Intra-arterial Cisplatin Infusion Research Articles

3-Fr steerable microcatheter system via the upper limb artery in RADPLAT for right maxillary cancer

Background To evaluate the efficacy of a catheter system using a 3-Fr sheath with a steerable microcatheter through right upper limb artery access for superselective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) to treat right maxillary sinus squamous cell carcinoma (MS-SCC). Material and methods We retrospectively studied 46 sessions in eight patients treated between November 2020 and February 2023 using the catheter system briefly described below. A 3-Fr sheath was inserted into the distal radial, conventional radial, or brachial arteries. A coaxial catheter system with a 2.9-Fr steerable microcatheter and a 1.9-Fr microcatheter was advanced into the brachiocephalic artery. The right common carotid artery was selected by bending the tip of the steerable microcatheter. Coil embolization and intra-arterial cisplatin infusion after selecting each external carotid artery branch were achieved using this catheter system. Results Cisplatin infusion and coil embolization were successful in all sessions. Arterial occlusion at the sheath insertion sites was found in 29.4% (5/17) of the distal radial arteries and 33.3% (3/9) of the conventional radial arteries. No other major complications were observed during the procedure. Conclusion Using a 3-Fr catheter system with a steerable microcatheter through right upper limb artery access is a feasible method for RADPLAT in treating right MS-SCC.

Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0

Background: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment. But this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas (MS-SCC). We herein report the results of the efficacy confirmation phase in the T4a cohort.Patients and methods: Patients received cisplatin 100 mg/m2 intra-arterially weekly for 7 weeks with concomitant radiotherapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (3yr OS), comparing RADPLAT with the historical control for 3yr OS in surgery (80%).Results: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 males and 11 females with a median age of 64 years (range, 40-78 years) and ECOG PS 0/1 (58/7). After excluding one ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3yr-OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (≥ grade 3), neutropenia (≥ grade 3), increased creatinine (≥ grade 2), hearing impairment (≥ grade 2), and stroke (≥ grade 2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported.Conclusion: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 MS-SCCs compared with the historical control for 3yr OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.

The superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is effective for metastatic lymph nodes in head and neck squamous cell carcinoma.

Superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT). A total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score. A comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04). This study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases.

Dose-finding and efficacy confirmation trial of the superselective intra-arterial infusion of cisplatin and concomitant radiotherapy for locally advanced maxillary sinus cancer (JCOG1212): Results of the efficacy confirmation phase in the T4a cohort.

6014 Background: The JCOG1212 trial seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT) for patients (pts) with T4aN0M0 or T4bN0M0 maxillary sinus squamous cell carcinomas (MS-SCC). T4aN0M0 MS-SCC requires radical surgery with or without complete resection of the orbital contents as a standard treatment, which results in disfigurement and functional impairment. We herein report the results of the efficacy confirmation phase in the T4a cohort. Methods: Eligible pts with T4aN0M0 MS-SCC were registered and received cisplatin 100 mg/m 2 intra-arterially weekly for 7 weeks with concomitant radiotherapy (total 70 Gy) as determined by the results of the previous dose-finding phase. The trial investigated the 3-year overall survival (3yr OS) of RADPLAT to demonstrate its non-inferiority to surgery, the current standard of care, and its superiority to IV-CRT, which is used for pts refusing surgery. From the results of observational study undertaken by our group, the historical control for the 3yr OS was set at 80% for surgery and 65% for IV-CRT. A margin of 15% was set to demonstrate its non-inferiority to surgery and superiority to IV-CRT. Thus, when the lower boundary of the two-sided 90% confidence interval (CI) exceeds the threshold of 65% for 3yr OS, RADPLAT will be confirmed as the new standard. A sample size of 62 was required to achieve 80% power with a one-sided 5% significance level. Results: From April 2014 to August 2018, 65 pts were registered in the T4a cohort from 18 institutions, consisting of 54 males and 11 females with a median age of 64 years (range, 40-78 years) and ECOG PS 0/1 (58/7). After the exclusion of one ineligible patient, 64 pts were included in the primary analysis of efficacy and safety. The complete clinical remission rate was 73.4% (47/64, 95% CI, 60.9%-83.7%), with 15 showing CR and 32 showing good PR. The median follow-up was 4.5 years in all eligible pts and the primary endpoint for 3yr-OS was 82.8% (90% CI, 73.4%-89.2%), which met the prespecified hypothesis. The 3yr event-free survival and 3yr local event-free survival were 60.9% (95% CI, 47.9%-71.7%) and 65.6 % (95% CI, 52.5%-75.8%), respectively. With regard to acute adverse events, neutropenia (≥ grade 3), increased creatinine (≥ grade 2), hearing impairment (≥ grade 2), mucositis (≥ grade 3), and stroke (≥ grade 2) were observed in 14.1%, 3.1%, 3.1%, 20.3%, and 1.6% of pts, respectively. One treatment-related death due to a thromboembolic event was reported. Conclusions: RADPLAT is non-inferior to surgery and superior to IV-CRT for pts with T4aN0M0 MS-SCCs and showed manageable toxicities. Therefore, RADPLAT, as well as surgery, should be considered the new standard treatment option for these pts. Clinical trial information: UMIN000013706.

Comparative Treatment Outcome in T3N0 Glottic Cancer With and Without Vocal Fold Fixation Receiving Radiation Therapy and Concurrent Low-Dose Intra-Arterial Cisplatin Infusion.

Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF.

Imaging predictor of ophthalmic involvement in maxillary sinus cancer during super selective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT)

ObjectiveTo investigate the predictability of ophthalmic artery involvement in maxillary sinus cancer using preprocedural contrast enhanced CT and MRI.MethodsWe analyzed advanced (T3, T4a, and T4b) primary maxillary sinus squamous cell carcinoma treated with super-selective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) from Oct 2016 to Mar 2020. Two diagnostic radiologists evaluated the tumor invasion site around the maxillary sinus using preprocedural imaging. These results were compared with the angiographic involvement of the ophthalmic artery using statistical analyses. We also evaluated our RADPLAT quality using complication rate, response to treatment, local progressive free survival (LPFS), and overall survival (OS).ResultsTwenty patients were included in this study. There were ten cases of ophthalmic artery tumor stain and there was a correlation between ophthalmic artery involvement and invasion for ethmoid sinus with statistically significant differences. Other imaging findings were not associated with ophthalmic artery involvement.ConclusionsEthmoid sinus invasion on preprocedural imaging could suggest ophthalmic artery involvement in maxillary sinus cancer. It may be useful in predicting prognosis and treatment selection.

Salvage surgery improves the treatment outcome of patients with residual/recurrent maxillary sinus cancer after superselective intra-arterial cisplatin infusion with concomitant radiation therapy.

We have performed superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) for patients with maxillary sinus cancer. The promising treatment outcomes of this non-surgical treatment were reported in past studies. However, few clinical studies have been conducted to evaluate the outcome of salvage surgery following RADPLAT. The purpose of this study was to analyze the treatment outcomes of salvage surgery for patients with recurrent maxillary sinus cancer after RADPLAT. We assessed 45 patients who had recurrence following RADPLAT between 1999 and 2017, and conducted a retrospective analysis. We excluded patients who did not complete RADPLAT. Patients were not considered to have completed RADPLAT if they underwent intra-arterial cisplatin less than three times or received a total radiation dose of less than 60Gy. The primary endpoint was overall survival. The median follow-up period for surviving patients after recurrence was 5.1years. Twenty-five of the 45 (56%) patients underwent salvage surgery. The 5-year overall survival rate was 68% in patients who underwent salvage surgery, while all patients who did not undergo salvage surgery died during the observation period. Fifteen of 24 (63%) patients with local recurrence underwent salvage surgery. Eight patients did not undergo salvage surgery because of unresectable disease; five of the eight patients had unresectable posterior extension. All nine patients with nodal recurrence underwent neck dissection. Treatment outcomes of salvage surgery following RADPLAT were favorable enough for it to be generally recommended. To reduce unresectable recurrence, the posterior section should be eradicated by RADPLAT.

Impact of Total Radiation Dose on the Treatment Outcomes in Radiotherapy and Concomitant Superselective Intra-arterial High Dose Cisplatin for Locally Advanced Maxillary Sinus Cancer

The purpose of this study is to analyze the relationship between the total radiation dose and the treatment outcomes in radiotherapy and concomitant superselective intra-arterial high dose cisplatin (RADPLAT) for locally advanced maxillary sinus cancer. We have evaluated 54 patients with locally advanced maxillary sinus cancer, who were treated with RADPLAT from March 2004 to February 2019. There were 45 males and 9 females. The median age was 68 years (range 38 to 87 years). T stage was T2 in 2 case, T3 in 10 cases, T4a in 31 cases, and T4b in 11 cases. All patients had no nodal involvement. There were 53 patients who had squamous cell carcinomas, and one with undifferentiated carcinoma. Thirty-four patients received three-dimensional conformal radiotherapy (3DCRT) until 2015, and 20 patients received intensity modulated radiotherapy (IMRT) using volumetric modulated arc therapy since 2016. Median prescribed dose to the local lesion was 66 Gy (range 50 to 66 Gy) in 3DCRT group and 66 Gy (range 60 to 70 Gy) in IMRT group. All patients were irradiated at 2 Gy/fraction. All patients did not receive either prophylactic neck irradiation or volume reduction surgery before RADPLAT. Superselective intra-arterial infusions of high-dose cisplatin (100-120 mg/m2) was performed with median 6 cycles per week (range 1 to 10 cycles) in combination with simultaneous intra-venous infusions of sodium thiosulfate to neutralize cisplatin toxicity. Superselective intra-arterial infusions were performed during or before radiotherapy in all patients. The median follow-up period was 30.3 months (range 2.9 to 193 months). The 3-year local control rate and overall survival rate in all patients were 70.7%, and 86.2%, respectively. The 3-year local control rate were 88.5% in IMRT group, which had a slightly better control rate than 3DCRT group (64.0%) (p = 0.149). However, the patients who were treated with 70 Gy of IMRT (n = 14) tended to have excellent local control rate (91.7%) than patients treated with 66 Gy of IMRT or 3DCRT (72.1%, n = 27) and 60 Gy or lower of 3DCRT (49.2%, n = 13). There was no difference in total dose of cisplatin between the three groups. The 3-year overall survival rate was 100 % in patients treated 70 Gy, 90.0% in patients with 66 Gy, and 82.0% in patients with 60 Gy or lower (p = 0.655). There were no treatment-related deaths. Acute grade 3 mucositis developed in 5 patients in IMRT group and 9 patients in 3DCRT group. No late grade 3 or higher eye disorders except for cataract developed in IMRT group, while blindness occurred in 4 patients in 3DCRT group. The patients who had received 70 Gy using IMRT showed excellent local control rate without increasing adverse events. The total dose may have an impact on local control rate and survival rate in radiotherapy with concomitant superselective intra-arterial high dose cisplatin.

A case of bleeding from maxillary carcinoma embolized from the maxillary and ophthalmic arteries

BackgroundThe majority of maxillary sinus cancers are advanced at initial detection due to anatomical limitations and lack of early symptoms. In patients with orbital invasion, the feeding arteries of the tumor are often associated with the ophthalmic artery in addition to the maxillary artery. We describe a case of tumor bleeding in a patient with recurrent maxillary carcinoma that was treated with embolization from the maxillary and ophthalmic arteries.Case presentationA 70-year-old man was treated for left maxillary carcinoma from the maxillary artery with 6 cycles of selective intra-arterial cisplatin infusion with concomitant radiation therapy. He subsequently had epistaxis and underwent arterial embolization for hemostasis. He had almost no sight by this time. Angiography of the left external carotid artery and internal carotid artery revealed blood supply from the maxillary and ophthalmic arteries. Regarding the maxillary artery, coil embolization was performed after embolization with 300-500 μm Embosphere. On the other hand, for the ophthalmic artery, the 3rd portion, supratrochlear artery and dorsal nasal artery, were selected and embolized with coils. Final angiography revealed disappearance of tumor staining and a residual choroidoretinal blush. There was no bleeding that needed treatment up to 2 months after embolization.ConclusionsIn embolization of the ophthalmic artery, it is necessary to embolize the second and subsequent parts because the arteries associated with visual function branch off from the first part. Even in patients whose visual acuity has been almost lost, like in this case, there is a risk of eye pain from embolization at the proximal end, and distal embolization is necessary.

Proton beam therapy combined with retrograde intra-arterial infusion chemotherapy for an extremely rapid growing recurrent ameloblastic carcinoma: A case report.

Ameloblastic carcinoma (AC) is a very rare malignant odontogenic tumor. Although surgical resection is generally performed, treatment approaches have not been established for recurrent cases. Chemotherapy and radiotherapy are positioned as adjunctive therapies, and few studies investigated definitive non-operative therapy. We present the case of a 71-year-old male with recurrent secondary-type AC arising from the right maxilla, who was treated with proton beam therapy (PBT; 71.4 Gy relative biological effectiveness in 32 fractions) combined with continuous intra-arterial infusion of cisplatin (40 mg/m2) and docetaxel (8 mg/m2). The patient experienced acute grade 3 mucositis, dermatitis and neutropenia, which were resolved within 3 months of treatment. Late adverse events were grade 1 skin atrophy, and grade 2 right optic nerve disorder and retinopathy. After ~8 years of treatment, the patient died from another cause but did not experience any relapse or metastasis during the follow-up period of 94 months. To the best of our knowledge, this is the first report of recurrent AC treated with PBT and intra-arterial infusion chemotherapy without any severe late adverse events. This combination therapy approach may be considered as an effective therapeutic option for inoperable AC.

Low-dose cisplatin administration through the superficial temporal artery combined with definitive radiotherapy for maxillary sinus squamous cell carcinoma.

e18562 Background: Although patients with locoregional advanced maxillary sinus squamous cell carcinoma (MSSCC) are often treated with surgery followed by postoperative radiotherapy (RT), the cosmetic and functional outcomes are unsatisfactory. Moreover, the efficacy and safety of intra-arterial chemoradiotherapy are controversial. Methods: In this study, we investigated the efficacy and safety of low-dose cisplatin administration through the superficial temporal artery (STA) combined with definitive RT in patients with MSSCC. Between January 2009 and December 2018, 57 patients were administered weekly intra-arterial infusions of cisplatin (30–50 mg/m2/5h) through the STA with simultaneous intravenous infusions of sodium thiosulfate. Overall response rate (ORR), local progression-free survival (LFS), maxillectomy-free survival (MFS), progression-free survival (PFS), overall survival (OS), and safety were evaluated retrospectively. The impact of clinical factors on survival was investigated using the Cox proportional hazard models. Results: The median follow-up time was 44 months (range, 10–80 months). There were 4, 26, 23, and 4 patients with cT2, cT3, cT4a, and cT4b, respectively. All patients completed the planned treatment except for one patient who discontinued owing to facial palsy. The ORR was 98% with 51 and 5 patients having complete and partial responses, respectively. The 3-year LFS, PFS, and OS were 74%, 63%, and 81%, respectively for all patients and 100%, 81%, and 94%, respectively for 22 patients received 70 Gy irradiation. Notably, the 3-year MFS was 95% for all patients and 100% in patients received 70 Gy RT. The most common grade 3 or more toxic event was oral mucositis (22.8%). Additionally, 4 (7.0%) patients had catheter-related infections. Late grade 3 or more adverse events included optic nerve disorder (8.8%), osteonecrosis (7.0%), encephalopathy (1.8%), and increased creatinine levels (1.8%). Salvage surgery including hard palate resection and orbital exenteration were performed in 2 and 1 patients, respectively. No clinical factor was correlated with survival outcomes in our study cohort. Conclusions: Low-dose cisplatin through STA combined with RT, especially 70 Gy RT, was associated with promising tumor response, high organ preservation rate, and tolerable adverse events in MSSCC patients. Further prospective studies are warranted to compare these outcomes with primary surgery.

Clinical study of superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus squamous cell carcinoma

Clinical study of superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus squamous cell carcinoma

Gain and loss from transcatheter intra-arterial limb infusion of cisplatin for extremity osteosarcoma: a retrospective study of 99 cases in the past six years.

PurposeWe intend to analyze the gain and loss from transcatheter intra-arterial (IA) limb infusion of cisplatin for extremity osteosarcoma in the past six years.Patients and methodsBetween December 2009 and August 2014, a total of 99 patients were analyzed for efficiency and followed up for long-term survival. Based on the different administration methods of cisplatin, we divided them into the following two cohorts: IA infusion of cisplatin (n=48) and intravenous (IV) infusion of cisplatin (n=51). Except for cisplatin, all the other drugs were given intravenously. Cisplatin was given intra-arterially with an infusion time of 3 hrs or 6 hrs using a pump, whereas historical controls received IV infusion of cisplatin within 60 mins. Tumor neovascularity (TNV) was analyzed before infusion, and subsequent arteriograms were compared with the baseline to determine percent changes. Definitive surgery with intended wide resection and postoperative pathological evaluation were performed in all these patients.ResultsNo local or overall survival benefit was found in the patients preoperatively treated with IA infusion of cisplatin compared with IV infusion (P=0.336 and 0.173, respectively). Furthermore, serial arteriography was used to predict a good histologic response with an accuracy of 73.1% and a sensitivity of 100%. There were sporadic cases with the telangiectatic subtype, which did not respond very well to IV chemotherapy, but later, the tumor obviously shrank after IA infusion of cisplatin. Our study also showed that the rates of the complication of skin and muscle necrosis were not so low as reported.ConclusionWe did not observe any survival advantage of chemotherapy using IA infusion in osteosarcoma of the extremities. Arteriography for TNV can be used to predict the tumor histologic response. Malposition of the catheter might severely increase the complication of skin or muscle necrosis.

Radiation with concomitant superselective intra-arterial cisplatin infusion for maxillary sinus squamous cell carcinoma.

To assess the efficacy and prognostic factors after superselective intra-arterial chemoradiation (RADPLAT) for maxillary sinus squamous cell carcinoma (MS-SCC). Prognostic significance of age, gender, T and N factors, gross tumor volume of the primary-site (GTV), total cisplatin dosage, and total cisplatin dosage per GTV (CDDP/GTV) for primary-site recurrence-free survival rate (PRFS) were analyzed. RADPLAT was administered to 27 patients. The median follow-up period was 42.1months. The 3-year rates of overall survival and PRFS were 59.2% and 53.9%, respectively. In univariate analysis, age, male, and total cisplatin dosage were significant factors for PRFS. In multivariate analysis, lymph node metastasis was significant factors for PRFS, and gender and total cisplatin dosage weakly influenced PRFS. In acute phase, no patient showed ≥ grade 3 hematologic toxicity, and grade 3 mucositis developed in 5 patients. Late toxicities were recognized in 3 patients (grade 2 phlegmon of the face, grade 3 maxillofacial osteonecrosis, and retinopathy). Twelve patients (44%) experienced recurrences. Of them, 8 patients showed recurrence at the primarysite. RADPLAT was effective for MS-SCC, with acceptable toxicity. Total cisplatin dosage is suggested to be important for primary tumor control.

Superselective Intra-arterial Cisplatin Infusion with Concomitant Radiation Therapy for Base of Tongue Cancer

Superselective Intra-arterial Cisplatin Infusion with Concomitant Radiation Therapy for Base of Tongue Cancer

Treatment Outcomes of Radiation Therapy Combined with Superselective Intra-arterial Infusion Therapy for Maxillary Sinus Cancer

The purpose of this retrospective study is to evaluate the efficacy of radiotherapy combined with superselective intra-arterial infusion therapy of cisplatin for locally advanced maxillary sinus cancer at single institution. We have evaluated 38 patients with locally advanced maxillary sinus cancer, who were treated with curative intent radiotherapy combined with superselective intra-arterial infusion therapy of cisplatin from 2002 to 2016. There were 31 males and 7 females. The median age was 67.5 years (range 47 to 87 years). Stage distribution was T2 in 1 case, T3 in 5 cases, T4a in 23 cases, and T4b in 9 cases. All patients have no nodal involvement. There were 36 patients who had squamous cell carcinomas, and 2 with undifferentiated carcinomas. Thirty-five patients received three-dimensional conventional radiotherapy, and the 3 most recent patients received intensity-modulated radiation therapy. We used 4 MV and/or 10 MV X-ray with or without electron beams. Median prescribed dose was 66 Gy (range 50 to 70 Gy) in 2 Gy/fraction. All patients did not receive either prophylactic neck irradiation or volume reduction surgery before radiotherapy. Superselective intra-arterial infusions of high-dose cisplatin was performed in 36 patients with simultaneous intra-venous infusions of thiosulfate to neutralize cisplatin toxicity, and 2 patients received selective intra-arterial infusion chemotherapy without sodium thiosulfate neutralization. All patients were treated with median 6 cycles (range 2 to 10 cycles) of intra-arterial infusion chemotherapy per week during radiotherapy. Systemic chemotherapy was also combined in 2 patients after the completion of radiotherapy. The median follow-up period was 38.9 months (range 3.6 to 178.3 months). The 5-year overall survival rate, disease-free survival rate, and local progression-free survival rate were 78.3% (T2-3/T4:100%/70.4%), 44.5% (T2-3/T4:83.3%/36.0%) and 58.3% (T2-3/T4:83.3%/53.7%), respectively. Although 13 patients had persistence of disease, delayed local failure occurred only in 2, regional recurrence in 3, and distant metastasis in 4. As salvage treatment, 9 patients underwent salvage surgery, and 2 patients underwent stereotactic radiotherapy. Although acute Grade 3 mucositis developed in 10 patients, no renal dysfunction occurred during the treatment. There were 9 late complications, including osteonecrosis (2 patients), carotid cavernous sinus fistula (1 patient), cateract (2 patients), blindness (4 patients) as late adverse reactions. Radiotherapy combined with superselective intra-arterial infusion therapy of cisplatin for maxillary sinus cancer appears to be efficient. However, further work is needed to decrease late complications.

Osteoradionecrosis of the hyoid bone after intra-arterial chemoradiotherapy for oropharyngeal cancer: MR imaging findings

BackgroundOsteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone.MethodsThe study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis.ResultsA total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone.ConclusionOur MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.

上顎洞癌に対するシスプラチンの超選択的動注と放射線治療の同時併用療法

上顎洞癌に対するシスプラチンの超選択的動注と放射線治療の同時併用療法

1012P - A multi-institutional dose-finding and efficacy confirmation trial of superselective intra-arterial infusion of cisplatin and concomitant radiotherapy for patients with locally advanced maxillary sinus cancer (JCOG1212, RADPLAT-MSC): Results of dose-finding phase

Superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT) has been performed for the patients with locally advanced maxillary sinus squamous cell carcinomas (LA-MSSCCs) in several institutions and has been reported to result in a favorable survival. This multi-institutional prospective trial was aimed to confirm the adequate dose and efficacy of RADPLAT for the patients with LA-MSSCCs. The dose-finding phase was performed to evaluate the incidence of dose-limiting toxicity (DLT) and to determine the recommended cycle of intra-arterial infusion of cisplatin. Eighteen patients were registered from 7 institutions for this study. In this dose-finding study, 100 mg/m2 of cisplatin was administered intra-arterially weekly for 7 weeks with concomitant radiotherapy (total 70 Gy). Cisplatin was skipped in the case of adverse events that met the skipping rule defined by the protocol. The recommended number of cycles was determined according to the distribution of the number of cycles of administered cisplatin and the incidence of DLT. The median age of all participants was 64 years old (range, 40-75 years old). Sixteen patients were diagnosed as T4aN0M0, and two patients as T4bN0M0. All patients achieved full dose of radiotherapy. The number of cycles of administered cisplatin was 7 in 13 patients and 6 in 5. DLT was observed in 5 patients; Gr 3 liver dysfunction (1), Gr 4 thrombocytopenia (1), Ccr < 40 (1), Gr 3 retinopathy (1), and Gr 3 retinal detachment (1). There was not either treatment-related death or neural complication. RADPLAT appears to be safe and well-tolerated at 7 cycles of cisplatin at a dose of 100 mg/m2 each cycle, which were determined to be the recommended number of cycles for LA-MSSCC.

T-status and an oral fluoropyrimidine, S-1, adjuvant chemotherapy are prognostic factors in reduced-RADPLAT for resectable hypopharyngeal cancer

Conclusion: Reduced-RADPLAT for HPC achieved comparative survival and locoregional control rates with lower toxicities compared with concurrent chemoradiotherapies including original RADPLAT. S-1 adjuvant chemotherapy showed a survival benefit. Objectives: To evaluate the efficacy and toxicities of targeted intra-arterial (IA) infusion of cisplatin with concurrent radiotherapy with a reduced dose (reduced-RADPLAT) for resectable hypopharyngeal cancer (HPC). Methods: Between 1999–2012, 50 patients with stage II–IVA HPC primarily treated by reduced-RADPLAT were analyzed. They were treated by 2–5 courses of IA cisplatin infusion (100 mg per body) with simultaneous systemic infusion of sodium thiosulfate concurrent with conventional radiotherapy (66–70 Gy). After 2003, S-1, an oral fluoropyrimidine, adjuvant chemotherapy was administered to all eligible patients. Results: During a median follow-up of 48.6 months, the estimated 3- and 5-year overall survival (OS), progression-free survival (PFS), locoregional control, and laryngoesophageal dysfunction-free survival (LEDFS) rates were 76.0% and 62.0%, 58.0% and 50.0%, 66.0% and 62.0%, and 56.0% and 54.0%, respectively. Grade 3 toxicities were observed in 30.0%. No patient had grade 4 or higher toxicities. No patient required tube feeding or tracheotomy at 3 months after treatment. T4-lesions and S-1 administration were significant factors predicting poor and good OS, PFS, and LEDFS, respectively.