Osama Mohamad

Carbon ion radiotherapy: A review of clinical experiences and preclinical research, with an emphasis on DNA damage/repair

Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most difficult to treat tumors, including those that are hypoxic, radio-resistant, or deep-seated. Clinical data, mostly from Japan and Germany, are promising, with favorable oncologic outcomes and acceptable toxicity. In this manuscript, we review the physical and biological rationales for CIRT, with an emphasis on DNA damage and repair, as well as providing a comprehensive overview of the translational and clinical data using CIRT.

Deep inspiration breathhold for left-sided breast cancer patients with unfavorable cardiac anatomy requiring internal mammary nodal irradiation

PURPOSE The purpose of this study was to evaluate the utility of moderate deep inspiration breathhold (mDIBH) in reducing heart exposure in left breast cancer patients who have unfavorable cardiac anatomy and need internal mammary lymph node (IMLN) radiation therapy (RT). METHODS AND MATERIALS We used maximum heart distance (MHD), defined as the maximum distance of the heart within the treatment field, >1 cm as a surrogate for unfavorable cardiac anatomy. Twenty-two left breast cancer patients with unfavorable cardiac anatomy requiring IMLN-RT underwent free-breathing (FB) and mDIBH computed tomography simulation and planning. Three-dimensional partially wide tangents (3D-PWTs) and intensity modulated RT plans were generated. Dose-volume histograms were used to compare heart and lung dosimetric parameters. Duration of treatment delivery was recorded for all fractions. RESULTS MHD decreased significantly in mDIBH scans. mDIBH significantly reduced mean heart dose (222.7 vs 578.4 cGy; P < .0001) and percentage of left lung receiving doses ≥20 Gy (V20; 31.93 vs 38.41%; P = .0006) in both 3D-PWT and intensity modulated RT plans. The change in MHD after breathhold reliably predicted mean heart dose reduction after mDIBH. Radiation was effectively delivered in 11.31 ± 3.40 minutes with an average of 10.06 ± 2.74 breathholds per fraction. CONCLUSIONS mDIBH is efficient and can effectively decrease mean heart dose in patients with unfavorable cardiac anatomy who need IMLN-RT, thus simplifying planning and delivery for them. The reduction in mean heart dose is proportional to the reduction in maximum heart distance.

Carbon ion radiotherapy for inoperable pediatric osteosarcoma

Background Unresectable pediatric osteosarcoma has poor outcomes with conventional treatments. Results Twenty-six patients aged 11–20 years (median 16) had inoperable osteosarcoma of the trunk (24 pelvic, 1 mediastinal and 1 paravertebral) without any other lesion at initial examination. There were 22 primary, 1 locally recurrent and 3 metastatic cases. Median CIRT dose was 70.4 Gy RBE (relative biological effectiveness) delivered in 16 fractions. Median follow-up was 32.7 months. Overall survival was 50.0% and 41.7% at 3 and 5 years, respectively. Ten patients survived for more than 5 years (range 5–20.7 years). Local control was 69.9% and 62.9% at 3 and 5 years, respectively and progression-free survival was 34.6% at 3 and 5 years. Only largest tumor diameter correlated with 5-year overall survival and local control. There were 4 grade 3-4 CIRT-related late toxicities, 1 case of bone fracture and no treatment-related mortalities. All patients (except 1) were able to ambulate after CIRT. Conclusions CIRT was safe and efficacious in the treatment of inoperable pediatric osteosarcoma with improved local control and overall survival compared to conventional treatments. Methods We retrospectively reviewed the records of pediatric and adolescent patients who received carbon ion radiotherapy (CIRT) for inoperable osteosarcoma between 1996 and 2014.

Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy

ABSTRACT Integration of hypofractionated body radiotherapy (H-RT) into immune checkpoint inhibitor (ICI) therapy may be a promising strategy to improve the outcomes of ICIs, although sufficient data is lacking regarding the safety and efficacy of this regimen. We, hereby, reviewed the safety and efficacy of this combination in 59 patients treated with H-RT during or within 8 weeks of ICI infusion and compared results with historical reports of ICI treatment alone. Most patients had RCC or melanoma. Median follow-up was 11 months. Most patients received either Nivolumab alone or with Ipilimumab; 83% received stereotactic RT and 17% received conformal H-RT. Any grade adverse events (AEs) were reported in 46 patients, and grade 3–4 in 12 patients without any treatment-related grade 5 toxicity. The most common grade 3 AEs were fatigue and pneumonitis. Grade 3–4 toxicities were higher with ICI combination and with simultaneous ICIs. Overall, most any-grade or grade ≥3 AE rates did not differ significantly from historically reported rates with single-agent or multi-agent ICIs. Toxicity did not correlate with H-RT site, dose, fraction number, tumor type, or ICI and H-RT sequencing. Median progression-free survival was 6.5 months. Objective response rate (ORR) was 26%; 10% had complete response (CR). Median duration of response was 9.4 ± 4.6 months. H-RT of lung lesions was more likely to achieve CR than other sites. H-RT of bone lesions had a lower ORR than non-bone H-RT. In conclusion, combining body H-RT with ICIs is safe and promising. Prospective validation is warranted.

Evolution of Carbon Ion Radiotherapy at the National Institute of Radiological Sciences in Japan

Charged particles can achieve better dose distribution and higher biological effectiveness compared to photon radiotherapy. Carbon ions are considered an optimal candidate for cancer treatment using particles. The National Institute of Radiological Sciences (NIRS) in Chiba, Japan was the first radiotherapy hospital dedicated for carbon ion treatments in the world. Since its establishment in 1994, the NIRS has pioneered this therapy with more than 69 clinical trials so far, and hundreds of ancillary projects in physics and radiobiology. In this review, we will discuss the evolution of carbon ion radiotherapy at the NIRS and some of the current and future projects in the field.