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).

Therapeutic Effect of Regional Chemotherapy in Diffuse Metastatic Cholangiocarcinoma.

BACKGROUND: Current therapeutic options in diffuse metastatic cholangiocarcinoma (CCC) are limited with unsatisfactory results. We evaluated the efficacy of regional chemotherapy (RegCTx) using arterial infusion (AI), hypoxic stop-flow abdominal perfusion (HAP), upper abdominal perfusion (UAP) and isolated-thoracic perfusion (ITP) in 36 patients with metastatic perihilar and intrahepatic CCC. METHODS: Ten patients had previously undergone a liver resection and in 14 patients the previous systemic chemotherapy (sCTx) approach had failed. A total of 189 RegCTx cycles (90 AI, 74 UAP, 13 HAP and 12 ITP) were applied using cisplatin alone or with Adriamycin and Mitomycin C. A minimum of three cycles were applied in 75% of the study population. The response was evaluated using RECIST criteria with MediasStat 28.5.14. Mortality, morbidity and survival analysis were performed using a prospective follow-up database and SPSS-28.0. RESULTS: No procedure related mortality occurred. The overall morbidity was 56% and dominated by lymph fistulas at the inguinal access site. No grade III or IV haematological complication occurred. The overall response rate was 38% partial response, 41% stable and 21% progressive disease. Median overall survival was 23 months (95%CI 16.3-29.7). The RegCTx specific survival was 12 months (95%CI 6.5-17.5) in completely therapy naive patients but also in patients who had failed a sCTx attempt previously. CONCLUSION: RegCTx is feasible, safe and superior to the current proposed therapeutic options in metastatic CCC. The role of RegCTx should be determined in a larger cohort of diffuse metastatic CCC patients but also at early stages especially in initially not resectable but potentially resectable patients.

Regional Chemotherapy Is a Valuable Second-Line Approach in Metastatic Esophageal Cancer after Failure to First-Line Palliative Treatment.

BACKGROUND: Therapeutic options in metastatic esophageal cancer (EC) are limited with unsatisfactory results. We evaluated the efficacy of regional chemotherapy (RegCTx) approach in diffuse metastatic EC using arterial infusion (AI), upper abdominal perfusion (UAP) and isolated-thoracic perfusion (ITP) in 14 patients (N = 8 adenocarcinoma (AC) and N = 6 squamous cell carcinoma (SQCC)) after failure to first-line palliative treatment. METHODS: All patients had previously failed first-line palliative treatment attempt with systemic chemotherapy (sCTx). In total 51 RegCTx cycles (12 AI, 3 UAP and 36 ITP) were applied using cisplatin, Adriamycin and Mitomycin C. The outcome was evaluated using RECIST criteria with MediasStat 28.5.14 and SPSS-28.0. RESULTS: No grade III or IV hematological complications occurred. The overall response rate was 41% partial response, 27% stable and 32% progressive disease. Median overall survival (OS) was 38 months (95%CI 10.1-65.9). The OS was better in SQCC with 51 months The RegCTx specific survival was 13 months (95%CI 2.9-23.1) in the entire cohort and 25 months in SQCC patients. CONCLUSION: RegCTx is a valuable safe approach and superior to the current proposed therapeutic options in metastatic EC after failure to first-line therapy.

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.

Hypoxic isolated abdominal perfusion breaks through chemoresistance in recurrent FIGO stage IIIC and IV ovarian cancer.

To overcome drug resistance in relapsed ovarian cancer, an isolated perfusion system was used to generate a higher local exposure to cytostatic drugs. In addition to cisplatin as the cytostatic agent of choice, the present study combined adriamycin and mitomycin in a three drugs regime due to their increased cytotoxicity under hypoxia. A total of 107 patients, including 87 patients with relapses after previous platinum-containing therapies, 46 stage IIIC and 41 stage IV cases, were enrolled in the present study. A total of 25 patients were chemonaive, including 20 stage IIIC. The systemically pretreated patients in stage IIIC survived a median of 12.8 months, and those in stage IV 10.9 months. The overall clinical response rate of stages IIIC and IV combined was 69%. A complete decrease in ascites was found in 43% of all patients, a significant reduction in 19%. Toxicity and side effects were very mild and the bone marrow suppression was mostly grade I and never exceeded grade II. The primary clinical symptom in patients with post-therapeutic tumor necrosis, which occurred in 10-15% of all cases, was fever, fatigue and poor performance. The isolated hypoxic abdominal perfusion treatment is a potent instrument to break an existing chemoresistance without significant side effects with a good quality of life and comparatively long survival time.

[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.

Tumor response and the quality of life after isolated hypoxic pelvic perfusion for advanced G3 cervical cancer: A case series.

INTRODUCTION: We present a case series of three patients with advanced cervical cancer who either refused the standard of care systemic or chemoradiation treatment or did not benefit from it. METHODS: We treated patients with isolated hypoxic pelvic perfusion (HPP). RESULTS: Two patients achieved complete clinicopathologic response and one patient required surgical excision of the necrotic residual mass containing no viable cancer cells. There were no long-term systemic or local side effects. All patients are cancer free for up to 15 years after conclusion of treatment. CONCLUSION: HPP is an effective option for treatment of advanced cervical cancer that generates rapid and onlasting remissions at low side effects. Gynecologic oncologists shall be aware of HPP to facilitate wider adaption of our technique.

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.

Hypoxic pelvic perfusion with cisplatin and mitomycin C in multidisciplinary palliative treatment of patients with unresectable recurrent rectal cancer: a retrospective study.

BACKGROUND: Patients with unresectable recurrent rectal cancer that progresses after systemic chemotherapy and radiotherapy may be candidates for palliation with hypoxic pelvic perfusion (HPP). The aim of this observational retrospective study was to evaluate if a multimodality treatment including HPP and targeted-therapy may be useful to prolong clinical responses and survival of these patients. METHODS: Thirty-seven patients with unresectable recurrent rectal cancer in progression after standard treatments underwent repeated HPP with mitomycin C (25 mg/m2) and cisplatin (70 mg/m2). Twenty patients, exhibiting epidermal growth factor receptor (EGFR) overexpression, also received cetuximab targeted-therapy, following the ultimate HPP treatment. RESULTS: Following initial HPP treatment, median progression-free survival was 7 months (range: 5-19 months), median time-to-death or termination of follow-up was 13 months (range: 9-18 months), one-year survival-rate was 59.45%, two-year survival rate was 10.81%, and three-year survival rate was 2.7%. Survival was significantly influenced by cetuximab targeted-therapy post-HPP and the presence of additional metastatic sites (P<0.03). CONCLUSIONS: Repeated HPP treatments with mitomycin C plus cisplatin, followed by cetuximab targeted-therapy, may represent a safe and efficacious palliative therapy in patients with unresectable recurrent rectal cancer, in progression following standard systemic chemo- and radio-therapy, and thus warrants confirmation in a larger phase III study.

Carotid artery infusion via implantable catheters for squamous cell carcinoma of the tonsils.

BACKGROUND: Chemoradiotherapy has a dominant role in therapy for head and neck cancers. However, impressive results are often disturbed by adverse events such as dysphagia, xerostomia, and functional speech and hearing loss. To avoid exceeding toxicity limits in patients with primary and recurrent cancers of the tonsils, chemotherapy was administered intra-arterially via implantable Jet-Port-Allround catheters. METHODS: We report on patients with primary and recurrent cancers of the tonsils. Eleven patients who refused chemoradiation were included in this trial. Of the seven patients without prior therapy, one was stage I, one was stage III, three were stage IVA, one was stage IVB, and one was stage IVC. The four patients who were in progression after prior chemoradiation were stage IVA. The median follow-up time was 47 months (20 to 125 months). After the implantation of a Jet-Port-Allround catheter into the carotid artery, the patients received intra-arterial infusion chemotherapy with venous chemofiltration for systemic detoxification. The stage I patient received lower-dose chemotherapy without chemofiltration. The stage IVC patient with lung metastases and a primary tumor that extended across the midline to the contralateral tonsil received additional isolated thoracic perfusion chemotherapy. RESULTS: All seven chemoradiation-naïve patients exhibited clinically complete responses and are still alive after 20 to 125 months. Among the four patients who had relapsed after prior chemoradiation, the intra-arterial therapy elicited only poor responses, and the median survival time was 7.5 months. After carotid artery infusion chemotherapy, none of the patients required tube feeding. No cases of dysphagia, xerostomia, or functional speech and hearing loss have been reported among the patients without prior chemoradiotherapy. CONCLUSION: Despite the administration of low total dosages, intra-arterial infusion generates high concentrations of chemotherapeutics. In combination with chemofiltration, the systemic toxicity is kept within acceptable limits. Among the non-pretreated patients, better tumor responses and long-term tumor control were noted compared with those who had prior chemoradiation. Implantable Jet-Port-Allround carotid artery catheters facilitate the application of regional chemotherapy.

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.

Celiac axis infusion and microembolization for advanced stage III/IV pancreatic cancer--a phase II study on 265 cases.

BACKGROUND: Despite various chemotherapeutic drugs and combinations given systemically, the impact of these agents on survival has not been convincing, and drug-related toxicity continues to be the limiting factor. PATIENTS AND METHODS: Two hundred and sixty-five patients with locally advanced or metastasizing (UICC III/IV) pancreatic cancer underwent celiac axis infusion with Mitomycin, Mitoxantrone and Cisplatin combined with degradable starch microspheres in 5 courses and 1 course of isolated hypoxic abdominal perfusion and chemofiltration. RESULTS: The study end-points were survival and quality of life. Seventy-five percent survival was 6 months, 50% (median) 9 months and 25% was 18 months. Eighty patients survived for one year and more. The longest actual survival time was ten years in a former unresectable stage IV patient. The quality of life improved in responders. No therapy-related hospitalization or increased morbidity was noted. The resectability rate after therapy in long-term survivors (>12 months) was 39%. Peritoneal carcinosis or progression of liver metastases occurred in 18%. The major cause of death in 48% was recurrence at the primary site. CONCLUSION: In good responders to arterial infusion and microembolization chemotherapy, the resectability rate increased remarkably. Relapses predominantly occurred at the primary site, and progression of distant metastases and peritoneal lesions may be reduced due to isolated abdominal perfusion.