Low-dose total skin electron beam therapy: Quality of life improvement and clinical impact of maintenance and adjuvant treatment in patients with mycosis fungoides or Sezary syndrome Abstract Purpose Total skin electron beam therapy (TSEBT) has proved to be a safe and effective treatment for cutaneous T‑cell lymphomas. Here, we examined the impact of this treatment on patient quality of life and outcome. Patients and methods Forty-four patients with mycosis fungoides (MF) or Sezary syndrome (SS) received 48 TSEBT courses with a median dose of 12 Gy within the past 8 years at our institute. Patient and treatment characteristics for these cases as well as the impact of TSEBT on quality of life and duration of response were retrospectively analyzed and compared. Results The median modified Severity-Weighted Assessment Tool score before the start of TSEBT was 44. The overall response rate was 88%, with a complete response (CR) rate of 33%. The median follow-up period was 13 months. The median duration of response (DOR) and progression-free survival (PFS) for the entire cohort were 10 months and 9 months, respectively. Patient-reported symptom burden was measured with the Dermatological Life Quality Index and Skindex-29 questionnaires. The mean symptom reductions were 6 ± 8 (P = 0.005) and 21 ± 24 (P = 0.002), respectively. In the Functional Assessment of Cancer Therapy-General Assessment, significant improvements in the emotional (P = 0.03) domains were observed after TSEBT. Patients who received maintenance or adjuvant treatments had a longer PFS (P = 0.01). Conclusion TSEBT improved disease symptoms and significantly improved emotional domains of patients’ quality of life in patients with MF or SS. In addition, our results indicate that maintenance or adjuvant therapy after TSEBT may improve the PFS.

Addition of chemotherapy to hyperfractionated radiotherapy in advanced head and neck cancer—a meta-analysis Abstract Background Adding concurrent chemotherapy (CTx) to definitive radiation therapy (RT) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) improves overall survival. A comparable effect has been reported for hyperfractionated radiotherapy (HFX-RT) alone. Adding concurrent CTx to HFX-RT has been investigated in multiple trials, yet an evident effect on oncological outcomes and toxicity profile has not been established to date. Thus, the aim of the current study was to perform a meta-analysis on the clinical outcome and toxicity of the addition of CTx to HFX-RT. Patients and methods We performed a literature search for randomized controlled trials comparing HFX-RT alone to HFX-RT + concurrent CTx in patients with LA-HNSCC undergoing definite RT. A meta-analysis was performed using the event rates and effect-sizes for overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), distant metastasis-free survival and distant recurrence-free interval (DMFS/DMFI) and locoregional recurrence (LRR) as investigated endpoints. Furthermore, we compared selected acute and late toxicities in the included studies. Statistical analysis was performed using the Microsoft Excel (Microsoft, Redmont, WA, USA) add-in MetaXL 5.3 (EpiGear International, Sunrise Beach, Australia), utilizing the inverse variance heterogeneity model. Results We identified six studies (n = 1280 patients) randomizing HFX-RT alone and the concurrent addition of CTx. OS was significantly improved in the HFX-RT + CTx group (HR = 0.77, CI95% = 0.66–0.89; p = <0.001). We found similar results in PFS (HR = 0.74, CI95% = 0.63–0.87; p < 0.001) and CSS (HR = 0.72, CI95% = 0.60–0.88; p = 0.001). In contrast, acute toxicities (≥grade 3 mucositis, ≥grade 3 dysphagia) and late adverse events including ≥grade 3 xerostomia, ≥grade 3 subcutaneous, ≥grade 3 bone, ≥grade 3 skin toxicity, and ≥grade 3 dysphagia did not significantly differ between the two groups. Conclusion The addition of CTx to HFX-RT in the definitive treatment of advanced LA-HNSCC improves OS, CSS, PFS, and LRR without a significant increase in high-grade acute and late toxicities.

Role of upper abdominal reirradiation for gastrointestinal malignancies: a systematic review of cumulative dose, toxicity, and outcomes on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Abstract Purpose Abdominal recurrences of gastrointestinal malignancies are common. Evidence in clinical studies has shown that re-irradiation (Re-I) is tolerable and efficient in different tumor locations. In contrast, little clinical data are available on normal long-term Re‑I tolerance doses. A systematic review of upper abdominal Re‑I was performed with the aim of exploring the cumulative dose, toxicity, and outcomes. Methods A computerized search was undertaken in MEDLINE, EMBASE, OVID, and the Cochrane database. Only studies reporting toxicity and/or outcomes were taken into consideration. To improve the comparability of the different Re‑I regimens and assess the relationship between Radiotherapy (RT) dose and toxicity, the equivalent dose in 2‑Gy fractions was calculated according to the linear quadratic model. Results Sixteen studies met the inclusion criteria, with the total patients numbering 408. Median follow-up Re‑I ranged from 5.9 to 45 months. The median time elapsed since previous RT treatment was 15 months (2–162 months). Re‑I prescription doses were variable (22.5 Gy in 3 fractions to 126.5 Gy with 125I). Cumulative doses calculated for acute- and late-responding tissues ranged from 67.25 to 136 Gy and 30.3 to 188.38 Gy, respectively. Comprehensively, the pooled ≥G3 toxicity was 12% (95%CI: 7.6–19%). The overall 1‑year survival and local recurrence-free survival rates were 53.7% (95%CI: 45.6–63.2%) and 66.5% (95% CI: 58.7–75.4%), respectively. Pain improvement was reported in 66.9% of patients. Conclusion Due to limited evidence as a result of the retrospective design of the majority of the studies, our review suggests that upper abdominal Re‑I is effective in terms of local control and palliation, with a moderate rate of severe toxicities.

Bevacizumab as a treatment option for radiation necrosis after cranial radiation therapy: a retrospective monocentric analysis Abstract Background and purpose Radiation necrosis is a possible adverse event after cranial radiation therapy and can cause severe symptoms, such as an increased intracranial pressure or neurological deterioration. The vascular endothelial growth factor (VEGF) inhibitor bevacizumab (BEV) has been shown to be a feasible therapeutic option for symptomatic radiation necrosis, either when traditional antiedematous steroid treatment fails, or as an alternative to steroid treatment. However, to the best of our knowledge, only one randomized study with a rather small cohort exists to prove a beneficial effect in this setting. Therefore, further real-life data are needed. This retrospective monocentric case study evaluates patients who received BEV due to radiation necrosis, with a specific focus on the respective clinical course. Methods Using the internal database for pharmaceutical products, all patients who received BEV in our department were identified. Only patients who received BEV as symptomatic treatment for radiation necrosis were included. Patient characteristics, symptoms before, during, and after treatment, and the use of dexamethasone were evaluated using medical reports and systematic internal documentation. The symptoms were graded using CTCAE version 5.0 for general neurological symptoms. Symptoms were graded directly before each cycle and after the treatment (approximately 6 weeks). Additionally, the daily steroid dose was collected at these timepoints. Patients who either improved in symptoms, received less dexamethasone after treatment, or both were considered to have a benefit from the treatment. Results Twenty-one patients who received BEV due to radiation necrosis were identified. For 10 patients (47.6%) symptoms improved and 11 patients (52.4%) remained clinically stable during the treatment. In 14 patients (66.7%) the dexamethasone dose could be reduced during therapy, 5 patients (23.8%) received the same dose of dexamethasone before and after the treatment, and 2 patients (9.5%) received a higher dose at the end of the treatment. According to this analysis, overall, 19 patients (90.5%) benefited from the treatment with BEV. No severe adverse effects were reported. Conclusion BEV might be an effective and safe therapeutic option for patients with radiation necrosis as a complication after cranial radiation therapy. Patients seem to benefit from this treatment by improving symptomatically or through reduction of dexamethasone.

Monitoring skin dose changes during image-guided helical tomotherapy for head and neck cancer patients Abstract Purpose An increase of skin dose during head and neck cancer (HNC) radiotherapy is potentially dangerous. Aim of this study was to quantify skin dose variation and to assess the need of planning adaptation (ART) to counteract it. Methods Planning CTs of 32 patients treated with helical tomotherapy (HT) according to a Simultaneous Integrated Boost (SIB) technique delivering 54/66 Gy in 30 fractions were deformably co-registered to MVCTs taken at fractions 15 and 30; in addition, the first fraction was also considered. The delivered dose-of-the-day was calculated on the corresponding deformed images. Superficial body layers (SL) were considered as a surrogate for skin, considering a layer thickness of 2 mm. Variations of SL DVH (∆SL) during therapy were quantified, focusing on ∆SL95% (i.e., 62.7 Gy). Results Small changes (within ± 1 cc for ∆SL95%) were seen in 15/32 patients. Only 2 patients experienced ∆SL95% > 1 cc in at least one of the two monitored fractions. Negative ∆SL95% > 1 cc (up to 17 cc) were much more common (15/32 patients). The trend of skin dose changes was mostly detected at the first fraction. Negative changes were correlated with the presence of any overlap between PTV and SL at planning and were explained in terms of how the planning system optimizes the PTV dose coverage near the skin. Acute toxicity was associated with planning DVH and this association was not improved if considering DVHs referring to fractions 15/30. Conclusion About half of the patients treated with SIB with HT for HNC experienced a skin-sparing effect during therapy; only 6% experienced an increase. Our findings do not support skin-sparing ART, while suggesting the introduction of improved skin-sparing planning techniques.

Image-based lung functional radiotherapy planning for non-small cell lung cancer Abstract Background This simulation study assessed the feasibility and impact of incorporating additional information from lung perfusion single-photon emission computed tomography (SPECT) into intensity-modulated radiotherapy planning for the treatment of non-small cell lung cancer (NSCLC). Methods In this simulation study, data of 13 patients with stage I–III NSCLC previously treated by radio(chemo)therapy were used. The SPECT was fused together with radiotherapy planning CT. Functional lung regions (FL) and non-functional lung regions (nFL) were defined based on SPECT images. Four treatment plans were created for each patient: an IMRT and a VMAT plan with planning CT (anatomical plans), and an IMRT and a VMATplan which integrate the additional information from lung perfusion scintigraphy (function plans). Dosimetric parameters were compared between all plans for PTV parameters and normal tissue preservation, focusing on optimizing the lung volume receiving at least 20 Gy (V20Gy). Results Compared to anatomical plans, functional IMRT and functional VMAT plans reduced functional lung V20Gy in all cases of local and diffuse hypoperfusion patterns of SPECT defects. Similar results were observed for functional lung V30Gy and median dose to functional lung Dmean, but were not statistically significant in any group. A significant increase in non-functional lung V20Gy resulted in both functional plans. There were no significant differences in conformity or heterogeneity indices or PTV median doses between either pair of anatomical and functional plans. Conclusion The incorporation of functional imaging for radiotherapy planning in non-small cell lung cancer is feasible and appears to be beneficial in preserving a functional lung in non-small cell lung cancer.

BRAF-mutierte metastasierte Melanome: Erste Daten zur langfristigen Wirksamkeit zielgerichteter Therapien

Relevanz stereotaktischer ablativer Strahlentherapie bei systemisch metastasierten Patienten

Stereotaktisch ablative Bestrahlung als Standardtechnik beim NSCLC im Stadium I bestätigt

Outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate Abstract Purpose To evaluate the potential benefit of curative radiotherapy (RT) to the primary tumor in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone. Materials and methods The clinical parameters of 106 mCRPC patients treated with abiraterone were retrospectively evaluated. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after the systemic treatment was analyzed. Local RT to the primary tumor and pelvic lymphatics was delivered in 44 patients (41%), and 62 patients (59%) did not have RT to the primary tumor. After propensity match analysis, a total of 92 patients were analyzed. Resultsn Median follow-up time was 14.2 months (range: 2.3–54.9 months). Median overall survival (OS) was higher in patients treated with local RT to the primary tumor than in those treated without local RT with borderline significance (24.1 vs. 21.4 months; p = 0.08). Local RT to the prostate and pelvic lymphatics significantly diminished the local recurrence rate (16 patients, 31% vs. 2 patients, 5%; p = 0.003). In multivariate analysis, the prostate specific antigen (PSA) response ≥50% of the baseline obtained 3 weeks after abiraterone therapy was the only significant prognostic factor for better OS and progression-free survival (PFS). Patients treated with primary RT to the prostate had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT. Conclusions Local prostate RT significantly improved OS and local control in mCRPC patients treated with abiraterone. The patients treated with primary RT had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.