The effect of dose-escalation radiotherapy with simultaneous-integrated-boost on the use of short-term androgen deprivation therapy in patients with intermediate risk prostate cancer.

PURPOSE: To compare the biochemical failure (FFBF) and prostate cancer specific survival (PCSS) rates of patients with intermediate-risk prostate cancer (IR-PC) who were treated with 6 months of androgen deprivation therapy (ADT) with 78 Gy to the prostate, those treated with ADT and focal boost (FB) of 86 Gy to intraprostatic lesion (IPL) using the simultaneous-integrated boost (SIB) technique, and those treated with SIB alone. MATERIALS AND METHODS: A retrospective analysis of 320 IR-PC patients treated between January 2012 and April 2021 was performed. Patients were divided into three groups based on their treatment arm: 78 + ADT (109 patients, 34.1%), 78/86 (102 patients, 31.8%), and 78/86 + ADT. Univariable and multivariable analyses were used to determine prognostic factors for FFBF and PCSS. RESULTS: Median follow-up was 8.8 years. The 8-year FFBF and PCSS rates were 88.6% and 99.0%. Patients who received ADT had significantly higher pretreatment PSA levels and clinical tumor stage. Disease progression occurred in 45 patients (7.3%) at a median of 41.9 months after definitive radiotherapy (RT). Younger age, positive core biopsy (PCB) ≥ 50%, and the absence of ADT were all independent predictors of poor FFBF in multivariate analysis, whereas patients with PCB < 50% who were also given ADT had better PCSS. Patients treated with 78/86 Gy alone had worse FFBF than those treated with 78 Gy and ADT (Hazard ratio [HR] = 3.39 [95% CI = 1.46-7.88]; p = 0.005), as well as than those treated with 78/86 Gy and ADT (HR = 3.21 [95% CI = 1.23-6.46]; p = 0.009). However, FB to IPL has no effect on PCSS in multivariable analysis. There was no significant difference between treatment groups in terms of acute and late Grade ≥2 genitourinary or gastrointestinal toxicity. CONCLUSIONS: Our findings demonstrated that patients who received 78/86 alone did worse than patients who received ADT with either 78 or 78/86 Gy. However, because IR-PC patients are so diverse, additional prospective trials are needed to validate our findings.

Long-term analysis of hematological parameters as predictors of recurrence patterns and treatment outcomes in cervical cancer patients undergoing definitive chemoradiotherapy.

PURPOSE: This study sought to determine the predictive and prognostic value of clinicopathological parameters and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin (Hgb) level in predicting recurrence patterns and locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) in cervical cancer patients receiving definitive chemoradiotherapy (ChRT). METHODS: This study included 261 cervical cancer patients treated with ChRT. The primary endpoints were the predictors of local recurrence (LR) and distant metastasis (DM), whereas the secondary endpoints were LRFS and DMFS. The association of survival with potential prognostic factors was analyzed using Cox regression analysis, and the predictors of LR and DM were identified using logistic regression analysis. RESULTS: The median follow-up time was 10.9 years. Recurrences occurred in 132 patients (50.6%) within a median of 11.2 months after definitive ChRT. NLR and PLR values were significantly higher in patients with LR and DM than in those without, with no significant differences in Hgb levels in patients with or without LR and DM. In the multivariable logistic regression analysis, lymph node metastasis, elevated NLR, and low Hgb level were significantly correlated with LR and DM. In the multivariable analysis, large tumor size, presence of lymph node metastasis, and elevated NLR were the independent predictors for poor LRFS and DMFS, and Hgb level was an additional prognostic factor for DMFS. CONCLUSION: Hematological markers, particularly NLR and Hgb, may serve as cost-effective and readily accessible indicators for predicting recurrence and survival in cervical cancer patients, contributing to their practical use in routine assessments.

Multi-institutional analysis of extracranial oligometastatic colorectal cancer patients treated with stereotactic body radiation therapy: TROD 02-008 study.

PURPOSE: To investigate the treatment outcomes of extracranial oligometastatic colorectal cancer (CRC) patients treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: The clinical data of 388 extra-cranial oligometastatic CRC (≤ 5 lesions) patients and 463 lesions treated with SBRT at 19 cancer institutions were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local control (LC) were assessed in uni- and multivariable analyses. RESULTS: The median age was 62 years (range, 29-92 years). The majority of the patients (90.5%) received surgery and systemic treatment for their primary tumor, had ≤ 2 metastasis (83.3%), had single organ involvement (90.3%), and staged using flouro-deoxyglucose positron emission tomography (FDG-PET/CT) (76%). The median fraction and total radiation doses were 10 Gy (range: 6-34 Gy) and 50 Gy (range: 8-64 Gy), respectively, delivered in a median of 4 fractions (range: 1-8). The median follow-up time for the entire cohort was 30.7 months (interquartile range: 27.0-34.3 months). The 3­year OS, PFS, and LC rates were 64.0%, 42.3%, and 72.7%, respectively. The 3­year LC rate was significantly higher in patients receiving BED10 ≥ 100 Gy than those receiving BED10 < 100 Gy (76.0% vs. 67.3%; p = 0.04). The 3­year PFS and OS rates were higher in patients receiving BED10 ≥ 100 Gy than those receiving BED10 < 100 Gy (33.2% vs. 25.2%; p = 0.03; 53.7% vs.  44.8%; p = 0.02). Single metastasis and complete response after SBRT were independent prognostic factors for survival in multivariable analysis. CONCLUSIONS: In this multi-center study, we demonstrated that SBRT is an effective treatment option of metastatic lesions in oligometastatic CRC patients by providing promising LC rates. Higher SBRT doses beyond BED10 ≥ 100 Gy were associated with improved LC and survival. LC of treated lesion and lower tumor burden after SBRT were associated with better outcomes.

Stereotactic body radiotherapy and tyrosine kinase inhibitors in patients with oligometastatic renal cell carcinoma: a multi-institutional study.

PURPOSE: Few studies have determined the viability of stereotactic body radiotherapy (SBRT) and tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell carcinoma (mRCC). We examined the results of RCC patients who had five or fewer lesions and were treated with TKI and SBRT. METHODS: The clinical data of 42 patients with 96 metastases treated between 2011 and 2020 were retrospectively evaluated. The prognostic factors predicting overall survival (OS) and progression-free survival (PFS) were assessed in uni- and multivariable analyses. RESULTS: Median follow-up and time between TKI therapy and SBRT were 62.3 and 3.7 months, respectively. The 2­year OS and PFS rates were 58.0% and 51.3%, respectively, and 2­year local control rate was 94.1% per SBRT-treated lesion. In univariable analysis, the time between TKI therapy and SBRT and treatment response were significant prognostic factors for OS and PFS. In multivariable analysis, a time between TKI therapy and SBRT of less than 3 months and complete response were significant predictors of better OS and PFS. Only 12 patients (28.6%) had a systemic treatment change at a median of 18.2 months after SBRT, mostly in patients with a non-complete treatment response after this therapy. Two patients (4.8%) experienced grade III toxicity, and all side effects observed during metastasis-directed therapy subsided over time. CONCLUSION: We demonstrated that SBRT in combination with TKIs is an effective and safe treatment option for RCC patients with ≤ 5 metastases. However, distant metastasis was observed in 60% of the patients, indicating that distant disease control still has room for improvement.

The significance of metabolic response to neoadjuvant androgen deprivation therapy detected with [68Ga]Ga-PSMA-11-PET/CT in high-risk prostate cancer patients treated with definitive radiotherapy.

PURPOSE: We examined the prognostic significance of early changes in primary tumor SUV measured with Gallium-68-labeled prostate-specific membrane antigen positron emission tomography ([68Ga]Ga-PSMA-11-PET/CT) and serum PSA values after neoadjuvant androgen deprivation treatment (nADT) in high-risk prostate cancer (PCa) patients treated with definitive radiotherapy (RT). METHODS: The clinical data and SUV parameters of 71 PCa patients were reviewed retrospectively. The serum PSA and primary tumor SUV values were calculated before and after the start of ADT. Using univariable and multivariable analyses, the prognostic factors predicting biochemical disease free survival (bDFS) and prostate cancer specific survival (PCSS) were investigated. In addition, logistic regression analysis was used to identify predictors of biochemical failure (BF). RESULTS: All but one patient responded with a 98.8% reduction in serum PSA (21.8 ng/mL vs. 0.3 ng/mL; p < 0.001), and 64 patients (91.1%) had a median 66.6% decrease in primary tumor SUV after ADT (13.2 vs. 4.8, p < 0.001). The primary tumor SUV response rate was significantly higher in patients with Gleason score (GS) of 7 than in patients with GS > 7 (59.5% vs. 40.5%; p = 0.04), and it was significantly lower in patients with inadequate treatment response than in those with complete (CR) or partial response (PR) (1.1% vs. 66.1%; p < 0.001). There was a strong and significant correlation (Spearman = 0.41, p < 0.001) and a high concordance (91.5%) between PSA response and SUV response after ADT. With a median follow-up time of 76.1 months, the 5-year bDFS and PCSS rates were 77.2% and 92.2%, respectively. Nineteen patients (26.7%) patients had recurrence at a median of 44.6 months after the completion of RT. In multivariate analysis, lymph node metastasis, GS greater than 7, and SD/PD after nADT were independent predictors of worse bDFS. However, no significant factor for PCSS was identified. In the multivariable logistic regression analysis, advanced age, GS of > 7 disease, lymph node metastasis, and SD or PD after nADT were independent predictors of BF. CONCLUSION: These results imply that the metabolic response measured with [68Ga]Ga-PSMA-11-PET/CT after nADT could be used to predict progression in high-risk PCa patients treated with definitive RT.

Prognostic significance of albumin and globulin levels in cervical cancer patients treated with chemoradiotherapy.

OBJECTIVE: Albumin-globulin ratio or albumin-globulin score predict survival in many cancers, but there are few data on cervical cancer patients. This study examined whether pre-treatment albumin and globulin levels, as well as the albumin-globulin ratio and albumin-globulin score, can predict treatment outcomes in cervical cancer patients undergoing definitive chemoradiotherapy. METHODS: A retrospective analysis of cervical cancer patients treated between January 2006 and July 2014 was performed. Receiver operating characteristic curves for serum albumin and globulin levels, as well as albumin-globulin ratio values, were generated in order to determine the cut-off values for these parameters and to predict their sensitivity and specificity for predicting recurrence and survival. Univariate and multivariate analyses were used to identify prognostic factors for overall survival and progression-free survival. RESULTS: A total of 139 patients were included. The median follow-up time was 11.5 years. The 5- and 10-year overall survival rates were 54.7% and 39.3%, while the 5- and 10-year progression-free survival rates were 48.9% and 36.4%, respectively. The optimal cut-off points were 3.79 g/dL for albumin, 3.27 g/dL for globulin, and 1.56 for albumin-globulin ratio. In the univariate analysis, significant prognostic factors for overall survival and progression-free survival were albumin-globulin ratio, albumin-globulin score, patient age, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, lymph node metastasis, and treatment response. Older age, advanced stage, low albumin-globulin ratio, albumin-globulin score of 2, and inadequate treatment response had poor overall survival and progression-free survival in multivariable analysis. However, serum albumin and globulin levels were not found to be a significantly predictive factor for survival. There was a significant correlation between albumin levels, globulin levels, tumor size, stage, lymph node metastasis, and treatment response. CONCLUSIONS: Pre-treatment albumin-globulin ratio and albumin-globulin score are useful prognostic factors in patients with cervical squamous cell cancer treated with definitive chemoradiotherapy, and may be suitable biomarkers for predicting treatment outcomes.

Multi-institutional study on the role of post-operative radiotherapy in elderly patients with endometrial cancer.

OBJECTIVE: To investigate the prognostic factors for survival and toxicities in elderly (≥65 years) patients with endometrial cancer who underwent post-operative radiotherapy. Additionally, to compare the treatment outcomes between the older elderly (≥75 years) and younger elderly (65-74 years) patients. METHODS: Medical records of patients with enometrial cancer treated between January 1998 and July 2019 were reviewed. Patients with stage IA to IIIC2, all histology subtypes, and any grade were included. All patients underwent total abdominal hysterectomy and received adjuvant radiotherapy with or without chemotherapy. All but 67 (8.4%) of 801 patients had lymph node dissection. Clinicopathological factors and treatment strategies were compared between the two age groups. The prognostic factors for overall survival and progression-free survival were investigated. RESULTS: A total of 801 patients with enometrial cancer, 627 patients (78.3%) younger elderly and 174 patients (21.7%) in the older elderly group were included. Median follow-up was 74.3 months (range 0.4-224.6). The older elderly patients had significantly higher rates of grade 3 tumors (51.7% vs 40.8%; p=0.04), cervical glandular involvement (21.8% vs 14.0%; p=0.03), and cervical stromal invasion (34.5% vs 27.9%; p=0.04) than the younger elderly patients. The rates of lymph node dissection (p=0.2), radiotherapy modalities (p=0.92), and systemic chemotherapy (p=0.2) did not differ between the two groups. The 5-year locoregional control and distant metastasis rates were 88.3% and 23.8%, respectively. The 5-year cause-specific survival and progression-free survival rates for younger and older elderly patients, were 79.8% vs 74.3% (p=0.04) and 67.5% vs 57.8% (p<0.001), respectively. In multivariate analysis, larger tumor size, non-endometrioid histology, cervical stromal involvement, and stage III disease were associated with poor cause-specific survival and progression-free survival. Age was an independent predictor of worse progression-free survival, but not of cause-specific survival. There was no significant difference in acute and late gastrointestinal and genitourinary toxicities between age groups. CONCLUSIONS: Post-operative radiotherapy for elderly patients with endometrial cancer is effective and well tolerated. Advanced age should not preclude appropriate treatment, especially in those with adequate quality of life, life expectancy, and functional status.

Treatment Outcomes of Stereotactic Body Radiotherapy in Patients with Synchronous and Metachronous Oligometastatic Renal Cell Carcinoma.

INTRODUCTION: The aim of this study was to investigate the clinical outcomes of metastasis-directed therapy (MDT) using stereotactic body radiotherapy (SBRT) in patients with synchronous or metachronous oligometastatic renal cell carcinoma (RCC). METHODS: The clinical data of 87 patients with 138 lesions who received MDT between February 2008 and January 2019 were retrospectively analyzed. All patients had ≤5 metastasis at diagnosis (synchronous) or during progression (metachronous) and were treated with SBRT for their metastasis. The primary endpoints were local control (LC) and progression-free survival (PFS). The secondary endpoint was overall survival (OS). RESULTS: Median follow-up was 20.4 months for entire cohort and 27.2 months for survivors. Synchronous oligometastatic disease was observed in 35 patients (40.2%), and 52 patients (59.8%) had metachronous disease. Seventy-two patients (82.8%) received systemic treatment synchronously or after MDT, while 15 patients (17.2%) did not receive any systemic treatment. The 1- and 2-year OS rates were 79.4% and 58.1%, respectively, and the 1- and 2-year PFS rates were 58.6% and 15.1%, respectively. The 1- and 2-year LC rates per lesion were 96.6% and 91.4%, respectively. There were no significant differences in survival between patients with synchronous oligometastasis and those with metachronous oligometastasis. All disease progressions were observed at a median time of 31.6 months (range: 1.9-196.9 months) after the completion of SBRT. Patients with solitary oligometastasis had significantly better OS compared to patients with >1 metastasis (p = 0.04). No patients experienced grade 3 or higher acute or late toxicities. CONCLUSION: SBRT is a successful treatment for oligometastatic RCC patients due to its excellent LC and minimal toxicity profile. There were no statistically significant survival differences between patients with synchronous and metachronous oligometastasis. Patients with solitary oligometastasis outlived their counterparts.

Comparison of helical and TomoDirect techniques with simultaneous integrated boost in early breast cancer patients.

Background: The aim of the study was to perform dosimetric comparisons of helical (H) and TomoDirect (TD) plans for whole-breast irradiation (WBI) with simultaneous integrated boost (SIB) in early-stage breast cancer patients undergoing breast conserving surgery. Materials and methods: Fifty patients, 25 with left-side and 25 with right-side tumors, were determined for a treatment planning system for a total dose of 50.4Gy in 1.8Gy per fraction to WBI, with a SIB of 2.3Gy per fraction delivered to the tumor bed. The planning target volume (PTV) doses and the conformity (CI) and homogeneity indices (HI) for PTVbreast and PTVboost, as well as organ-at-risk (OAR) doses and treatment times, were compared between the H and TD plans. Results: All plans met the PTV coverage criteria for the H plan, except for mean V107 of PTVbreast for TD plan. The H plan yielded better homogeneity and conformity of dose distribution compared to the TD plan. The ipsilateral mean lung doses were not significantly different between the two plans. The TD plans is advantageous for mean doses to the heart, contralateral breast and lung, spinal cord, and esophagus than the H plans. In both the H and TD plans, the right-sided breast patients had lower heart dose parameters than the left-sided breast patients. The TD plan is superior to the H plan in sparing the contralateral breast and lung by decreasing low-dose volumes. Conclusions: While the OAR dose advantages of TD are appealing, shorter treatment times or improved dose homogeneity and conformity for target volume may be advantageous for H plan.

Significance of liver metastasis volume in breast cancer patients treated with stereotactic body radiotherapy.

PURPOSE: This study analyzed the impact of liver metastasis (LM) volume on treatment outcomes in breast cancer (BC) patients treated with stereotactic body radiotherapy (SBRT). METHODS: This single-institution retrospective analysis included 40 oligometastatic (≤ 5 metastases) BC patients with 58 liver metastases treated with SBRT between April 2013 and March 2021. The prognostic factors for local control (LC), overall survival (OS), and progression-free survival (PFS) rates were assessed. RESULTS: Median follow-up time was 28.1 months. Isolated and solitary LM were seen in 26 (65%) and 24 (60%) patients, respectively. Median time to disease recurrence was 10.7 months post liver SBRT. The 2­year OS, PFS, and LC rates were 71.4%, 27.5%, and 86.8%, respectively. In univariate analysis, patients with a gross tumor volume (GTV) of ≤ 6 cc and a planning target volume (PTV) of ≤ 38 cc demonstrated a significantly better median OS than those with GTV > 6 cc and PTV > 38 cc. In multivariate analysis, the predictive factors for worse OS were GTV > 6 cc (HR = 3.07 [95% CI, 1.14-8.22; p = 0.03]) and PTV > 38 cc (HR = 5.91 [95% CI, 1.92-18.21; p = 0.002]). No significant factor for PFS was found. Only 2 patients experienced rib fracture at 4 and 6 months post treatment, and 1 patient had a grade II duodenal ulcer. CONCLUSION: Liver SBRT is an effective and safe treatment option for oligometastatic BC patients with excellent LC, promising survival, and limited toxicity. Patients with smaller tumors displayed better OS than their counterparts, validating the effectiveness of a local treatment for this group.

Bone-only oligometastatic renal cell carcinoma patients treated with stereotactic body radiotherapy: a multi-institutional study.

PURPOSE: This study aimed to analyze the prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in patients with bone-only metastatic renal cell carcinoma (RCC) who have five or fewer lesions treated with stereotactic body radiotherapy (SBRT). METHODS: The clinical data of 54 patients with 70 bone metastases undergoing SBRT treated between 2013 and 2020 with a dose of at least 5 Gy per fraction and a biologically effective dose (BED) of at least 90 Gy were retrospectively evaluated. RESULTS: The majority of lesions were located in the spine (57.4%) and had only one metastasis (64.8%). After a median follow-up of 22.4 months, the 1­ and 2­year OS rates were 84.6% and 67.3%, respectively, and median OS was 43.1 months. The 1­ and 2­year PFS rates and median PFS were 63.0%, 38.9%, and 15.3 months, respectively. In SBRT-treated lesions, the 1­year local control (LC) rate was 94.9%. Age, metastasis localization, and number of fractions of SBRT were significant prognostic factors for OS in univariate analysis. In multivariate analysis, patients with spinal metastasis had better OS compared to their counterparts, and patients who received single-fraction SBRT had better PFS than those who did not. No patient experienced acute or late toxicities of grade 3 or greater. CONCLUSION: Despite excellent LC at the oligometastatic site treated with SBRT, disease progression was observed in nearly half of patients 13 months after metastasis-directed local therapy, particularly as distant disease progression other than the treated lesion, necessitating an effective systemic treatment to improve treatment outcomes.

Uterine papillary serous and clear cell carcinomas: Comparison of characteristics and clinical outcomes.

INTRODUCTION: To assess the rate of disease control and survival after adjuvant treatment in patients with uterine papillary serous (PSC) and clear cell carcinoma (CCC) and compare the results between these two subtypes. METHODS: The medical charts of 199 patients with de novo uterine PSC or CCC who underwent radiotherapy (RT) following surgery between 2001 and 2019 in three radiation oncology departments were retrospectively evaluated. Adjuvant treatment was decided by a multidisciplinary tumor board. All patients were planned to undergo adjuvant 4-6 cycles of chemotherapy with external beam RT (EBRT) and/or vaginal brachytherapy (VBT). RESULTS: Median age was 63 years for all, 64 years for PSC, and 59 years for CCC, respectively. Complete surgical staging was applied in 98% of patients. Histopathologic subtype was PSC in 142 (71%) and pure CCC in 57 (29%) patients, respectively. FIGO stage was I in 107 (54%), II in 35 (18%), and III in 57 (28%) patients, respectively. Lympho-vascular space invasion and positive peritoneal cytology (PPC) were present in 42% and 10% of patients, respectively. All patients but 23 (12%) underwent adjuvant chemotherapy. Median follow-up was 49.5 months for all patients, 43.9 months for patients with PSC, and 90.4 months for patients with CCC, respectively. During follow-up, 20 (10%) patients developed pelvic recurrence (PR) and 37 (19%) developed distant metastasis (DM). PSC subtype increased the PR and DM rates, although the latter not statistically significant. The 5-year overall survival and disease-free survival rate was 73% and 69% for all patients, 71% and 66% for patients with PSC, and 77% and 75% for patients with CCC, respectively. The difference was more prominent in patients with stage ≥ IB disease. In multivariate analysis, advanced age and PPC significantly decreased all survival rates. CONCLUSION: PSC has a worse prognosis than CCC with regard to pelvic and distant recurrence with a trend for decreased survival rates. Therefore, a more aggressive therapy is needed for patients with uterine PSC, particularly in patients with stage ≥ IB disease.

The impact of serum albumin-to-alkaline phosphatase ratio in cervical cancer patients treated with definitive chemoradiotherapy.

We retrospectively analysed the prognostic significance of serum albumin, alkaline phosphatase (ALP) and albumin to ALP ratio (AAPR) and other prognostic factors affecting the overall survival (OS) and progression-free survival (PFS) in 200 cervical cancer patients treated with definitive chemoradiotherapy (CRT). The prognostic factors for OS and DFS, in addition to the predictive factors of albumin, ALP and AAPR, were investigated. Older age, lymph node metastasis, non-complete response (CR) to treatment and low serum albumin levels emerged as predictors of poor OS and PFS in multivariate analysis. However, with a cut-off value of 0.51, AAPR was not a significant prognostic factor of survival in multivariable analysis. There were no significant differences in clinicopathological factors between patients with low and high AAPR, except for lymph node metastasis, where lymph node metastasis rate was significantly higher in patients with a low AAPR compared to those with a high AAPR. Patients with CR had a significantly higher serum albumin level and AAPR compared to patients without CR. The pre-treatment serum albumin level was independent predictive for survival; therefore, it could be a suitable biomarker to guide systemic therapy and predict patient outcomes. Impact StatementWhat is already known on this subject? Two major determinants of tumour progression are nutritional status and inflammation. The albumin-to-alkaline phosphatase ratio (AAPR), which was originally proposed as a marker for nutritional status and immune response, was recently discovered to be a prognostic factor for various cancer types. However, its utility in the treatment of cervical cancer has not been established.What do the results of this study add? Low serum albumin levels were associated with a significantly shorter OS and PFS in cervical cancer patients treated definitively with CRT. AAPR, on the other hand, was not a significant prognostic factor for survival with a cut-off value of 0.51. Regional lymph node metastasis was significantly more common in patients with a low AAPR than in those with a high AAPR.What are the implications of these findings for clinical practice and/or further research? Patients with multiple clinicopathological risk factors and low serum albumin levels had an increased risk of disease recurrence and a poorer prognosis, highlighting the importance of additional adjuvant treatment strategies in these patients. Due to the preliminary nature of our findings, additional research is required to corroborate them.

Clinical parameters and nomograms for predicting lymph node metastasis detected with 68 Ga-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy.

BACKGROUND: Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naïve nonmetastatic prostate cancer (PC) patients. MATERIALS AND METHODS: The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves. RESULTS: A total of 288 lymph node metastases were identified in 121 patients (27.3%) using 68 Ga-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS ≥7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF. CONCLUSION: The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from 68 Ga-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, 68 Ga-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning.

Stereotactic radiotherapy to oligoprogressive lesions detected with 68Ga-PSMA-PET/CT in castration-resistant prostate cancer patients.

PURPOSE: We assessed the outcomes of stereotactic body radiotherapy (SBRT) to treat oligoprogressive castration-resistant prostate cancer (CRPC) patients with ≤5 lesions using gallium prostate-specific membrane antigen-positron emission tomography (68Ga-PSMA-PET/CT). METHODS: The clinical data of 67 CRPC patients with 133 lesions treated with 68Ga-PSMA-PET/CT-based SBRT were retrospectively analyzed. All of the patients had oligoprogressive disease during androgen-deprivation therapy (ADT). The prognostic factors for overall- (OS) and progression-free survival (PFS) and the predictive factors for switching to next-line systemic treatment (NEST) and NEST-free survival (NEST-FS) were analyzed. RESULTS: With a median follow-up of 17.5 months, the 2-year overall survival (OS) and PFS rates were 86.9% and 34.4%, respectively. The PSA response was observed in 49 patients (73.1%). Progression was observed in 37 patients (55.2%) at a median of 11.0 months following SBRT. A total of 45 patients (67.2%) remained on ADT after SBRT, and 22 patients (32.8%) had a NEST change at a median of 16.4 months after metastasis-directed treatment (MDT). Patients with a NEST change had higher post-SBRT PSA values and fewer PSA nadirs after MDT than their counterparts. In multivariate analysis, higher pre-SBRT PSA values were the only significant predictor for worse OS and NEST-FS, and no significant factor was found for PFS. No serious acute or late toxicities were observed. CONCLUSION: This study demonstrated the feasibility of MDT using SBRT to treat oligoprogressive lesions by 68Ga-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST.

Outcome and safety analysis of endometrial cancer patients treated with postoperative 3D-conformal radiotherapy or intensity modulated radiotherapy.

BACKGROUND: We sought to analyze the toxicity rates and the treatment outcomes in endometrial cancer (EC) patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). MATERIAL AND METHODS: The clinical data of 646 EC patients treated with postoperative adjuvant 3DCRT (265 patients, 41%) or with IMRT (381 patients, 59%) between April 2007 and August 2019 were retrospectively analyzed. The primary endpoints were treatment-related acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. The secondary endpoints were LC and overall survival (OS) and disease-free survival (DFS). RESULTS: Median follow-up time was 37 months. The rates for acute GI and GU toxicities of any grade for the entire group were 55.6% and 46.8%, respectively. Acute grade ≥2 GI toxicity was significantly less in patients treated with IMRT compared to those treated with 3DCRT (11.0% vs. 19.2%, p=.004). However, no significant difference grade ≥2 GU toxicities was observed between the 3DCRT and IMRT groups (15.1% vs. 11.0%; p=.15). Acute grade ≥2 GI and GU toxicities were higher in patients receiving systemic chemotherapy, while paraaortic field irradiation increases only the risk of acute grade ≥2 GI toxicity. Estimated 3-year late grade ≥3 GI toxicity rates in the 3DCRT- and IMRT-treated patients were 4.6% and 1.9% (p= .03), respectively. The patients treated with adjuvant ChT had higher rates of late serious GI complications than those without adjuvant ChT. No significant difference in terms of survival and disease control was observed between the 3DCRT and IMRT treatment groups. No significant factor for LC was found in the multivariate analysis. CONCLUSION: In this multicentric study involving one of largest patient population, we found that IMRT-treated EC patients showed comparable clinical outcomes but with a lower incidence of GI toxicities compared with those treated with 3DCRT.

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.

Role of vaginal brachytherapy boost following adjuvant external beam radiotherapy in cervical cancer: Turkish Society for Radiation Oncology Gynecologic Group Study (TROD 04-002).

OBJECTIVE: There are a limited number of studies supporting vaginal brachytherapy boost to external beam radiotherapy in the adjuvant treatment of cervical cancer. The aim of this study was to assess the impact of the addition of vaginal brachytherapy boost to adjuvant external beam radiotherapy on oncological outcomes and toxicity in patients with cervical cancer. METHODS: Patients treated with post-operative external beam radiotherapy ± chemotherapy ± vaginal brachytherapy between January 2001 and January 2019 were retrospectively evaluated. The treatment outcomes and prognostic factors were analyzed in patients treated with external beam radiotherapy with or without vaginal brachytherapy. RESULTS: A total of 480 patients were included in the analysis. The median age was 51 years (range 42-60). At least two intermediate risk factors were observed in 51% of patients, while 49% had at least one high-risk factor. The patients in the external beam radiotherapy + vaginal brachytherapy group had worse prognostic factors than the external beam radiotherapy alone group. With a median follow-up time of 56 months (range 33-90), the 5-year overall survival rate was 82%. There was no difference in 5-year overall survival (87% vs 79%, p=0.11), recurrence-free survival (74% vs 71%, p=0.49), local recurrence-free survival (78% vs 76%, p=0.16), and distant metastasis-free survival (85% vs 76%, p=0.09) rates between treatment groups. There was no benefit of addition of vaginal brachytherapy to external beam radiotherapy in patients with positive surgical margins. In multivariate analysis, stage (overall survival and local recurrence-free survival), tumor histology (recurrence-free survival, local recurrence-free survival and distant metastasis-free survival), parametrial invasion (recurrence-free survival and distant metastasis-free survival), lymphovascular space invasion (recurrence-free survival), and lymph node metastasis (distant metastasis-free survival) were found as negative prognostic factors. CONCLUSION: Adding vaginal brachytherapy boost to external beam radiotherapy did not provide any benefit in local control or survival in patients with cervical cancer.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statementWhat is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous.What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups.What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.

Treatment outcomes of metastasis-directed treatment using 68Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

PURPOSE: The aim of this study was to evaluate the outcomes of 68Ga prostate-specific membrane antigen (68Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC). METHODS: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with 68Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation. RESULTS: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2­year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2­year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT. CONCLUSION: 68Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.