External Beam Radiotherapy in the Management of Uveal Melanoma.

OPINION STATEMENT: Uveal melanoma is the most common primary ocular tumor in adults. With the evidence demonstrating that episcleral plaque brachytherapy (EPB) has similar survival rates as enucleation in the Collaborative Ocular Melanoma Study (COMS), eye-sparing treatments have come to the fore today. External radiotherapy techniques (proton beam radiotherapy and stereotactic radiosurgery/fractionated stereotactic radiosurgery) are an important treatment option for globe-sparing treatments. There are no prospective randomized trials comparing these techniques; however, retrospective series, meta-analyses, and reviews indicate that these EPB and external radiotherapy techniques are equal. With this review, we aimed to examine the external radiotherapy techniques used in the treatment of uveal melanoma in detail with reference to the current literature.

Simultaneous integrated or sequential boost to clinically involved lymph nodes in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy.

OBJECTIVE: The optimal treatment of metastatic lymph nodes (LNs) in locally-advanced cervical cancer (LACC) is controversial. With the widespread use of modern radiotherapy (RT) techniques, it is become possible to perform dose escalation in clinically involved LNs. This study aimed to evaluate the oncologic outcomes of dose escalation to the involved LNs with the simultaneous-integrated (SIB) or sequential boost (SEB) techniques as a part of definitive chemoradiotherapy (CRT) for patients with LACC. METHODS: The data of 47 patients treated with definitive CRT with either a SIB or SEB technique to the metastatic LNs between 2015 and 2021 were retrospectively analyzed. All patients received 50.4 Gy/28 fractions of external-beam RT and 28 Gy/4 fractions of brachytherapy. RESULTS: The number of boosted LNs was 146. The median size of the LNs was 2 cm (range, 1-5 cm). The median cumulative equivalent dose in 2-Gy fractions for the LNs was 64.2 Gy (range, 57.6-71.2 Gy). During the median 30 months of follow-up (range, 14-91 months), no boosted LNs recurred and the local control (LC) rate was 100%. The 2-year overall, disease-free, local recurrence-free, and distant metastasis-free survival rate was 83.1%, 70.5%, 77.5%, and 74.4%, respectively. In multivariate analysis, the non-squamous cell histology was the only negative independent prognostic factor for DFS and DMFS. Treatment was well tolerated without any serious acute toxicity. Serious late toxicity developed in three (6%) patients as ureteral stenosis, rectal bleeding and pelvic fracture in one patient each. CONCLUSIONS: RT dose escalation provides excellent LC for the clinically involved LNs, even for bulky ones, with a low toxicity profile. Routine LN dissection may not be necessary. However, randomized trials are needed to determine the optimal treatment approach.

Improving normal tissue sparing using scripting in endometrial cancer radiation therapy planning.

The aim of this study was to improve the protection of organs at risk (OARs), decrease the total planning time and maintain sufficient target doses using scripting endometrial cancer external beam radiation therapy (EBRT) planning. Computed tomography (CT) data of 14 endometrial cancer patients were included in this study. Manual and automatic planning with scripting were performed for each CT. Scripts were created in the RayStation™ (RaySearch Laboratories AB, Stockholm, Sweden) planning system using a Python code. In scripting, seven additional contours were automatically created to reduce the OAR doses. The scripted and manual plans were compared to each other in terms of planning time, dose-volume histogram (DVH) parameters, and total monitor unit (MU) values. While the mean total planning time for manual planning was 368 ± 8 s, it was only 55 ± 2 s for the automatic planning with scripting (p < 0.001). The mean doses of OARs decreased with automatic planning (p < 0.001). In addition, the maximum doses (D2% and D1%) for bilateral femoral heads and the rectum were significantly reduced. It was observed that the total MU value increased from 1146 ± 126 (manual planning) to 1369 ± 95 (scripted planning). It is concluded that scripted planning has significant time and dosimetric advantages over manual planning for endometrial cancer EBRT planning.

Impact of lymph node ratio in patients with stage IIIC endometrial carcinoma treated with postoperative radiotherapy.

Aim: To evaluate the prognostic value of the lymph node ratio (LNR) and other clinicopathological factors in patients with stage IIIC endometrial cancer. Methods: Factors affecting overall survival (OS) and progression-free survival (PFS) were assessed in 397 patients with stage IIIC endometrial cancer treated with postoperative radiotherapy. Patients undergoing the removal of at least ten lymph nodes were included in the study. Results: The 5-year OS and PFS rates were 58% and 52%, respectively, with a median follow-up time of 35.7 months. The LNR cutoff value was 9.6%. In the multivariate analysis, advanced age (≥60 years), grade III tumor, presence of cervical stromal invasion, higher LNR and lack of adjuvant chemotherapy were independent predictors for worse OS and PFS. Conclusion: The LNR is an independent predictor for OS and PFS in patients with stage IIIC endometrial cancer treated with postoperative radiotherapy.

Treatment outcomes of endometrial cancer patients with paraaortic lymph node metastasis: a multi-institutional analysis.

OBJECTIVE: To analyze the prognostic factors and treatment outcomes in endometrial cancer patients with paraaortic lymph node metastasis. METHODS: Data from four centers were collected retrospectively for 92 patients with endometrial cancer treated with combined radiotherapy and chemotherapy or adjuvant radiotherapy alone postoperatively, delivered by either the sandwich or sequential method. Prognostic factors affecting overall survival and progression-free survival were analyzed. RESULTS: The 5-year overall survival and progression-free survival rates were 35 % and 33 %, respectively, after a median follow-up time of 33 months. The 5-year overall survival and progression-free survival rates were significantly higher in patients receiving radiotherapy and chemotherapy postoperatively compared with patients treated with adjuvant radiotherapy alone (P < 0.001 and P < 0.001, respectively). In a subgroup analysis of patients treated with adjuvant combined chemotherapy and radiotherapy, the 5-year overall survival and progression-free survival rates were significantly higher in patients receiving chemotherapy and radiotherapy via the sandwich method compared with patients treated with sequential chemotherapy and radiotherapy (P = 0.02 and P = 0.03, respectively). In the univariate analysis, in addition to treatment strategy, pathology, depth of myometrial invasion, and tumor grade were significant prognostic factors for both overall survival and progression-free survival. In the multivariate analysis, grade III disease, myometrial invasion greater than or equal to 50%, and adjuvant radiotherapy alone were negative predictors for both overall survival and progression-free survival. CONCLUSION: We demonstrated that adjuvant combined treatment including radiotherapyand chemotherapy significantly increases overall survival and progression-free survival rates compared with postoperative pelvic and paraaortic radiotherapy.

Definitive Chemoradiotherapy in Elderly Cervical Cancer Patients: A Multiinstitutional Analysis.

OBJECTIVE: The aim of the study was to investigate the prognostic factors for survival and treatment-related toxicities in older (≥65 years) cervical cancer patients treated with definitive chemoradiotherapy. In addition, we sought to compare the outcomes between the older elderly (≥75 years) and their younger old counterparts (age, 65-74 years). MATERIALS AND METHODS: We retrospectively reviewed medical records from 269 biopsy-proven nonmetastatic cervical cancer patients treated with external radiotherapy and intracavitary brachytherapy at the departments of radiation oncology in 2 different universities. The prognostic factors for survival, local control, and distant metastasis (DM) were analyzed. RESULTS: The median follow-up time was 38.8 months (range, 1.5-175.5 months) for the entire cohort and 70.0 months (range, 6.1-175.7 months) for survivors. The 2- and 5-year overall survival (OS), disease-free survival (DFS), and cause-specific survival rates were 66% and 42%, 63% and 39%, and 72% and 55%, respectively. Patients 75 years or older showed significantly worse OS compared with patients aged 65 to 74 years but showed no significant difference in DFS. The 2- and 5-year local control rates were 86% and 71%, respectively. The incidences of DMs at 2 and 5 years were 22% and 30%, respectively. In multivariate analysis, vaginal infiltration and lymph node metastasis were predictive of OS, DFS, local recurrence, and DM. Concomitant chemotherapy was predictive of OS, DFS, and local recurrence, and larger tumor (>4 cm) was a significant prognostic factor for local recurrence. None of the patients had toxicity that necessitated the discontinuation of radiotherapy. All patients were evaluable for acute toxicity, and no grade higher than 3 adverse events occurred during external beam radiation therapy or brachytherapy. CONCLUSIONS: Although age limited the delivery of aggressive treatment, concurrent chemoradiotherapy in elderly patients associated with improved outcomes similar as in younger counterparts without increasing serious acute and late toxicities.

Post-induction lymph node delineation in nasopharyngeal cancer: A single-center experience.

BACKGROUND: We routinely delineate the gross tumor volume (GTV) for the lymph nodes (LN) based on post-induction chemotherapy (IC) MRI in nasopharyngeal carcinoma (NPC). Herein, we investigated the sufficiency of this method, particularly in high-risk LNs. METHODS: Eighty-one LNs with a high-risk of clinical extranodal extension and/or ≥3-cm diameter in 58 patients were evaluated. A new GTV covering the pre-IC LN volume was delineated for each LN. RESULTS: The median volume reduction was 72.5% for the GTV and 53.1% for the planning target volume. After a median 43 months, the overall LN local control rate was 97.5%. The 2- and 5-year LN recurrence-free survival, overall survival, and disease-free survival rate was 88.3% and 84.4%, 92.5% and 85.1%, and 86.8% and 79.2%, respectively. CONCLUSION: IC yields a significant reduction in nodal target volumes, and post-IC nodal volume-based radiotherapy provides excellent LC in NPC, even in high-risk LNs.

Inter-observer variation of target volume delineation for CT-guided cervical cancer brachytherapy.

Purpose: Delineation is a critical and challenging step in radiotherapy planning. Differences in delineation among observers are common, despite the presence of contouring guidelines. This study aimed to identify the inter-observer variability in the target volume delineation of computed tomography (CT)-guided brachytherapy for cervical cancer. Material and methods: Four radiation oncologists (ROs) with different expertise levels delineated high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) according to GYN GEC-ESTRO recommendations, in a blinded manner on every CT set of ten locally advanced cervical cancer cases. The most experienced RO's contours were determined as the index and used for comparison. Dice similarity coefficient (DSC) and pairwise Hausdorff distance (HD) metrics were applied to compare the overlap and gross deviations of all contours. Results: Median DSC for HR-CTV and IR-CTV were 0.73 and 0.76, respectively, and a good concordance was achieved for both in majority of contours. While there was no difference in DSC measurements for HR-CTV among the three ROs, RO-3 provided improved DSC values for IR-CTV (p = 0.01). Median HD95 was 5.02 mm and 6.83 mm, and median HDave was 1.69 mm and 2.21 mm for HR-CTV and IR-CTV, respectively. There was no significant difference among ROs in HR-CTV for HD95 or HDave; however, IR-CTV value was significantly improved according to RO-3 (p = 0.01). Case-by-case HD analysis showed no significant inter-observer variations, except for two cases. Conclusions: The inter-observer agreement is generally high for target volumes in CT-guided brachytherapy for cervical cancer. The agreement is lower for IR-CTV than HR-CTV. The individual characteristics of each case and different expertise levels of the ROs may have caused the differences. Despite the good concordance for delineation, dosimetric consequences can still be clinically significant.

Revisiting the Radical Radiotherapy-Radiochemotherapy Results in Anal Canal Cancers: (TROD Gastrointestinal Group Study 02-005).

BACKGROUND AND AIM: This study aimed to determine treatment outcomes and factors affecting prognosis in patients diagnosed with anal canal cancer who received radical radiotherapy (RT) or radiotherapy combined with chemotherapy (CT-RT) in radiation oncology centers in Turkey and compare the results with literature. MATERIAL AND METHOD: The study included 193 patients with anal canal cancer reported between 1995 and 2019, of which 162 had complete data. The study was conducted in 11 radiation oncology centers, and a joint database was shared among them. Patients received radiotherapy doses of 45 Gy to 60 Gy. Data analysis was done using SPSS for Windows version 20. RESULTS: Median follow-up was 48.51 months (2-214). All patients received radiotherapy, and 140 (86.4%) received concurrent chemotherapy. Radiotherapy doses of 50.4 Gy to 60 Gy were administered to 74 patients (45.7%) using 2-dimensional-3-dimensional (2D-3D) conformal therapy and 70 patients (43.2%) using intensity modulated radiotherapy technique (IMRT). Acute phase hematologic toxicity was observed in 62 patients (38.3%), and nonhematologic toxicity in 123 patients (75.9%). The 5-year overall survival (OS) rate was 75.1% and disease-specific survival (DSS) rate was 76.4%. OS without colostomy was achieved in 79,8 % at 5 years, and complete response in 112 patients (69.1%). OS rate was significantly higher in 142 patients with positive response (P < .000) and 112 with complete response (P < .000). Anemia (P < .002), local progression, and systemic progression (P < .000) resulted in lower OS (P < .002). In univariate analysis, factors affecting OS rate were: gender, age, stage, lymph node status, T stage, RT treatment duration, and treatment planning with PET fusion, which were found to be statistically significant. Completing radiotherapy in less than 45 days, concurrent chemotherapy, and continued administration of mitomycin and 5 FU as chemotherapy had a significant positive effect on overall survival. OS rate was higher in patients receiving RT dose of 58 Gy or less and undergoing IMRT planning in radiotherapy. IMRT was associated with lower acute and late side effects. CONCLUSION: Radiochemotherapy is the primary treatment for anal canal cancer and advanced radiotherapy techniques may increase survival by reducing side effects and improving treatment continuation. Higher treatment doses require further investigation. The efficacy of treatment can be improved by including patients treated with modern radiotherapy techniques in multicenter prospective studies using new and more effective chemotherapy and immunotherapy agents.

Automatic contouring using deformable image registration for tandem-ring or tandem-ovoid brachytherapy.

PURPOSE: To investigate the effectiveness of deformable image registration (DIR)-based automatic contouring for tandem-ring (T-R) or tandem-ovoid (T-O) 3-dimensional computed tomography (CT)-based image-guided brachytherapy (IGBT). MATERIAL AND METHODS: CT images of 28 patients with intact cervical cancer were retrospectively analyzed. Selected group had T-R or T-O insertion for IGBT. Hybrid DIR was performed between first fraction CT and subsequent CTs for IGBT. First IGBT CT images were reference images. All DIRs were performed based on these first IGBT CT scans. Contour similarities between manual and automated segmentations were evaluated with dice similarity coefficient (DSC) score. Mean volumes of the structures were delineated manually and automatically compared. Finally, dosimetric comparisons were performed in order to obtain how contour differences affect the doses to target and organs at risk (OARs). RESULTS: In general, mean volumes of the automatic contours were larger than manual contours for both T-R and T-O insertions. However, the difference in volume was statistically significant for the small bowel only (p < 0.05 and p < 0.01 for T-R and T-O, respectively). The DSC scores were small for the small bowel and the sigmoid in both applicator sets. When the two different applicator sets were compared, the performance of DIR-based contour propagation for the rectum was worse in T-O compared to T-R application. Dosimetric comparisons showed that volume differences between the manual and propagated contours did not affect dose-volume parameters. The treatment plans based on manually contoured targets also well-covered DIR contours. The average time for DIR was 2.0 ±0.1 minutes per fraction compared to 14.0 ±0.4 minutes in manual contouring (p < 0.001). CONCLUSIONS: DIR-based automatic contouring of the structures seems successful for both the T-R and T-O applications in cervical IGBT. DIR significantly decreased the time for contouring. Our results indicate that automatic contouring in IGBT is safe and time-saving.

Results of concurrent radiotherapy and immunotherapy in recurrent and metastatic head and neck cancer: A single-center experience.

OBJECTIVES: In metastatic and recurrent head and neck cancer (M/R HN-SCC), the median survival is less than a year and locoregional recurrence is the main cause of death. Our aim was to evaluate the results of concurrent stereotactic body radiotherapy (SBRT) and immunotherapy (ICI) in these patients. MATERIALS AND METHODS: Fifteen patients diagnosed with M/R HN-SCC were evaluated retrospectively. All patients received SBRT (3x8 Gy) to all recurrent and metastatic foci with concurrent ICI. RESULTS: Six months overall survival (OS) rates and progression-free survival (PFS) rates were 93% and 86%, respectively. Local control (LC) rate in the site of SBRT was 96%. Higher survival and LC rates were achieved with lower doses of radiotherapy with the synergistic effect of SBRT and ICI. CONCLUSION: Concurrent ICI and SBRT was feasible with excellent LC.

Every other day stereotactic radiation therapy for the treatment of uveal melanoma decreases toxicity.

BACKGROUND AND PURPOSE: To report the long-term results of stereotactic radiosurgery and fractionated stereotactic radiation therapy (SRS/FSRT) in patients with uveal melanoma (UM). MATERIALS AND METHODS: We retrospectively evaluated the results of patients treated between 2007 and 2019. The primary endpoints were local control (LC), local recurrence-free survival (LRFS), enucleation-free survival (EFS) and treatment toxicity. RESULTS: 443 patients with 445 UMs were treated via CyberKnife®. According to the COMS classification, 70% of the tumors were small/medium and 30% were large. Median total RT dose was 54 Gy, median BED10 was 151 Gy. After a median 74-months follow-up, SRS/FSRT yielded an 83% overall LC rate. The 5- and 10-year LRFS rate was 74% and 56%, respectively. Patient age and the COMS size were prognostic for all survival endpoints. An increased SRS/FSRT dose was associated with higher LRFS and EFS rates. SRS/FSRT-related toxicity was observed in 49% of the eyes. Median visual acuity (VA) significantly deteriorated after SRS/FSRT in 76% of the treated eyes. The overall eye preservation rate was 62%, and the 5- and 10-year EFS rate was 64% and 36%, respectively. The delivery of FSRT every other day resulted in a significantly lower rate of toxicity and enucleation compared to FSRT on consecutive days. CONCLUSION: A total dose of ≥45 Gy and BED10Gy ≥ 112.5 SRS/FSRT is associated with a higher LC rate in patients with UM. Despite the favorable outcomes, treatment toxicity is the major limitation of this treatment. Toxicity and enucleation can be minimized by treating the eye every other day.

Parotid gland stem cells: Mini yet mighty.

BACKGROUND: Our aim was to evaluate the correlation between the radiation doses to parotid gland (PG) stem cells and xerostomia. METHODS: Patients diagnosed with head and neck cancer (HNC) were retrospectively evaluated, and xerostomia inventory (XI) was applied to these patients. PG stem cells were delineated on the treatment planning CT, and the mean doses to the PG stem cells calculated. RESULTS: The total test score and mean doses to bilateral PGs were significantly correlated (r = .34, P = .001), and the mean doses to bilateral PG stem cell niches were significantly correlated with the total test score (r = .32, P = .002). CONCLUSIONS: In this study, we found that the mean dose to PG stem cells can predict dry mouth as much as the mean dose to the PG.

Adjuvant vaginal cuff brachytherapy: dosimetric comparison of conventional versus 3-dimensional planning in endometrial cancer.

PURPOSE: To evaluate dosimetric differences between point-based 2-dimensional (2D) vaginal brachytherapy (VBT) treatment planning technique and volume-based 3-dimensional (3D) VBT method for endometrial cancer (EC). MATERIAL AND METHODS: Ten patients with uterine-confined EC treated with VBT were included in this study. All patients received 27.5 Gy in 5 fractions. Three different treatment plans were performed for each patient: plan A for dose prescribed to the entire vaginal wall thickness delineated via computed tomography guidance, plan B for dose prescribed to the vaginal mucosa/cylinder surface, and plan C for dose prescribed to 5 mm beyond the vaginal mucosa/cylinder surface. Dose-volume histograms (DVH) of treatment volumes and organs at risk (OARs) were evaluated and compared. RESULTS: DVH analysis of target volume doses (D100, D95, and D90) showed a significant difference between plan A and plan B (p = 0.005), and plan B was found lower. D100 for plan C was significantly higher than plan A (p = 0.009), but for D95 and D90, no statistically significant difference was found (p = 0.028 and p = 0.028, respectively). In terms of OARs doses, including vagina, rectum, bladder, and sigmoid, D2cm3 doses were significantly higher in plan A than plan B (p = 0.009, p = 0.009, p = 0.005, and p = 0.005, respectively). All these doses were also significantly lower than in plan C (p = 0.005, p = 0.012, and p = 0.013, respectively), except for sigmoid (p = 0.155). CONCLUSIONS: In this dosimetric analysis, we have shown that the volume-based 3D VBT technique provides the ability to balance the target dose against the sparing of OARs. Therefore, in the new modern 3D treatment era, instead of normalization of the dose to standard reference points, customized 3D volume-based VBT planning should be recommended.

A multi-institutional analysis of sequential versus 'sandwich' adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma.

OBJECTIVE: To analyze the outcomes of sequential or sandwich chemotherapy (ChT) and radiotherapy (RT) in patients with node-positive endometrial cancer (EC). METHODS: Data from 4 centers were collected retrospectively for 179 patients with stage IIIC EC treated with postoperative RT and ChT (paclitaxel and carboplatin). Patients were either treated with 6 cycles of ChT followed by RT (sequential arm; 96 patients) or with 3 cycles of ChT, RT, and an additional 3 cycles of ChT (sandwich arm; 83 patients). Prognostic factors affecting overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: The 5-year OS and PFS rates were 64% and 59%, respectively, with a median follow-up of 41 months (range, 5-167 months). The 5-year OS rates were significantly higher in the sandwich than sequential arms (74% vs. 56%; p=0.03) and the difference for 5-year PFS rates was nearly significant (65% vs. 54%; p=0.05). In univariate analysis, treatment strategy, age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology, rate of myometrial invasion, and grade were prognostic factors for OS and PFS. In multivariate analysis, non-endometrioid histology, advanced FIGO stage, and adjuvant sequential ChT and RT were negative predictors for OS, whereas only non-endometrioid histology was a prognostic factor for PFS. CONCLUSION: Postoperative adjuvant ChT and RT for stage IIIC EC patients, either given sequentially or sandwiched, offers excellent clinical efficacy and acceptably low toxicity. Our data support the superiority of the sandwich regimen compared to the sequential strategy in stage IIIC EC patients for OS.