Francesco Dionisi

Is there a role for proton therapy in the treatment of hepatocellular carcinoma? A systematic review

This paper aimed to review the literature concerning the use of proton therapy systematically in the treatment of hepatocellular carcinoma, focusing on clinical results and technical issues. The literature search was conducted according to a specific protocol in the Medline and Scopus databases by two independent researchers covering the period of 1990-2012. Both clinical and technical studies referring to a population of patients actually treated with protons were included. The PRISMA guidelines for reporting systematic reviews were followed. A final set of 16 studies from seven proton therapy institutions worldwide were selected from an initial dataset of 324 reports. Seven clinical studies, five reports on technical issues, three studies on treatment related toxicity and one paper reporting both clinical results and toxicity analysis were retrieved. Four studies were not published as full papers. Passive scattering was the most adopted delivery technique. More than 900 patients with heterogeneous stages of disease were treated with various fractionation schedules. Only one prospective full paper was found. Local control was approximately 80% at 3-5years, average overall survival at 5years was 32%, with data comparable to surgery in the most favorable groups. Toxicity was low (mainly gastrointestinal). Normal liver V0Gy<30%volume and V30Gy<18-25%volume were suggested as cut-off values for hepatic toxicity. The good clinical results of the selected papers are counterbalanced by a low level of evidence. However, the rationale to enroll patients in prospective studies appears to be strong.

The use of proton therapy in the treatment of gastrointestinal cancers: liver.

AbstractThis article reviews the role of proton therapy in the treatment of primary liver cancer focusing on hepatocellular carcinoma (HCC). The dose-sparing physical properties of protons are of great advantage in the treatment of HCC. To date, the clinical experience with the use of protons for HCC is encouraging. Most studies come from East Asia and show improved local control and survival with low toxicity. More importantly, when high-enough radiation doses are delivered to early liver cancers, a substantial fraction of patients are alive at 5 years, results not dissimilar from surgical resection. The technical details related to the use of proton therapy for HCC are also reviewed. The combination of proton therapy with other locoregional or systemic therapies is currently being tested and holds promise to improve survival while maintaining an acceptable level of toxicity.

Proton therapy in adjuvant treatment of gastric cancer: Planning comparison with advanced x-ray therapy and feasibility report

Abstract Background. Adjuvant chemoradiotherapy improves both overall- and relapse-free survival in patients with resected gastric cancer. However, this comes at the cost of increased treatment-related toxicity. Proton therapy (PT) has distinct dosimetric characteristics that may reduce dose to normal tissues, improving the therapeutic ratio. The purpose of this treatment planning study is to compare PT and intensity-modulated x-ray therapy (IMXT) in gastric cancer with regards to normal tissue sparing. Material and methods. The patient population consisted of resected gastric cancer patients treated at a single institution between 2008 and 2013. Patients who had undergone 4D CT simulation were replanned to the originally delivered doses (45–54 Gy in 25–30 daily fractions) using six-field photon IMXT and 2–3-field PT (double scattering-uniform scanning techniques). Results. Thirteen patients were eligible for the planning comparison. IMXT provided slightly higher homogeneity indices (median values 0.04 ± 0.01 vs. 0.07 ± 0.01, p = 0.03). PT resulted in significantly (p < 0.05) lower intermediate-low doses for all the normal tissues examined (small bowel V15 82 ml vs. 133 ml, liver mean doses Gy 11.9 vs. 14.4 Gy, left/right kidney mean doses 5/0.9 Gy vs. 7.8/3.1 Gy, heart mean doses 7.4 Gy vs. 9.5 Gy). The total energy deposited outside the target volume was significantly lower with PT (median integral dose 90.1 J vs. 129 J). Four patients were treated with PT: treatment was feasible and verifications scans showed that target coverage was robust. Conclusion. PT can contribute to normal tissue sparing in the adjuvant treatment of gastric cancer, with a potential benefit in terms of compliance to treatment, acute and late toxicities.

Nasal cavity reirradiation: a challenging case for comparison between proton therapy and volumetric modulated arc therapy.

Background The aim of this case report is to report on a dosimetric comparison between volumetric modulated arc therapy (RapidArc technique and active scanning proton therapy (single-field (SFO) and multifield (MFO) techniques) in a case of nasal cavity cancer recurrence. Case Report A 72-year-old man, who received adjuvant radiotherapy for a carcinoma of the nasal cavity, experienced an unresectable local recurrence in the previous surgical bed. Hence, the patient was evaluated for reirradiation by comparing different modalities, with a total prescribed dose of 50 Gy in standard fractionation. RA plan was revealed to be equivalent to the MFO plan in terms of target dose coverage and conformity index. SFO plan was not able to respect a maximum dose of 9 Gy to nervous structures, in contrast to RA and MFO plans. Conclusions In this challenging scenario, although a clear preference would be given to the MFO proton plan, the RA plan was revealed to be adequate for the clinical goal of target coverage and sparing of organs at risk.

Gastrointestinal cancer: nonliver proton therapy for gastrointestinal cancers.

AbstractMultimodality therapy for gastrointestinal (GI) cancers carries considerable risk for toxicity; even single-modality radiation therapy in this population carries with it a daunting side effect profile. Supportive care can certainly mitigate some of the morbidity, but there remain numerous associated acute and late complications that can compromise the therapy and ultimately the outcome. Gastrointestinal cancers inherently occur amid visceral organs that are particularly sensitive to radiotherapy, creating a very narrow therapeutic window for aggressive cell kill with minimal normal tissue damage. Radiation therapy is a critical component of locoregional control, but its use has historically been limited by toxicity concerns, both real and perceived. Fundamental to this is the fact that long-term clinical experience with radiation in GI cancers derives almost entirely from 2-dimensional radiation (plain x-ray–based planning) and subsequently 3-dimensional conformal radiation. The recent use of intensity-modulated photon-based techniques is not well represented in most of the landmark chemoradiation trials. Furthermore, the elusive search for efficacious but tolerable local therapy in GI malignancies raises the possibility that proton radiotherapy’s physical and dosimetric differences relative to conventional therapy may make it better suited to the challenge. In many sites, local recurrences after chemoradiation pose a particular challenge, and reirradiation in these sites may be done successfully with proton radiotherapy.

Comparison between intensified neoadjuvant treatment and standard preoperative chemoradiation for rectal cancer.

Objectives The aim of the current study was to compare a neoadjuvant regimen containing oxaliplatin with standard preoperative treatment for rectal cancer. Methods From December 2006 to December 2007, 20 patients with rectal cancer were treated at our Institution with the weekly addition of oxaliplatin (50 mg/m2) to radiotherapy (50.4–54.0 Gy in 28–30 daily fractions) and continuous infusion of 5-fluorouracil (200 mg/m2). The results of the regimen were compared with a historical control group including 21 consecutive patients previously treated with standard 5-fluorouracil treatment from December 2004 to October 2006. Results Both the rate of sphincter preservation in low rectal cancer (91.7% vs 36.4%, P = 0.009) and the rate of downstaging (84.2% vs 47.6%, P = 0.023) were higher in the oxaliplatin group than in the control group. Pathological complete response was achieved in 8 patients (42.1%) in the oxaliplatin group and in 4 patients (19.0%) in the control group (P = 0.172). When ypT0-pT1 stages were analyzed together, the P value was 0.051. Acute toxicity was increased in the oxaliplatin group, with a higher incidence of G3 diarrhea and pelvic pain than in the control group (30.0% vs 14.3%, P = NS). Conclusions Our data seem to correlate the addition of oxaliplatin to the standard treatment for rectal cancer with higher rates of sphincter preservation, down-staging and complete response. Toxicity is increased and requires careful monitoring. However, our results refer to a retrospective comparison of a small series of patients and need to be validated by the large, phase III randomized trial currently ongoing.

Pre-operative Radio-Chemotherapy of Rectal Cancer: Toxicity and Preliminary Results with the Addition of Weekly Oxaliplatin

The standard pre-operative treatment of rectal cancer consists of radiotherapy combined with continuous infusion of fluorouracil (FU) at a dose of 200 mg/m2/day. Platinum compounds can increase the anti-tumour activity of radiotherapy and are suitable agents to be combined with FU. We report our experience with the addition of oxaliplatin to radiotherapy and FU in the pre-operative treatment of patients with rectal cancer.

Unresectable Ameloblastoma Successfully Treated with Definitive Proton Therapy

We report the case of an 87-year-old man affected by an unresectable ameloblastoma of the right jaw that was successfully treated by definitive proton therapy up to a dose of 66 Gy in 33 fractions. Treatment was well tolerated, and there were no interruptions due to toxicity. At follow-up visits, the patient experienced complete response to treatment with no evidence of disease and complete recovery from acute side effects. In this report, we discuss the potential and possible pitfalls of proton therapy in the treatment of specific settings.