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).

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.

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.

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.

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).

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.

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.

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.

Involved-field irradiation and elective nodal irradiation for esophageal squamous cell carcinoma: a systematic review and meta-analysis / 中华放射肿瘤学杂志

Objective:To analyze whether involved-field irradiation (IFI) was associated with improved survival and reduced treatment-related adverse events compared with elective nodal irradiation (ENI) in Chinese patients with esophageal squamous cell carcinoma receiving radiotherapy.Methods:Literature review was conducted from CNKI, Wanfang Data, PubMed, Embase, Web of Science and Cochrane Central databases (until July 31, 2022). Relevant data were collected according to the inclusion and exclusion criteria. Primary outcomes included overall survival (OS) rate and treatment-related adverse events. Secondary outcomes included progression-free survival (PFS) rate and local control rate (LCR). Risk of bias was assessed using the Cochrane Risk of Bias tool. The quality of the results was assessed by using the meta analysis of Evidence Evaluation and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methods.Results:A total of 7 articles with 918 patients were included of which 465 received IFI and 453 received ENI. The 1-, 2-, 3-and 5-year OS rates in the IFI group were not significantly different from those in the ENI group (1-year OS rate: RR=1.00, 95% CI=0.94-1.07, P=0.97, high certainty; 2-year OS rate: RR=1.01, 95% CI=0.90-1.13, P=0.90, high certainty; 3-year OS rate: RR=0.86, 95% CI=0.71-1.05, P=0.14, high certainty; 5-year OS rate: RR=0.76, 95% CI=0.42-1.37, P=0.36, low certainty). In the IFI group, patients with ≥grade 2 acute radiation esophagitis ( RR=0.71, 95% CI=0.58-0.87, P=0.001, high certainty), ≥grade 3 acute radiation esophagitis ( RR=0.39, 95% CI=0.24-0.64, P<0.001, high certainty) and ≥grade 2 acute radiation pneumonitis ( RR=0.72, 95% CI=0.52-0.99, P=0.04, high certainty) were significantly lower compared with those in the ENI group. However, no significant differences were observed in the incidence of ≥grade 3 late radiation esophagitis, ≥grade 3 acute radiation pneumonitis and ≥grade 3 late radiation pneumonitis between two groups. No significant differences were noted in the 1-, 2-, 3-PFS rates and LCR between two groups. Conclusions:For Chinese patients with esophageal squamous cell carcinoma, IFI and ENI yield similar efficacy in terms of OS, PFS and LCR. However, IFI has a lower incidence of ≥grade 2 acute radiation esophagitis, ≥grade 3 acute radiation esophagitis and ≥grade 2 acute radiation pneumonitis than ENI.

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.

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.

＜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.

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.

Comparison of curative effect between elective nodal irradiation and involved field irradiation combined with nedaplatin for cervical and upper thoracic esophageal cancer / 肿瘤研究与临床

Objective:To compare the efficacy and prognosis of elective nodal irradiation (ENI) combined with nedaplatin chemotherapy and involved field irradiation (IFI) combined with nedaplatin chemotherapy in the radical radiotherapy treatment of patients with cervical or upper thoracic esophageal cancer.Methods:Seventy-eight patients with cervical or upper thoracic esophageal cancer in Hai'an Traditional Chinese Medicine Hospital from February 2017 to February 2020 were selected and divided into ENI group and IFI group according to random number table method, with 39 cases in each group. The ENI group was treated with ENI combined with nedaplatin chemotherapy, while the IFI group was treated with IFI combined with nedaplatin chemotherapy. After 2 months of treatment, the therapeutic effect and the dose of lung irradiation were compared between the two groups, and the occurrence of adverse reactions and prognosis were compared.Results:The total effective rate and disease control rate were 69.23% (27/39) and 82.05% (32/39) in IFI group, and 64.10% (25/39) and 74.36% (29/39) in ENI group, there was no significant difference between the two groups ( χ2 = 0.23, P = 0.631; χ2 = 0.68, P = 0.411). The lung irradiation doses of V 5 Gy and V 20 Gy in IFI group were lower than those in ENI group (both P < 0.05). The incidence rates of bone marrow suppression and radiation lung injury in IFI group were lower than those in ENI group (all P < 0.05). By the end of follow-up, the survival rates of IFI group and ENI group were 76.92% (30/39) and 66.67% (26/39), respectively. There was no significant difference in overall survival between the two groups ( χ2 = 1.06, P = 0.300). Conclusions:ENI and IFI combined with nedaplatin chemotherapy in the radical radiotherapy treatment of cervical and upper thoracic esophageal cancer have similar efficacy and prognosis, but IFI can reduce the lung radiation dose and the incidence of adverse reactions.

Efficacy analysis of elective nodal irradiation and involved field irradiation combined with chemotherapy in treatment of esophageal cancer / 肿瘤研究与临床

Objective:To explore the efficacy of elective nodal irradiation (ENI) and involved field irradiation (IFI) combined with chemotherapy in treatment of esophageal cancer.Methods:A total of 104 patients with esophageal cancer in Affiliated Hospital of Jiangnan University from May 2018 to May 2020 were selected as subjects for prospective study. All patients were randomly divided into observation group and control group by lottery method with 52 cases in each group. The target volume of observation group was delineated with IFI, and the control group was delineated with ENI. The curative effects, the levels of serum tumor markers [carbohydrate antigen 50 (CA50), squamous cell carcinoma (SCC) and carcinoembryonic antigen (CEA)] before and after treatment, the 1-year overall survival (OS) rate, the incidence of adverse reactions and the scores of various dimensions of health survey summary (SF-36) after treatment were compared between the two groups.Results:The total effective rate in the observation group was 90.38% (47/52), the total effective rate in the control group was 84.62% (44/52), and the difference was not statistically significant ( χ2 = 0.79, P =0.374). There was no statistical difference in CA50, CEA, SCC levels between the two groups before and after treatment (all P > 0.05). After treatment, the CA50, CEA and SCC levels in the two groups were lower than those before treatment, and the differences were statistically significant (all P < 0.05). The 1-year OS rate of the observation group was 94.23%, the control group was 90.38%, and the difference in OS between the two groups was not statistically significant ( χ2 = 0.54, P = 0.462). The incidence of acute radiation esophagitis in the observation group was lower than that in the control group, and the difference was statistically significant ( P < 0.001). There was no statistical difference between the two groups in SF-36 scale scores of physical functioning, role-physical, bodily pain, mental health, vitality, social functioning, role-emotional, and general health after treatment (all P > 0.05). Conclusions:Both ENI and IFI are effective treatments for patients with esophageal cancer. There is no significant difference in the quality of life of patients between the two delineation methods, but the incidence of acute radiation esophagitis is lower in patients with IFI regimen.

Elective pelvic nodal irradiation with a simultaneous hypofractionated integrated prostate boost for localized high risk prostate cancer: Long term results from a prospective clinical trial.

BACKGROUND: To report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer. MATERIALS AND METHODS: This was a prospective single-arm study. Patients with high-risk disease (cT3, PSA >20 ng/mL, or Gleason score 8-10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2-3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0. RESULTS: 230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1-12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4-11.8, p < 0.001) and distant metastases (HR 7.5, 95% CI 3.9-14.5, p < 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2-12, p = 0.0001) and ADT use ≤12 months (versus >24 months) (HR 2.3, 95% CI 1.3-3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively. CONCLUSION: EPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity.

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.