a 43-year - old woman developed recurrent osteosarcoma in the left supraorbital area . while originally recommended to undergo surgery , she declined and underwent carbon ion radiotherapy at another institution . a total dose of 70.4 gray equivalents ( gye ) in 16 fractions was administered over 4 weeks . irradiation was performed according to dose distributions based on planning computed tomography ( ct ) ( figure 1 ) . the yellow line indicates the target volume ; red line , 100% dose ; pink line , 95% dose ; orange line , 90% dose ; green line , 50% dose ; blue line , 30% dose ; and purple line , 10% dose . physical examination revealed a hard , 24 cm non - tender mass located in the left supraorbital area . the protrusion measured 1 cm in length . the area of skin that had been exposed to carbon ion irradiation was slightly red . vision in her left eye was poor due to cataract , and her left frontal lobe was edematous , possibly due to a reaction to carbon ion radiotherapy . ct of the head revealed a 1.82.5 cm frontal bone mass ( figures 2a , b ) . a low - density area indicated edema in the left frontal lobe ( figure 2b ) . compared to the images obtained after treatment , the mass was larger in size , with increased calcification . stable disease was maintained for a prolonged period ; the mass was clinically diagnosed as recurrence of osteosarcoma rather than residual disease .   computed tomography scan of the head showing a frontal bone mass . the patient underwent wide resection of the mass and normal tissue considered to have been damaged by carbon ion radiotherapy . wide resection was performed with a 2-cm margin from the edge of swelling ( figure 3a ) , and included the left eyeball , part of the frontal bone , dura mater , the left frontal skull base , and the region of reddish tissue damaged by carbon ion radiotherapy ( figure 3b ) . the dural defect was reconstructed with a free non - vascularized fascia lata graft ( figure 3c ) . a galeal pericranial flap pedicled on the ipsilateral superficial temporal artery was applied over the fascia lata . although reconstruction of the defect required free tissue transfer , the distance between the defect and recipient vessels was too long . to overcome this problem , we harvested a radial forearm ( rf ) flap and anterolateral thigh ( alt ) flap . the rf flap was anastomosed end - to - end to the recipient vessels in the ipsilateral neck ( superior thyroid artery , external jugular vein , and facial vein ) , and the alt flap was anastomosed end - to - end to the distal end of the rf flap ( figure 3d , 4 ) . ( a ) wide resection with a 2-cm margin from the edge of swelling was performed . ( b ) the left eye ball , dura mater , left frontal skull base , and the region of reddish tissue damaged by carbon ion radiotherapy were resected . ( c ) the dural defect was reconstructed using a free non - vascularized fascia lata graft ( white arrow ) . ( d ) the soft tissue defect was reconstructed using a radial forearm flap ( black arrow ) and an anterolateral thigh flap ( white arrow ) . the rf flap was anastomosed end - to - end to recipient vessels in the ipsilateral neck , and the alt flap was anastomosed end - to - end to the distal end of the rf flap . histopathological examination of the resected specimen revealed increased dysplastic spindle cells , leading to a histological diagnosis of osteoblastic osteosarcoma . the degree of reaction to carbon ion radiotherapy , such as fibrosis , was comparatively low . systemic adjuvant chemotherapy with ifosfamide , carboplatin , and etoposide was administered for 4 months . the patient survived and has remained well for 2 years postoperatively ( figure 5 ) . carbon ion radiotherapy offers several physical and biological advantages over conventional photon radiotherapy . physically , carbon ion beams allow for increased energy deposition with increasing depth , and the penetration depth achieves a sharp maximum at the end of its range to form a bragg peak . biologically , cellular damage caused by carbon ions is different from those caused by protons and photons , in that the rate of cancer cell recovery from sublethal damage is lower and variations in sensitivity by cell - cycle stage and changes in oxygen concentration are smaller . carbon ion radiotherapy can also deliver a large mean energy per unit length of path in the body . thus , strong biological effects can be achieved with improved dose distribution , thereby permitting dose escalation within the tumor region without causing extensive damage to neighboring normal tissue . our patient received carbon ion radiotherapy with a total dose of 70.4 gye in 16 fractions over 4 weeks . this dose was determined based on a report by kamada et al . , who conducted a phase i / ii dose escalation study on carbon ion radiotherapy in patients with bone and soft tissue sarcomas . they found that this irradiation schedule was appropriate for patients with subcutaneous tumor involvement . furthermore , acute and late skin reactions were observed in all patients treated with the same total dose of 70.4 gye . 
  with the exception of a skin reaction , schulz - ertner et al . also reported that 4% of patients who had undergone carbon ion radiotherapy with a prescribed target dose of 5770 gye ( median , 60 ) for skull base chondrosarcoma developed white matter changes in the temporal lobe within the high - dose area near the tumor site without developing symptoms . our patient presented with mild late skin toxicity , eye toxicity , and asymptomatic white matter changes on ct . a few english reports have been published on salvage surgery cases following carbon ion radiotherapy . however , the impact of preceding carbon ion radiotherapy on salvage surgery is not discussed and is currently unclear . moreover , it is also unclear how postoperative complications can be reduced . for instance , patel et al . conducted an international collaborative study on craniofacial surgery for malignant skull base tumors and found that prior history of radiotherapy was significantly associated with the development of postoperative complications . one of the main problems with wide resection is the management of irradiated normal tissue adjacent to the tumor . theoretically , carbon ion radiotherapy can deliver more focused beams to the tumor compared to other types of radiotherapy . however , its potency is so high that even the limited field adjacent to the tumor can be seriously damaged . the healing ability of irradiated normal tissue exhibiting mild skin reaction is unclear and should not be clinically disregarded . to avoid postoperative wound complications , it is better to resect tissue that has been " heavily injured " along with the tumor . given the lack of pertinent literature , much weight was placed on safety and thus the tumor was resected with a wide safety margin in the present case . however , considering the nature of carbon ion radiotherapy , it may be sufficient to resect a more limited region if only taking into account tissue affected by carbon ion radiotherapy . in other words , although the resection was sufficiently conservative , there is the possibility of resecting slightly more than actually necessary . actually , in our case , histopathological change as a reaction to carbon ion radiotherapy was low . use of preoperative carbon ion radiotherapy has been reported in the fields of esophageal and pancreatic cancers by akutsu et al . and shinoto et al . while these two studies used a low dose of carbon ion radiotherapy relative to ours and had a short duration between irradiation and surgery , they found little fibrosis and no adverse findings in the normal tissues of resected specimens in the radiation field . these studies also found that carbon ion radiotherapy did not affect peri- and postoperative morbidity . dural reconstruction is important in separating the oropharynx from the meninges and preventing cerebrospinal fluid leak , which is potentially life threatening . accordingly , we utilized a fascia lata graft to achieve watertight dural closure , and applied a pedicled galeal pericranial flap with abundant blood supply over the fascia . as for soft tissue reconstruction , numerous studies have demonstrated that complication rates are acceptably low when free flaps are used to reconstruct large - volume defects , and furthermore , this technique has been proven effective for low - volume skull base defects . aggressive use of microvascular repair is recommended in patients who have received a full course of radiation to the skull base . free flaps , which provide highly vascularized and voluminous tissue , can fill dead space with separation of the oropharynx from meninges and fulfill the reconstructive goal of primary healing . accordingly , we performed soft tissue reconstruction using an alt flap , and to address the issue of long - distance , we used a rf flap as a bridge flap . we performed salvage and reconstructive surgery for the recurrence of osteosarcoma following carbon ion radiotherapy . the irradiated field was determined , and tumor resection was performed with a wide margin , including tissue considered to have been damaged by carbon ion radiotherapy . the patient developed no postoperative complications , including wound - healing delay , which enabled early initiation of adjuvant chemotherapy .
abstractcarbon ion radiotherapy has recently emerged as an alternative choice of treatment for malignant tumors of the head and neck . 
 however , it is still in the infant stages and its influence on subsequent salvage surgery remains unclear . 
 here we report the case of a 43-year - old woman who underwent salvage surgery for left frontal bone osteosarcoma recurrence following carbon ion radiotherapy . 
 tumor resection was performed with a wide margin including the tissue considered to have been damaged by carbon ion radiotherapy . 
 the dural defect was reconstructed using a fascia lata graft and pedicled galeal pericranial flap . 
 the soft tissue defect was reconstructed using an anterolateral thigh flap anastomosed to the ipsilateral neck interposed by the radial forearm flap . 
 as the patient developed no postoperative wound complications , she was able to initiate adjuvant chemotherapy early . 
 carbon ion radiotherapy is useful for its focused distribution and strong biological effects . 
 although the affected field may be limited , its high potency may severely damage adjacent normal tissue and lead to serious postoperative complications . despite these concerns , 
 satisfactory results were achieved in this case .