Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy-a multicenter retrospective study.

PURPOSE: Approximately 40-70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in 68gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases' site on outcome after metastasis-directed radiotherapy (MDR). METHODS: Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis. RESULTS: All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04-47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03-18.30). After a median follow-up of 16 months (1-57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up. CONCLUSION: Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months.

Combination of stereotactic radiotherapy and targeted therapy: patterns-of-care survey in German-speaking countries.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is increasingly used in metastasized patients receiving targeted/immunotherapy. Information on safety and effectivity of concurrent SBRT and targeted/immunotherapy remains limited, resulting in a lack of consensus on treatment strategies. This study aimed to investigate how SBRT-experienced centers in German-speaking countries combine both therapies. MATERIALS AND METHODS: Patterns-of-care of combined treatment with SBRT and targeted/immunotherapy were assessed in 27 radiation oncology centers (19 German, 1 Austrian and 7 Swiss centers). A survey was performed to analyze the details of SBRT, SBRT planning and combined modality treatment. Consensus was defined as ≥75% agreement among participants. RESULTS: Most participants (60%) were university centers. SBRT for oligometastases has been performed since the year 2008 (median, range 1997-2016), since then a median of 140 cases (5-1100) of SBRT have been performed. In all, 67% performed concurrent SBRT and targeted agents. BRAF inhibitors and VEGF/EGFR inhibitors (bevacizumab [90%], erlotinib [11%], sorafenib [19%], lapatinib [4%]) were considered a contraindication. Bevacizumab was never given simultaneously with SBRT; other agents were given concurrently in 7-52% of centers. A majority (59%) paused targeted agents 1 week before/after SBRT. Only 1 center reduced SBRT dose when combined with targeted agents. CONCLUSION: Although evidence for safety and efficacy of concurrent SBRT and targeted agents is limited, it is regularly performed outside of clinical trials. The survey showed consensus not to combine SBRT with antiangiogenic agents, especially bevacizumab. Furthermore, SBRT with concurrent BRAF inhibitors should be practiced with caution and BRAF inhibitors should be paused at least 1 week before SBRT.

Clinical efficacy of bipolar radiofrequency ablation of small renal masses.

PURPOSE: The new development of bipolar radiofrequency ablation (RFA) can overcome problems observed with monopolar RFA for the treatment of small renal masses (SRM). Energy is more homogeneously delivered, and higher current densities can be used. Data on treatment of renal tumors with bipolar RFA are still limited. The aim of this study was to examine the clinical efficacy of bipolar multiprobe RFA for treatment of SRM, according to the IDEAL recommendations. METHODS: Ten SRMs in 10 consecutive patients were ablated using multipolar RFA. Outcome measures were technical success, applied energy, and observed complications. Hereafter, tumors were excised in an open surgical fashion and histologically analyzed for RFA lesion volume and presence of viable cells. RESULTS: Median patient age was 59.5 (range 39.2-69.8) years. Median tumor diameter was 2.5 (range 1.6-4.5) cm. Technical success rate was 100 %. In five procedures, two probes were used, and in five procedures three probes were used. Median ablation time was 18 (range 12-38) minutes in which a median of 30.5 (range 23.6-102) kJ was applied. Complications included one patient who developed a urinoma. Median ablated volume was 4.4 (2.2-29.9) cm(3). In all cases, the ablated volume was larger than the tumor. No viable cells were present within the ablated tissue. CONCLUSIONS: Multipolar RFA is clinically successful for treating SRMs. Using preoperatively calculated energy settings, tailored size tumor lesions could be created. Clinical efficacy and oncological outcomes need to be investigated further in studies using multipolar RFA in a percutaneous fashion.

FDG PET versus CT radiomics to predict outcome in malignant pleural mesothelioma patients.

BACKGROUND: Careful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and harbors a high risk of substantial toxicity. Radiomics-a quantitative method for image analysis-has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated. MATERIALS AND METHODS: This study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS. RESULTS: For the PFS a concordance index (c-index) of 0.67 (95% CI 0.52-0.82) and 0.66 (95% CI 0.57-0.78) for the training cohort (n = 36) and internal validation cohort (n = 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS. CONCLUSION: We were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.

SBRT for oligoprogressive oncogene addicted NSCLC.

Lung cancer is one of the leading causes of cancer death in men and women and treatment outcome continues to lag behind other common cancer types. A subset of lung adenocarcinoma patients exhibit a somatic mutation in EGFR or an ALK rearrangement. In these patients, targeted TKI therapy results in higher response rates, improved PFS and reduced side effects compared with platinum-based chemotherapy. Despite initial activity of the TKIs, ultimately all patients present with disease progression after about a year on TKI therapy due to resistance development. About 15-47% of patients present with limited oligoprogressive disease (OPD): such patients show only a limited number of metastases with progression in radiological imaging. Radical local treatment to all oligoprogressive lesions is thought to eradicate the de-differentiated clones and restore overall sensitivity of the metastatic disease. Retrospective studies suggest that aggressive local treatment using stereotactic body radiotherapy (SBRT), surgery or others can be used to eradicate TKI-resistant subpopulations enabling prolonged TKI treatment "beyond progression", which may lead to increased PFS and overall survival. This review focuses on the biological background of resistance development, systemic and local treatment options with a focus on SBRT, as well as challenges in defining the state of OPD and current clinical studies in oligoprogressive oncogene addicted NSCLC.

Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma.

PURPOSE: Approximately one-third of all Renal Cell Carcinoma (RCC) patients undergoing a nephrectomy face metastatic disease. The availability of novel therapeutics for metastatic patients underscores the importance of identifying patients at risk of recurrence or patients responding well to specific therapies. Unlike clear cell RCC (ccRCC), information on biomarkers for the papillary subtype (pRCC) remains limited. In this review, we identified tissue markers that are differentially expressed between subtypes and may be of diagnostic use. In addition, markers with promising prognostic power for ccRCC and/or pRCC are described and their clinical value is discussed. MATERIALS AND METHODS: To identify diagnostic markers that differentiate between pRCC and ccRCC a Pubmed search was performed, limited to original articles published in the English language between 1990 and 2009, using the terms pRCC/papillary RCC/papillary renal cell carcinoma/papillary kidney cancer, biomarker/biomarkers, protein expression, mass spectrometry and immunohistochemistry. Prognostic markers for ccRCC and pRCC were identified using the search terms kidney cancer, renal cell carcinoma, prognostic marker, biomarker and prognosis. Only markers with independent prognostic value in multivariable analysis were included. RESULTS: 25 proteins are differentially expressed between ccRCC and pRCC, reflecting the molecularly distinct nature of these subtypes. 5 of these proteins were externally validated, which shows their diagnostic potential. Whereas 48 biomarkers with independent prognostic power have been identified for ccRCC patients, only CD44, CA9, p53, Ki67 and PCNA have shown prognostic value in multiple studies. Expression of IMP-3 and VEGF-R2 are independent predictors of survival of pRCC patients, although this is shown in single studies. CONCLUSIONS: So far 5 validated diagnostic markers are able to differentiate between ccRCC and pRCC. Few independent prognostic markers have been identified for pRCC in single studies, compared to numerous biomarkers identified for the more common ccRCC. Despite the abundance of promising markers for ccRCC, their exact role in clinical decision making still needs to be established through validation studies.