Stereotactic body radiotherapy for pancreatic cancer - A systematic review of prospective data.

Purpose: This systematic review aims to comprehensively summarize the current prospective evidence regarding Stereotactic Body Radiotherapy (SBRT) in various clinical contexts for pancreatic cancer including its use as neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC), induction therapy for locally advanced pancreatic cancer (LAPC), salvage therapy for isolated local recurrence (ILR), adjuvant therapy after radical resection, and as a palliative treatment. Special attention is given to the application of magnetic resonance-guided radiotherapy (MRgRT). Methods: Following PRISMA guidelines, a systematic review of the Medline database via PubMed was conducted focusing on prospective studies published within the past decade. Data were extracted concerning study characteristics, outcome measures, toxicity profiles, SBRT dosage and fractionation regimens, as well as additional systemic therapies. Results and conclusion: 31 studies with in total 1,571 patients were included in this review encompassing 14 studies for LAPC, 9 for neoadjuvant treatment, 2 for adjuvant treatment, 2 for ILR, with an additional 4 studies evaluating MRgRT. In LAPC, SBRT demonstrates encouraging results, characterized by favorable local control rates. Several studies even report conversion to resectable disease with substantial resection rates reaching 39%. The adoption of MRgRT may provide a solution to the challenge to deliver ablative doses while minimizing severe toxicities. In BRPC, select prospective studies combining preoperative ablative-dose SBRT with modern induction systemic therapies have achieved remarkable resection rates of up to 80%. MRgRT also holds potential in this context. Adjuvant SBRT does not appear to confer relevant advantages over chemotherapy. While prospective data for SBRT in ILR and for palliative pain relief are limited, they corroborate positive findings from retrospective studies.

Adjuvant Therapy for Elderly Breast Cancer Patients after Breast-Conserving Surgery: Outcomes in Real World Practice.

We aimed to evaluate the standard of care of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elderly female patients (≥65 years) treated outside of clinical trials and to identify potential factors related to the omission of RT and the interaction with endocrine therapy (ET). All women treated with BCS at two major breast centers between 1998 and 2014 were evaluated. Data were provided by the Tumor Registry Munich. Survival analyses were conducted using the Kaplan-Meier method. Prognostic factors were identified using multivariate Cox regression analysis. The median follow-up was 88.4 months. Adjuvant RT was performed in 82% (2599/3171) of patients. Irradiated patients were younger (70.9 vs. 76.5 years, p < 0.001) and were more likely to receive additional chemotherapy (p < 0.001) and ET (p = 0.014). Non-irradiated patients more often had non-invasive DCIS tumors (pTis: 20.3% vs. 6.8%, p < 0.001) and did not undergo axillary surgery (no axillary surgery: 50.5% vs. 9.5%, p < 0.001). Adjuvant RT was associated with improved locoregional tumor control after BCS in invasive tumors (10-year local recurrence-free survival (LRFS): 94.0% vs. 75.1%, p < 0.001, 10-year lymph node recurrence-free survival (LNRFS): 98.1% vs. 93.1%, p < 0.001). Multivariate analysis confirmed significant benefits for local control with postoperative RT. Furthermore, RT led to increased locoregional control even in patients who received ET (10-year LRFS 94.8% with ET + RT vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.2% vs. 95.0%, p = 0.003). Similarly, RT alone had significantly better locoregional control rates compared to ET alone (10-year LRFS 92.6% with RT alone vs. 78.1% with ET alone, p < 0.001 and 10-year LNRFS: 98.0% vs. 95.0%, p = 0.014). The present work confirms the efficacy of postoperative RT for breast carcinoma in elderly patients (≥65 years) treated in a modern clinical setting outside of clinical trials, even in patients who receive ET.

An Analysis of the Distribution of PSMA PET/CT-Positive Lymph Nodes and Their Coverage by Different Elective Nodal Radiation Volumes in Postoperative Prostate Cancer Patients.

Salvage elective nodal radiotherapy (ENRT) is a treatment option for patients with biochemically persistent or recurrent prostate cancer who have lymph node metastases (LNs) after prostatectomy. Possible ENRT templates were proposed by the Radiation Therapy Oncology Group (RTOG; 2009), the PIVOTAL trialists (2015), and the NRG Oncology Group (2021). The goal of this study was to analyze the distribution of prostate-specific membrane antigen (PSMA) PET/CT-positive LNs and to compare the templates regarding their LN coverage. Methods: We analyzed the PSMA PET/CT scans of 105 patients with PET-positive LNs treated with salvage ENRT from 2014 to 2019. All LNs were mapped in an exemplary dataset, classified by region, and assessed with regard to their potential coverage by the 3 ENRT templates. The primary endpoint was the number of missed LNs. The secondary endpoint was the number of patients with full coverage. To compare the templates, a t test and McNemar test were used. Results: Three hundred thirty-five LNs were contoured (3.19 per patient; 95% CI, 2.43-3.95). Most frequently, LNs were seen in the internal iliac (n = 94, 28.1%), external iliac (n = 60, 17.9%), periaortic (n = 58, 17.3%), common iliac (n = 55, 16.4%), perirectal (n = 26, 7.8%), and presacral (n = 19, 5.7%) regions. The NRG template missed fewer LNs per patient (1.01, 31.7%) than the RTOG (1.28, 40.1%, P < 0.001) and PIVOTAL templates (1.19, 37.3%, P = 0.003). No difference was observed in the number of patients with full coverage of all LNs: 52 (49.5%) with the NRG template versus 50 (47.6%) with the RTOG (P = 0.625) and 49 (46.7%) with the PIVOTAL template (P = 0.250). Conclusion: The NRG template showed better coverage than the RTOG and PIVOTAL templates. Nevertheless, in this cohort, it would have missed almost one third of all contoured LNs and would have resulted in incomplete coverage in half the patients. This result underlines the importance of advanced imaging, such as PSMA PET/CT scans, before salvage ENRT and shows the need for further individualization of ENRT fields.

Elective nodal radiotherapy with a gapless radiation field junction for oligorecurrent prostate cancer after previous radiotherapy.

Purpose: To evaluate the feasibility of subsequent elective nodal radiotherapy (ENRT) for nodal recurrences after previous radiotherapy with a defined planning approach for a gapless radiation field junction. Methods: Patients with 1) previous radiotherapy of prostate or prostatic fossa and subsequent pelvic ENRT or 2) previous pelvic radiotherapy and subsequent ENRT to paraaortic lymph nodes (LN) and gapless junction of both radiation fields were analyzed. The cumulative maximum dose (Dmax-cum) and the maximum cumulative dose in 1 cc (D1cc-cum) were estimated. Absolute toxicity and the toxicity exceeding baseline were evaluated. Results: Twenty-two patients with PSMA-PET/CT-staged nodal oligorecurrence after prior radiotherapy were treated with pelvic (14 patients) or paraaortic ENRT (9 patients). One patient was treated sequentially at both locations. Median time between first and second RT was 20.2 months. Median doses to the lymphatic pathways and to PET-positive LN were 47.5 Gy and 64.8 Gy, respectively. The planning constraint of an estimated Dmax-cum ≤ 95 Gy and of D1cc-cum < 90 Gy were achieved in 23/23 cases and 22/23 cases, respectively. Median follow-up was 33.5 months. There was no additional acute or late toxicity ≥ grade 3. Worst acute toxicity exceeding baseline was grade 1 in 68.2% and grade 2 in 22.7% of patients. Worst late toxicity exceeding baseline was grade 1 in 31.8% and grade 2 in 18.2% of patients. Conclusion: ENRT for nodal recurrences after a previous radiotherapy with gapless junction of radiation fields seems to be feasible, applying the dose constraints Dmax-cum ≤ 95 Gy and D1cc-cum < 90 Gy without grade 3 acute or late toxicities exceeding baseline.

Clinical outcome of combined intracavitary / interstitial brachytherapy using a hybrid applicator in locally advanced cervical cancer.

OBJECTIVE: The aim of this study was to evaluate the clinical outcome in locally advanced cervical cancer (LACC) after image-guided adaptive brachytherapy (IGABT) with combined intracavitary and interstitial (IC/IS) techniques using the hybrid Venezia applicator (Elekta AB, Sweden). METHODS: LACC patients (UICC Stage IIB - IVB) treated with radiochemotherapy followed by IGABT with the hybrid IC/IS Venezia applicator at a single institution were retrospectively analyzed. Treatment comprised EBRT of the pelvis with 45 Gy and concomitant weekly cisplatin chemotherapy (40 mg/m2) followed by MRI-based IGABT. Dosimetry, oncological outcome and toxicity were investigated. RESULTS: Forty-six patients underwent a total of 184 fractions of IGABT between 2017 and 2020. Median follow-up was 24 months. Combined IC/IS techniques were used in 40 patients (87%). The median HRCTV volume was 31.2 cm3 and the median HRCTV D90% was 92.3 Gy (EQD210). The median D2cm3 was 74.8 Gy for bladder, 57.9 Gy for rectum, 60.0 Gy for sigmoid and 52.2 Gy for bowel (EQD23). The 3-yr actuarial rates were 97.6% for local control, 97.6% for pelvic control, 59.9% for distant metastasis-free survival and 81.6% for overall survival. The crude rate for G2 and G3 late toxicity was 21.7% and 4.3%. CONCLUSIONS: IGABT with the hybrid Venezia applicator and a pronounced use of a combined IC/IS technique achieved high target doses, while maintaining low doses to organs at risk, leading to excellent local control and overall survival rates with acceptable toxicity.

Radiotherapy in oligometastatic prostate cancer-a pattern of care survey among members of the German Society for Radiation Oncology (DEGRO).

PURPOSE: Due to improved imaging, oligometastatic prostate cancer (OMPC) is diagnosed more frequently. Growing evidence shows that patients with a limited number of metastases benefit from primary-directed radiotherapy (PDT) as well as from metastasis-directed radiotherapy (MDT). This survey investigates the current treatment practice for OMPC among German-speaking radiation oncologists. METHODS: Members of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie [DEGRO]) were surveyed regarding their current treatment practice via an anonymous online questionnaire sent by email. The survey included six general items and 14 specific items regarding treatment characteristics. Questionnaires with at least 50% of questions completed were considered for further analysis. RESULTS: A total of 204 responses were received (15% response rate), 167 were considered for further analysis. Most respondents stated to be specialized in treating prostate cancer patients and to treat 10-30 patients with OMPC per annum; 97% considered PSMA-PET/CT necessary to define oligometastatic disease. Opinions differed regarding the use of systemic therapies: 63% of the respondents aimed to defer systemic therapy using radiotherapy in OMPC, whereas 37% considered systemic therapy necessary. In the setting of synchronous OMPC, 97% recommended PDT with or without a combination of MDT and/or systemic therapy. For metachronous nodal or bone oligometastatic recurrence, 98 and 99%, respectively, would opt for MDT. The majority would combine MDT with systemic therapy in patients with metachronous oligorecurrence. Respondents recommended normofractionation, hypofractionation, and SBRT for lymph node metastases in 49, 27, and 24%, respectively. No consensus existed regarding the field size for MDT of lymph node metastases. Most respondents preferred > 5 fractions for treatment of bone metastases. CONCLUSION: Local radiotherapy for PDT and MDT is routinely used among respondents of this survey, representing 12% of all German-speaking radiation oncologists. The timing of systemic therapy, fractionation schedules, and field sizes are handled differently and remain an area of active investigation.

MR-guided SBRT boost for patients with locally advanced or recurrent gynecological cancers ineligible for brachytherapy: feasibility and early clinical experience.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) followed by a brachytherapy (BT) boost is the standard of care for patients with locally advanced or recurrent gynecological cancer (LARGC). However, not every patient is suitable for BT. Therefore, we investigated the feasibility of an MR-guided SBRT boost (MRg-SBRT boost) following CRT of the pelvis. MATERIAL AND METHODS: Ten patients with LARGC were analyzed retrospectively. The patients were not suitable for BT due to extensive infiltration of the pelvic wall (10%), other adjacent organs (30%), or both (50%), or ineligibility for anesthesia (10%). Online-adaptive treatment planning was performed to control for interfractional anatomical changes. Treatment parameters and toxicity were evaluated to assess the feasibility of MRg-SBRT boost. RESULTS: MRg-SBRT boost was delivered to a median total dose of 21.0 Gy in 4 fractions. The median optimized PTV (PTVopt) size was 43.5ccm. The median cumulative dose of 73.6Gy10 was delivered to PTVopt. The cumulative median D2ccm of the rectum was 63.7 Gy; bladder 72.2 Gy; sigmoid 65.8 Gy; bowel 59.9 Gy (EQD23). The median overall treatment time/fraction was 77 min, including the adaptive workflow in 100% of fractions. The median duration of the entire treatment was 50 days. After a median follow-up of 9 months, we observed no CTCAE ≥ °II toxicities. CONCLUSION: These early results report the feasibility of an MRg-SBRT boost approach in patients with LARGC, who were not candidates for BT. When classical BT-OAR constraints are followed, the therapy was well tolerated. Long-term follow-up is needed to validate the results.

Outcome after PSMA-PET/CT-based salvage radiotherapy for nodal recurrence after radical prostatectomy.

PURPOSE: Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. METHODS: A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method and uni- and multivariate analysis was performed. RESULTS: Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1-40.1) in patients with bcP and 1.4 ng/ml (range 0.3-5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD21.5 Gy of 66 Gy (60-70 Gy) was delivered to the prostatic fossa, 70 Gy (66-72 Gy) to the local recurrence, if present, 65.1 Gy (56-66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4-50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. CONCLUSIONS: Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome.

Interstitial High-Dose-Rate Brachytherapy of Liver Metastases in Oligometastatic Patients.

Local ablative treatments have emerged as a promising treatment strategy for patients with oligometastatic disease. Among others, interstitial brachytherapy (iBT) is an upcoming treatment option for unresectable liver metastases. We report the feasibility and oncologic outcome of iBT of oligometastatic liver metastases performed in patients with limited tumor burdens in a high-volume center. Patients undergoing iBT between August 2017and March 2019 were included. A retrospective analysis of patient outcomes and treatment complications was performed. Patients treated for metastatic colorectal carcinoma (CRC) were compared to other histologies. A total of 141 iBT procedures were performed in 106 patients (male:52; female:54) and 244 liver metastases. Overall, 51% (54/106) of patients had a diagnosis of metastatic CRC. The median follow-up was 9 months, and overall survival (OS) was 92.3% at 6 months and 76.3% at 12 months. Local-relapse-free survival (LRFS) was 88.4% at 6 months and 71.5% at 12 months, with a significant difference between patients with CRC (84.1% and 50.6%) versus other histologies (92.4% and 92.4%, p < 0.001). A sub-group analysis showed a significant advantage in patients with CRC receiving a minimal dose (D100) of 20 Gy to the planning target volume. Treatments of smaller total liver-tumor volumes (<18 ccm) resulted in better LRFS rates. iBT is a safe and effective treatment approach for oligometastatic liver disease. A higher treatment dose is needed for patients with CRC. Moreover, lower metastatic burdens may be favorable for LRFS. Prospective studies are needed to assess the role of iBT in the oligometastatic setting as an alternative to other local ablative treatment approaches in patients with liver metastases.

Patient-Reported and Oncological Outcomes of Salvage Therapies for PSMA-Positive Nodal Recurrent Prostate Cancer: Real-Life Experiences and Implications for Future Trial Design.

INTRODUCTION: The role of salvage lymph node dissection (SLND) and radiotherapy (SLNRT) in the management of nodal-only recurrent prostate cancer (PC) remains controversial. In addition, impact on health-related quality of life (HRQOL) has not been adequately evaluated yet. MATERIALS AND METHODS: Analysis was limited to patients that were diagnosed with nodal-only recurrent PC via PSMA-PET/CT. SLND was performed via open approach. For SLNRT, dose regimens were normo- or slightly hypo-fractionated with a simultaneous boost to the PET-positive recurrences. EORTC QLQ-C30 and PR-25 questionnaires were used to assess HRQOL. Continence status was assessed using daily pad usage and the validated ICIQ-SF questionnaire. For multivariable analysis, Cox regression models were used (p<0.05). RESULTS: 138 patients (SLND: 71; SLNRT: 67) were included in the retrospective analysis. Median follow-up was 47 months (mo) for SLNRT patients (IQR 40-61), and 33mo for SLND patients (IQR 20-49; p<0.001). In total, 61 patients (91.0%) in the SLNRT cohort and 43 patients (65.2%; p<0.001) in the SLND cohort underwent ADT anytime during the follow-up period. In multivariate Cox regression analysis, SLNRT could be confirmed as an independent predictor for increased PSA progression-free survival (PFS; HR 0.08, 95%CI 0.040 - 0.142, p<0.001). Estimated median metastasis-free survival (MFS) was 70mo for the total cohort without statistically significant differences between both subgroups (p=0.216). There were no significant differences regarding general HRQOL, daily pad usage, and ICIQ-SF scores between the respective cohorts. CONCLUSIONS: In a large contemporary series of patients with nodal-only recurrent PC based on PSMA-PET/CT staging, we observed significantly increased PSA PFS in patients undergoing SLNRT while no significant differences could be observed in MFS, and functional outcomes including HRQOL.

Outcomes of metastasis-directed therapy of bone oligometastatic prostate cancer.

BACKGROUND: The aim of this work was to investigate the outcome of metastasis-directed radiotherapy (MDT) in prostate cancer patients with bone metastases following current ESTRO/EORTC subclassifications for oligometastatic disease. METHODS: Clinical data of 80 consecutive oligometastatic patients with 115 bone lesions receiving MDT between 2011 and 2019 were retrospectively evaluated. Hormone-sensitive (77.5%) and castrate-resistant (22.5%) patients were included. MDT was delivered with conventional fractionated or stereotactic body radiotherapy (SBRT) techniques. Kaplan-Meier method, log rank test, as well as Cox regression were used to calculate local control (LC) and biochemical and clinical progression-free survival (bPFS/cPFS). RESULTS: At the time of MDT 31% of patients had de-novo synchronous oligometastatic disease, 46% had de-novo metachronous oligorecurrence after primary treatment and 23% had either de-novo oligoprogressive disease, repeat oligometastatic disease or induced oligometastatic disease. The median BED3 was 93.3 Gy (range 75.8-95.3 Gy). Concomitant ADT was administered in 69% of patients. After a median follow-up of 23 months the median bPFS and cPFS were 16.5 and 21.5 months, respectively. The 2-year LC rate was 98.3%. In multivariate analysis, age ≤ 70 (HR = 2.60, 95% CI 1.20-5.62, p = 0.015) and concomitant ADT (HR = 0.26, 95% CI 0.12-0.58, p = 0.001) significantly correlated with cPFS. Category of oligometastatic disease and hormone-sensitivity were predictive for cPFS in univariate analysis. Of 45 patients with biochemical relapse, nineteen patients (42.2%) had repeat oligometastatic disease. Fourteen patients (31%) underwent a second course of MDT. No patients experienced grade ≥ 3 toxicities. CONCLUSIONS: MDT is safe and offers high local control rates in bone oligometastases of prostate cancer. At 2 years after treatment, more than 2 out of 5 patients are progression-free. Trial registration Retrospectively registered.

Feasibility and Early Clinical Experience of Online Adaptive MR-Guided Radiotherapy of Liver Tumors.

PURPOSE: To assess the feasibility and early results of online adaptive MR-guided radiotherapy (oMRgRT) of liver tumors. METHODS: We retrospectively examined consecutive patients with primary or secondary liver lesions treated at our institution using a 0.35T hybrid MR-Linac (Viewray Inc., Mountain View, CA, USA). Online-adaptive treatment planning was used to account for interfractional anatomical changes, and real-time intrafractional motion management using online 2D cine MRI was performed using a respiratory gating approach. Treatment response and toxicity were assessed during follow-up. RESULTS: Eleven patients and a total of 15 lesions were evaluated. Histologies included cholangiocarcinomas and metastases of neuroendocrine tumors, colorectal carcinomas, sarcomas and a gastrointestinal stroma tumor. The median BED10 of the PTV prescription doses was 84.4 Gy (range 59.5-112.5 Gy) applied in 3-5 fractions and the mean GTV BED10 was in median 147.9 Gy (range 71.7-200.5 Gy). Online plan adaptation was performed in 98% of fractions. The median overall treatment duration was 53 min. The treatment was feasible and successfully completed in all patients. After a median follow-up of five months, no local failure occurred and no ≥ grade two toxicity was observed. OMRgRT resulted in better PTV coverage and fewer OAR constraint violations. CONCLUSION: Early results of MR-linac based oMRgRT for the primary and secondary liver tumors are promising. The treatment was feasible in all cases and well tolerated with minimal toxicity. The technique should be compared to conventional SBRT in further studies to assess the advantages of the technique.

Radiotherapy of oligometastatic prostate cancer: a systematic review.

BACKGROUND: Due to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients. METHODS: A systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence. FINDINGS: Evidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called "synchronous" versus "metachronous" oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of 68Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing. CONCLUSIONS: To our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.

Outcome After 68Ga-PSMA-11 versus Choline PET-Based Salvage Radiotherapy in Patients with Biochemical Recurrence of Prostate Cancer: A Matched-Pair Analysis.

The purpose of this analysis was primarily to analyze biochemical-recurrence free survival (BRFS) after positron emission tomography (PET)-guided salvage radiotherapy (sRT) in a large cohort, and to further compare BRFS after PSMA vs. choline PET/ computer tomography (CT)-based sRT. This retrospective analysis is based on 421 patients referred for PSMA or choline PET/CT after radical prostatectomy due to biochemically recurrent or persistent disease. BRFS (PSA: 0.2 ng/mL) was defined as the study endpoint. Cox regression analyses were performed to assess the impact of different clinical parameters on BRFS. Additionally, propensity score matching was performed to adjust patient cohorts (PSMA vs. choline PET/CT-based sRT). The median follow-up time was 30 months. BRFS at three years after sRT was 58%. In the multivariate analysis, only PSA before PET imaging and PSA before sRT were significantly associated with BRFS (p < 0.05). After propensity score matching, 272 patients were further analyzed; there was no significant difference in three-year BRFS between patients with PSMA PET-based vs. choline PET-based sRT (55% vs. 63%, p = 0.197). The present analysis confirmed the overall high BRFS rates after PET-based sRT and the strong prognostic effect of PSA level prior to sRT. PSMA PET-based sRT did not have superior BRFS rates when compared with choline PET-based sRT.

Establishment and Validation of an Individualized Cell Cycle Process-Related Gene Signature to Predict Cancer-Specific Survival in Patients with Bladder Cancer.

More accurate models are essential to identify high-risk bladder cancer (BCa) patients who will benefit from adjuvant therapies and thus helpful to facilitate personalized management of BCa. Among various cancer-related hallmarks and pathways, cell cycle process (CCP) was identified as a dominant risk factor for cancer-specific survival (CSS) in BCa. Using a series of bioinformatic and statistical approaches, a CCP-related gene signature was established, and the prognostic value was validated in other independent BCa cohorts. In addition, the risk score derived from the gene signature serves as a promising marker for therapeutic resistance. In combination with clinicopathological features, a nomogram was constructed to provide more accurate prediction for CSS, and a decision tree was built to identify high-risk subgroup of muscle invasive BCa patients. Overall, the gene signature could be a useful tool to predict CSS and help to identify high-risk subgroup of BCa patients, which may benefit from intensified adjuvant therapy.

PSMA-positive nodal recurrence in prostate cancer : Salvage radiotherapy is superior to salvage lymph node dissection in retrospective analysis.

PURPOSE: This analysis compares salvage lymph node dissection (SLND) to salvage lymph node radiotherapy (SLNRT) of 68Ga-PSMA PET-positive nodal recurrences after radical prostatectomy (RPE). METHODS: A total of 67 SLNRT and 33 SLND consecutive patients with pelvic and/or para-aortic nodal recurrences after RPE were retrospectively analyzed. Biochemical recurrence-free survival rates (bRFS; PSA <0.2 ng/mL) were calculated according to Kaplan-Meier and survival curves were compared using the log rank test. For multivariable analysis, binary logistic regression analysis was performed (p < 0.05). RESULTS: Median follow-up was 17 months (range, 6-53 months) in SLND patients and 31 months (range, 3-56 months) in SLNRT patients (p = 0.027). SLNRT patients had significantly more tumours of pT3 and pT4 category (82% vs. 67%; p = 0.006), pathologically involved lymph nodes (45% vs. 27%; p = 0.001) and positive surgical margins (54% vs. 12%; p = 0.001) at time of RPE than SLND patients. PSA persistence after RPE was significantly more frequently observed in the SLNRT cohort (73% vs. 27%; p = 0.001). There was no significant difference in the distribution of PET-positive lymph nodes. Median PSA before SLND was higher than before SLNRT (3.07 ng/ml vs. 1.3 ng/ml; p = 0.393). The 2­year bRFS was significantly higher in the SLNRT vs. the SLND cohort (92% vs. 30%; p = 0.001) with lower rates of distant metastases (21% vs. 52%; p = 0.002) and secondary treatments (5% vs. 39%; p = 0.011) irrespective of ongoing androgen deprivation therapy at last contact. In multivariable analysis, SLNRT was significantly associated with prolonged bRFS (regression coefficient 1.436, hazard ratio 4.204, 95% CI 1.789-9.878; p = 0.001). CONCLUSION: Based on this retrospective study SLNRT might be the preferred treatment option for patients with nodal recurrence after previous RPE.

Impact of a low FODMAP diet on the amount of rectal gas and rectal volume during radiotherapy in patients with prostate cancer - a prospective pilot study.

BACKGROUND: Small inter- and intrafractional prostate motion was shown to be a prerequisite for precise radiotherapy (RT) of prostate cancer (PCa) to achieve good local control and low rectal toxicity. As rectal gas and rectal volume are known to have a relevant effect on prostate motion, this study aims to reduce these parameters by using a Low FODMAP Diet (LFD) and to show feasibility of this intervention. METHODS: We compared a prospective intervention group (IG, n = 25) which underwent RT for PCa and whose patients were asked to follow a LFD during RT with a retrospective control group (CG, n = 25) which did not get any dietary advice. In the planning CT scan and all available cone beam CT scans rectal gas was classified based on a semiquantitative score (scale from 1 to 5) and rectal volume was measured. Furthermore, patients' compliance was evaluated by a self-assessment questionnaire. RESULTS: Clinical and treatment characteristics were well balanced between both groups. A total of 266 (CG, 10.6 per patient) and 280 CT scans (IG, 11.2 per patient), respectively, were analysed. The frequency distribution of gas scores differed significantly from each other (p < .001) with the IG having lower scores. Rectal volume was smaller in the IG (64.28 cm3, 95% CI 60.92-67.65 cm3, SD 28.64 cm3) than in the CG (71.40 cm3, 95% CI 66.47-76.32 cm3, SD 40.80 cm3) (p = .02). Mean intrapatient standard deviation as a measure for the variability of rectal volume was 22 cm3 in the IG and 23 cm3 in the CG (p = .81). Patients' compliance and contentment were satisfying. CONCLUSIONS: The use of a LFD significantly decreased rectal gas and rectal volume. LFD was feasible with an excellent patients' compliance. However, prospective trials with a larger number of patients and a standardized evaluation of gastrointestinal toxicity and quality of life are reasonable. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00012955. Registered 29 August 2017 - Retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012955.

A Novel Gene Signature-Based Model Predicts Biochemical Recurrence-Free Survival in Prostate Cancer Patients after Radical Prostatectomy.

Abstract: Currently, decision-making regarding biochemical recurrence (BCR) following prostatectomy relies solely on clinical parameters. We therefore attempted to develop an integrated prediction model based on a molecular signature and clinicopathological features, in order to forecast the risk for BCR and guide clinical decision-making for postoperative therapy. Using high-throughput screening and least absolute shrinkage and selection operator (LASSO) in the training set, a novel gene signature for biochemical recurrence-free survival (BCRFS) was established. Validation of the prognostic value was performed in five other independent datasets, including our patient cohort. Multivariate Cox regression analysis was performed to evaluate the importance of risk for BCR. Time-dependent receiver operating characteristic (tROC) was used to evaluate the predictive power. In combination with relevant clinicopathological features, a decision tree was built to improve the risk stratification. The gene signature exhibited a strong capacity for identifying high-risk BCR patients, and multivariate Cox regression analysis demonstrated that the gene signature consistently acted as a risk factor for BCR. The decision tree was successfully able to identify the high-risk subgroup. Overall, the gene signature established in the present study is a powerful predictor and risk factor for BCR after radical prostatectomy.

Impact of 68Ga-PSMA PET/CT on the Radiotherapeutic Approach to Prostate Cancer in Comparison to CT: A Retrospective Analysis.

68Ga-prostate-specific membrane antigen PET/CT (68Ga-PSMA PET/CT) offers unprecedented accuracy for staging of primary, persistent, or recurrent prostate cancer. Thus, we hypothesized that 68Ga-PSMA PET/CT before radiotherapy significantly affects the radiotherapeutic approach in comparison to the current standard, a CT-based approach. Methods: Between February 2014 and December 2017, 172 patients underwent 68Ga-PSMA PET/CT before radiotherapy and were included in this retrospective analysis. Twenty-two (13%) patients were referred for primary definitive radiotherapy, 51% (88/172) for prostate-specific antigen (PSA) persistence, and 36% (62/172) for PSA recurrence after radical prostatectomy. An experienced radiation oncologist, masked to the CT and PET/CT results, decided on the radiation treatment management of all patients on the basis of the clinical and pathologic variables. The potential increase in diagnostic accuracy, and the subsequent change in radiotherapeutic approach, were documented separately for PET/CT versus CT. Results: The overall detection rate was 70% (120/172) for 68Ga-PSMA PET/CT. Patients with a pre-PET/CT PSA level of more than 0.5 ng/mL (98/111; 88%) had PET-positive results significantly more often. Overall, PSMA PET/CT revealed 171 lesions, PET alone 156, and CT alone 85. For all patients, a continuous diagnostic increase in positive findings was observed for primary tumor/local recurrence (CT, 18%, vs. PET/CT, 37%), pelvic lymph nodes (CT, 21%, vs. PET/CT, 44%), and distant metastases (CT, 7%, vs. PET/CT, 19%) when comparing CT with PET/CT. Compared with CT, the combination of PET/CT information resulted in a change in treatment in 107 of 172 (62%) patients, that is, 8 of 22 (36%) patients before any treatment, 31 of 62 (50%) with PSA recurrence, and 68 of 88 (77%) with PSA persistence. Comparing the different radiotherapy indications with one another, there was a higher rate of change in management for postoperative patients than for patients before any treatment. Conclusion: Compared with conventional CT, 68Ga-PSMA PET/CT had a remarkable impact on radiotherapeutic approach, especially in postoperative patients. Thus, considering the growing amount of data on the impact of 68Ga-PSMA PET/CT on postoperative patients, 68Ga-PSMA PET/CT has recently been endorsed by a few cancer guidelines as an imaging modality in patients with PSA persistence or recurrence (e.g., the German S3 guideline and the European Association of Urology guideline).

Pattern of care of adjuvant radiotherapy in male breast cancer patients in clinical practice: an observational study.

BACKGROUND AND PURPOSE: Due to the rarity of male breast cancer (male BC), no consensus has been reached regarding the most appropriate curative treatment strategy. The objective of the present observational study was to identify patient and tumor characteristics and assess the role of radiotherapy (RT) in clinical practice. METHODS: Between 1998 and 2014, data of male BC patients treated at two breast centers were consecutively collected and retrospectively analyzed. Patients were stratified based on the addition of adjuvant RT. Data on overall survival (OS) and local recurrence-free survival (LRFS) were estimated with the Kaplan-Meier method and compared by the log-rank test. RESULTS: A consecutive cohort of 58 male BC patients was evaluated. Median follow-up was 56 months. Twenty-one patients (36.2%) received adjuvant RT. Overall, patients undergoing postoperative RT were characterized by more high-risk features. Patients receiving postoperative RT had significantly more frequently a high UICC stage (50 vs. 9.7% UICC III, p = 0.018) and positive lymph nodes as compared to patients undergoing surgery alone (65 vs. 34.4% pN+, p = 0.046). Accordingly, there was a higher proportion of patients receiving axillary lymph node dissection in the RT group (71.4 vs. 35.6%). Mastectomy was performed in 31/37 (86.1%) in the surgery group as compared to 14/21 (66.7%) in patients receiving postoperative RT. In addition, RT patients were more likely to receive endocrine therapy (78.9 vs. 39.3%, p = 0.016). Outcome was not significantly different between the groups (5-year LRFS: 89.8 vs. 80.0%, p = 0.471 and 5­year OS 88.4 vs. 88.9%, p = 0.819). CONCLUSION: The present observational study evaluated the pattern of care in male BC patients treated in clinical practice. Due to its rarity, randomized clinical trials are unlikely and male BC remains an entity with a poor evidence base. Nevertheless, RT remains a crucial component of the multidisciplinary treatment strategy in male BC.