PIK3/Akt/mTOR pathway alterations in metastatic castration-sensitive prostate cancer.

BACKGROUND: Alterations in the PIK3/Akt/mTOR pathway are commonly seen in metastatic castration-sensitive prostate cancer (mCSPC), however their role in outcomes is unknown. We aim to evaluate the prognostic significance as well as the genetic landscape of PIK3/Akt/mTOR pathway alteration in mCSPC. METHODS: Fourhundred and seventy-two patients with mCSPC were included who underwent next generation sequencing. PIK3/Akt/mTor pathway alterations were defined as mutations in Akt1, mTOR, PIK3CA, PIK3CB, PIK3R1, PTEN, TSC1, and TSC2. Endpoints of interests were radiographic progression-free survival (rPFS), time to development of castration resistant prostate cancer (tdCRPC), and overall survival (OS). Kaplan-Meier analysis was performed and Cox regression hazard ratios (HR) were calculated. RESULTS: One hundred and fifty-two (31.9%) patients harbored a PIK3/Akt/mTOR pathway alteration. Median rPFS and tdCRPC were 23.7 and 21.0 months in PIK3/Akt/mTOR altered compared to 32.8 (p = 0.08) and 32.1 months (p = 0.002) in wildtype tumors. On multivariable analysis PIK3/Akt/mTOR pathway alterations were associated with tdCRPC (HR 1.43, 95% CI, 1.05-1.94, p = 0.02), but not rPFS [Hazard ratio (HR) 1.20, 95% confidence interval (CI), 0.90-1.60, p = 0.21]. PIK3/Akt/mTOR pathway alterations were more likely to be associated with concurrent mutations in TP53 (40% vs. 28%, p = 0.01) and TMPRSS2-ERG (37% vs. 26%, p = 0.02) than tumors without PIK3/Akt/mTOR pathway alterations. Concurrent mutations were typically associated with shorter median times to rPFS and tdCRPC. DAVID analysis showed p53 signaling and angiogenesis pathways were enriched in PIK3/Akt/mTOR pathway altered tumors while beta-catenin binding and altered BRCA pathway were enriched in PIK3/Akt/mTOR pathway wildtype tumors. CONCLUSIONS: PIK3/Akt/mTOR pathway alterations were common in mCSPC and associated with poorer prognosis. The genetic landscape of PIK3/Akt/mTOR pathway altered tumors differed from wildtype tumors. Additional studies are needed to better understand and target the PIK3/Akt/mTOR pathway in mCSPC.

Genomic Determinants Associated with Modes of Progression and Patterns of Failure in Metachronous Oligometastatic Castration-sensitive Prostate Cancer.

BACKGROUND AND OBJECTIVE: Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better outcomes in comparison to those with higher disease burden. Despite the generally more indolent nature, there is still much heterogeneity, with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Our aim was to investigate correlation of tumor genomics with the mode of progression (MOP) and pattern of failure (POF) following first treatment (metastasis-directed and/or systemic therapy) for omCSPC. METHODS: We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC who underwent tumor next-generation sequencing with at least 1 yr of follow-up after their first treatment. Descriptive MOP and POF results are reported with respect to the presence of genomic alterations in pathways of interest. MOP was defined as class I, long-term control (LTC; no radiographic progression at last follow-up), class II, oligoprogression (1-3 lesions), or class III, polyprogression (≥4 lesions). POF included the location of lesions at first failure. Genomic pathways of interest included TP53, ATM, RB1, BRCA1/2, SPOP, and WNT (APC, CTNNB1, RNF43). Genomic associations with MOP/POF were compared using χ2 tests. Exploratory analyses revealed that the COSMIC mutational signature and differential gene expression were also correlated with MOP/POF. Overall survival (OS) was calculated via the Kaplan-Meier method from the time of first failure. KEY FINDINGS AND CLINICAL IMPLICATIONS: We included 267 patients in our analysis; the majority had either one (47%) or two (30%) metastatic lesions at oligometastasis. The 3-yr OS rate was significantly associated with MOP (71% for polyprogression vs 91% for oligoprogression; p = 0.005). TP53 mutation was associated with a significantly lower LTC rate (27.6% vs 42.3%; p = 0.04) and RB1 mutation was associated with a high rate of polyprogression (50% vs 19.9%; p = 0.022). Regarding POF, bone failure was significantly more common with tumors harboring TP53 mutations (44.8% vs25.9%; p = 0.005) and less common with SPOP mutations (7.1% vs 31.4%; p = 0.007). Visceral failure was more common with tumors harboring either WNT pathway mutations (17.2% vs 6.8%, p = 0.05) or SPOP mutations (17.9% vs 6.3%; p = 0.04). Finally, visceral and bone failures were associated with distinct gene-expression profiles. CONCLUSIONS AND CLINICAL IMPLICATIONS: Tumor genomics provides novel insight into MOP and POF following treatment for metachronous omCSPC. Patients with TP53 and RB1 mutations have a higher likelihood of progression, and TP53, SPOP, and WNT pathway mutations may have a role in metastatic organotropism. PATIENT SUMMARY: We evaluated cancer progression after a first treatment for metastatic prostate cancer with up to five metastases. We found that mutations in certain genes were associated with the location and extent of further metastasis in these patients.

Evaluation of Treatment Outcomes of Prostate Cancer Patients With Lymph Node Metastasis Treated With Definitive Radiotherapy: Comparative Analysis of PSMA PET/CT and Conventional Imaging.

PURPOSE: We investigated the impact of prostate-specific membrane antigen (PSMA) PET/CT compared with conventional imaging on treatment outcomes for node-positive prostate cancer (PCa) patients who underwent androgen deprivation therapy (ADT) and external radiotherapy (RT). PATIENTS AND METHODS: A multicentric, retrospective study recruited patients with node-positive PCa patients who underwent conventional radiological evaluation or PSMA PET/CT and received ADT and RT at 3 hospitals from 2009 to 2021 were enrolled. Patients underwent prostate and pelvis RT, accompanied by a minimum of 6 months of ADT. The primary endpoints were progression-free survival (PFS) and PCa-specific survival (PCSS). Cox regression analyzed the association of survival with potential prognostic factors, whereas logistic regression identified the predictors of bone and lymph node metastasis. RESULTS: The median follow-up time was 64.0 months. The majority of patients (64.1%) underwent PSMA PET/CT for staging. The 5-year rates of PFS and PCSS were 63.7% and 83.7%, respectively. Disease progression was observed in 90 patients (36.3%). In multivariable analysis, ADT duration of less than 24 months and post-RT prostate-specific antigen (PSA) nadir were prognostic for PFS. Early clinical T stage and PSMA PET/CT predicted better PCSS. Patients staged with PSMA PET/CT had exhibited significantly higher 5-year PCSS rates than compared with those staged with conventional imaging (95.1% vs 76.9%; P = 0.01). Shorter ADT duration and higher PSA levels after RT independently predicted bone metastasis in multivariable logistic regression. Advanced T stage, shorter ADT duration, and higher PSA levels after neoadjuvant ADT predicted nonregional lymph node recurrence. CONCLUSIONS: ADT with pelvis RT is an effective treatment option for node-positive PCa patients. The PSMA PET/CT outperformed conventional imaging in PCSS, emphasizing the importance of precise clinical staging for patients undergoing definitive RT.

Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival After Stereotactic Ablative Radiation in Oligometastatic Prostate Cancer.

Purpose: Emerging data suggest that metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease, and PSMA response has been proposed as a biomarker for treatment response. Herein, we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC. Methods and Materials: We performed an international multi-institutional retrospective study of patients with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation who underwent PSMA-PET/computed tomography (CT) before and after (median, 6.2 months; range, 2.4-10.9 months) treatment. Pre- and post-MDT PSMA-PET/CT maximum standardized uptake value (SUVmax) was measured for all lesions, and PSMA response was defined as the percent change in SUVmax of the least responsive lesion. PSMA response was both evaluated as a continuous variable and dichotomized into PSMA responders, with a complete/partial response (at least a 30% reduction in SUVmax), and PSMA nonresponders, with stable/progressive disease (less than a 30% reduction in SUVmax). PSMA response was correlated with conventional imaging-defined metastasis-free survival (MFS) via Kaplan-Meier and Cox regression analysis. Results: A total of 131 patients with 261 treated metastases were included in the analysis, with a median follow-up of 29 months (IQR, 18.5-41.3 months). After stereotactic ablative radiation, 70.2% of patients were classified as PSMA responders. Multivariable analysis demonstrated that PSMA response as a continuous variable was associated with a significantly worse MFS (hazard ratio = 1.003; 95% CI, 1.001-1.006; P = .016). Patients classified as PSMA responders were found to have a significantly improved median MFS of 39.9 versus 12 months (P = .001) compared with PSMA nonresponders. Our study is limited as it is a retrospective review of a heterogenous population. Conclusions: After stereotactic ablative radiation, PSMA-PET response appears to be a radiographic biomarker that correlates with MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated in a prospective setting.

A Comparative Analysis of Implant-sparing Plan Versus Conventional Plans Utilizing Helical Tomotherapy in Breast Cancer Patients Undergoing Breast Reconstruction.

BACKGROUND/AIM: To compare implant sparing irradiation with conventional radiotherapy (RT) using helical (H) and TomoDirect (TD) techniques in breast cancer patients undergoing immediate breast reconstruction (IBR). PATIENTS AND METHODS: The dosimetric parameters of 40 patients with retropectoral implants receiving 50.4 Gy delivered in 28 fractions were analyzed. Three plans were created: H plan using conventional planning target volume (PTV) that included the chest wall, skin, and implant; TD plan using conventional PTV; and Hs plan using implant-sparing PTV. The H, TD, and Hs plans were compared for PTV doses, organ-at-risk (OAR) doses, and treatment times. RESULTS: Dose distribution in the Hs plan was less homogeneous and uniform than that in the H and TD plans. The TD plan had lower lung, heart, contralateral breast, spinal cord, liver, and esophagus doses than the Hs plan. Compared to the Hs plan, the H plan had lower lung volume receiving 5Gy (V5) (39.1±3.9 vs. 41.2±3.9 Gy; p<0.001), higher V20 (12.3±1.3 vs. 11.5±2.6 Gy; p=0.02), and higher V30 (7.5±1.6 vs. 4.4±1.7 Gy; p<0.001). H plan outperformed Hs plan in heart dosimetric parameters except V20. The Hs plan had significantly lower mean implant doses (43.4±2.1 Gy) than the H plan (51.4±0.5 Gy; p<0.001) and the TD plan (51.9±0.6 Gy; p<0.001). Implementing an implant sparing technique for silicone dose reduction decreases lung doses. CONCLUSION: Conventional H and TD plans outperform the implant sparing helical plan dosimetrically. Because capsular contracture during RT is unpredictable, long-term clinical outcomes are required to determine whether silicon should be spared.

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 assessment of clinical parameters and positron emission tomography parameters in predicting recurrence in uterine cervical cancer patients receiving definitive chemoradiotherapy.

OBJECTIVE: The objective of this study was to assess the prognostic value of clinical factors and metabolic parameters measured using fluorodeoxyglucose PET (FDG-PET/CT) in predicting disease recurrence, as well as distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and overall survival (OS) in patients with uterine cervical cancer who received definitive chemoradiotherapy. METHODS: The clinical data and FDG-PET parameters, including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 194 patients with biopsy-confirmed squamous cell carcinoma of cervical cancer were retrospectively analyzed. Univariate and multivariate analyses were used to ascertain prognostic factors associated with DMFS, LRFS, and OS. RESULTS: With a median follow-up of 12.5 years, 96 patients (49.5%) presented with disease recurrence, at a median of 9.9 months after chemoradiotherapy. Patients who experienced recurrence had significantly higher values for all FDG-PET parameters compared to patients who did not. In multivariate regression analysis, lymph node metastasis, MTV, and SUV mean were significantly correlated with distant metastasis, while local recurrence was only predicted by SUV max . Lymph node metastasis, high MTV, SUV mean , and TLG predicted shorter DMFS, while only the primary tumor SUV max predicted LRFS. Age, regional nodal metastasis, and higher MTV independently predicted shorter OS in multivariate analysis. CONCLUSION: We found that metabolic parameters derived from FDG-PET/CT could serve as surrogates for disease recurrence in patients with cervical cancer who were treated with definitive chemoradiotherapy. Patients at high risk of distant metastasis could be defined using SUV mean and MTV, and for local recurrence, by using SUV max .

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.

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.

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study.

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26-87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients' performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78-7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79-6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12-2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did.

Treatment outcomes of simultaneous integrated boost to intraprostatic lesions with external beam radiotherapy in localized prostate cancer patients.

BACKGROUND: To evaluate the treatment outcomes and toxicity of definitive radiotherapy (RT) for prostate cancer (PC) patients using the simultaneous integrated boost (SIB) technique, which delivered 78 Gy to the entire prostate and 86 Gy to the intraprostatic lesion (IPL) in 39 fractions. MATERIALS AND METHODS: Univariable and multivariable analyses were conducted of the prognostic factors for freedom from biochemical failure (FFBF), progression-free survival (PFS), and PC-specific survival (PCSS) of 619 PC patients who received definitive RT between September 2012 and August 2021. Predictors of late Grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicities were also identified using logistic regression. RESULTS: The median follow-up for entire cohort was 68.5 months. The 5-year FFBF, PFS, and PCSS rates were 93.2%, 83.2%, and 98.6%, respectively. They were predicted by the serum prostate-specific antigen, Gleason score (GS), clinical nodal stage, and D'Amico risk group. Only 45 patients (7.3%) developed disease recurrence 41.9 months after RT. The 5-year FFBF rates for low-, intermediate-, and high-risk disease were 98.0%, 93.1%, and 88.5%, respectively (p < 0.001). The 5-year PFS and PCSS rates according to risk groups were 91.0%, 82.1%, and 77.4% (p < 0.001), and 99.2%, 96.4%, and 95.9% (p = 0.03), and, respectively. GS > 7 and lymph node metastasis negatively predicted FFBF and PCSS in multivariable analysis. Ninety (14.6%) and 44 (7.1%) patients had acute Grade ≥2 GU and GI toxicities, respectively, and 42 (6.8%) and 27 (4.4%) patients had late Grade ≥2 GU and GI toxicities, respectively. Diabetes and transurethral resection independently predicted late Grade 2 GU toxicity, but no significant predictor of late Grade ≥2 GI toxicity was found. CONCLUSIONS: Localized PC was effectively and safely treated with definitive RT using the SIB technique to deliver 86 Gy to the IPL in 39 fractions without severe late toxicity. This finding must be validated with long-term results.

The impact of the apparent diffusion coefficient for the early prediction of the treatment response after definitive radiotherapy in prostate cancer patients.

PURPOSE: We assessed early changes in apparent diffusion coefficient (ADC) and serum prostate specific antigen (PSA) values after definitive radiotherapy (RT) without androgen deprivation treatment in low- and intermediate-risk prostate cancer (PC) patients. MATERIALS AND METHODS: The clinical data and ADC parameters of 229 PC patients were retrospectively evaluated. Pre-treatment and post-treatment serum PSA and primary tumor ADC values were calculated. Post-treatment DW-MRI was performed median 4.1 months after completion of definitive RT. The prognostic factors predicting freedom from biochemical failure (FFBF) and progression-free survival (PFS) were analyzed using univariable and multivariable analyses. RESULTS: With a median follow-up time of 80.8 months, the 5-year FFBF and PFS rates were 95.9% and 89.3%, respectively. Eleven patients (4.8%) had PSA relapse, with a median of 34.4 months after the completion of RT. A statistically significant difference in post-treatment ADC values was noted between patients with and without recurrence (0.94 ± 0.07 vs. 1.10 ± 0.20 × 10-3 mm2/sec; p< 0.001). Patients with a Gleason score (GS) of 6 and low-risk disease had significantly higher post-treatment tumor ADC and PSA levels than patients with a GS of 7 and intermediate-risk disease. The 5-year FFBF rate in patients with tumor ADC ≤ 0.96 × 10-3 mm2/sec was significantly lower than patients with tumor ADC > 0.96 × 10-3 mm2/sec (85.5% vs. 100; p< 0.001). In the multivariable analysis, a lower ADC value, GS 4 + 3 and intermediate-risk disease were independent predictors of worse FFBF. In the multivariate analysis, a lower post-treatment ADC value and a GS of 4 + 3 were significant prognostic factors for a lower PFS. CONCLUSION: These findings suggest that the post-treatment tumor ADC value could be used for early treatment response evaluation after definitive RT in PC patients.

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.

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.

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.

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.