Consolidative active scanning proton therapy for mediastinal lymphoma: selection criteria, treatment implementation and clinical feasibility.

AIMS: Proton therapy (PT) represents an advanced form of radiotherapy with unique physical properties which could be of great advantage in reducing long-term radiation morbidity for cancer survivors. Here, we aim to describe the whole process leading to the clinical implementation of consolidative active scanning proton therapy treatment (PT) for mediastinal lymphoma. METHODS: The process included administrative, technical and clinical issues. Authorization of PT is required in all cases as mediastinal lymphoma is currently not on the list of diseases reimbursable by the Italian National Health Service. Technically, active scanning PT treatment for mediastinal lymphoma is complex, due to the interaction between actively scanned protons and the usually irregular and large volumes to be irradiated, the nearby healthy tissues and the target motion caused by breathing. A road map to implement the technical procedures was prepared. The clinical selection of patients was of utmost importance and took into account both patient and tumor characteristics. RESULTS: The first mediastinal lymphoma was treated at our PT center in 2018, four years after the start of the clinical activities. The treatment technique implementation included mechanical deep inspiration breath-hold simulation computed tomography (CT), clinical target volume (CTV)-based multifield optimization planning and plan robustness analysis. The ultimate authorization rate was 93%. In 4 cases a proton-photon plan comparison was required. Between May 2018 and February, 2021, 14 patients were treated with consolidative PT. The main clinical reasons for choosing PT over photons was a bulky disease in 8 patients (57%), patient's age in 11 patients (78%) and the proximity of the lymphoma to cardiac structures in 10 patients (71%). With a median follow-up of 15 months (range, 1-33 months) all patients but one (out-of-field relapse) are without evidence of disease, all are alive and no late toxicities were observed during the follow-up period. CONCLUSIONS: The clinical implementation of consolidative active scanning PT for mediastinal lymphoma required specific technical procedures and a prolonged experience with PT treatments. An accurate selection of patients for which PT could be of advantage in comparison with photons is mandatory.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic carcinoma: is it useful?

AIMS AND BACKGROUND: Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant). METHODS: A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. RESULTS: With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis. CONCLUSIONS: The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.

Hypofractionated radiation therapy for inoperable advanced stage non-small cell lung cancer.

AIMS AND BACKGROUND: Inoperable advanced stage lung cancer is usually treated by radiation therapy. Although a minority of patients may achieve prolonged survival with aggressive therapeutic approaches, most patients present with adverse prognostic factors that do not allow curative treatment. For these cases palliation of symptoms becomes the main treatment purpose, and short treatment schedules are commonly employed. METHODS: Fifty-two inoperable patients with stage IIIB or IV non-small cell lung cancer (NSCLC) were treated with a hypofractionated schedule of radiotherapy. Initially all patients received 20 Gy in five fractions, and approximately one month after irradiation completion patients underwent clinical and radiological evaluation. Those that achieved a >50% reduction in tumor load and respiratory symptoms were submitted to a second similar short course of radiotherapy. RESULTS: Thirty-three (63%) patients received only one course of radiotherapy. After the first evaluation, 19 patients (37%), all stage IIIB, fulfilled the criteria to receive a total dose of 40 Gy. Survival rates at one and two years were 33% and 0%, respectively, in the group of patients that received 20 Gy, and 52% and 21% respectively, in the group treated with 40 Gy. Two-year survival rates were 10% for stage IIIB and 0% for stage IV patients. Among the patients that were irradiated with a dose of 20 Gy, a subjective reduction of dyspnea and cough and remission of hemoptysis were observed in 97%, 82% and 80% cases, respectively. Complete remission of dyspnea and coughing was observed in 17 (89%) and 14 (74%) patients treated with two irradiation courses. Only mild toxicity was recorded. CONCLUSIONS: Our treatment schedule achieved symptom control in the majority of patients. Early evaluation after 20 Gy allowed selection of responsive patients that could benefit from more prolonged treatment.