Case report: Extended Isolated Stopflow Limb Infusion (EISLI) for highly malignant osteosarcoma - complete pathological tumor remission and implantation of a knee joint prosthesis.

INTRODUCTION AND IMPORTANCE: An 18-year old osteosarcoma patient with a huge tumor mass at the distal femur and inguinal metastases was treated with the intention to preserve the leg and additionally treat the pelvic metastases locally. Therefore we modulated the technique of isolated limb perfusion. CASE PRESENTATION: Isolated Limb Perfusion was performed as an Extended Isolated Limb Stop-Flow Infusion (EISLI) where the pelvis was included into the perfusion bed. Balloon catheters were placed in the arterial and venous bifurcation in the pelvis. For increasing the drug concentration at the tumor site, an angiographic catheter was placed arterially with the tip right in front of the tumor region. A Stop-Flow phase before the perfusion phase was applied. CLINICAL DISCUSSION: After 4 cycles of EISLI the lesions in the pelvis disappeared and surgical resection of the tumor and implantation of an endoprosthesis was possible and successful. Histopathological findings showed no vital cells in the resected tumor region. Currently the patient is tumor free and does not show recurrence or pulmonal metastases for 18 months after the last induction treatment cycle. CONCLUSION: With EISLI the inclusion of the pelvis is possible during isolated limb perfusion. In addition with low total dosages EISLI enabled drug concentrations many times higher at the tumor site than possible during systemic chemotherapy or standard isolated limb perfusion. It is a technique that allows limb preservation and treatment of positive lymphnodes in the groin. Quality of life is maintained during the Regional Chemotherapy (RCT).

Efficacy of Regional Chemotherapy Approach in Peritoneal Metastatic Gastric Cancer.

Peritoneal spread is frequent in gastric cancer (GC) and a palliative condition. After failure to systemic chemotherapy (sCTx) remaining therapeutic options are very limited. We evaluated the feasibility and efficacy of locoregional chemotherapy (RegCTx) in peritoneal metastatic GC. In total, 38 (23 male and 15 female) patients with peritoneal metastatic GC after failure of previous sCTx and unresectable disease were enrolled in this study. Using the hypoxic abdominal stop-flow perfusion, upper abdominal perfusion and intraarterial infusion technique in total 114 cycles with Cisplatin, Adriamycin and Mitomycin C were applied. No significant procedure related toxicity was noticed- especially no Grade 3 or 4 toxicity occurred. With the RegCTx approach a median overall survival of 17.4 months was achieved. Patients who had undergone previously resection of the GC the median overall survival was even better with 23.5 months. RegCTx is a promising, safe and efficient approach in diffuse metastatic GC. The evaluation of RegCTx in the setting of multimodal treatment approach at less advanced stages is also warranted.

[It's a matter of time and dosage - intra arterial chemotherapy for carcinoma of the oropharynx]. / Eine Frage der Zeit und Dosierung ­ intraarterielle Chemotherapie beim Oropharynxkarzinom.

INTRODUCTION: Advanced head and neck cancer (HNC) patients have good response rates with radiochemotherapy. However, quality of life is often severely affected and the main reason for high rates of suicide. For a deliberately milder treatment, there is an option to selectively treat the tumor region with chemotherapy. This study reports on the treatment of oropharyngeal carcinoma with intra arterial short-term infusion. METHODS: 55 patients, suffering from inoperable carcinoma of the oropharynx have been treated with intra-arterial short-term infusion chemotherapy via angiocatheters or implanted arterial port catheters. Infusion time of 7 to 12 minutes. Patients with high tumor load or lung metastases had additional treatment of isolated thoracic perfusion. RESULTS: Divergent overall survival rates have been noted depending on the pretreatment of the patients. One-, two-, and three-year survival rates of 76 %, 54 % and 35 % for patients without prior irradiation and 40 %, 7 % und 7 % for priorly irradiated patients have been observed. Particularly long overall survival rates have been observed for the subgroup of patients with pretreatment but without irradiation suffering from relapsed cancer, who reached median survival rates of 33.5 months. In contrast, the median survival of irradiated patients suffering from recurrent cancer was 8.2 months. Tracheostomy and tube feeding could be avoided in any case. DISCUSSION: Randomized clinical trials are necessary to support these results. However, small dosages can generate high concentrations in limited volumes and therefore have an increased effect while keeping side effects low.

Approaching 10 years disease-free survival after isolated thoracic perfusion for advanced stage IV tonsil carcinoma: A case report.

INTRODUCTION: This is a report about the first case of an advanced stage IV tonsil carcinoma treated with isolated thoracic perfusion and chemofiltration. PRESENTATION OF CASE: The tumor extended beyond the midline with bilateral lymphnode metastases. Playing on wind instruments was impossible. As a professional Jazz saxophonist he refused mutilating surgery and chemoradiotherapy. After one isolated thoracic perfusion there was substantial tumor shrinkage. After three additional cycles of carotid artery infusion with chemofiltration a complete remission has been noted without systemic or local toxicity since 9 ½ years. DISCUSSION: Knowing the often considerable long-term damage after surgery and chemoradiotherapy of head and neck tumors, some patient reject conventional therapy. Because of the steep dose response curve in cancer chemotherapy, an increased drug exposure in terms of intra-arterial short-term infusions or isolated perfusion can induce rapid remission induction without significantly affecting the quality of life. Further studies comparing regional chemotherapies with conventional chemoradiotherapy are warranted. CONCLUSION: Intra-arterially applied short-term chemotherapy may generate rapid and onlasting remissions at low side-effects.

Hypoxic Isolated Abdominal Perfusion (HAP) chemotherapy for non-operable advanced staged ovarian cancer with peritoneal carcinosis: an experience in 45 platinum-refractory ovarian cancer patients.

In order to break through drug resistance in platinum-refractory ovarian cancer, augmented drug exposure was administered to the abdomen by means of an isolated perfusion system. Four cycles of isolated hypoxic abdominal perfusion with cisplatin, adriamycin, and mitomycin were conducted in 4-week intervals. Cisplatin and adriamycin were chosen because of their increased cytotoxicity under hypoxic conditions. Chemofiltration was performed for prophylaxis of cumulative toxicity of adriamycin and mitomycin. The study included 45 patients with recurrent epithelial ovarian cancer who had prior platinum containing therapies (3, stage Federation of Gynecology and Obstetrics (FIGO) IIIB; 20, stage FIGO IIIC; 22; stage FIGO IV). The median survival rate in stage FIGO IIIBC was 12 months, and in stage IV was 10 months. The tumor marker decreased to complete response or partial response at 17.8% and 55.6% of the patients. CT or MRI visualization showed complete response in 4.1%, and partial response was in 54.1%. Complete resolution of ascites was noted in 30% of cases and substantial reduction in another 43%. Toxicity was generally low. Quality of life was improved in the majority of cases. Bone-marrow suppression ranged between WHO grade 1 and 2, and in patients with previous third- or fourth-line chemotherapy, it was WHO grade 3. Isolated hypoxic abdominal perfusion with chemofiltration for patients with progressive and platinum-refractory stage III and IV ovarian cancer is an effective therapy, breaking through chemoresistance and offering comparably long survival at good quality of life.

Intra-arterial infusion chemotherapy versus isolated upper abdominal perfusion for advanced pancreatic cancer: a retrospective cohort study on 454 patients.

PURPOSE: The treatment of pancreatic carcinoma remains a challenge as prognosis is poor, even if confined to a single anatomical region. A regional treatment of pancreatic cancer with high drug concentrations at the tumor site may increase response behaviour. Intra-arterial administration of drugs generates homogenous drug distribution throughout the entire tumor volume. METHODS: We report on treatment outcome of 454 patients with advanced pancreatic carcinoma (WHO stage III: 174 patients, WHO stage IV: 280 patients). Patients have been separated to two different treatment protocols. The first group (n = 233 patients) has been treated via angiographically placed celiac axis catheters. The second group (n = 221 patients) had upper abdominal perfusion (UAP) with stopflow balloon catheters in aorta and vena cava. Both groups have been treated with a combination of cisplatin, adriamycin and mitomycin. RESULTS: For stage III pancreatic cancer, median survival rates of 8 and 12 months were reached with IA and UAP treatment, respectively. For stage IV pancreatic cancer, median survival rates of 7 and 8.5 months were reached with IA and UAP treatment, respectively. Resolution of ascites has been reached in all cases by UAP treatment. Toxicity was generally mild, WHO grade I or II, toxicity grade III or IV was only noted in patients with severe systemic pretreatment. The techniques, survival data and detailed results are demonstrated. CONCLUSIONS: Responsiveness of pancreatic cancer to regional chemotherapy is drug exposure dependent. The isolated perfusion procedure is superior to intra-arterial infusion in survival times.

Short-term intra-arterial infusion chemotherapy for head and neck cancer patients maintaining quality of life.

PURPOSE: Head and neck cancer treatment achieves good locoregional tumor control rates while causing severe side effects. Therapy with chemotherapeutic drugs administered intravenously is limited because either the concentrations at the tumor site are too low or the total dosages are too high. The evaluation of a technique for short-term intra-arterial infusion chemotherapy is described herein. METHODS: In a retrospective study, we reviewed the medical records of 97 patients with head and neck cancers who received short-term intra-arterial infusion chemotherapy (62 patients previously untreated, 35 patients with prior radiotherapy). All patients refused further radiotherapy. Response rates, overall survival and adverse effects were the study endpoints. The blood supply of the tumors was controlled with indigocarmine blue infusion and staining of the tumor region. RESULTS: Complete or partial response was found in 67%, 52% and 63% of previously untreated patients and in 25%, 30% and 29%, respectively, of previously irradiated patients for staging groups I-III, IVA and IVB/C. Patients with T3/T4 tumors who were previously irradiated showed a median overall survival of 9 months, and those without pretreatment showed a median overall survival of 22.5 months. None of the patients required tube feeding. No new case of dysphagia, xerostomia, or functional speech and hearing loss was reported. Pain and clinical symptoms were reduced for all patient groups. Indigocarmine staining showed reduced tumor blood supply in previously irradiated regions but good blood supply in untreated regions. CONCLUSIONS: Short-term intra-arterial infusion chemotherapy achieves promising response rates and lacks severe adverse effects.

Isolated thoracic perfusion with chemofiltration for progressive malignant pleural mesothelioma.

INTRODUCTION: Therapy of malignant pleural mesothelioma and especially the adequate role of surgery in this context remain the subject of controversial discussions. Radical surgery in particular, which is associated with substantial morbidity, failed to translate into a definite survival advantage. We report on interim results of an ongoing Phase II study of regional chemotherapy in terms of isolated thoracic perfusion with chemofiltration (ITP-F). PATIENTS AND METHODS: Twenty-eight patients (25 male, 3 female, mean age 63.4 years) with advanced pleural mesothelioma were included in this study. Isolation of the chest was achieved by insertion of a venous and arterial stop-flow balloon catheter via a femoral access. The aorta and inferior vena cava were blocked at the level of the diaphragm and the upper arms were blocked by pneumatic cuffs. Chemotherapy, consisting of 60 mg/m2 cisplatin and 15 mg/m2 mitoxantrone, was administered directly into the aorta. The isolated circuit was maintained for 15 minutes followed by45 minutes of chemofiltration with a hemoprocessor until 5 L of filtrate were reached. The endpoints of the study were overall survival and quality of life (QoL). RESULTS: Out of 28 patients enrolled in the study, 5 had prior surgeries, 10 patients had systemic chemotherapy, and 5 patients additional irradiation. In all patients in restaging, clinical progress was noted. In all, 162 cycles were administered. Due to chemofiltration, toxicity was within tolerable limits, revealing World Health Organization grade I leucopenia and thrombocytopenia in 9 patients and mucositis grade I in 6 patients. The major surgical complication was inguinal lymphatic fistula in 40% of the cases. Gastrointestinal toxicity and/or neurotoxicity were never observed. One-year survival was 49%, 2-year and 3-year survival was 31%, and 5-year survival was 18%. Median overall survival was 12 months and progression-free survival 9 months. CONCLUSION: ITP-F for patients with advanced pleural mesothelioma, progressive after standard therapies, is an effective and well-tolerated treatment modality, offering comparably long survival data at a good QoL.