Defining Minimum Treatment Parameters of Ablative Radiation Therapy in Patients With Hepatocellular Carcinoma: An Expert Consensus.

PURPOSE: External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. METHODS AND MATERIALS: Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC. RESULTS: Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions. CONCLUSIONS: Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.

Clinical outcomes and timing on the combination of focal radiation therapy and immunotherapy for the treatment of brain metastases.

Introduction: Radiotherapy is one of the standard treatments for brain metastases (BM). Over the past years, the introduction of immunotherapy as routine treatment for solid tumors has forced investigators to review and evaluate how it would interact with radiation. Radiation and Immunotherapy have shown a synergic effect activating the host's immune system and enhancing treatment response. The combinatory effect on BM is currently under investigation. Methods: Data published on Pubmed to determine toxicity, survival, treatment characteristics and timing on the combination of radiotherapy and immunotherapy for the treatment of BM has been reviewed. Results: Mostly retrospective reviews report an improvement of intracranial progression free survival (iPFS) when combining radioimmunotherapy for BM patients. Two systematic reviews and meta-analysis and one phase II prospective trial also report a benefit on iPFS without an increase of toxicity. Among the published literature, the definition of concurrency is heterogeneous, being one month or even narrowed intervals correlated to better clinical outcomes. Toxicity due to concurrent radioimmunotherapy, specifically symptomatic radionecrosis, is also directly analyzed and reported to be low, similar to the toxicity rates secondary to stereotactic radiosurgery alone. Conclusion: Radiation combined with immunotherapy has shown in predominantly retrospective reviews a synergic effect on the treatment of BM. The concurrent combination of radioimmunotherapy is a feasible therapeutic strategy and seems to improve clinical outcomes, especially iPFS, when delivered within <30 days. Larger prospective and randomized studies are needed to establish reliable outcomes, best delivery strategies and toxicity profile.

Management of high-risk and post-operative non-metastatic prostate cancer in Catalonia: an expert Delphi consensus.

BACKGROUND: To reach a consensus on recommendations for the management of high-risk and post-operative non-metastatic prostate cancer by a group of Radiation Oncologists in Catalonia dedicated to prostate cancer. METHODS: A modified Delphi approach was employed to reach consensus on controversial topics in Radiation Oncology on high-risk non-metastatic (eight questions) and post-operative (eight questions) prostate cancer. An agreement of at least 75% was considered as consensus. The survey was electronically sent 6 weeks before an expert meeting where topics were reviewed and discussed. A second-round survey for the controversial questions only was sent and answered by participants after the meeting. RESULTS: After the first round of the survey, 19 experienced Radiation Oncologists attended the meeting and 74% fulfilled the second-round online questionnaire. An agreement of 9 of the 16 questions was accounted for the first round. After the meeting, an additional agreement was reached in 3 questions leading to a final consensus on 12 of the 16 questions. There are still controversial topics like the use of PET for staging of high-risk and post-operative non-metastatic prostate cancer and the optimal dose to the prostate bed in the salvage setting. CONCLUSION: This consensus contributes to establish recommendations and a framework to help in prostate cancer radiation therapy and pharmacological management in daily clinical practice of high-risk and post-operative non-metastatic prostate cancer.

Analgesic effects of low-dose radiotherapy in greater trochanteric pain syndrome: results in a clinical series of 155 patients with recurrent or refractory symptoms

PurposeThis prospective study assessed the effects of low-dose radiotherapy in patients diagnosed with greater trochanteric pain syndrome (GTPS) with recurrent symptoms or refractory to previous conservative measures.MethodsWe evaluated a total of 155 patients (90.3% women, mean age 69 years). Most patients (n = 136) received 10 Gy (1 Gy/day/3 fractions per week on alternate days), but after recommendations of DEGRO guidelines published in 2015, the remaining 19 patients (12.2%) received 6 Gy (1 Gy/day/3 fractions per week on alternate days).ResultsAt the pre-treatment visit, the mean (standard deviation, SD) visual analog scale (VAS) score was 8), which decreased to 5 (SD 2.2) after 1 month of the end of treatment and to 4 (SD 2.3) after 4 months. An objective symptom response with increased mobility, better sleep quality, and reduction of analgesic medication was found in 56% of patients at 1 month. In 129 patients (83.2%), there was a decrease of at least 1 point in the VAS score, and in 49 patients (29.0%), the VAS score was lower than 3. The mean length of follow-up was 45 months. The probability of maintaining the analgesic response estimated by the Kaplan-Meier method was 53% at 5 years.ConclusionLow dose radiotherapy effectively improved pain in the trochanteric area in most patients with recurrent or refractory GTPS, allowing a reduction in the need for analgesic medications and, more, importantly, better functioning and mobility. Further randomized studies in selected populations of GTPS are needed to define the treatment position of low-dose radiotherapy in this clinical setting.

Analgesic effects of low-dose radiotherapy in greater trochanteric pain syndrome: results in a clinical series of 155 patients with recurrent or refractory symptoms.

PURPOSE: This prospective study assessed the effects of low-dose radiotherapy in patients diagnosed with greater trochanteric pain syndrome (GTPS) with recurrent symptoms or refractory to previous conservative measures. METHODS: We evaluated a total of 155 patients (90.3% women, mean age 69 years). Most patients (n = 136) received 10 Gy (1 Gy/day/3 fractions per week on alternate days), but after recommendations of DEGRO guidelines published in 2015, the remaining 19 patients (12.2%) received 6 Gy (1 Gy/day/3 fractions per week on alternate days). RESULTS: At the pre-treatment visit, the mean (standard deviation, SD) visual analog scale (VAS) score was 8), which decreased to 5 (SD 2.2) after 1 month of the end of treatment and to 4 (SD 2.3) after 4 months. An objective symptom response with increased mobility, better sleep quality, and reduction of analgesic medication was found in 56% of patients at 1 month. In 129 patients (83.2%), there was a decrease of at least 1 point in the VAS score, and in 49 patients (29.0%), the VAS score was lower than 3. The mean length of follow-up was 45 months. The probability of maintaining the analgesic response estimated by the Kaplan-Meier method was 53% at 5 years. CONCLUSION: Low dose radiotherapy effectively improved pain in the trochanteric area in most patients with recurrent or refractory GTPS, allowing a reduction in the need for analgesic medications and, more, importantly, better functioning and mobility. Further randomized studies in selected populations of GTPS are needed to define the treatment position of low-dose radiotherapy in this clinical setting.

Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC-contribution of IASLC recommendations.

BACKGROUND: Neoadjuvant treatment (NT) with chemotherapy (Ch) is a standard option for resectable stage III (N2) NSCLC. Several studies have suggested benefits with the addition of radiotherapy (RT) to NT Ch. The International Association for the Study of Lung Cancer (IASLC) published recommendations for the pathological response (PHR) of NSCLC resection specimens after NT. AIM: To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy (ChRT). METHODS: We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020. After NT, all patients were evaluated for radiological response (RR) according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons. All histological samples were examined by the same two pathologists. PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes. RESULTS: Forty patients underwent NT ChRT and 27 NT Ch. Fifty-six (83.6%) patients underwent surgery (35 ChRT and 21 Ch). The median time from ChRT to surgery was 6 wk (3-19) and 8 wk (3-21) for Ch patients. We observed significant differences in RR, with disease progression in 2.5% and 14.8% of patients with ChRT and Ch, respectively, and partial response in 62.5% ChRT vs 29.6% Ch (P = 0.025). In PHR we observed ≤ 10% viable cells in the tumor in 19 (54.4%) and 2 cases (9.5%), and in the resected lymph nodes (RLN) 30 (85.7%) and 7 (33.3%) in ChRT and Ch, respectively (P = 0.001). Downstaging was greater in the ChRT compared to the Ch group (80% vs 33.3%; P = 0.002). In the univariate analysis, NT ChRT had a significant impact on partial RR [odds ratio (OR) 12.5; 95% confidence interval (CI): 1.21 - 128.61; P = 0.034], a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5% increased probability for achieving downstaging (OR 8; 95%CI: 2.34-27.32; P = 0.001). CONCLUSION: We found significant benefits in RR and PHR by adding RT to Ch as NT. A longer follow-up is necessary to assess the impact on clinical outcomes.

Magnetic resonance guided elective neck irradiation targeting individual lymph nodes: A new concept.

BACKGROUND AND PURPOSE: Conventional elective neck irradiation (ENI) in head and neck cancer consists of radiotherapy (RT) to the regional lymph node (LN) levels contoured on computed tomography. Hybrid Magnetic Resonance (MR) - RT modalities, such as combined magnetic resonance imaging - linear accelerators (MRLs), might enable new ENI strategies in which individual non-suspect lymph nodes (i-LNs) are targeted. In this treatment planning study, new MR-based strategies targeting i-LNs (i-ENI) were compared to conventional treatment. MATERIALS AND METHODS: All i-LNs were delineated on MR images of ten retrospectively selected patients with T2-4aN0M0 laryngeal cancer. Three strategies were considered. Strategy A: Conventional ENI delivered with a conventional linear accelerator (35x 1.55 Gy). Strategy B: MRL-based i-ENI (35x 1.55 Gy) to the individual lymph nodes including a background dose to the conventional elective neck volumes (35x 1.03 Gy). Strategy C: Same as Strategy B, but without background dose. In all plans the dose prescription to the primary tumor was 35x 2 Gy. Mean dose (D mean) reductions in the organs at risk (OAR) were compared using the Wilcoxon signed rank test. RESULTS: Compared to conventional ENI (strategy A), significant D mean reductions of 6.0 Gy and 8.0 Gy were observed in the submandibular glands, of 9.4 Gy and 13 Gy in the carotid arteries and of 9.9 Gy and 19.4 Gy in the thyroid for strategy B and C, respectively. Large inter-patient variations of D mean reductions were observed in all OARs. CONCLUSION: MRL-based i-ENI is a new promising concept that could reduce the mean dose to OARs in the neck significantly for patients with laryngeal cancer.