Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate “FLASH” irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.

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evaluated post-operative complications and the correlation with treatment factors using the CCI. Materials/Methods: Eighty-three patients with mid to distal esophageal cancer were treated with nCRT followed by resection between 2004 and 2016. 94% had adenocarcinoma. Almost all patients had a KPS 80 at onset of treatment (99%). Total doses ranged from 39.6 to 52.5 Gy. Treatment was planned using IMRT (41%), 3D-CRT (47%) and tomo-IMRT (12%). There were 29 patients who had VMAT. Concurrent chemotherapy regimens were carboplatin/taxol (59%), cisplatin/5-FU (17%), or other (24%). Resection was performed at a median of 9 weeks, generally by Ivor-Lewis (67%), esophagogastrectomy (14%), or trans-hiatal (11%). Complications were evaluated at 30, 60, and 90 day after surgery. Pulmonary, cardiac, gastrointestinal, infectious, and nervous system complications were retrospectively reviewed and graded using the Clavien-Dindo scale. CCI scores were calculated with a web-based calculator at AssessSurgery.com and means were evaluated using ANOVA. Results: Among the 83 patients, 47 experienced post-operative complications (57%). There were a total of 5 post-operative deaths (6%). There were 3 deaths in the cohort receiving up to 45 Gy of total radiation (12%), 2 deaths between >45 and <50 Gy (10%), and zero deaths in the group who received 50.4 Gy or more. The mean CCI scores for all complications within 60 days were 25.1 (< or Z to 45 Gy), 28.2 (>45 and <50.4 Gy), and 19.4 (> or Z to 50.4), with the majority initiating within 30 days. The mean CCI for IMRT and 3D-CRT was 27.4 and 21.8, respectively. Patients who received concurrent carboplatin/taxol had a mean CCI of 26.2, and those who received concurrent cisplatin/5-FU had a mean CCI of 28.3. No statistical significance was found when mean CCI scores were compared for total radiation doses or when comparing chemotherapy regimens. Conclusion: There did not appear to be a difference in the severity of postoperative complications as measured by the CCI when comparing total radiation dose or concurrent chemotherapy agents. Additional studies are needed to further elucidate the optimal radiation dose combined with systemic agents with the goal of improving disease outcomes and minimizing toxicity.