Selective Intra-arterial Chemotherapy Research Articles

Feasibility Study of Transarterial Chemotherapy Followed by Chemoembolization for Recurrent Breast Cancer

PurposeTo assess the treatment response to transarterial chemotherapy followed by chemoembolization for locally recurrent breast cancer. Materials and MethodsThirty-nine women with locally recurrent breast cancer after standard therapy underwent selective intra-arterial chemotherapy followed by embolization using drug-eluting microspheres for locally recurrent tumors and axillary lymph node metastases. Tumor response and toxicity were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and Common Terminology Criteria for Adverse Events (CTCAE), and survival was evaluated by the Kaplan‒Meier method. ResultsThe local responses of breast tumors at 3 and 6 months were as follows: complete response, 5.1% and 7.2%; partial response, 35.9% and 67.8%; stable disease, 59.0% and 21.4%; and progressive disease, 0.0% and 3.6%, respectively. All adverse events were mild and did not require treatment. The median overall survival (OS) was 46.5 months, and the OS rates for 1 and 2 years were 81.4% and 69.2%, respectively. The size of recurrent tumors and axillary lymph node metastases did not impact prognosis, but both liver and bone metastases adversely affected survival. ConclusionTransarterial chemotherapy followed by chemoembolization may provide a favorable tumor response in patients with locally recurrent breast cancer in whom conventional therapy has failed.

Clinical cases of successful treatment of life-threatening complications of selective intraarterial chemotherapy in children with retinoblastoma

Introduction. Retinoblastoma (RB), a malignant neoplasm, is the most common pediatric intraocular tumor worldwide. With the advent of intra-arterial chemotherapy, interventional surgeons have assumed a central role in the treatment of this pediatric disease. Intra-arterial chemotherapy is a new treatment modality for RB in which chemotherapeutic agents are precisely delivered into the ocular artery, minimizing systemic toxicity. This procedure has shown impressive results and has significantly reduced the rate of enucleation in advanced and refractory RB. However, the procedure entails potentially serious acute respiratory and hemodynamic disturbances.Purpose of the study – present our experience with and features of anesthesia management in the development of life-threatening conditions during superselective intraarterial chemotherapy (SIAC) in two patients with RB.Materials and methods. We present clinical cases in 2 2-year-old patients with RB who received three courses of SIAC for RB with development of severe trigeminocardial reaction.Conclusion. SIAC is one of the new promising treatments for RB. Prominent cardiorespiratory complications are frequently observed during general anesthesia for repeated sessions of SIAC and can be potentially life-threatening. Presumably, these complications represent an autonomic reflex response to ocular catheterization. Therefore, all patients with RB who are scheduled for SIAC should be included in the high-risk group. The timing of occurrence of the trigeminocardiac reflex is predictable and temporary, but the anesthesiologist must be prepared to treat the developed complication with the help of emergency drugs (adrenaline).

EVALUATION OF THE TUMOR PROLIFERATIVE ACTIVITY INDEX PCNA IN A VARIETY OF ROUTES OF DELIVERY OF CHEMOTHERAPEUTIC DRUGS IN PATIENTS WITH LOCALLY ADVANCED BREAST CANCER

Introduction. Breast cancer is one of the most live issue of the modern oncology, as it holds the leading position among the causes of female mortality and disability. A special place in the structure of this pathology is occupied by locally advanced forms of malignant tumor in which the effectiveness of the treatments used is unfortunately very low, therefore the prognosis is rather unfavorable. This determines there levance of them search for new methods of diagnosis and treatment in such patients. In the context of this research, we identified the role of neoadjuvant selective intra-arterial polychemotherapy in adverse primary inoperable forms of breast cancer. To determine and predict the effectiveness of this treatment, we used tumor proliferative activity. The research examined the expression of a PCNA nuclear proliferation marker for prognostic and diagnostic evaluation in the light of unsatisfactory literature on the subject in the context of determining similar parameters by other criteria. PCNA level was taken as the main dichotomous point of prognostic assessment of neoadjuvant therapy based on the results of retrospective analysis of the efficacy of preoperative treatment and determination of statistically significant difference between the results in the subgroups with lower and higher marker levels, which in our study were divided according to the median value of the immunohistochemical parameter level in the total sample of 25 %. Objective. Evaluation of the effectiveness of neoadjuvant treatment using systemic and selective intraarterial routes of chemotherapy administration in patients with locally advanced breast cancer using the tumor proliferative index based on the PCNA marker. Materials and methods. A retrospective analysis of the results of a comprehensive treatment of patients with initially inoperable locally advanced breast cancer based on selective and systemic routes of administration of chemotherapy was performed. The study included 63 patients. The sample was divided into 2groups depending on the selected type of neoadjuvant polychemotherapy: 1st group – control group were formed (based on systemic therapy) and 2nd group – study group (the selective intraarterial delivery route was used). The control group consisted of 22 patients, the study – 41 patients. All patients revealed stage IIIb of the disease. In accordance with the clinical manifestations, the patients were distributed as follows: control group include 12 patients with сT4bN1M0, 6 patients with сT4aN1M0 and 4 patients with сT4cN1M0; study group include 23 patients with сT4bN1M0, 7 patients with сT4aN1M0 and 11 patients with сT4cN1M0. All patients included in the study had luminal type B. In parallel with routine methods, the dynamics of proliferative activity of the tumor by the PCNA nuclear antigen was additionally studied in all patients. This study demonstrates the level of the PCNA marker at the start of treatment and after the completion of polychemotherapy (PCT). After PCT, all patients underwent surgical intervention. Taking into account the pathological examination, the patients were reassigned as follows: in the control group, 4 patients has pT4aN0M0, 2 patients – pT4aN1M0, 4 patients – pT4bN0M0, 8 patients – pT4bN1M0, 1 patient – pT4cN0M0 and 3 patients – pT4cN1M0; in the study group, 3 patients has PT4aN1M0, 4 patients – PT4aN0M0, 15 patients – PT4bN1M0, 8 patients – PT4bN0M0, 6 patients – PT4cN1M0 and 5 patients – PT4cN0M0. Since the patients belonged to the group with Luminal type of tumor, each of them received hormone therapy in an adjuvant regimen. Patients of reproductive age were treated with the group of estrogen antagonists, while postmenopausal patients received aromatase inhibitors. Targeted therapy was not used in the study. A statistical analysis was performed between the comparison groups; the median marker level in 25 % was taken as the critical value. Results. According to the degree of PCNA regression, it was determined that selective intra-arterial chemotherapy for breast cancer with a low proliferative activity index has a statistical advantage in overall survival and average life expectancy (p < 0.05) compared with control group. Conclusions. Using the PCNA indicator, one can reliably evaluate the proliferative activity of the tumor, thus predicting the effect of neoadjuvant chemotherapy and choosing the optimal tactics of complex treatment. Keywords: locally advanced breast cancer, proliferative activity index, marker of nuclear antigen of proliferating cells, systemic polychemotherapy, selective intra-arterial polychemotherapy.

The role of three-component selective intra-arterial chemotherapy in the failure of standard organ-preserving treatment in children with intraocular retinoblastoma

Introduction. Retinoblastoma (RB) is a malignant tumor of the retina, the survival rate for the intraocular form reaches 99 %. According to the researchers, the risk factors for the occurrence of refractory or recurrent forms of RB are the size of the tumor at primary diagnosis (more than 15 mm), the child's age at the onset of the disease (up to one year), bilateral RB, and the presence of subretinal and vitreal screenings. If methods of local destruction of the tumor are not applicable for the successful treatment of intraocular refractory or recurrent RB, then they resort to the second line of polychemotherapy as an alternative to enucleation. New versions of local chemotherapy and radiation therapy (gamma knife) are being developed and applied. Nowadays, researchers have a negative attitude towards traditional radiation therapy (EBRT) as a method of organ-preserving treatment due to serious consequences (asymmetry of the facial skeleton and second radio-induced tumors).Aim of the study — to increase the effectiveness of organ-preserving treatment in patients with refractory or recurrent intraocular RB.Materials and methods. In the period from 10.2018 to 12.2019 at the N.N. Blokhin National Medical Research Centre of Oncology it was received three-component selective intra-arterial chemotherapy (SIAC) in 15 patients (15 eyes) aged 11 to 52 months. Eyes initially affected by RB (n = 15), according to the IIRC (Murphree) classification, had the following groups: group B in 1 case, group C in 3, group D in 7, and group E in 4 eyes. It should be noted that all patients initially received intensive combined conservative therapy: in 11 (73 %) of 15 cases — systemic chemotherapy VEC; in 13 (86 %) of 15 — SIAC with melphalan, in all cases, additionally, two-component SIAC was used in combination with melphalan with topotecan. In some cases, local therapy in the form of intravitreal chemotherapy (IVIC) was added to the treatment of 6 (40 %) of 15 patients in the form of melphalan monotherapy and in one case (6 %) a doublet was used in combination with melphalan and topotecan. Also, in some patients, additional local ophthalmic therapy was used: transpupillary thermotherapy (TTT) in 6 out of 15 patients, including in combination with cryotherapy (CT) in 1 patient and in combination with brachytherapy (BT) in one case. At the same time, incomplete tumor regression (refractory form of the disease) was noted in 7 out of 15, and a recurrent course of the disease — in 8 out of 15 patients. Incomplete tumor regression and recurrent RB were the reasons for the appointment of a three-component SIAC using carboplatin, melphalan and topotecan, in combination with IVIC with pronounced endophytic growth of RB, as an alternative to irradiation and enucleation of the eye.Results. The average number of three-component SIAC courses was 1.46 ± 0.63 (rang 1—3). The combination of SIAHT with IVHT was performed in 3 out of 15 patients. All children (n = 15) are alive with a median period of follow-up of23.92 ± 15.68 (10—64) months. One in 15 patients was lost from observation due to their parents’ desire to be treated abroad. It is known that the child is alive, but there is no data on the condition of his eyes. 9 out of 14 patients needed additional treatment after SIAC intensification. To consolidate the resulting effect as a full regression in 2 cases, the final IVIC courses were conducted (n = 2). In connection with the presence of residual tumor and/or intraocular progression and/or appearance of new lesions in 1 of 9 patients were IVIC and TTT, 2 of 9 — IVIC, SIAC, CT, TTT. In 4 out of 9 cases, enucleation was performed, and in 2 out of 4 — the operation was performed after continuing the attempt of organ-preserving treatment: after CT and TTT (n = 1) and IVIC, CT, TTT and BT (n = 1). No child was given ERBT. There were no cases of stroke after SIAC. We managed to save 10 (71.4 %) of 14 eyes with visual acuity: object vision in 4 (40 %) out of 10, eye fixation in 3 (30 %) out of 10, and light perception in 3 (30 %) out of 10 cases. The average follow-up period from the end of three-component SIAC in 14 patients was 13.57 ± 5.27 (6—22) months.Conclusion. Thus, the three-component SIAC is effective and safe for patients with refractory and recurrent retinoblastoma, as evidenced by a high percentage of retained eyes and the presence of visual functions from light perception to object vision.

Proton beam therapy combined with intra-arterial infusion chemotherapy for stage Ⅳ adenoid cystic carcinoma of the base of the tongue

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15–116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue.

Ретинобластома. Часть 2. Принципы терапии интраокулярной ретинобластомы

Retinoblastoma is one of the most common retinal tumors in young children. Current early diagnostic and treatment strategies focus on the possibility to implement eye-preserving therapies. The 5-year overall survival for children with retinoblastoma is now 100%. First-line eye removal is recommended in extensive intraocular seeding and poor visual prognosis. The volume of adjuvant therapy is based on the histological risk factors for disease progression. This paper discusses the algorithms to determine risk factors and further systemic treatment strategy in several large study groups. Eye and even vision preservation is now possible in at least 65–75% of retinoblastoma patients. The paper also describes in detail the methods of locally administering chemotherapy which are considered eye-preserving treatment options, i.e., selective intra-arterial chemotherapy and intravitreal chemotherapy. Various physical methods of eye-preserving treatment which underwent significant development over the past decade are highlighted. In conclusion, the authors emphasize that retinoblastoma survivors, their siblings and offspring should be carefully monitored.Keywords: children, retinoblastoma, enucleation, polychemotherapy, selective intra-arterial chemotherapy, intravitreal chemotherapy, laser photocoagulation, transpupillary thermotherapy, cryotherapy, brachytherapy, monitoring.For citation: Ivanova S.V., Kuleva S.A., Sadovnikova N.N. et al. Retinoblastoma. Part 2. Treatment strategies for intraocular retinoblastoma. Russian Journal of Clinical Ophthalmology. 2020;20(4):197–203. DOI: 10.32364/2311-7729-2020-20-4-197-203.

Long-lasting full remission after selective intra-arterial chemotherapy for recurrence of locally advanced oral mucosa carcinoma

Long-lasting full remission after selective intra-arterial chemotherapy for recurrence of locally advanced oral mucosa carcinoma

Proton Beam Therapy Combined with Intra-Arterial Infusion Chemotherapy for Stage IV Adenoid Cystic Carcinoma of the Base of the Tongue.

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15–116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue.

Life-Threatening Complications During Superselective Ophthalmic Arterial Chemotherapy for Retinoblastoma: Retrospective Cohort Study

Background. Retinoblastoma is the most common intraocular malignant tumor in children. Substantial advances have been made in field of local treatment, in particular, through the development of selective intraarterial chemotherapy (SIAC). Life-threatening cardio-respiratory disorders were reported during the course of SIAC at the moment of a.ophthalmica catheterization. Objective. Our aim was to improve the safety and effectiveness of anesthetic management in children with retinoblastoma. Methods. The retrospective study included patients (n=203) who underwent SIAC (517) under general anesthesia in 2013–2018. Results. Hemodynamic parameters in patients who underwent SIAC procedure for the first time (211) were analyzed, in 186 (88%) cases, smooth anesthesia was observed, the deviations of blood pressure and heart rate did not exceed 20% of the baseline values. In 25 (12%) cases, patients who underwent the first SIAC procedure developed bronchospasm with a decrease in respiratory volume of up to 30% from the initial values 10–20 seconds after catheterization of a.ophthalmica with microcatheter. When analyzing hemodynamic parameters in patients who underwent repeated SIAC procedures (2nd, 3rd sessions, etc.) (306), in 177 (58%) cases, a clinical picture of the trigemino-pulmonary reflex of varying severity manifested. Conclusion. Severe cardio-respiratory complications are often observed during SIAC in children with retinoblastoma. These reactions occur predominantly during the second or subsequent procedures and can be potentially life-threatening. All patients with retinoblastoma who undergo SIAC should be considered at high risk.

Досвід неоад’ювантної селективної внутрішньоартеріальної хіміотерапії за схемою FOLFIRINOX, проведеної пацієнту з умовно резектабельним раком правого анатомо-хірургічного сегмента підшлункової залози

Досвід неоад’ювантної селективної внутрішньоартеріальної хіміотерапії за схемою FOLFIRINOX, проведеної пацієнту з умовно резектабельним раком правого анатомо-хірургічного сегмента підшлункової залози

Efficacy and safety of retrobulbar blockade with ropivacaine during selective intraarterial chemotherapy in children with retinoblastoma. Article

Background. The goal of treatment of retinoblastoma is not only the preservation of life and vision, but also the minimization of systemic complications, a cosmetic defect, which is achieved through the development of selective intraarterial chemotherapy (SIACT). Repeated conduction of the SIACT at the time of catheterization a. ophtalmica is accompanied by cardio-respiratory disorders (CRD). Objectives. We analyze the effectiveness and safety of retrobulbar blockade with a 0.,5 % solution of ropivacaine to prevent or reduce CRD. Materials and methods. The study included patients from the Blokhin National Medical Research Center of Oncology with retinoblastoma under conditions of general anesthesia in 2017–2018 SIACT procedures were performed (n = 267). 83 patients were primary. 83 % of them had a mild and moderate degree of cardio-respiratory disorders during the second SIAHT procedure, 17 % of patients who were included in the study developed marked CRD (n = 14), for the prevention of which, during the third procedure of SIACT was performed retrobulbar blockade (RBB). Results. 4 (28.57 %) patients after retrobulbar blockade did not develop CRD in the third SIACT procedure, in 5 (35.7 %) patients after performing RBB, CRD symptoms decreased to moderate and in 5 (35.7 %) mild expressiveness. After the RBB, there was a lesser increase in airway resistance during inhalation of Pinsp 25.4 ± 7.4, versus 33.8 ± 3.2 with OA and more stable hemodynamics. When conducting retrobulbar blockade with a solution of ropivacaine 0.5 % with a volume of up to 1.5 ml, no complications were observed in children with retinoblastoma. Conclusion. In our experience, pronounced cardio-respiratory complications are often observed during repeated sessions of SIACТ in children with retinoblastoma and can be potentially life-threatening. Using of retrobulbar blockade with severe CRD may reduce the frequency and degree of development of respiratory disorders and is accompanied by greater hemodynamic stability.

Modern Possibilities of Organ-Preserving Treatment in Children with Intraocular Retinoblastoma

Retinoblastoma is one of highly curable diseases; today the total 5-year survival rate in patients with retinoblastoma exceeds 95%. The article summarizes the current world experience on treatment of patients with intraocular retinoblastoma. The treating skills of intraocular malignant tumor in children are a balance between the patient’s life and the preservation of an eye and its visual functions. The complex and challenging task is the treatment of common intraocular retinoblastoma groups «C», «D», «E» when the large size or localization of the tumor does not allow performing the local (focal) destruction of the tumor. As a rule, in such cases neoadjuvant chemotherapy (CT) is performed at the first stage in order to reduce the size of the tumor for further focal therapy. However, the analysed data on the effectiveness of neoadjuvant CT in combination with focal or radiotherapy demonstrated the limited possibilities of the proposed therapy. Local drug delivery in cancer therapy became a real breakthrough in the organ-preserving treatment of children with large intraocular retinoblastoma. The most widely used current methods of local drug delivery are intravitreal (IVitC) and selective intra-arterial chemotherapy (SIAC) as monotherapy or in combination with neoadjuvant CT and focal therapy which significantly increased the percentage of preserved eyes without radiotherapy administration or damage to the patient survival. The review discusses the different IVitC and SIAC techniques, chemotherapy schemes, dosages of chemotherapy, immediate and long-term complications of treatment.

A New Era of Organ-Preserving Treatment in Pediatric Intraocular Retinoblastoma in Russia: A Multicenter Cohort Study

Background.Retinoblastoma (RB) is a life threatening cancer disease. A breakthrough in the treatment of children with RB is associated with the improvement of conservative treatment that was administered in at least one of the two tumor-affected eyes in most bilateral cases, that was chemotherapy both systemic and local (selective intra-arterial and intravitreal) in most cases combined with laser therapy, cryotherapy, or brachytherapy. The development of such techniques as local chemotherapy is focused on preservation of visual functions, reducing the number of enucleations and radiotherapy (RT) course. The success of the healing of RB is closely associated with a multidisciplinary approach to diagnosis and treatment, as well as specialized longterm follow-up clinical examination.Objective.eye and vision preservation against large intraocular tumors with different growth types and localization without the course of remote radiation therapy was the main purpose.Methods.In the period from September 2012 to January 2016, the study enrolled 45 patients with RB when at least one eye had intraocular tumor spread corresponding to the group C or D. According to the ABC international classification, patients have a relatively good prognosis for organ-preserving treatment. 4 of 18 children with bilateral RB had undergone primary enucleation of worse eye the worst eye, group E; 49 (77.8%) of the 63 affected eyes had features for groups C and D. In this study, no patient received local chemotherapy initially, only after prior systemic chemotherapy. Selective intra-arterial chemotherapy (SIAC) was applied to 41 patients (45 eyes; mean course number was 2), and 32 patients (34 eyes) had undergone intravitreal chemo therapy (IViC) (mean course number was 2). Focal therapy and local chemotherapy were the main methods of treatment for progression (new lesions on the retina) in 8 (16.3%) of 49 eyes with tumors of group C (n=1) and D (n=7); the relapse in 14 of 49 (new lesions on the retina) in eyes with tumors of group C (n=5) and D (n=6) and (new lesions on the retina and the vitreous) in eyes with tumors of group D (n=3) (28.5%), and stabilization of disease n=23 (46.9%). We should note that 2 patients underwent repeated course of in case of systemic chemotherapy, 1 patient — a Gamma Knife procedure due to registered disease stabilization, progression or relapse.Results.10 (20.4%) of 49 eyes saved due to the combined chemotherapy. In 45 patients diseasefree survival rate was 56.1±8.9 % (with mean follow-up period 26.9±2.5 months). 1 of 45 patients died from leukemia. 44 of 45 patients are alive without metastasis. The mean follow-up was 20 months (3 to 43 months). Eye salvage rate in group C — 14 (93.3%) of 15, in group D — 31 (91.2%) of 34.Conclusion.These methods: second line of systemic chemotherapy, RT, and a Gamma Knife procedure should be considered as a failure of primary treatment. Our study demonstrated a high efficacy of local chemotherapy with promissing techniques of conservation therapy, which safety increases due to experience.

SELECTIVE INTRA-ARTERIAL CHEMOTHERAPY (IAC) IN TREATMENT AT CHILDREN WITH THE INTRAOCULAR RETYNOBLASTOMA

Treatment of intraocular retinoblastoma is challenging. It requires a multidisciplinary personalized approach that includes focal treatments, chemotherapy, surgery and radiotherapy. Today, the focus of therapy has shifted to eye preservation with the major aim to save the child’s life and to preserve the eyeball as a functioning organ of vision with minimal complications. One of the most promising therapy approaches is selective intra-arterial chemotherapy (IAC), by which a cytostatic agent is given directly into the eye. This treatment modality has been shown to provide survival benefit and improvement of quality of life, reducing toxicity and minimizing side effects.

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.

Recent advances and challenges in the management of retinoblastoma.

The treatment of retinoblastoma (Rb) has improved significantly in recent times. Worldwide, there is an increasing trend to use conservative treatment modalities that aim to preserve the globe as well as vision with minimum morbidity. Recently, the use of targeted delivery of chemotherapy to the eye in the form of selective intra-arterial and intravitreal chemotherapy has shown promising results. Radiotherapy is beneficial in selected cases, either in the form of plaque brachytherapy or as external beam radiotherapy. Orbital disease carries a poor prognosis for survival. However, a multimodal treatment protocol has improved survival in children with extraocular disease. Nevertheless, challenges remain, especially for the developing world. This review aims to highlight recent advances in the management of Rb that have contributed towards improving treatment outcomes and also discuss the challenges ahead, with special reference to the Indian scenario.

Intra-arterial chemotherapy for retinoblastoma: Two-year results from tertiary eye-care center in India.

Aim:The aim of this study is to describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC) for intraocular retinoblastoma (RB).Materials and Methods:A retrospective, interventional series of 10 eyes with RB which underwent IAC using melphalan (5 mg/7.5 mg) and topotecan (1 mg), or melphalan (5 mg/7.5 mg) alone. Treatment outcomes were evaluated in terms of tumor control, vitreous seeds (VS) and subretinal seeds (SRS) control, and globe salvage rates.Results:Ten eyes of 10 patients underwent 38 IAC sessions (mean = 3.8; median = 4; range = 3–5 sessions). Following IAC, complete regression of main tumor was seen in 9 eyes (90%) and partial regression in 1 (10%). All four eyes with SRS showed complete regression (100%). Of 5 eyes with VS, 3 eyes (60%) showed complete regression, 1 eye (20%) showed relapse, while 1 eye (20%) showed no response. Globe salvage was achieved in 8 of 10 eyes (80%). Complications included transient ophthalmic artery narrowing (n = 2), branched retinal vein occlusion (n = 1), forehead skin pigmentation (n = 1), and vitreous hemorrhage (n = 2). There was no case of stroke, hemiplegia, metastasis, or death. Transient hematological changes included relative pancytopenia (n = 4), relative leukopenia (n = 5), and relative thrombocytopenia (n = 4). Mean follow-up was 26 months (median = 28, range = 13–36) from the initiation of first IAC.Conclusions:IAC is an effective therapy for globe preservation in eyes with intraocular RB, in the setting of a developing country like India. Larger studies with longer follow-up are required to validate these results.

P2.02-059 New Treatment Strategy in Inoperabl Locoregionally Advanced NSCLC: C Arm Cone Beam CT-GuıDed Selective Intraarterial Chemotherapy

The optimal treatment of patients with stage III Non-small cell lung cancer (NSCLC) has not been clearly defined. Although there are many treatment options, none of them have a high probability of cure. A multidisciplinary approach is important for this patients. Aim of this study was to determine efficacy and toxicity of C arm Cone Beam CT (CACBCT) guided selective intraarterial chemotherapy (IACH) for patients who had inoperable locoregionally advanced NSCLC. Patients: Our study included 27 Non-small cell lung cancer (NSCLC) patients who were treated with IACT in the Department of Medical Oncology at Antalya Memorial Cancer Center between September 2012 and March 2016. Only patients with inoperable NSCLC who had a life expectancy longer than 3 months were included in study. They were previously untreated patients. Chemoembolization: The treatment was performed using intra-arterial platin based combination chemotherapy every 21 days for 2-4 cycles by CACBCT. In all patients, via the femoral artery, CACBCT angiographies were taken and the feeding arteries of the tumors were identified. These arteries were then selectively catheterized and cisplatin+docetaxel combination was infused. If patients had good response the treatment after first two cycles, they underwent the surgery. Other patients had continued chemoradiotherapy. Two patients were female and twenty-five patients were male. Thirteen of patients had non-squamous, fourteen patients had squamous cell lung cancer. The average age of the patients was 58.9 years (range 46-78 years). The post-treatment radiological response evaluation of the patients is as follows: 3 patients (11,1%) had stable disease, 19 patients (70,3%) had a partial response, 3 patients (11.1%) had a complete response and progressive disease was observed in 2 patients (7.4%). Objective Response Rate was 90.5%. Surgical resection was performed thirteen (48.1%) of the patients. A pathological complete response was achieved in 5 patients who were operated on after receiving IACH. Other patients: two patients were stage 1A; two were stage 2A while four patients were stage 3A. Median follow-up time 21.2 months and this time OS was 63%. In terms of toxicity grade 1-2 anemia in five patients, grade 3 neutropenia in two patients, grade 2 thrombocytopenia in one patient was detected. However, no other complications are observed in any other patients. This study has shown that in our experience IACH is an effective and less toxic in inoperable locoregionally advanced NSCLC regardless of the histology. This treatment strategy is combinations of surgery or chemoradiotherapy hopeful for this patients.

Safety Study of Targeted and Localized Intra-Arterial Delivery of Gemcitabine in Patients with Locally Advanced Pancreatic Adenocarcinoma

Purpose: This is a first-in-man safety study in locally advanced pancreatic cancer (LAPC) using a targeted intra-arterial delivery catheter (RenovoCath™).Methods: Twenty patients were enrolled in a four-stage dose escalation of intra-arterial, locally delivered gemcitabine, at doses up to 1000 mg/m2. Patients' symptoms and laboratory values were monitored for safety and tolerability. Secondary endpoints included the effect on tumor size, tumor markers, and survival.Results: One hundred one treatments were administered to 20 patients. Five patients dropped out early due to adverse events or withdrawing consent. Serious adverse events and complications were as follows: sepsis (n = 3), grade 3 neutropenia (n = 3), guide-mediated vascular dissection (n = 3), and pulmonary toxicity (n = 1). There were no cases of elevated liver or pancreatic enzymes. All sepsis cases occurred in patients with biliary stent/drains, prompting the addition of periprocedural treatment with antibiotics, which effectively prevented further sepsis in the study. Efficacy analysis was limited to 15 patients who received more than two treatments. Fifty-eight percent of these patients had a reduction in CA 19-9 tumor markers, 3 patients had tumor progression, 1 had partial response, and 11 showed disease stability. The survival rate at 12 months was 60%.Conclusions: The results demonstrate feasibility of localized and selective intra-arterial chemotherapy delivery to the pancreas utilizing the RenovoCath. With gemcitabine, this approach is safe, with the sole prerequisite of perioperative antibiotics for patients with prior biliary drainage/stent. Efficacy results suggest a survival benefit when compared to historical control, especially in patients with prior radiation therapy.

A review of the literature for intra-arterial chemotherapy used to treat retinoblastoma.

Retinoblastoma is a malignancy of the retina that usually presents before the age of 5years. Sporadic retinoblastoma is most often unilateral and with no hereditary influence, whereas familial retinoblastoma presents unilaterally or bilaterally in conjunction with genetic inheritance. Several treatments have been attempted with the goals of saving the child's life, salvaging the eye, and preserving vision. Alternative methods including external beam radiation, systemic chemotherapy and focal therapies have been shown to be effective but carry a risk of enucleation and other complications proportional to the severity of the tumor. Selective intra-arterial chemotherapy for retinoblastoma began in 1988 in Japan and has emerged in the last 7years in the United States as a feasible, effective and minimally invasive treatment option. We review the retinoblastoma treatment literature focusing on intra-arterial chemotherapy.