Strahlentherapie und Onkologie

Wirksamkeit und Sicherheit einer Kohlenstoffionentherapie lokal rezidivierter Rektumkarzinome: Ergebnisse der J‑CROS-Studie 1404 Rektum

Ganzbrust- oder Teilbrustbestrahlung nach 5 Jahren aus Patientensicht: Longitudinale Analyse der IMPORT-LOW-Phase III-Studie

Eine definitive Strahlentherapie mit einer Kurzzeit Androgendeprivationstherapie von 18 Monaten kann bei Patienten mit lokal begrenztem Prostatakarzinom mit hohen Risikofaktoren gegenüber dem Standard von 28–36 Monaten ausreichend sein

Adjuvant radiochemotherapy vs. chemotherapy alone in gastric cancer: a meta-analysis Abstract Background As an adjuvant therapeutic strategy in advanced gastric cancer, both adjuvant chemotherapy (CTx) and postoperative radiochemotherapy (RCTx) can be considered. Both approaches have been shown to improve overall survival compared to resection alone. Several prospective randomized trials have compared the two postoperative concepts. Methods We performed a literature search to identify prospective randomized trials which compared adjuvant chemotherapy to adjuvant radiochemotherapy in patients with advanced gastric cancer. As effect sizes, we extracted hazard ratios (HR) as well as event rates from the included trials for the endpoints overall survival, disease-free survival and locoregional control. Results We identified seven studies that enrolled 1807 patients overall. Combined radiochemotherapy showed no significant improvement of overall survival in comparison to chemotherapy alone (HR = 0.93; 95%CI: 0.82–1.06; p = 0.28). For disease-free survival (HR = 0.86; 95%CI: 0.76–0.98; p = 0.023) and locoregional control (odds ratio [OR] = 0.56; 95%CI: 0.42–0.75; p = <0.001) we detected significant advantages from the addition of radiation to chemotherapy. A subgroup analysis demonstrated an improvement in survival when the radiochemotherapy protocol was not de-intensified. Conclusions Adjuvant chemotherapy or radiochemotherapy demonstrate similar oncologic efficacy and therapy-associated toxicity. Individual patient characteristics should therefore determine the therapeutic approach in a multidisciplinary discussion. Irradiation added to standard-dose chemotherapy possibly results in a survival benefit.

Detectability and structural stability of a liquid fiducial marker in fresh ex vivo pancreas tumour resection specimens on CT and 3T MRI Abstract Purpose To test the detectability of a liquid fiducial marker injected into ex vivo pancreas tumour tissue on magnetic resonance imaging (MRI) and computed tomography (CT). Furthermore, its injection performance using different needle sizes and its structural stability after fixation in formaldehyde were investigated. Methods Liquid fiducial markers with a volume of 20–100 µl were injected into freshly resected pancreas specimens of three patients with suspected adenocarcinoma. X‑ray guided injection was performed using different needle sizes (18 G, 22 G, 25 G). The specimens were scanned on MRI and CT with clinical protocols. The markers were segmented on CT by signal thresholding. Marker detectability in MRI was assessed in the registered segmentations. Marker volume on CT was compared to the injected volume as a measure of backflow. Results Markers with a volume ≥20 µl were detected as hyperintensity on X‑ray and CT. On T1- and T2-weighted 3T MRI, marker sizes ranging from 20–100 µl were visible as hypointensity. Since most markers were non-spherical, MRI detectability was poor and their differentiation from hypointensities caused by air cavities or surgical clips was only feasible with a reference CT. Marker backflow was only observed when using an 18-G needle. A volume decrease of 6.6 ± 13.0% was observed after 24 h in formaldehyde and, with the exception of one instance, no wash-out occurred. Conclusions The liquid fiducial marker injected in ex vivo pancreatic resection specimen was visible as hyperintensity on kV X‑ray and CT and as hypointensity on MRI. The marker’s size was stable in formaldehyde. A marker volume of ≥50 µL is recommended in clinically used MRI sequences. In vivo injection is expected to improve the markers sphericity due to persisting metabolism and thereby enhance detectability on MRI.

Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia—a prospective observational study Abstract Purpose To prospectively evaluate the time course of pain response and toxicity after linear accelerator-based whole-nerve-encompassing radiosurgery (LINAC-SRS) using a uniform treatment schedule for dosing and target volume definition in patients with refractory trigeminal neuralgia. Methods From December 2012 to December 2016, 21 patients were treated using a standardized protocol. Patients received LINAC-SRS with 70 Gy to the cisternal portion while aiming for the 90% isodose to fully envelope the nerve in one cross-sectional plane. Data on pain, analgesics, and toxicity were gathered prospectively. Four time intervals (1–6, 6–12, 12–18, and 18–24 months) were defined and compared to baseline and each other. Results The median follow-up from radiotherapy was 16 months. Freedom from pain was achieved at least once in 90.5, 81.0, and 85.7% of patients for everyday pain, rest pain, and pain peaks, respectively. At 1–6 months, pain was significantly reduced in everyday routine (mean VAS, 2.0/10 vs. 5.8/10; P = 0.004), at rest (1.5/10 vs. 4.0/10; P = 0.002), and for pain peaks (2.9/10 vs. 10/10; P < 0.001), as was the number of analgesics (mean 1.5 vs. 2.9; P < 0.001). No significant increase in pain or analgesics was observed for subsequent time intervals. At last follow-up, reduction in pain compared to baseline for everyday routine (2.1/10 vs. 5.8/10; P = 0.010) and for pain peaks (3.3/10 vs. 10/10; P < 0.001) was significant, whereas it was not for rest pain (1.8/10 vs. 3.9/10; P = 0.073). Most toxicities were related to trigeminal nerve impairment, with 42.9% reporting new-onset hypoesthesia at last follow-up. Conclusion This study provides prospective data after whole nerve encompassing LINAC-SRS for trigeminal neuralgia. No significant pain relapse was observed.

Role of perilesional edema and tumor volume in the prognosis of non-small cell lung cancer (NSCLC) undergoing radiosurgery (SRS) for brain metastases Abstract Aim To assess the role of perilesional edema (PE) in non-small cell lung carcinoma (NSCLC) brain metastases (BM) undergoing radiosurgery (SRS). Methods This series includes 46 patients with 1–2 BM treated with SRS, selected out of all patients referred for radiotherapy (RT) for BMs over 5 years (2013 to 2017). Both the PE and gross tumor volume (GTV) were contoured on MRI images, and the PE/GTV ratio and PE + GTV value (TV, total volume) were calculated. Our clinical endpoints were brain recurrence free-survival, divided into local brain control (in field, LBC) and distant brain control (out of field, DBC) and overall survival (OS). We analyzed the role of the previously described volumetric parameters and of known clinical prognosticators (disease specific GPA, DS-GPA; chemotherapy, CHT) with Cox regression analyses. Results Only four patients (9%) developed in-field progression, whereas 10 patients (22%) showed new out-of-field BM and thirty-eight patients died in the follow up (83%). In univariate analysis, both volumetric parameters and clinical parameters were correlated with DBC and OS, whereas we did not find any correlation with LBC. In the multivariate analysis of DBC, the significant parameters were PE/GTV ratio (HR 0.302), sex (HR 0.131), and DS-GPA (HR 0.261). The OS multivariate analysis showed that the only significant parameters were DS-GPA (HR 0.478) and TV (HR: 1.038). Conclusion Our study, although with the limitations of a monocentric retrospective study analyzing a small cohort of patients, suggests the role of PE/GTV ratio for the development of new BMs. TV also seems to be correlated with OS, together with known clinical prognosticators. These findings, if validated in a larger prospective dataset, could help in selecting patients for the most suitable RT modality (or systemic therapy approach).

Predicting tumor responses and patient survival in chemoradiotherapy-treated patients with non-small-cell lung cancer using dynamic contrast-enhanced integrated magnetic resonance–positron-emission tomography Abstract Purpose We investigated whether radiologic parameters by dynamic contrast-enhanced (DCE) integrated magnetic resonance–positron-emission tomography (MR-PET) predicts tumor response to treatment and survival in non-metastatic non-small-cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT). Methods Patients underwent DCE integrated MR-PET imaging 1 week before CRT. The following parameters were analyzed: primary tumor size, gross tumor volume, maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), reverse reflux rate constant (kep), extracellular extravascular volume fraction (ve), blood plasma volume fraction (vp), and initial area under the time-concentration curve defined over the first 60 s post-enhancement (iAUC60). CRT responses were defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Results Thirty patients were included. Non-responders demonstrated higher baseline TLG (p = 0.012), and lower baseline Ktrans (p = 0.020) and iAUC60 (p = 0.016) compared to responders, indicating the usefulness of DCE integrated MR-PET to predict treatment responses. Receiver operating characteristic curve indicated that TLG has the best differentiation capability to predict responders. By setting the threshold of TLG to 277, the sensitivity, specificity, and accuracy were 66.7%, 83.3%, and 75.0%, respectively, with an area under the curve of 0.776. The median follow-up time was 19.6 (range 7.8–32.0) months. In univariate analyses, baseline TLG >277 (p = 0.005) and baseline Ktrans <254 (10−3 min−1; p = 0.015) correlated with poor survival after CRT. In multivariate analysis, baseline TLG >277 remained the significant factor in predicting progression (p = 0.012) and death (p = 0.031). Conclusions The radiologic parameters derived from DCE integrated MR-PET scans are useful for predicting treatment response in NSCLC patients treated with CRT; furthermore, these parameters are correlated with clinical and survival outcomes including tumor progression and death.

Re-irradiation in locally recurrent lung cancer patients Abstract Purpose Lung cancer remains one of the tumour diagnoses with high lethality, although innovative treatment approaches have yielded improvements in local control and survival rates. There is still no consensus on how to treat local relapse in patients after first-line treatments. Radiotherapy may be considered in this situation; however, data supporting its effectiveness are rare. The purpose of this retrospective analysis was to evaluate outcomes of patients re-irradiated for thoracic tumours in terms of overall survival (OS), local progression-free survival (LPFS), toxicity and dose–volume parameters. Patients and methods Sixty-two patients with locally recurrent previously irradiated lung cancer were analysed retrospectively (NSCLC n = 52, SCLC n = 10). Target volumes both in lung and mediastinum were re-irradiated with conventional three-dimensional or intensity-modulated radiotherapy techniques. Median overall dose of re-irradiation was 38.5 Gy (range 20–60 Gy) with a median single dose per fraction of 2 Gy (1.8–3.0 Gy). Clinical documents and treatment plans were evaluated. Results Median follow-up was 8.2 months (range 0–27 months). OS following re-irradiation was 9.3 months (range: 0–27 months) and LPFS was 6.5 months (range: 0–24 months). OS and LPFS were not affected by histology, total dose or patient age and gender. OS was improved in patients whose re-irradiation volumes included less than two mediastinal lymph node stations (p = 0.016). Twelve patients suffered from pneumonitis ≥grade II (19%) and two from pneumonitis grade III. One patient presumably died from pneumonitis grade V. A slight decline in forced expiratory volume (FEV1) was detected in post-re-irradiation lung function testing. Conclusions Re-irradiation is an option for patients with tumour recurrence to control local progression and lower the symptom burden. Oncological outcome appears to be affected by size, location of mediastinal target volumes and lung function. Prospective clinical trials are warranted to substantiate the role of re-irradiation in recurrent lung cancer.

Stereotactic body radiotherapy of central lung malignancies using a simultaneous integrated protection approach Abstract Aim It is recognized that stereotactic body radiotherapy (SBRT) for centrally located lung metastases is affected by higher rates of severe toxicity. In the present study, we report the clinical outcomes following a novel intensity-modulated radiotherapy prescription dose, termed simultaneous integrated protection (SIP), for nearby organs at risk (OARs). Materials and methods The prescribed total doses of SBRT were 70 Gy in 10 fractions and 60 Gy in 8 fractions. For ultra-centrally located lesions, a dose of 60 Gy in 10 fractions was delivered. The main planning instructions were: (1) to remain within the limits of the given dose constraints for an OAR; (2) to make use of the maximum possible dose to the OARs to minimize dose inhomogeneity for the Planning Target Volume (PTV). SBRT-related toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The primary clinical endpoint was the SBRT-related toxicity. Secondary endpoint was local control. Results Forty patients affected by a single central malignancy were analyzed. The median follow-up was 20 months (range, 6–58 months). Acute and late clinical pulmonary toxicity ≥grade 2 was recorded in 2 out of 40 patients (5%) and 3 out of 40 patients (7%), respectively. No patient experienced cardiac toxicity. No narrowing or stenosis of any airway or vessel was registered. One-year local control rate was 91%. The median time to local progression was 13 months (range, 6–46 months). Conclusion SBRT using a PTV-SIP approach for single central lung metastases achieved low SBRT-related toxicity with acceptable local control.