The effect of incidental dose to pelvic nodes in bladder-only irradiation in the era of IMRT: a dosimetric study.

PURPOSE: While three-dimensional radiotherapy (RT) causes high incidental nodal doses in bladder-only irradiation for muscle-invasive bladder cancer (MIBC), the impact on pelvic lymphatics is unclear in the era of intensity-modulated RT (IMRT). This study evaluates incidental doses to pelvic lymphatics in MIBC patients treated with IMRT. METHODS: The data of 40 MIBC patients treated with bladder-only IMRT and concurrent chemotherapy were retrospectively evaluated. The pelvic lymphatics were contoured on initial simulation images and incidental nodal doses were evaluated. The Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was used for statistics. RESULTS: Median RT dose to the bladder was 60 Gy in 30 fractions. In dosimetric analysis, median values of mean dose (Dmean) of the obturator, presacral, external iliac, internal iliac, and distal common iliac lymphatics were 33 Gy (range 4-50 Gy), 3 Gy (range 1-28 Gy), 9.5 Gy (range 3-41 Gy), 7.5 Gy (range 2-14 Gy), and 1 Gy (range 0-15 Gy), respectively. The Dmean of the obturator lymphatics was significantly higher (p < 0.001) and the Dmean of the distal common iliac lymphatics was significantly lower (p < 0.001) than all remaining lymphatic stations. The Dmean of the external iliac lymphatics was significantly higher than that of the presacral lymphatics (p < 0.001), but the difference with the internal iliac lymphatics was not statistically significant (p = 0.563). CONCLUSION: The incidental nodal doses with bladder-only IMRT are heterogeneous and remain below the generally accepted doses for microscopic disease eradication for bladder cancer.

A phase III randomized controlled trial comparing local field with additional prophylactic irradiation in chemoradiotherapy for clinical-T1bN0M0 esophageal cancer: ARMADILLO trial (JCOG1904).

Chemoradiotherapy has been considered as one of the standard treatment options for clinical T1bN0M0 esophageal squamous cell carcinoma with organ preservation. However, 20% of patients develop locoregional recurrence after chemoradiotherapy, which requires salvage treatment including salvage surgery and endoscopic resection. Salvage surgery can cause complications and treatment-related death. Interestingly, chemoradiotherapy with elective nodal irradiation has been reported to reduce the locoregional recurrence of advanced esophageal squamous cell carcinoma. Hence, we are conducting a clinical trial to confirm whether modified chemoradiotherapy with elective nodal irradiation was superiority to that without elective nodal irradiation for the patients with cT1bN0M0 esophageal squamous cell carcinoma. The primary endpoint is major progression-free survival, defined as the time from randomization to the date of death or disease progression, excluding successful curative resection through salvage endoscopic resection. We plan to enroll 280 patients from 54 institutions over 4 years. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031200067).

HYpofractionated, dose-redistributed RAdiotherapy with protons and photons to combat radiation-induced immunosuppression in head and neck squamous cell carcinoma: study protocol of the phase I HYDRA trial.

BACKGROUND: Radiotherapy (RT) is the standard of care for most advanced head and neck squamous cell carcinoma (HNSCC) and results in an unfavorable 5-year overall survival of 40%. Despite strong biological rationale, combining RT with immune checkpoint inhibitors does not result in a survival benefit. Our hypothesis is that the combination of these individually effective treatments fails because of radiation-induced immunosuppression and lymphodepletion. By integrating modern radiobiology and innovative radiotherapy concepts, the patient's immune system could be maximally retained by (1) increasing the dose per fraction so that the total dose and number of fractions can be reduced (HYpofractionation), (2) redistributing the radiation dose towards a higher peak dose within the tumor center and a lowered elective lymphatic field dose (Dose-redistribution), and (3) using RAdiotherapy with protons instead of photons (HYDRA). METHODS: The primary aim of this multicenter study is to determine the safety of HYDRA proton- and photon radiotherapy by conducting two parallel phase I trials. Both HYDRA arms are randomized with the standard of care for longitudinal immune profiling. There will be a specific focus on actionable immune targets and their temporal patterns that can be tested in future hypofractionated immunoradiotherapy trials. The HYDRA dose prescriptions (in 20 fractions) are 40 Gy elective dose and 55 Gy simultaneous integrated boost on the clinical target volume with a 59 Gy focal boost on the tumor center. A total of 100 patients (25 per treatment group) will be recruited, and the final analysis will be performed one year after the last patient has been included. DISCUSSION: In the context of HNSCC, hypofractionation has historically only been reserved for small tumors out of fear for late normal tissue toxicity. To date, hypofractionated radiotherapy may also be safe for larger tumors, as both the radiation dose and volume can be reduced by the combination of advanced imaging for better target definition, novel accelerated repopulation models and high-precision radiation treatment planning and dose delivery. HYDRA's expected immune-sparing effect may lead to improved outcomes by allowing for future effective combination treatment with immunotherapy. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov; NCT05364411 (registered on May 6th, 2022).

Long-term results of chemoradiotherapy with elective nodal irradiation for resectable locally advanced esophageal cancer in three-dimensional planning system.

BACKGROUND: We evaluated the long-term results of definitive chemoradiotherapy (CRT) with elective nodal irradiation (ENI) using a three-dimensional (3D) planning system for resectable, locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: This retrospective study included 65 patients with LA-ESCC who started CRT between 2006 and 2017. Patients with Stage I-IV LA-ESCC according to the Union for International Cancer Control TNM classification (eighth edition) were included. In stage IV, only supraclavicular lymph node (LN) metastasis was included. All patients received radiotherapy with ENI and concurrent chemotherapy with platinum and 5-fluorouracil. RESULTS: The median age of the patients was 70 years (range 52-83 years). Stage I, II, III, and IV diseases were observed in 3 (5%), 28 (43%), 22 (34%), and 12 patients (18%), respectively. The median prescription dose was 66 Gy (range 50.4-66 Gy). The median follow-up period for the survivors was 71 months (range 8-175 months). The 5-year overall survival (OS) and progression-free survival rates were 54 and 43%, respectively. The 5-year OS rates for stages I-II and III-IV were 67 and 42%, respectively. Recurrence occurred in 29 patients (45%), and recurrence of regional LNs only occurred in 2 patients (3%). Grade 3 or higher late adverse events were observed in 8 patients (12%). Grade 5 heart failure occurred in two patients (3%); both had cardiovascular disease before treatment. CONCLUSION: The long-term results of definitive CRT with ENI for resectable LA-ESCC were favorable. ENI with a 3D planning system may reduce regional LN recurrence and late adverse events.

Caution against simultaneous integrated boost radiotherapy for upper thoracic esophageal squamous cell carcinoma: results from a single-arm phase II trial.

PURPOSE: To explore the feasibility and safety of simultaneous integrated boost technology (SIB) with elective nodal irradiation (ENI) to the cervical and upper mediastinal lymph node (LN) regions in upper thoracic esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS: Patients with pathologically proven unresectable upper thoracic ESCC were assigned 50.4 Gy/28 fractions (F) to the clinical target volume (encompassing the ENI area of cervical and upper mediastinal LN regions) and a boost of 63 Gy/28 F to the gross tumor volume. Chemotherapy consisted of courses of concurrent cisplatin (20 mg/m2) and docetaxel (20 mg/m2) weekly for 6 weeks. The primary endpoint was toxicity. RESULTS: Between Jan 2017 and Dec 2019, 28 patients were included. The median follow-up time for all patients was 24.6 months (range 1.9-53.5). Radiation-related acute toxicity included esophagitis, pneumonia and radiodermatitis, all of which were well managed and reversed. Late morbidity included esophageal ulcer, stenosis, fistula and pulmonary fibrosis. Grade III esophageal stenosis and fistula was seen in 11% (3/28) and 14% (4/28) patients, respectively. The cumulative incidence rate of late esophageal toxicity was 7.7%, 19.2% and 24.6% at 6, 12 and 18 months, respectively. There was significant difference of the occurrence of severe late esophageal toxicity among the different volume levels of the esophagus, and cervical and upper mediastinal LNs which received ≥ 63 Gy stratified by the tertiles (p = 0.014). CONCLUSIONS: Despite the acceptably tolerated acute toxicity of SIB in concurrent CRT with ENI to the cervical and upper mediastinal LN regions for upper thoracic ESCC, the incidence of severe late esophageal toxicity was relatively high. Cautions are provided against easy clinical application of SIB (50.4 Gy/28F to the CTV, 63 Gy/28F to the GTV) in upper thoracic ESCC. Further exploration on dose optimization is warranted.

[Clinical outcomes of different irradiation ranges in definitive intensity-modulated radiotherapy for esophageal cancer].

Objective: To explore the therapeutic efficacy and safety of elective nodal irradiation (ENI) and involved field irradiation (IFI) in intensity-modulated radiotherapy for esophageal cancer, screen the patients suitable to undergo ENI radiotherapy and provide evidences for individual treatment of esophageal cancer. Methods: A retrospective analysis was performed on the clinical data of 924 patients with esophageal cancer who received definitive intensity-modulated radiotherapy in our hospital from January 2006 to December 2015. Among them, 272 patients received ENI and the other 652 patients received IFI. The clinicopathologic characteristics of 272 cases in ENI group and 652 cases in IFI group, who were recruited according to the balance of propensity score matching method, were compared. The Kaplan-Meier method was used to calculate 1-year, 3-years and 5-years local-regional failure-free survival (LRFFS), progression-free survival (PFS) and overall survival (OS) rates. The univariate and multivariate analysis of prognostic factors were also determined by Cox proportional hazard model and Long-rank test. Results: The clinicopathologic characteristics of these two group were not significantly different (P>0.05). The median follow-up time was 85.9 months and the follow-up rate was 95.9%. The 1-year, 3-years, 5-years PFS rates of the ENI groups were 65.3%, 31.7%, 18.4%, respectively, higher than 54.0%, 20.9%, 12.7% of the IFI group (P=0.001). The 1-year, 3-years, 5-years OS rates of the ENI groups were 79.0%, 43.7%, 24.9%, respectively, higher than 75.0%, 31.8%, 17.2% of the IFI group (P=0.003). In multivariate analysis, the sex, tumor volume, N stage and radiation field were independent factors for PFS and OS (P<0.05). Subgroup analysis showed that patients with male, age≤66 year, cervical and upper-thoracic location, tumor length≤6 cm, T1-2 stage, N0-1 stage, Ⅰ-Ⅱ stage, tumor volume≤50 cm(3), dosage>60 Gy and≤2 cycles of chemotherapy in the ENI group had a better survival rate than those in the IFI group (P<0.05). The total failure rate, local-regional failure rate in ENI group were significantly lower than those of IFI group (P=0.001, P=0.004). The incidence of bone marrow depression≥ grade 2 and 3 in ENI group was higher than that of the IFI group (P<0.05). However, the incidences of radioactive esophagitis≥ grade 3, radioactive pneumonia and late adverse reactions were not significantly different between these two groups (P>0.05). Conclusion: Compared with IFI, ENI can significantly improve the long-term survival for young, early TN stage and cervical/upper-thoracic esophageal cancer patients underwent chemotherapy.

Simultaneous Integrated Boost Volumetric Modulated Arc Therapy for Middle or Lower Esophageal Cancer Using Elective Nodal Irradiation: Comparison with 3D Conformal Radiotherapy.

We investigated the feasibility of simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) using elective nodal irradiation (ENI) for middle or lower esophageal cancer and compared it with three-dimensional conformal radiotherapy (3D-CRT). The study included 15 patients. The prescribed doses included a standard dose (50.4 Gy) and a high dose (60 Gy) for the planning target volume (PTV) of the involved lesions. The objective of the whole lung volume receiving ≥ 20 Gy (V20Gy) was < 30%, and the mean lung dose (MLD) was < 20 Gy. The volumes of the lung receiving 5 Gy (V5Gy) and the heart receiving 30-50 Gy (V30-50Gy) were kept as low as reasonably achievable. As a result, SIB-VMAT showed superior dose conformity for the PTV (p<0.001). Although the lung V5Gy was significantly increased (p<0.001), the V20Gy and MLD showed no significant increase. The heart V30-50Gy showed a > 20% reduction in the mean against 3D-CRTs. Our results demonstrate the feasibility of SIB-VMAT for the treatment of middle or lower esophageal cancer with ENI. Although attention should be paid to the low-dose area of the lungs, SIB-VMAT would be a promising treatment option with improved outcomes for esophageal cancer.

Long-term outcome of concurrent chemoradiotherapy with elective nodal irradiation for inoperable esophageal cancer.

Elective nodal irradiation (ENI) might improve overall survival in patients with inoperable esophageal cancer. We conducted a retrospective analysis to assess the long-term survival and toxicity of esophageal cancer patients treated with ENI versus conventional-field irradiation (CFI). All data in the present study were based on our institutional experience from 2000 to 2005 of patients with inoperable esophageal cancer treated with ENI or CFI plus two concurrent cycles of paclitaxel/cisplatin. Based on the inclusion and exclusion criteria, 89 patients were included in the analysis. Of these patients, 51 were treated with ENI, whereas 38 were treated with CFI. For the per-protocol population, the patients in the ENI group significantly improved in terms of their 10-year disease-specific overall survival (43.1% vs 10.5%, P = 0.019), 10-year disease-free survival (36.7% vs 10.2%, P = 0.040) and 10-year local recurrence-free survival (47.2% vs 17.2%, P = 0.018) compared with the CFI group. Aside from radiation esophagitis, the incidence of grade 3 or greater acute toxicities did not differ between the two groups. Multivariate analysis showed that radiation field, tumor length and clinical stage were independent prognostic factors associated with OS. Concurrent chemoradiotherapy with ENI improves both disease-specific overall survival and loco-regional control in patients with inoperable esophageal cancer receiving per-protocol treatment. The regimen has a manageable tolerability profile.

Phase II study of concurrent chemoradiotherapy at the dose of 50.4 Gy with elective nodal irradiation for Stage II-III esophageal carcinoma.

OBJECTIVE: Definitive chemoradiotherapy is one of the curative options for resectable esophageal squamous cell carcinoma with organ preservation. We evaluated the efficacy and toxicity of radiotherapy at a dose of 50.4 Gy concurrent with chemotherapy for Stage II-III esophageal cancer. METHODS: Esophageal cancer patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) were eligible. Radiotherapy was administered to a total dose of 50.4 Gy with elective nodal irradiation of 41.4 Gy. Concurrent chemotherapy comprised two courses of 5-fluorouracil (1000 mg/m(2)/day) on days 1-4 and 2-h infusion of cisplatin (75 mg/m(2)) on Day 1; this was repeated every 4 weeks. Two courses of 5-fluorouracil with cisplatin were added. RESULTS: Fifty-one patients were enrolled in the study from June 2006 to May 2008. The characteristics of the 51 patients enrolled were as follows: median age 64 years; male/female, 45/6; performance status 0/1, 32/19 patients; Stage IIA/IIB/III, 9/20/22 patients, respectively. A complete response was achieved in 36 patients (70.6%). The 1- and 3-year overall survival rate was 88.2 and 63.8%, respectively. The median 1- and 3-year progression-free survival rate was 66.7% (80% CI: 57-74%) and 56.6% (80% CI: 47.1-64.9%), respectively. Acute toxicities included Grade 3/4 anorexia (45%), esophagitis (35%) and febrile neutropenia (20%). Eight patients (15.6%) underwent salvage surgery due to residual or recurrent disease. There were no deaths related to salvage surgery. CONCLUSION: Chemoradiation therapy at a dose of 50.4 Gy with elective nodal irradiation is promising with a manageable tolerability profile in esophageal cancer patients.

Elective nodal irradiation versus involved-field irradiation for stage II-IV cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy: a retrospective propensity study with 8-year survival outcomes.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the 8-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI). MATERIALS AND METHODS: Patients with stage II-IV CESCC treated with dCCRT at the Fourth Hospital of Hebei Medical University between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage, clinical N stage, clinical TNM stage and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated. RESULTS: The 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 91.1 months (range, 23.8-182.0 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.1%, 38.3%, and 27.2%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.5%, 38.5% and 31.1% versus 45.2 months, 89.8%, 52.5%, 37.5%, 26.1%, respectively (P = 0.966; HR 0.99, 95% CI 0.61-1.61). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% vs. 38.8%; P = 0.068 and 30.6% vs. 14.3%; P = 0.089) at the end of dCCRT. CONCLUSION: Cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.

A comparative study of elective nodal irradiation and involved field irradiation in elderly patients with advanced esophageal cancer.

Objective: This comparative study aimed to explore the feasibility of involved field irradiation (IFI) in the radiotherapy of elderly patients with advanced esophageal cancer, compared with elective nodal irradiation (ENI). Methods: A total of 245 elderly patients (age ≥70 years) with advanced esophageal cancer, who received radiotherapy in our department from January 2014 to December 2020, were divided into the ENI group (n=111) and the IFI group (n=134). Clinical efficacy, toxicities, survival rates, treatment failures, and multifactorial survival analyses were conducted for both groups. Results: The ENI group and the IFI group showed no significant differences in terms of short-term efficacy (91.9% vs 91.0%, P=0.814), 1-year overall survival (OS) (81.1% vs 74.6%, P=0.228), 2-year OS (22.5% vs 25.4%, P= 0.603), 1-year progression-free survival (PFS) (56.8% vs 51.5%, P= 0.198), 2-year PFS (8.1% vs 9.0%, P=0.814), regional failures (38.7% vs 31.3%, P=0.226), and distant metastasis (21.6% vs 14.9%, P=0.174). The median overall survival (OS) was 19 months in the ENI group and 18 months in the IFI group (Log-rankχ 2 = 0.012, P=0.913). The median progression-free survival (PFS) was 13 months in the ENI group and 11 months in the IFI group (Log-rankχ 2 = 1.834, P=0.176). There were no significant statistical differences in both OS and PFS (P>0.05). The incidence of grade ≥3 radiation pneumonia and grade ≥3 radiation esophagitis in the IFI group was 8.2% and 11.2%, respectively, which were significantly lower than those in the ENI group (17.1%, P=0.034; 21.6%, P=0.026). Univariate analysis revealed that age, gender, T stage, N stage, and synchronous chemotherapy were factors affecting prognosis. Multivariate analysis showed that age, gender, T stage, and synchronous chemotherapy were independent prognostic factors, with hazard ratios of 1.227, 1.466, 2.441, and 2.714, and P values of <0.001, 0.006, <0.001, and<0.001, respectively. Conclusion: IFI is a suitable choice for elderly patients with advanced esophageal cancer, as it yields similar efficacy to ENI while reducing toxicities. Age, gender, T stage, and synchronous chemotherapy are independent prognostic factors for elderly patients with esophageal cancer.

Evaluation of Exposure Doses of Elective Nodal Irradiation in Chemoradiotherapy for Advanced Esophageal Cancer.

We evaluated elective nodal irradiation (ENI) doses during radical chemoradiotherapy (CRT) for esophageal cancer (EC). A total of 79 patients (65 men and 14 women) aged 52-80 years with T1-3, N0-3, and M0 (including M1ly) who underwent CRT for EC during November 2012-September 2019 were eligible for this retrospective analysis. Patients were divided into two groups: the high-dose group (HG), including 38 patients who received ≥40 Gy as ENI; and the low-dose group (LG), including 41 patients who received <40 Gy. The median doses were 40.0 and 36.0 Gy in HG and LG, respectively. During the follow-up (median: 36.7 months), no lymph node recurrence was observed in the ENI field in all patients. Lymph node recurrence near the ENI field was observed in six patients. No significant differences were observed between the two groups in median overall survival, progression-free survival, and local control. Grade 3-4 acute and late adverse events were observed in five patients of HG and six patients of LG, respectively. No ulceration or stricture was observed in the ENI field on endoscopy examined with 58 Gy irradiation. In conclusion, an ENI dose of 36 Gy could be considered to control the elective nodes of EC.

Involved-field irradiation or elective-nodal irradiation in neoadjuvant chemo-radiotherapy for locally-advanced esophageal cancer: comprehensive analysis for dosimetry, treatment-related complications, impact on lymphocyte, patterns of failure and survival.

Purpose: To compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Materials and methods: We retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups. Results: The median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p<0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p=0.004) and pericardial effusion (26.7% vs. 11.8%, p=0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively (p=0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN- patients, especially in the first year of follow-up (6.67% vs. 0.56%, p=0.003). Conclusion: The ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted.

Failure Patterns of Recurrence in Patients With Localized Esthesioneuroblastoma Following Surgery and Adjuvant Radiotherapy Without Elective Nodal Irradiation.

BACKGROUND: Esthesioneuroblastoma (ENB), a rare malignancy arising from the olfactory epithelium, poses clinical challenges owing to its propensity for local invasion and recurrence. Its management typically involves surgical resection and adjuvant radiotherapy. However, debate persists regarding the optimal treatment strategy, particularly the use of elective nodal irradiation (ENI). This study aimed to investigate recurrence patterns in patients with localized ENB treated with surgery and adjuvant radiotherapy without ENI. METHODS: Our retrospective analysis included patients who underwent surgery followed by adjuvant radiotherapy for treatment of ENB between January 2011 and November 2022. Patients with incomplete data or who had received neoadjuvant radiotherapy were excluded. Patient characteristics, radiotherapy data (type, dose, and duration), and follow-up data were collected. Recurrence patterns were evaluated, and overall survival (OS), disease-free survival (DFS), and local control rates were determined using the Kaplan-Meier method. RESULTS: Twelve patients with ENB (median age, 56 years) were included. Most had stage C disease. The median radiation dose was 60 Gy, and the median treatment duration was six weeks. Only one death was confirmed during the observation period, and the five-year DFS rates were 64.3%. Local control was achieved in 11 patients, with only one experiencing local recurrence. Regional lymph node recurrence occurred in three patients and was successfully managed via neck dissection. The timing of recurrence varied, emphasizing the importance of long-term surveillance. CONCLUSION: Adjuvant radiotherapy without ENI is a viable treatment option for ENB, resulting in favorable local control and OS outcomes. Regional lymph node metastases were observed but effectively managed via salvage therapy. Prospective studies with larger cohorts are warranted to confirm the effectiveness of this treatment strategy and to define optimal radiotherapy fields.

Stereotactic Body Radiotherapy: Hitting Harder, Faster, and Smarter in High-Risk Prostate Cancer.

Stereotactic body radiotherapy (SBRT) is a technologically sophisticated form of radiotherapy that holds significant potential to effectively treat high-risk prostate cancer (HRPC). Prostate SBRT has been the subject of intense investigation in the context of low- and intermediate-risk disease, but less so for HRPC. However, emerging data are demonstrating its potential to safely and efficiently delivery curative doses of radiotherapy, both to the prostate and elective lymph nodes. SBRT theoretically hits harder through radiobiological dose escalation facilitated by ultra-hypofractionation (UHRT), faster with only five treatment fractions, and smarter by using targeted, focal dose escalation to maximally ablate the dominant intraprostatic lesion (while maximally protecting normal tissues). To achieve this, advanced imaging modalities like magnetic resonance imaging and prostate specific membrane antigen positron emmission tomography (PSMA-PET) are leveraged in combination with cutting-edge radiotherapy planning and delivery technology. In this focused narrative review, we discuss key evidence and upcoming clinical trials evaluating SBRT for HRPC with a focus on dose escalation, elective nodal irradiation, and focal boost.

Concurrent Chemoradiotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil for T3 N0 Glottic Carcinoma Without Vocal Cord Fixation.

BACKGROUND/AIM: We retrospectively evaluated the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin, and 5-fluorouracil (TPF) for T3 N0 glottic carcinoma without vocal cord fixation. PATIENTS AND METHODS: Twenty-five patients underwent TPF-CCRT without elective nodal irradiaion (ENI). After the RT of 40 Gy, five patients (20%) without tumor regression underwent surgery. Others underwent RT with a median total dose of 66 Gy. RESULTS: Of the five patients who underwent surgery after the RT of 40 Gy, two showed residual carcinoma pathologically and the other three were confirmed to have complete pathological response to the treatment. The 5-year local control rate was 87%. No patients exhibited regional failure. No acute toxicities of grade 5 or late toxicities ≥grade 3 were observed. CONCLUSION: TPF-CCRT provides excellent tumor control with acceptable toxicities. CCRT while omitting ENI is a reasonable approach for T3 N0 glottic carcinoma without vocal cord fixation.

＜Editors' Choice＞ Elective nodal irradiation versus involved field radiotherapy for limited disease small cell lung cancer: a single-institution experience.

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with limited-disease small cell lung cancer (LD-SCLC). However, no solid consensus exists on their optimal target volume. The current study aimed to assess the clinical outcomes of patients with LD-SCLC who received definitive ENI or IFRT. A retrospective single-institution study of patients who received definitive radiotherapy between 2008 and 2020 was performed. All patients underwent whole-body positron emission tomography/computed tomography before three-dimensional conformal radiotherapy. Among the 37 patients analyzed, 22 and 15 received ENI and IFRT, respectively. The thoracic radiotherapy dose was mostly either 60 Gy in 30 fractions delivered in 2-Gy fractions once daily or 45 Gy in 30 fractions delivered in 1.5-Gy fractions twice daily. The median follow-up period was 21.4 months. A total of 12 patients (32%) experienced locoregional relapse: 10 within and 2 outside the irradiation fields. One patient in the IFRT group experienced isolated nodal failure. Differences in locoregional relapse-free, progression-free, and overall survival rates between ENI and IFRT were not significant. Overall, IFRT did not promote a significant increase in locoregional recurrence compared to ENI. Our findings suggested the utility of IFRT in standard clinical practice and support its use for patients with LD-SCLC.

The role of involved field irradiation versus elective nodal irradiation in definitive radiotherapy or chemoradiotherapy for esophageal cancer- a systematic review and meta-analysis.

Objective: This study aimed to analyze whether involved field irradiation (IFI) is associated with improving survival outcomes and reducing adverse events compared with elective nodal irradiation (ENI) in patients of esophageal cancer who underwent definitive radiotherapy or chemoradiotherapy. Summary background data: Radiotherapy plays an important role for not surgery patients. However, the role of radiation target size is still uncertain. Methods: We searched Web of Science, Embase, PubMed, and Cochrane Central for English and non-English publications comparing esophageal cancer patients who received radiotherapy with IFI with those with ENI. Primary outcomes included overall survival (OS) and adverse events related to radiotherapy. The risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality Standard for non-randomized studies. We evaluated the certainty of evidence by Grading of Recommendations, Assessment, Development, and Evaluation. Results: Totally, 23 studies with 4120 patients were included. IFI group demonstrated significant improvement in the OS rates at 5 years, but not at 1, 2, and 3 years, compared with the ENI group (pooled Risk Ratio [RR], 0.78; 95% confidence interval [CI], 0.68-0.90; P = 0.0004; high certainty). In addition, IFI demonstrated a significant decrease in the incidence of grade ≥2 acute esophagitis (AE) (pooled RR, 0.79; 95% CI, 0.69-0.90; P = 0.0005; high certainty) and grade ≥3 AE (pooled RR, 0.51; 95% CI, 0.38-0.69; P < 0.00001; high certainty) compared with ENI, but not in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia. Conclusions: Compared to ENI, IFI demonstrated significant improvement in OS at 5 years. The addition of intensity-modulated radiotherapy (IMRT) to IFI increased the 5-year OS; however, similar results were not observed with the addition of three-dimensional conformal radiotherapy to IFI and ENI. Furthermore, IFI demonstrated a significant decrease in grade ≥2 and grade ≥3 AE, while IMRT demonstrated no difference in the incidence of grade ≥3 AE. IFI and ENI do not differ in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia.

Invasion of the pterygoid plates: an indicator for regional lymph node failure in maxillary sinus cancer.

BACKGROUND: The aim of this study was to evaluate the long-term treatment results of combined superselective intraarterial chemotherapy and radiation therapy for advanced maxillary sinus cancer (MSC) and the incidence of regional lymph node failure, and to reveal the clinical and anatomical predictive factors for metastasis. METHODS: We retrospectively evaluated 55 consecutive patients with locally advanced squamous cell carcinoma of the maxillary sinus who were treated with external radiotherapy and superselective intraarterial chemotherapy. Elective nodal irradiation (ENI) was performed only in the clinical node-positive (cN+) cases and not in the clinical node-negative (cN0) cases. RESULTS: Thirty-eight patients were cN0, and 17 were cN+ at diagnosis. Regional lymph node metastases occurred in 7 of 38 patients with cN0, and 2 of 17 with cN+ during the median follow-up period of 36 months. There were more cases of high-grade (3 or 4) late adverse events in the ENI group than in the non-ENI group (13% vs. 41%, respectively; p = 0.03). In cN0 cases without ENI, invasion of the pterygoid plates (57% vs. 90%; p < 0.01) and oral cavity (35% vs. 92%, with invasion vs without invasion, respectively; p = 0.02) was significantly correlated with a low 5-year regional recurrence-free rate. CONCLUSIONS: Patients with MCS and invasion of the pterygoid plates and oral cavity can be considered appropriate candidates for ENI.

Patterns of Recurrence in Locally Advanced Resectable Oesophageal Carcinoma: Retrospective Review from a Tertiary Cancer Centre in South India.

PURPOSE: The study aims to analyse patterns of recurrence following neoadjuvant treatment and surgery in carcinoma oesophagus with an intent to postulate optimal nodal radiation. METHODOLOGY: A retrospective review of patients who presented to our centre within a 5-year period (2014-2018), with recurrence following sequential neoadjuvant treatment and radical surgery, was conducted in this single-institution study. The patterns of recurrence and duration of disease-free survival were analysed. RESULTS: Twenty-one patients (14 men, 7 women) presented with recurrence, of which 13, 7, and 1 patient(s) had received NACT, NACTRT, or both, respectively. Six patients who did not receive neoadjuvant radiotherapy received adjuvant RT. Among the 10 patients who had nodal recurrence after RT (either neoadjuvant or adjuvant), 6 and 4 patients had in-field and out-of-field nodal recurrences, respectively-the latter were equally distributed within 5 cm and outside 5 cm of the PTV margin. CONCLUSION: Among the patients who presented with recurrence, more than half had not received neoadjuvant RT (treated in the 'pre-CROSS era' or due to long-segment disease), reasserting the therapeutic superiority of NACTRT. Increased regularity of recurrences in the draining nodal region was not noted in this study, but large-scale, prospective, randomised head-to-head comparative trials to determine optimal nodal irradiation in carcinoma oesophagus are required.