European association of urology risk stratification predicts outcome in patients receiving PSMA-PET-planned salvage radiotherapy for biochemical recurrence following radical prostatectomy.

PURPOSE: The European Association of Urology (EAU) proposed a risk stratification (high vs. low risk) for patients with biochemical recurrence (BR) following radical prostatectomy (RP). Here we investigated whether this stratification accurately predicts outcome, particularly in patients staged with PSMA-PET. METHODS: For this study, we used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients who were treated with salvage radiotherapy (SRT) for BR, at 11 centers in 5 countries. Patients with lymph node metastases (pN1 or cN1) or unclear EAU risk group were excluded. The remaining cohort comprised 526 patients, including 132 low-risk and 394 high-risk patients. RESULTS: The median follow-up time after SRT was 31.0 months. The 3-year biochemical progression-free survival (BPFS) was 85.7 % in EAU low-risk versus 69.4 % in high-risk patients (p = 0.002). The 3-year metastasis-free survival (MFS) was 94.4 % in low-risk versus 87.6 % in high-risk patients (p = 0.005). The 3-year overall survival (OS) was 99.0 % in low-risk versus 99.6 % in high-risk patients (p = 0.925). In multivariate analysis, EAU risk group remained a statistically significant predictor of BPFS (p = 0.003, HR 2.022, 95 % CI 1.262-3.239) and MFS (p = 0.013, HR 2.986, 95 % CI 1.262-7.058). CONCLUSION: Our data support the EAU risk group definition. EAU risk grouping for BCR reliably predicted outcome in patients staged lymph node-negative after RP and with PSMA-PET before SRT. To our knowledge, this is the first study validating the EAU risk grouping in patients treated with PSMA-PET-planned SRT.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy.

AIM: The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. METHODS: This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. RESULTS: Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20-46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. CONCLUSION: Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

Salvage radiotherapy is effective in patients with PSMA-PET-negative biochemical recurrence- results of a retrospective study.

BACKGROUND/PURPOSE: The present study aimed to assess whether SRT to the prostatic fossa should be initiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomography (PSMA-PET). MATERIALS AND METHODS: This retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradiation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint. RESULTS: The median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive cases. This difference was significant in univariate (p = 0.019), but not multivariate analyses (p = 0.366, HR: 1.46, 95%CI: 0.64-3.32). The 3-year BPFS in PET-negative cases was significantly influenced by age (p = 0.005), initial pT3/4 (p < 0.001), pathology scores (ISUP) ≥ 3 (p = 0.026), and doses to fossa > 70 Gy (p = 0.027) in univariate analyses. In multivariate analyses, only age (HR: 1.096, 95%CI: 1.023-1.175, p = 0.009) and PSA-doubling time (HR: 0.339, 95%CI: 0.139-0.826, p = 0.017) remained significant. CONCLUSION: To our best knowledge, this study provided the largest SRT analysis in patients without ADT that were lymph node-negative on PSMA-PET. A multivariate analysis showed no significant difference in BPFS between locally PET-positive and PET-negative cases. These results supported the current EAU recommendation to initiate SRT in a timely manner after detecting BR in PET negative patients.

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET-Based Salvage Radiotherapy for Recurrent Prostate Cancer.

Importance: Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. Objective: To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. Design, Setting, and Participants: This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. Exposures: Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. Main Outcomes and Measures: The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. Results: In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. Conclusions and Relevance: This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.

Guideline concordant therapy improves survival in high-grade endometrial cancer patients.

PURPOSE: Data from randomized controlled trials in high-grade endometrial cancer are scarce due to its low prevalence. Therefore, guideline recommendations in this cancer subtype rely on relatively few randomized trials and data from retrospective studies. The aim of this study was to evaluate the benefits from guideline-concordant therapy in high-grade endometrial cancer in a real-world patient group. METHODS: The effect of treatment according to German S3 guidelines and the former S2k guideline on overall survival (OS) and recurrence-free survival (RFS) was evaluated in a cohort of 293 high-grade endometrial cancer patients. RESULTS: Treatment concordant with the S3 guideline significantly improved OS (HR 0.623, CI 0.420-0.923, p = 0.018) and RFS (HR 0.578, CI 0.387-0.863, p = 0.007). Treatment concordant with the S2k guideline did not result in a significantly higher OS (HR 0.783, CI 0.465-1.316, p = 0.335) or RFS (HR 0.741, CI 0.347-1.740, p = 0.242). CONCLUSION: Therapy according to the German S3 guideline improved OS and RFS in univariate as well as multivariate analysis in this cohort of high-grade endometrial cancer patients.

Intracavitary brachytherapy with additional Heyman capsules in the treatment of cervical cancer.

PURPOSE: Brachytherapy is a mandatory component of primary radiochemotherapy in cervical cancer. The dose can be applied with a traditional intracavitary approach (IC alone) or with multiple catheter brachytherapy to optimize dose distribution in an individual concept. We therefore evaluated whether the utilization of a tandem-ring applicator plus additional intracavitary applicators (add IC) provides an advantage over the traditional IC alone approach, as this method is less time consuming and less invasive compared to a combined intracavitary/interstitial brachytherapy. METHODS: Twenty three procedures of intracavitary brachytherapy for cervical cancer with additional intracavitary applicators performed in seven patients treated between 2016 and 2018 in our institution were included in this study. Plans were optimized for D90 HR-CTV with and without the utilization of the additional applicators and compared by statistical analysis. RESULTS: D90 for HR-CTV was 5.71 Gy (±1.17 Gy) for fractions optimized with add IC approach and 5.29 Gy (±1.24 Gy) for fractions without additional applicators (p < 0.01). This translates to a calculated mean EQD2 HR-CTV D90 of 80.72 Gy (±8.34 Gy) compared to 77.84 Gy (±8.49 Gy) after external beam therapy and four fractions of brachytherapy for add IC and IC alone, respectively (p < 0.01). The predictive value of improved coverage of HR-CTV in the first fraction was high. CONCLUSION: In a subgroup of cases, the addition of intracavitary Heyman capsules can be an alternative to interstitial brachytherapy to improve the plan quality compared to standard IC alone brachytherapy. The benefit from the addition of applicators in the first fraction is predictive for the following fractions.

Impact of Dose Escalation on the Efficacy of Salvage Radiotherapy for Recurrent Prostate Cancer-A Risk-Adjusted, Matched-Pair Analysis.

Previous randomized trials have not provided conclusive evidence about dose escalations and associated toxicities for salvage radiotherapy (SRT) in prostate cancer. Here, we retrospectively analyzed whether dose escalations influenced progression-free survival in 554 patients that received salvage radiotherapy for relapses or persistently elevated prostate cancer antigen (PSA) after a radical prostatectomy. Patients received SRT between 1997 and 2017 at two University Hospitals in Germany. We compared patient groups that received radiation doses <7000 cGy (n = 225) or ≥7000 cGy (n = 329) to analyze the influence of radiation dose on progression-free survival. In a second matched-pair analysis of 216 pairs, we evaluated prognostic factors (pT2 vs. pT3−4, Gleason score [GS] ≤ 7 vs. GS ≥ 8, R0 vs. R1, and pre-SRT PSA <0.5 vs. ≥0.5 ng/mL). After a median follow-up of 6.8 (4.2−9.2) years, we found that escalated doses significantly improved progression-free survival (p = 0.0042). A multivariate analysis indicated that an escalated dose, lower tumor stages (pT2 vs. pT3/4), and lower GSs (≤7 vs. 8−10) were associated with improved progression-free survival. There was no significant effect on overall survival. Our data suggested that escalating the radiation dose to ≥7000 cGy for SRT after a prostatectomy significantly improved progression-free survival. Longer follow-ups are needed for a comprehensive recommendation.

First experiences with PET-MRI/CT in radiotherapy planning for cervical cancer.

PURPOSE: PET-CT has recently been included in the NCCN staging recommendations for cervical cancer stages II-IV and is already routinely applied to radiotherapy planning for other malignancies, as it is expected to provide higher accuracy for the detection of areas with tumor cell spread. In this study, we report on our first experiences of PET-based radiotherapy planning for cervical cancer. METHODS: 19 patients with cervical cancer that underwent pre-therapeutic PET imaging treated at our institution between January 2016 and April 2019 were included in the study. Information on the primary tumor, lymph node involvement, metastatic spread and changes in the radiotherapy procedure based on the PET findings are described. RESULTS: A previously unknown primary tumor extension that was detected by PET imaging in one patient. In patients who underwent a PET before the systematic pelvic and paraaortic lymphonodectomy (n = 2), PET was false negative for pelvic lymph node metastases in 50%. In patients who underwent a PET after the systematic LNE (n = 13), additional lymph node metastases were detected in seven patients (53.80%). Distant metastases were suspected in three patients (15.7%) based on PET imaging. The suspicion was confirmed in one patient (peritoneal spread) and excluded in two patients (supra-diaphragmatic lymph nodes). In 13 patients (68.4%), RT procedures were altered due to findings in PET imaging. CONCLUSION: PET-based radiochemotherapy planning may improve control rates by identifying areas of tumor cell spread eligible for dose escalation. False positivity, however, should be excluded in patients with findings that lead to major modifications of the therapeutic strategy.

Factors influencing treatment decision and guideline conformity in high-grade endometrial cancer patients: a population-based study.

PURPOSE: Treatment according to guidelines has been demonstrated to improve survival in a number of different cancer entities. Deviations from guidelines depend on several factors, including the patient's preferences, age and comorbidities. The aim of this study was to assess the adherence to guideline recommendations concerning surgical and adjuvant treatment in endometrial cancer. Furthermore, we sought to evaluate the reasons for non-adherence to guidelines by further examining the influence of comorbidities and age. METHODS: The influence of age, comorbidities, tumor stage and histological subtype on guideline adherence was evaluated by multivariable logistic regression in a cohort of 353 high-grade endometrial cancer patients. High-grade endometrial cancer was defined as carcinosarcoma, Type II (serous, clear cell, mixed cell carcinoma) and Type I G3 histology. RESULTS: Extensive surgical procedures, particularly systematic LNE, were less frequently applied in patients with comorbidities (p = 0.015) or higher age (p < 0.01). Guideline adherence was not affected by comorbidities (p = 0.563), but was significantly reduced with higher age (p < 0.01). In a multivariable model, higher age (p < 0.01), obesity (p = 0.011), higher FIGO Stage (p < 0.01) and histologic subtype (p < 0.01) significantly decreased OS. Surgery (p < 0.001), chemotherapy (p < 0.01) and systematic LNE (p = 0.011) were associated with higher OS. CONCLUSION: Age seems to be the strongest independent factor leading to guideline deviation. Comorbidities were associated with less aggressive treatment, but not with deviations from guidelines.

Comparison of survival outcomes and effects of therapy between subtypes of high-grade endometrial cancer - a population-based study.

BACKGROUND: Similarities in outcome between grade 3 endometrioid cancer and non-endometrioid histologies have been reported by a number of studies. Other reports, however, stated a significantly better prognosis for G3 endometrioid compared to type II histology. In this population-based study, we compared the outcome and treatment approaches of high-grade endometrial cancer patients with FIGO stages I-III depending on their histology. MATERIAL AND METHODS: 284 high-grade endometrial cancer patients diagnosed between 1998 and 2015 were retrospectively analyzed. Overall survival (OS), recurrence-free survival (RFS), and recurrence rates were compared depending on histology. RESULTS: Type I G3 patients had a statistically significant OS advantage over women suffering from type II carcinoma (HR 1.527, 95%-CI 1.024-2.276; p = 0.038) and carcinosarcoma (HR 2.106, 95%-CI 1.270-3.493; p = 0.004) in univariable and multivariable Cox-regression analysis. RFS in Type I G3 was significantly superior compared to patients with carcinosarcoma (HR 1.719, 95%-CI 1.018-2.901; p = 0.043) and not significantly superior to type II patients (HR 1.368, 95%-CI 0.920-2.036; p = 0.122). Cumulative recurrence rates were significantly higher in carcinosarcoma compared to type I G3 (HR 2.217, 95%-CI 1.096-4.485; p = 0.027) in univariable analysis, but not after risk adjustment (HR of 1.472, 95%-CI 0.654-3.311; p = 0.350). CONCLUSION: The prognosis of patients with type I G3 endometrial cancer patients seems to be significantly superior to patients with type II cancer and particularly carcinosarcoma. Systematic LND seemed to be beneficial in all of the three subtypes. The benefit of adjuvant treatment methods may differ between histologies.

Is there a benefit for adjuvant radio(chemo)therapy in early cervical cancer? Results from a population-based study.

PURPOSE: Due to insufficient and conflicting prospective evidence, the recommendations on when to apply adjuvant radiochemotherapy in early-stage cervical cancer vary between international guidelines. In this population-based study, we evaluated the outcome of patients with early-stage cervical cancer based on risk factors and the adjuvant therapy they received. METHODS: The effect of primary therapy (surgery and radiochemotherapy RCT, surgery and radiotherapy RT, and surgery alone) on overall survival (OS) and recurrence-free survival (RFS) was evaluated in the complete cohort of 442 patients and in subgroups according to risk profile and nodal status. RESULTS: In low-risk patients, there was no difference in OS (p = 0.276) depending on whether patients received adjuvant therapy or not. Concerning RFS, patients with RT (including one patient with RCT) exhibited a significantly worse outcome compared to the group with surgery alone (p = 0.015). In intermediate-risk patients, the administration of adjuvant RT significantly benefited RFS when compared to surgery only in multivariate analysis (p = 0.031). Concerning OS, no significant influence for adjuvant treatment could be seen (p = 0.354). Though trends towards better OS and RFS could be observed in patients of the high-risk group-both in RCT and RT groups compared to surgery alone-the effects did not prove to be significant. CONCLUSION: Our study reaffirms the evidence against the use of adjuvant radio(chemo)therapy in low-risk early-stage cervical cancer. In intermediate-, and less pronounced in high-risk patients, however, it seems to be beneficial. The role of adjuvant radio(chemo)therapy in early cervical cancer should be further investigated in prospective randomized trials.

Sentinel lymph node detection by means of indocyanine green using the Karl Storz VITOM® fluorescence camera: a comparison between primary sentinel lymph node biopsy versus sentinel lymph node biopsy after neoadjuvant chemotherapy.

PURPOSE: The usage of radioactive Technetium99m (Tc99m) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium99m (Tc99m) like limited availability, high costs and radioactivity exposure for both patients and surgeons. METHODS: In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium99m (Tc99m) in the identification of the SLN in early breast cancer. RESULTS: Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc99m. The conventional Technetium99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone. CONCLUSIONS: Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606.

Is local radiotherapy a viable option for patients with an opening of the ventricles during surgical resection of brain metastases?

BACKGROUND: Local hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity is emerging as the standard of care in the treatment of patients with a limited number of brain metastases as it warrants less neurological impairment compared to whole brain radiotherapy. In periventricular metastases surgical resection can lead to an opening of the ventricles and subsequently carries a potential risk of cerebrospinal tumour cell dissemination. The aim of this study was to assess whether local radiotherapy of the resection cavity is viable in these cases. METHODS: From our institutional database we analyzed the data of 125 consecutive patients with resected brain metastases treated in our institution with HFSRT between 2009 and 2017. The incidence of LMD, overall survival (OS), local recurrence (LC) and distant recurrence were evaluated depending on ventricular opening (VO) during surgery. RESULTS: From all 125 patients, the ventricles were opened during surgery in 14 cases (11.2%). None of the patients with VO and 7 patients without VO during surgery developed LMD (p = 0.371). OS (p = 0.817), LC (p = 0.524) and distant recurrence (p = 0.488) did not differ in relation to VO during surgical resection. However, the incidence of distant intraventricular recurrence was slightly increased in patients with VO (14.3% vs. 2.7%, p < 0.01). CONCLUSION: VO during neurosurgical resection did not affect the outcome after HFSRT of the resection cavity in patients with brain metastases. Particularly, the incidence of LMD was not increased in patients receiving local HFSRT after VO. HFSRT can therefore be offered independently of VO as a local treatment of tumor bed after resection of brain metastases.

Value of indocyanine green pelvic lymph node mapping in the surgical approach of cervical cancer.

PURPOSE: Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients and relevant for therapeutic strategies. We evaluated the clinical value of indocyanine green (ICG) by measuring the sensitivity and negative predictive value of sentinel lymph node mapping compared with the gold standard of complete lymphadenectomy in detecting lymph node metastases for cervical cancer. METHODS: We utilized the near-infrared imaging agent ICG to detect tumor-infested lymph nodes in the pelvis analogue to a classical sentinel lymph node procedure by analyzing data from 20 patients who had undergone surgery for cervical cancer at our institution. A laparoscopic lymph node mapping procedure by means of ICG, followed by a complete pelvic lymphadenectomy with or without paraaortic lymphadenectomy was done in all patients. RESULTS: Histological examination identified seven patients with tumor-positive pelvic nodes, whereas mapping with ICG identified only five of these patients. Detection rate of positive nodes by ICG mapping and false negative rate was 71.4% and 28.6%, respectively; bilateral detection rate was 83.3%. One of the two false negative patients additionally suffered from deep infiltrating endometriosis. CONCLUSIONS: Our results indicate that ICG can identify the relevant pelvic nodes independent of tumor size, provided bilateral detection is achieved and additional, related diseases are excluded. TRIAL REGISTRATION: This trial is registered within the German Clinical Trial Register (DRKS-ID: DRKS00014692).

Long-term outcome of patients with intermediate- and high-risk endometrial cancer after pelvic and paraaortic lymph node dissection: a comparison of laparoscopic vs. open procedure.

OBJECTIVE: The primary therapy for intermediate- and high-risk endometrial cancer includes pelvic and paraaortic lymph node evaluation. Laparoscopic surgery is an increasingly popular intervention due to decreased risk and better short-term morbidity; however, a recent study casts doubt on the benefit of this approach in terms of oncological safety. In this cancer registry study, we sought to evaluate the benefit of laparoscopy versus laparotomy and retrospectively compared overall survival, recurrence rates, and recurrence-free survival among patients with intermediate- and high-risk endometrial cancer who underwent either laparoscopic or open surgery. METHODS: This observational study included 419 patients who have been treated from 2011 to 2017. We employed Kaplan-Meier method, and univariable and multivariable Cox-regression to compare overall survival, recurrence rates, and recurrence-free survival in 110 patients, who underwent laparoscopic, with 309 patients, who underwent open surgery. To address the confounding bias in this retrospective study, we also performed a propensity score matching (PSM) analysis including 357 patients (laparoscopy: n = 107; open surgery: n = 250). RESULTS: We found a benefit for laparoscopic over open surgery in patients with intermediate- and high-risk endometrial cancer for overall survival in both univariable (p = 0.002; PSM: p = 0.016) and multivariable analyses (p = 0.019; PSM: p = 0.007). In contrast, there was no statistically significant difference between both patient groups regarding the cumulative recurrence rates. A univariable analysis identified a significant benefit for laparoscopy regarding recurrence-free survival (p = 0.003; PSM: p = 0.029) but a multivariable analysis failed to confirm this finding (p = 0.108; PSM: p = 0.118). CONCLUSIONS: Our study provides evidence that laparoscopic systematic lymphadenectomy does not present a lower oncological efficacy than open surgery in the treatment of patients with endometrial cancer.

Stereotactic irradiation of the resection cavity after surgical resection of brain metastases - when is the right timing?

Purpose: This study aimed to evaluate whether an early beginning of the adjuvant stereotactic radiotherapy after macroscopic complete resection of 1-3 brain metastases is essential or whether longer intervals between surgery and radiotherapy are feasible.Material and methods: Sixty-six patients with 69 resection cavities treated with HFSRT after macroscopic complete resection of 1-3 brain metastases between 2009 and 2016 in our institution were included in this study. Overall survival, local recurrence and locoregional recurrence were evaluated depending on the time interval from surgery to the start of radiation therapy.Results: Patients that started radiotherapy within 21 days from surgery had a significantly decreased OS compared to patients treated after a longer interval from surgery (p < .01). There was no significant difference between patients treated ≥ 34 and 22-33 days from surgery (p = .210). In the univariate analysis, local control was superior for patients starting treatment 22-33 days from surgery compared to a later start (p = .049). This effect did not prevail in a multivariate model. There was no significant difference between patients treated within 21 days and patients treated more than 33 days after surgery (p = .203). Locoregional control was not influenced by RT timing (p = .508).Conclusion: A short delay in the start of radiotherapy does not seem to negatively impact the outcome in patients with resected brain metastases. We even observed an unexpected reduction in OS in patients treated within 21 days from surgery. Further studies are needed to define the optimal timing of postoperative radiotherapy to the resection cavity.

Impact of nodal status and treatment strategy on overall survival in advanced stage cervical cancer.

PURPOSE: The lack of prognostic data impedes implementation of optimal therapy for cervical cancer. For instance, recommended therapy for FIGO IIB cervical cancer is radical hysterectomy or radiochemotherapy. To enlighten different therapeutic approaches, we investigated the benefit of individual therapies or combination thereof in patients with or without infested lymph nodes. METHODS: The German Tumor Centre Regensburg registered 389 patients with FIGO IIB, IIIA, IIIB, and IVA cervical cancer between 2002 and 2015. We estimated hazard ratios (HR) for overall survival against different therapies using univariable and multivariable cox regression. After risk adjustment with respect to clinicopathological parameters, we performed model selection using conditional stepwise reverse selection. RESULTS: We demonstrated the need for thorough assessment of the nodal status to obtain reliable data for treatment strategy. Our analysis showed significant differences for overall survival in FIGO IIB depending on therapy and nodal status. Outcome was inferior with radiochemotherapy without surgery for patients with N0 compared to surgery and radiochemotherapy combined (HR 3.012; 95% CI 1.075-8.441; p = 0.036); however, for N1, radiochemotherapy without surgery resulted in comparable outcome (HR 0.808; 95% CI 0.189-3.403; p = 0.765), whereas surgery alone yielded in poor outcome (HR 2.889; 95% CI 1.356-6.156; p = 0.006). Regardless of the nodal status, chemotherapy was superior in advanced stage cervical cancer FIGO III to IVA. CONCLUSIONS: Our study suggests that in terms of oncological outcome FIGO IIB cervical cancer patients benefit from a combination of surgery and radiochemotherapy. However, in the presence of lymph node infestation, surgery does not add substantial benefit to the patient.

Cavity volume changes after surgery of a brain metastasis-consequences for stereotactic radiation therapy.

PURPOSE: For a large or symptomatic brain metastasis, resection and adjuvant radiotherapy are recommended. Hypofractionated stereotactic radiotherapy (HFSRT) is increasingly applied in patients with a limited number of lesions. Exact target volume definition is critical given the small safety margins. Whilst technical advances have minimized inaccuracy due to patient positioning and radiation targeting, little is known about changes in target volume. This study sought to evaluate potential changes in the resection cavity of a brain metastasis. METHODS: In all, 57 patients treated with HFSRT after surgical resection of one brain metastasis between 2008 and 2015 in our institution were included in this study. Gross tumor volume (GTV) of the initial metastasis and the volume of the resection cavity in the post-operative, planning, and follow-up MRIs were measured and compared. RESULTS: The mean cavity size decreased after surgery with the greatest change of -23.4% (±41.5%) occurring between post-operative MRI and planning MRI (p < 0.01). During this time period, the cavity volume decreased, remained stable, and increased in 79.1, 3.5, and 17.4%, respectively. A further decrease of -20.7% (±58.1%) was perceived between planning MRI and first follow-up (p < 0.01). No significant difference in pattern of change could be observed depending on the volume of initial GTV, size of the post-operative resection cavity, initial or post-resection FLAIR (fluid-attenuated inversion recovery) hyper-intensity, postsurgical ischemia, or primary tumor. The resection cavities of patients with post-operative ischemia were significantly larger than resection cavities of patients without ischemia. CONCLUSION: The resection cavity seems to be very dynamic after surgery. Hence, it remains necessary to use very recent scans for treatment planning.

Quality of life and oncological outcome in endometrial cancer patients after vaginal brachytherapy: comparison of two dosing schemes.

PURPOSE: Vaginal brachytherapy reduces the risk of local recurrence and was shown to be equieffective in preventing vaginal vault recurrence, but less toxic compared to external-beam radiotherapy in a subset of high intermediate-risk endometrial cancer patients and is administered as single adjuvant treatment in those patients. Different radiotherapeutic approaches with various dosing schemes exist toward brachytherapy. The aim of this study was to compare the outcome and long-term quality of life after brachytherapy with two different high-dose-rate dosing schemes. METHODS: Retrospective analysis was conducted of the recurrence and survival rates of 104 patients with endometrial cancer FIGO stage I-II that underwent adjuvant brachytherapy with three times 5 Gy or four times 5 Gy to the upper two-thirds of the vaginal vault in two different institutions between January 2010 and December 2013. Quality of life was assessed by EORTC QLQ-30 questionnaire and EN 24 module. RESULTS: The vaginal vault recurrence rates were 4.9% and 5.0% for patients treated with 3 × 5 Gy and 4 × 5 Gy, respectively (p = 0.98). We did not observe a difference in pelvic recurrence (p = 0.96), overall survival (p = 0.33) or quality of life between the different radiotherapy regimens. Metastatic recurrence and the use of chemotherapy contribute to impairment on quality of life. Younger patients (< 70 years) reported worse emotional functioning (p = 0.02) and higher symptom scales of diarrhea (p = 0.01) and financial problems (p = 0.03). Sexual activity was lower in patients younger than 70 years (p = 0.05). CONCLUSIONS: Further prospective studies are needed to evaluate the effect of dosing schemes on recurrence rates and quality of life. Younger patients (< 70 years) seem to experience greater reduction in quality of life due to endometrial cancer diagnosis.