OS and LRC was observed in the univariate analysis: HR 3.76, CI 95%: 0.95-14.881, p = 0.059 and HR 2.165 CI 95%: 0.916-5.114, p = 0.078 CONCLUSIONS: The survival rate for pelvic recurrence in gynecological malignancies remains poor and comparable with historical data from the last two decades. Particularly HDR-IORT, appears to provide a long-term oncological benefit in carefully selected patients.

Outcome of intraoperative brachytherapy as a salvage treatment for locally recurrent rectal cancer.

BACKGROUND: Locally advanced recurrent rectal cancer (RRC) requires a multimodal approach. Intraoperative high-dose-rate brachytherapy (HDR-BT) may reduce the risk of local recurrence. However, the optimal therapeutic regimen remains unclear. The aim of this retrospective monocentric study was to evaluate the toxicity of HDR-BT after resection of RRC. METHODS: Between 2018 and 2022, 17 patients with RRC received resection and HDR-BT. HDR-BT was delivered alone or as an anticipated boost with a median dose of 13 Gy (range 10-13 Gy) using an 192iridium microSelectron HDR remote afterloader (Elekta AB, Stockholm, Sweden). All participants were followed for assessment of acute and late adverse events using the Common Terminology Criteria for Adverse Events version 5.0 and the modified Late Effects in Normal Tissues criteria (subjective, objective, management, and analytic; LENT-SOMA) at 3­ to 6­month intervals. RESULTS: A total of 17 patients were treated by HDR-BT with median dose of 13 Gy (range 10-13 Gy). Most patients (47%) had an RRC tumor stage of cT3­4 N0. At the time of RRC diagnosis, 7 patients (41.2%) had visceral metastases (hepatic, pulmonary, or peritoneal) in the sense of oligometastatic disease. The median interval between primary tumor resection and diagnosis of RRC was 17 months (range 1-65 months). In addition to HDR-BT, 2 patients received long-course chemoradiotherapy (CRT; up to 50.4 Gy in 1.8-Gy fractions) and 2 patients received short-course CRT up to 36 Gy in 2­Gy fractions. For concomitant CRT, all patients received 5­fluorouracil (5-FU) or capecitabine. Median follow-up was 13 months (range 1-54). The most common acute grade 1-2 toxicities were pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and lymphedema in 2 patients (11.8%). Chronic toxicities were similar: grade 1-2 pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and incontinence in 2 patients (11.8%). No patient experienced a grade ≥3 event. CONCLUSION: Reirradiation using HDR-BT is well tolerated with low toxicity. An individualized multimodality approach using HDR-BT in the oligometastatic setting should be evaluated in prospective multi-institutional studies.

Measurement of the distance between tumor micro-foci and gross tumor in rectal cancer pathological specimens: implication on margin distance of clinical target volume treated with high-dose radiotherapy for rectal cancer.

PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.

Significance of androgen-deprivation therapy for intermediate- and high-risk prostate cancer treated with high-dose radiotherapy: A literature review.

The real-world benefits of adding androgen-deprivation therapy (ADT) and its optimal duration when combined with current standard high-dose radiation therapy (RT) remain unknown. We aimed to assess the efficacy of and toxicities associated with ADT in the setting of combination with high-dose RT for intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). This article is a modified and detailed version of the commentary on Clinical Question 8 described in the Japanese Clinical Practice Guidelines for Prostate Cancer (ver. 2023). A qualitative systematic review was performed according to the Minds Guide. All relevant published studies between September 2010 and August 2020, which assessed the outcomes of IR or HR PCa treated with high-dose RT, were screened using two databases (PubMed and ICHUSHI). A total of 41 studies were included in this systematic review, mostly consisting of retrospective studies (N = 34). The evidence basically supports the benefit of adding ADT to high-dose RT to improve tumor control. Regarding IR populations, many studies suggested the existence of a subgroup for which adding ADT had no impact on either overall survival or the BF-free duration. On the other hand, regarding HR populations, several studies suggested the positive impact of adding ADT for ≥1 year on overall survival. Adding ADT increases not only the risk of sexual dysfunction but also that of cardiovascular toxicities or bone fracture. Although the benefit of adding ADT was basically suggested for both IR and HR populations, further investigations are warranted to identify subgroups of patients for whom ADT has no benefit, as well as the appropriate duration of ADT for those who do derive benefit.

The Immunomodulatory Potential of Concurrent High-Dose Radiotherapy and Immune Checkpoint Inhibitor Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Initial Results.

In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary endpoints of this study are objective tumor response, assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST), and time to treatment failure (disease progression). In all patients, surgery was deemed not amenable, due to its potential functional and aesthetic impact. Therefore, upon multidisciplinary agreement, radiotherapy and immunotherapy with cemiplimab were alternatively administered. After 6 months, an early objective tumor response was observed in 9/11 patients, with 17/20 cutaneous lesions (85%) presenting either a complete or partial response. Only 2/11 patients, with a total of 3/20 cutaneous lesions (15%), had stable disease. These benefits persisted at a longer follow-up (21.4 ± 9.7 months), with no patients presenting disease progression. Despite the retrospective nature of this study and small sample size, our experience highlights the ability of concomitant radiotherapy and cemiplimab to promote an early objective response in patients with advanced CSCC. Moreover, in our population, the clinical benefits were also related to a longer progression-free survival, without any safety alert reported.

Long-Term Disease Control of Locally Invasive Epithelial-Myoepithelial Carcinoma of Parapharyngeal Salivary Glands With Definitive Radiotherapy.

Epithelial-myoepithelial carcinoma (EMC) is a rare clinical entity that affects glandular tissues, most commonly salivary glands. EMC of parapharyngeal space is exceedingly rare. Surgery is the mainstay of treatment with or without chemotherapy, radiotherapy, or both. Due to the rarity of the disease, select cases where surgery is not possible present a management conundrum. We present a case of locally advanced, stage IVa EMC of parapharyngeal space that was treated with upfront definitive radiotherapy. Radiotherapy treatment alone led to long-term disease control in both clinical and radiological follow-ups. The patient was followed for more than eight years posttreatment with no disease recurrence, enjoying the normal activities of life with no late toxicities including xerostomia. This case report highlights the role of radiotherapy in the management of such patients, and more studies are required in this context for surgical candidates with positive disease margins.

Functional plasticity of neutrophils after low- or high-dose irradiation in cancer treatment - A mini review.

Over the last several decades, radiotherapy has been considered the primary treatment option for a broad range of cancer types, aimed at prolonging patients' survival and slowing down tumor regression. However, therapeutic outcomes of radiotherapy remain limited, and patients suffer from relapse shortly after radiation. Neutrophils can initiate an immune response to infection by releasing cytokines and chemokines to actively combat pathogens. In tumor immune microenvironment, tumor-derived signals reprogram neutrophils and induce their heterogeneity and functional versatility to promote or inhibit tumor growth. In this review, we present an overview of the typical phenotypes of neutrophils that emerge after exposure to low- and high-dose radiation. These phenotypes hold potential for developing synergistic therapeutic strategies to inhibit immunosuppressive activity and improve the antitumor effects of neutrophils to render radiation therapy as a more effective strategy for cancer patients, through tumor microenvironment modulation.

Long-term follow-up results of spine tumor treatment using high-dose radiotherapy after 3-dimensional-printed vertebral bodies implantation.

OBJECTIVE: To investigate the long-term safety and efficacy of high-dose radiotherapy after 3D-printed vertebral body implantation in the treatment of spinal tumors. METHODS: Thirty-three participants were recruited between July 2017 and August 2019. 3D-printed vertebral bodies were implanted in each participant, followed by postoperative robotic stereotactic radiosurgery at a dose of 35-40 Gy/5f. The tolerance of the 3D-printed vertebral body and the participant to the high-dose radiotherapy were evaluated. In addition, the local control of tumor and the local progression-free survival of the study participants following 3D-printed vertebral body implantation and high-dose radiotherapy were measured as indexes of effectiveness. RESULTS: Of the 33 participants included in the study, 30, including three participants (10%) with esophagitis of grade 3 or above and two participants (6.7%) with advanced radiation nerve injury, successfully underwent postoperative high-dose radiotherapy. The median follow-up was 26.7 months, and IQR was 15.9 months. Most participants had primary bone tumors with 27 cases (81.8%), and the rest had bone metastases in six cases (18.2%). After high-dose radiotherapy, the 3D-printed vertebrae maintained good vertebral stability and exhibited histocompatibility, without implant fractures. The local control rates were 100%, 88%, and 85% 6 months, 1 year, and 2 years after high-dose radiotherapy, respectively. Tumors recurred in four participants (12.1%) during the follow-up period. The median local progression-free survival after treatment was 25.7 months, with a range of 9.6-33.0 months. CONCLUSION: High-dose radiotherapy for spinal tumors after 3D-printed vertebral body implantation is feasible, elicits low toxicity, and yields satisfactory tumor control.

Flash radiotherapy-gateway to promised land or another mirage.

Radiation therapy damages cancer cells with ionizing radiation, leading to their death. However, radiation­induced toxicity limits the dose delivered to the tumor, thereby constraining the control effect of radiotherapy n tumor growth. In addition, the delayed toxicity caused by radiotherapy significantly harms the physical and mental health of patients. FLASH­RT, an emerging class of radiotherapy, causes a phenomenon known as the 'FLASH effect', which delivers radiotherapy at an ultra­high dose rate with lower toxicity to normal tissue than conventional radiotherapy to achieve local tumor control.

Laparoscopic spacer placement for bulky lymph node metastasis of cervical cancer: A case report.

•Spacers focus high-dose radiotherapy towards the target lesion.•Laparoscopic insertion of spacers allows for rapid initiation of radiotherapy.•Spacers may be applied to patients requiring multidisciplinary treatment beyond standard therapy.

A 'Hybrid' Radiotherapy Regimen Designed for Immunomodulation: Combining High-Dose Radiotherapy with Low-Dose Radiotherapy.

Radiotherapy (RT) affects anti-tumor immunity. However, the exact impact of RT on anti-tumor immune response differs among cancer types, RT dose and fractions, patients' innate immunity, and many other factors. There are conflicting findings on the optimal radiation dose and fractions to stimulate effective anti-tumor immunity. High-dose radiotherapy (HDRT) acts in the same way as a double-edged sword in stimulating anti-tumor immunity, while low-dose radiotherapy (LDRT) seems to play a vital role in modulating the tumor immune microenvironment. Recent preclinical data suggest that a 'hybrid' radiotherapy regimen, which refers to combining HDRT with LDRT, can reap the advantages of both. Clinical data have also indicated a promising potential. However, there are still questions to be addressed in order to put this novel combination therapy into clinical practice. For example, the selection of treatment site, treatment volume, the sequencing of high-dose radiotherapy and low-dose radiotherapy, combined immunotherapy, and so on. This review summarizes the current evidence supporting the use of HDRT + LDRT, explains possible immune biology mechanisms of this 'hybrid' radiotherapy, raises questions to be considered when working out individualized treatment plans, and lists possible avenues to increase efficiency in stimulating anti-tumor immunity using high-dose plus low-dose radiotherapy.

Application of individualized multimodal radiotherapy combined with immunotherapy in metastatic tumors.

Radiotherapy is one of the mainstays of cancer treatment. More than half of cancer patients receive radiation therapy. In addition to the well-known direct tumoricidal effect, radiotherapy has immunomodulatory properties. When combined with immunotherapy, radiotherapy, especially high-dose radiotherapy (HDRT), exert superior systemic effects on distal and unirradiated tumors, which is called abscopal effect. However, these effects are not always effective for cancer patients. Therefore, many studies have focused on exploring the optimized radiotherapy regimens to further enhance the antitumor immunity of HDRT and reduce its immunosuppressive effect. Several studies have shown that low-dose radiotherapy (LDRT) can effectively reprogram the tumor microenvironment, thereby potentially overcoming the immunosuppressive stroma induced by HDRT. However, bridging the gap between preclinical commitment and effective clinical delivery is challenging. In this review, we summarized the existing studies supporting the combined use of HDRT and LDRT to synergistically enhance antitumor immunity, and provided ideas for the individualized clinical application of multimodal radiotherapy (HDRT+LDRT) combined with immunotherapy.

Long-term survival of a patient with diffuse midline glioma in the pineal region: A case report and literature review.

BACKGROUND: Diffuse midline glioma (DMG) is an invasive astrocytic tumor arisen from midline structures, such as the pons and thalamus. Five cases of DMG in the pineal region have been reported, but the clinical course was poor; there was no case of survival for more than 2 years. CASE DESCRIPTION: We report the case of a 12-year-old boy with DMG in the pineal region who is living a normal daily life for more than 6 years following multimodal treatment. He complained of a headache accompanied by vomiting that had gradually worsened 1 month previously, and initial magnetic resonance imaging revealed a pineal tumor. Germinoma was initially suspected; however, a combination of chemotherapy using carboplatin and etoposide was ineffective. The first surgery was performed through the left occipital transtentorial approach (OTA); the diagnosis was DMG. After 60 Gy radiotherapy concomitant with temozolomide (TMZ), the tumor enlarged. Second surgery was performed through bilateral OTAs, and 90% of the tumor was removed. In addition, stereotactic radiotherapy (30 Gy, six fractions) was administered, and the local equivalent dose in 2 Gy/fraction reached 97.5 Gy. Maintenance chemotherapy using TMZ and bevacizumab was continued for 2 years. After finishing chemotherapy, the enhancing lesion enlarged again, and bevacizumab monotherapy was effective. Now, at 6 years after diagnosis, the patient leads an ordinary life as a student. CONCLUSION: Maximum resection and high-dose radiotherapy followed by bevacizumab may have been effective in the present case.

High-dose Radiotherapy for Oligo-progressive NSCLC Receiving EGFR Tyrosine Kinase Inhibitors: Real World Data.

BACKGROUND/AIM: Local ablative treatments for oligo-progressive, EGFR mutated non-small cell lung cancer (mut-NCSLC) may improve long-term disease control and survival. We analyzed the efficacy of hypo-fractionated, high-dose radiation therapy (HDRT), in association with prolonged EGFR tyrosine kinase inhibitors (TKI) in oligo-progressive, EGFR mutant-NSCLC. PATIENTS AND METHODS: Progression-free survival-1 (PFS-1, date from initiation of TKI therapy until oligo-progression or death), and progression-free survival-2 (PFS-2, date of focal progression until further progression or death) were evaluated. RESULTS: Thirty-six patients were analyzed. The median PFS 1 was 12.5 months. HDHRT consisted of intensity-modulated RT and stereotactic RT in 23 (64%) and 13 (36%) patients respectively. The median PFS 2 was 6.3 months. Overall survival was 38.7 months. CONCLUSION: Hypo-fractionated HDRT plus TKI therapy, is associated with a significant prolongation of disease control (overall PFS: 18.8 months), with manageable side effects. These real-world data support the use of local ablative approaches in oligo-progressive EGFR mut-NSCLC.

Prognostic Nomogram for Overall Survival in Early Stage Extranodal Natural Killer/T Cell Lymphoma Treated With High-Dose Radiotherapy.

BACKGROUND: The aim of this study was to develop a prognostic nomogram for early stage extranodal natural killer/T-cell lymphoma, nasal type (ENKL) treated with high-dose radiotherapy (RT). PATIENTS AND METHODS: A total of 81 patients at 2 cancer centers with stage I to IIE ENKL who received chemotherapy (CT) and high-dose RT were retrospectively analyzed. The development of the nomogram was on the basis of the Cox proportional hazards model. We implemented the concordance index (C-index) and performed a calibration curve to determine its predictive and discriminatory capacity and compared our nomogram with the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI). RESULTS: The nomogram included 4 important variables and used a multivariate analysis: lactate dehydrogenase, primary tumor invasion, tumor response, and CT regimen. The 5-year OS rate and progression-free survival were 64.7% and 57.5%, respectively for the entire group. The C-index of the nomogram for overall survival (OS) prediction was 0.87, and it was superior to the predictive power of the IPI and KPI. The calibration curve showed that the nomogram accurately predicted the 5-year OS. CONCLUSION: The proposed nomogram could provide an individualized risk estimate of the OS for early stage ENKL treated with CT and high-dose RT.

Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System.

In cancer treatments, especially high-dose radiotherapy (HDRT) is applied. Patients suffering from chronic inflammatory diseases benefit from low-dose radiation therapy (LDRT), but exposure to very low radiation doses can still steadily increase for diagnostic purposes. Yet, little is known about how radiation impacts on forms of cell death in human immune cells. In this study, the radiosensitivity of human immune cells of the peripheral blood was examined in a dose range from 0.01 to 60 Gy with regard to induction of apoptosis, primary necrosis, and secondary necrosis. Results showed that immune cells differed in their radiosensitivity, with monocytes being the most radioresistant. T cells mainly died by necrosis and were moderately radiosensitive. This was followed by B and natural killer (NK) cells, which died mainly by apoptosis. X-radiation had no impact on cell death in immune cells at very low doses (≤0.1 Gy). Radiation doses of LDRT (0.3⁻0.7 Gy) impacted on the more radiosensitive NK and B cells, which might contribute to attenuation of inflammation. Even single doses applied during RT of tumors did not erase the immune cells completely. These in vitro studies can be considered as the basis to optimize individual radiation therapy schemes in multimodal settings and to define suited time points for further inclusion of immunotherapies.

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy.

AIM: To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT) for cervical esophageal cancer (CEC). METHODS: We reviewed a total of 62 consecutive patients who received definitive RT for stage I to III cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local (occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed. RESULTS: Grade 1, 2, and 3 esophagitis occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of which 7 cases (43.8%) were malignant. Four patients (6.5%) developed tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4 (P = 0.001), complete circumference involvement (P < 0.0001), stenosis at diagnosis (P = 0.024), and endoscopic complete response (P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis (P = 0.003). A higher dose (≥ 60 Gy) was not associated with occurrence of post-RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement (P = 0.023), stenosis at diagnosis (P < 0.0001), and occurrence of post-RT stenosis or TEF (P < 0.001) in univariate analysis, while stenosis at diagnosis (P = 0.004) and occurrence of post-RT stenosis or TEF (P = 0.023) were significant in multivariate analysis. CONCLUSION: Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.