Superselective Intra-arterial Infusion Research Articles

Analysis of rescue strategies for acute thrombosis during STA-MCA bypass surgery and the literature review

Background and objectivesSTA-MCA bypass surgery is mainly used for Moyamoya disease, giant intracranial aneurysms, and resection of intracranial tumors requiring sacrifice of blood vessels. The intraoperative patency of the reconstructive vessels is critical to the efficacy of the procedure. This study aimed to evaluate the efficacy of intra-arterially infused tirofiban for the treatment of acute thrombosis during STA-MCA bypass surgery and countermeasures for acute thrombosis.MethodsThis study involved 209 patients (272 hemispheres) who underwent STA-MCA surgery between November 2020 and December 2023. Intraoperative acute thrombosis occurred in eight patients (3.83%,8 hemispheres). We retrospectively reviewed the clinical and imaging data, surgical procedure, and follow-up outcomes of eight patients. We implemented the different thrombolytic methods to evaluate the optimal thrombosis management during the bypass surgery. After three months, we assessed neurological functions using the modified Rankin Scale (mRS) and conducted a literature review using PubMed.ResultsEight patients (four male patients and four female patients) developed acute thrombosis during the bypass surgery. Of the eight patients, two underwent re-anastomosis after thrombus removal, three received local injections of tirofiban into the anastomosis or the branches of the superficial temporal artery, and three underwent superselective intra-arterial tirofiban infusion using a microcatheter. Thrombosis were resolved, and arteries were recanalized in all patients. The mRS score was 0 in all patients. No major ischemic or hemorrhagic complications occurred.ConclusionOur treatment methods were efficacious in the management of acute thrombosis. Intra-arterial tirofiban administration seems to be a simple and effective treatment option for acute thrombosis during STA-MCA bypass surgery.

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.

Endovascular Applications for the Management of High-Grade Gliomas in the Modern Era.

High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood-brain barrier (BBB) penetration, hemodynamic complexities, and drug-tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care.

Blood-Brain Barrier Disruption for the Treatment of Primary Brain Tumors: Advances in the Past Half-Decade.

To review relevant advances in the past half-decade in the treatment of primary brain tumors via modification of blood-brain barrier (BBB) permeability. BBB disruption is becoming increasingly common in the treatment of primary brain tumors. Use of mannitol in BBB disruption for targeted delivery of chemotherapeutics via superselective intra-arterial cerebral infusion (SIACI) is the most utilized strategy to modify the BBB. Mannitol is used in conjunction with chemotherapeutics, oligonucleotides, and other active agents. Convection-enhanced delivery has become an attractive option for therapeutic delivery while bypassing the BBB. Other technologic innovations include laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) which have emerged as prime modalities to directly target tumors and cause significant local BBB disruption. In the past 5years, interest has significantly increased in studying modalities to disrupt the BBB in primary brain tumors to enhance treatment responses and improve clinical outcomes.

Safety and feasibility of intra-arterial delivery of teniposide to high grade gliomas after blood-brain barrier disruption: a case series.

This case series describes the safety and efficacy of superselective intra-arterial (IA) cerebral infusion of teniposide for the treatment of patients with glioma, to provide new ideas and methods for the treatment of high grade gliomas. 12 patients with glioma who were previously treated with standard therapy were treated with superselective IA cerebral infusion of teniposide. Patients received at least two cycles of treatment (one cycle: 150 mg/time, used for 1 day, repeated at 28 day intervals) after blood-brain barrier disruption. Patients received individualized treatment on the tumor location. The ophthalmic artery was bypassed during the super-selective arterial infusion. No significant differences in biochemical indexes and Karnofsky performance status (KPS) score were observed before and after treatment, and no evident adverse events occurred (P>0.05). In a recent response evaluation (August 2023), two (8%) patients presented with a complete response (16.7%), four had a partial response (33.3%), four had stable disease (33.3%), and two showed progressive disease (16.7%). The overall response rate and disease control rate were 50.0% and 83.3%, respectively. In addition, we described the detailed course of treatment in two patients. Case No 1 (recurrent tumor) and case No 2 (primary tumor) received six and three cycles of teniposide infusion, respectively. After treatment, the tumors of the patients were significantly reduced without evident adverse effects. This small series suggests that superselective IA cerebral infusion of teniposide may be a safe and effective therapy in the multimodal treatment of malignant glioma and warrants further study in larger prospective investigations.

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.

Efficacy of concurrent chemoradiotherapy with retrograde super selective intra-arterial infusion combined with cetuximab for synchronous multifocal oral squamous cell carcinomas

BackgroundThe incidence of multicentric oral cancer is increasing. However, treatment encounters difficulty if each tumor needs to be treated simultaneously. The objective of this clinical case report is to highlight the effect of concurrent chemoradiotherapy with retrograde superselective intra-arterial infusion combined with systemic administration of cetuximab on synchronous multifocal oral squamous cell carcinomas.Case presentationA 70-year-old man presented to the hospital with multiple tumors and oral pain. Three independent tumors were found in the right dorsal tongue, left edge of the tongue, and left lower lip. Based on the characteristic appearance of the lesions and further evaluation, clinical diagnoses of right tongue cancer “T3”, left tongue cancer “T2” and lower left lip cancer “T1”, N2cM0 were made. Treatment was initiated with systemic administration of cetuximab, followed by intra-arterial chemoradiotherapy. Treatment results were complete response on all three local lesions, and left neck dissection was performed following the initial treatment. The patient showed no evidence of recurrence during the 4 years follow-up period.ConclusionsThis novel combination treatment seems to be a promising strategy for patients with synchronous multifocal oral squamous cell carcinoma.

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.

Superselective intra-arterial chemoradiotherapy using altered blood flow compared to conventional systemic chemoradiotherapy for locally advanced oral squamous cell carcinoma: a single-center retrospective study.

To evaluate the efficacy and safety of superselective intra-arterial (IA) chemoradiotherapy with cisplatin and transcatheter arterial embolization (TAE) on advanced oral cancer, and to compare it with that of systemic chemoradiotherapy. This single-center retrospective study included 23 consecutive patients with locally advanced oral squamous cell carcinoma from November 2011 to November 2019. Of these, 15 received superselective IA cisplatin chemoradiotherapy with altered blood flow in the branches of the external carotid artery, and eight received systemic chemoradiotherapy. Medical charts were reviewed for the evaluation of patient data, drug toxicity, and antitumor efficacy. Local control rate for the superselective IA infusion group, who underwent 6-7 cycles was significantly higher than that of the systemic chemotherapy group (11/13, 85% vs 3/8, 38%; p = 0.04). Regional control, locoregional control, disease-free survival, and overall survival rates were not significantly different between the groups (p = 0.15-0.907). Acute toxicity rates of grade 3 or higher were not significantly different between the IA and IV chemotherapy groups (p = 0.221). Superselective IA chemoradiotherapy with cisplatin using altered blood flow in the branches of the external carotid artery with TAE may be useful for inoperable oral cancer.

Applicability of a single camera-based catheter navigation system using teeth arch as an anatomical landmark for superselective intraarterial infusion in advanced oral cancer treatment

Superselective intraarterial infusion chemoradiotherapy is a modality of oral cancer therapy in which the artery feeding the tumor is catheterized. 3D information about the carotid artery is required to enable the surgeon to judge whether to advance, retract, or rotate the catheter. For this purpose, we proposed and conducted a model experiment to assess a new method of catheterization that applies a tracking system using registration with a monocular camera using the maxillary arch as the anatomical landmark. In this method, the preoperative 3D computer tomography angiographic image of the carotid artery that the catheter will be passed through is overlaid on the 2D video image. The mean TRE was 0.96 ± 0.36 mm and 0.88 ± 0.31 mm and 1.12 ± 0.46 mm when images were registered with the anterior and posterior teeth as the landmarks, respectively; the difference was not significant (p = 0.21). This tracking system that enables markerless registration simply by taking images of the maxillary anterior teeth with a single camera was convenient and effective for catheterization. In this study, we propose the new application of this tracking system and a novel method of catheterization for superselective intraarterial infusion chemoradiotherapy for oral cancer.Graphical abstractIn retrograde superselective intraarterial catheterization, a catheter is inserted into a tumor-feeding artery originating from the external carotid artery (ECA) (the lingual artery [LA], facial artery [FA], or maxillary artery [MA]). Because the maxillary dentition is located near the external carotid artery, we focused on real-time markerless registration using maxillary dentition fixed to the skull.

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.

Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood-brain barrier disruption: where are we now, and where we are going.

Intra-arterial (IA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration therapeutics through a targeted vascular territory, while potentially limiting systemic toxicity. Studies have demonstrated IA methods to be safe and efficacious for a variety of therapeutics. However, further characterization of the clinical efficacy of IA therapy for the treatment of brain tumors and refinement of its potential applications are necessary. We have reviewed the preclinical and clinical evidence supporting superselective intraarterial cerebral infusion (SSIACI) with BBB disruption for the treatment of brain tumors. In addition, we review ongoing clinical trials expanding the applicability and investigating the efficacy of IA therapy for the treatment of brain tumors. Trends in recent studies have embraced the use of SSIACI and less neurotoxic chemotherapies. The majority of trials continue to use mannitol as the preferred method of hyperosmolar BBB disruption. Recent preclinical and preliminary human investigations into the IA delivery of Bevacizumab have demonstrated its safety and efficacy as an anti-tumor agent both alone and in combination with chemotherapy. IA drug delivery may significantly affect the way treatments are delivered to patients with brain tumors, and in particular GBM. With refinement and standardization of the techniques of IA drug delivery, improved drug selection and formulations, and the development of methods to minimize treatment-related neurological injury, IA therapy may offer significant benefits for the treatment of brain tumors.

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

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.

Daily concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion for locally advanced squamous cell carcinoma of the mandibular gingiva

ObjectiveWe previously reported that daily concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion for locally advanced oral cancer provided good local control and overall survival rates. This study was performed to evaluate the therapeutic results of daily concurrent intra-arterial chemoradiotherapy for patients with locally advanced squamous cell carcinoma of the mandibular gingiva. MethodsSixteen patients with T3, 4 mandibular gingiva cancer who refused surgery underwent definitive intra-arterial chemoradiotherapy between August 2006 and July 2014. Treatment consisted of concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion (60 Gy, total dose; 60 mg/m2 for docetaxel and 150 mg/m2 for cisplatin). ResultsComplete response of the primary site was obtained in 14 patients (87.5%). Five-year local control and survival rates were 73.4%and 81.3%, respectively. Grade 3 or 4 toxicities including mucositis and neutropenia were seen in 13 patients (81.3%) and 6 patients (37.5%), respectively. Grade 3 osteoradionecrosis occurred as a late adverse event in 1 patient (6.3%). ConclusionsRetrograde daily concurrent intra-arterial chemoradiotherapy for locally advanced carcinoma of the mandibular gingiva provided good local control and overall survival rates. This method can become one of the therapeutic options for patients with locally advanced carcinoma of the mandibular gingiva.

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

Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma.

Using trace three-dimensional culture, the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) can be tested even in cases with a small number of cells, including oral squamous cell carcinoma (OSCC), and evaluation of the antitumor effect with a drug concentration close to the in vivo level is possible. The present report aimed to evaluate the utility of the CD-DST in the assessment of the in vitro efficacy of single-agent and multidrug combination chemotherapy for OSCC in comparison with the clinical response rates and to examine the possible clinical application of CD-DST for such cases. A total of 33 OSCC patients from whom 33 samples were obtained from January 2010 to September 2015 were included. CD-DST was performed, individually and in combination, on the three drugs [i.e., cisplatin (CDDP), 5-fluorouracil (5-FU), and docetaxel (DOC)] and on super selective intra-arterial infusion chemoradiotherapy (IACRT). The overall evaluable rate of the CD-DST in OSCC was 81.8% (27 of 33 cases) and the sensitivity to each anticancer drug was evaluated. The in vitro efficacy rates of IACRT, cisplatin + 5-fluorouracil, and docetaxel + cisplatin + 5-fluorouracil (TPF) confirmed the estimated clinical response rates. In 14 of 33 patients, the results of CD-DST were compared with clinical efficacy, which was judged based on measurable lesions on imaging. For TPF therapy, the sensitivity test of the IACRT had a positive predictive value of 90.9% (10 of 11 cases) and a negative predictive value of 100% (3 of 3 cases); the accuracy of the susceptibility test for the anticancer agents was 92.8% (13 of 14 cases). The CD-DST may be useful in selecting multidrug combination chemotherapy and IACRT for OSCC, however, accumulation of further clinical data is required in the future.

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.