Surgery For Metastatic Disease Research Articles

Phase II study to evaluate efficacy and safety of irinotecan, capecitabine, and bevacizumab in patients with metastatic colorectal cancer (mCRC).

e13018 Background: XELIRI regimen (combination of capecitabine and irinotecan) is an active and well tolerated treatment for mCRC. However, data available on the combination of XELIRI regimen with bevacizumab (BVZ) in patients (pts) with mCRC are limited at present. Therefore the aim of this study is to evaluate the efficacy and safety of the biweekly (biw) scheme with XELIRI regimen, plus BVZ in pts with mCRC. Methods: A multicentric, prospective, open-label phase II trial. Treatment scheme: irinotecan (175mg/m2 iv infusion 90 min, day 1, every 2 weeks) + capecitabine (1,000mg/m2 bid oral, days 2-8; pts aged ≥65, max dose: 800mg/m2 bid) + bevacizumab (5mg/kg, iv, day 1, every 2 weeks).Safety results from an interim analysis are presented. Results: A total of 77 pts were evaluated (66.2%, male) with a median age of 65.1 yrs (41.1-81.1). ECOG PS was ≤1 in 96.1% of pts. Primary tumor locations were: colon (51.9%), rectum (31.2%) and rectum/colon (16.9%).Twenty-seven pts (35.1%) received adjuvant chemotherapy. Mean time to primary tumor diagnosis was 16.3±30.3 months. Metastases were detected in liver (63.6%), lung (51.9%), nodes (14.3%), and peritoneum (11.7%). Surgery of metastatic disease was performed in 7.8% of pts. The most frequent grade 3-4 toxicities registered were: diarrhea (15.6%), asthenia (13%) and neutropenia (9.1%). The frequency of occurrence for the most frequently AEs related to BVZ were 2.6% hypertension, 1.3% proteinuria; while for the least frequent AEs: 3.9% intestinal perforation, 6.5% pulmonary embolism, 2.6% thrombosis and 1.3% DVT. A total of 59 pts discontinued the study treatment, being the most common reasons: AEs (16.9%), disease progression (14.3%) and surgery (14.3%). Twelve pts (15.6%) died during the study due to disease progression (7 pts), AEs (4 pts), or unknown reason (1 patient). Three of the 4 AEs causing pts’ death occurred as a result of toxicity (2 cases of multi-organ failure and 1 case of intestinal perforation). Conclusions: These preliminary results show that biw scheme with XELIRI regimen, plus BVZ has a feasible and manageable safety profile for the treatment of pts with mCRC. Further analysis will be necessary to confirm these results.

Outcomes of palliative surgery in metastatic disease of the cervical and cervicothoracic spine

This prospective study was undertaken to assess the clinical outcome of 26 consecutive patients who underwent surgery for symptomatic metastases of the cervical or cervicothoracic spine. All patients suffered axial or radicular pain, with or without neurological deficit, including radicular weakness (23%), quadriplegia or paraplegia (12%), and urinary sphincter dysfunction (8%). All patients underwent palliative decompression and stabilization surgery via an anterior (18 patients), posterior (7 patients) or combined approach (1 patient) depending on the topography of the metastases, and were prospectively followed up for 1 year. Thirteen patients received adjuvant chemotherapy and 7 patients received radiotherapy to the cervical lesion. Clinical data as well as data from the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire were obtained pre- and postoperatively and at regular follow-up intervals. Median survival was 6 months and 10 patients were known survivors at 12 months. Postoperatively, 1 patient developed neurological deterioration and died while an inpatient. There were no other early postoperative complications in any patients. From pre- to postoperatively there was an immediate and significant improvement in axial and radicular pain and overall quality of life. There was also overall improvement in cognitive, emotional, social, role, and physical functioning. The observed improvement in pain, functioning, and quality of life was maintained for the duration of the follow-up period. Furthermore, neurological function was improved or preserved until death in the majority of patients. Together with adjuvant medical management, surgery for cervical metastases produces low morbidity and can achieve good symptomatic palliation in the majority of patients for their remaining lifetime.

Phase 0 Clinical Trials in Oncology: An Exploratory Methodology for Constructing a Study With Patients Undergoing Surgery for Metastatic Disease

Unite´ de Pharmacologie Chimique et Ge´ne´tique et Imagerie, Universite´ Paris Descartes; Unite´ 1022, Insti-tut National de la Sante´ et de la Recherche Me´dicale; Unite´ Mixte de Recherche 8151, Centre National de la RechercheScientifique; and Ecole Nationale Supe´rieure de Chimie de Paris, Paris, France

Gemcitabine-capecitabine in platinum-refractory patients with thymic epithelial tumors

7590 Background: Platinum based combination chemotherapy is the actual standard of care for advanced and recurrent Thymic epithelial tumours-TET (thymoma and thymic carcinoma). Additional agents are needed in this setting. We have designed a pilot study, phase II multicenter, to evaluate the efficacy and safety of no tested schedule gemcitabine-capecitabine in patients refractory to platinum based chemotherapy. Methods: Eligible patients had pathologically confirmed TET and were treated with at least 2 lines of chemotherapy, one of this being a platinum based schedule. From January 2007 to September 2008 twelve pts were enrolled. Treatment Schedule: Gemcitabine 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks plus oral capecitabine 650 mg/m2 twice daily on days 1 to 14. Response was evaluated at 3 and 6 cycles. Results: Pts Characteristics: 12 pts (7 M-5F, Median Age 51,3 yrs,range 27–76). 7 pts had received Thymectomy and 4 of this had received also surgery for metastatic disease. 5 pts have received only thymic biopsy. Performance status sec. Karnofsky was 90% (range 80–100). Site of disease: liver, lung, bone, nodal, pleural and pericardium. All pts were staged IVB sec. Masaoka. Tumors were classified by WHO classification as follows: 4-B2, 8-B2/B3. All pts were evaluated as concerns performance status and all had Karnofcky 90% (range 80–100). Sites of metastatic disease were: liver,lung,bone,nodal, pleural and pericardium. Associated paraneoplastic syndromes were: myasthenia in 7 pts, B-lymphopenia 11 pts. The minimum number of cycles administered on study was 3 (range 3–8).Among the 12 enrolled pts there were 10 objective response: 2 CR, 8 PR. 2 pts had SD. Prolonged maintenance of absence of disease was obtained in the 2 pts reporting a CR (more than 6 months in 1 patient). Treatment was well tolerated, no grade 4 toxicities was registered. Conclusions: The combination schedule gemcitabine-capecitabine have an high activity in Thymic malignancies in pts heavily pretreated with advanced recurrent TET and appears to be a safe option in platinum-refractory TET pts. This schedule must be proposed to be used also in randomized clinical trial compared with platinum based treatment. No significant financial relationships to disclose.

Phase II dose escalation study of sorafenib in patients with metastatic renal cell carcinoma (mRCC) who have had prior treatment with VEGFR-TKI antiangiogenic treatment

e16027 Background: Sorafenib is an orally active multikinase inhibitor (Raf kinase, VEGFR 1, 2, 3 and PDGFR inhibitor) for the treatment of advanced RCC. The purpose of this study was to assess the efficacy and toxicity of Sorafenib in mRCC patients (pts) previously treated with an anti-angiogenic VEGFR-TKI using escalating dose levels. Methods: Pts with mRCC, PS 0–2 and adequate organ function were eligible. Pts received Sorafenib 400 mg/BID/continuously in 4-wk cycles. Pts with no progressive disease (evaluated at 12 weeks) continued to receive Sorafenib at the standard dose, while progressive pts received an increasing dose (600 mg BID) with early disease restaging after 4 weeks. Pts who progressed at 600 mg BID were taken off study. Efficacy was assessed by RECIST criteria. Results: 18 pts were entered; baseline characteristics: PS 0–1: 94%; median age 62 years (41–82); nephrectomy: 100%; surgery for metastatic disease: 28%, clear-cell 78%, papillary-cell 16%, sarcomatoid 6%.≥ 2 metastatic sites: 84%. 10 pts were refractory to cytokine treatment and all progressed or experienced unacceptable toxicity after anti-angiogenic VEGFR-TKI treatment, Sunitinib (13 pts) or Pazopanib (5 pts). Median number of cycles was 7.5 (1–16). Overall, 72% of pts had disease control without significant correlations between response to prior therapy and hypertension. 14 pts had progression free survival (PFS) of 4.3 months (mos). 4 pts are still in treatment with a median PFS > 8 mos. Of 6 pts in which the dose was escalated, 3 benefitted with a PFS of > 3 mos. The most common toxicity (NCIC 3.0, all pts) was grade (g) ≥ 1 diarrhea in 10 pts, g2–3 hand-foot syndrome in 7 pts and g-3 mucositis in 1 pt. Other hematological and non-hematological toxicities were g1 with a frequency < 15%. Conclusions: Sorafenib at doses of 400–600 mg/BID/continuosly results in acceptable and well tolerated salvage treatment after VEGFR-TKI failure. In progressive patients, treatment with a higher dose could be a valid option. Final and mature data will be presented in combination with translational research evaluating biological characteristics on tissue and blood. No significant financial relationships to disclose.

Primary colon cancer: ESMO Clinical Recommendations for diagnosis, adjuvant treatment and follow-up

Staging provides essential prognostic information relevant for choosing adequate therapy and should also identify patients with resectable distant metastases. Preoperative staging consists of clinical examination, blood counts, liver and renal function tests, carcino-embryonic antigen (CEA), chest X-ray or preferably chest CT-scan, CT scan of the abdomen including the pelvis and a colonoscopy of the entire large bowel, i.e. with postoperative repeat colonoscopy if proximal parts of the colon were not accessible preoperatively. Pathologic staging should be done according to the 2002TNM system with optional listing of the modified Dukes stage, as described in Table 1. Risk factors for colorectal cancer are: family history, familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) syndromes, hereditary non-polyposis colorectal cancer (HNPCC) syndrome, past history of colorectal cancer or adenoma, chronic ulcerative colitis and Crohn’s disease. prognosis

Prognoseadaptierte operative Behandlung von Knochenmetastasen

Surgery in metastatic disease to the bone is the most common procedure in orthopaedic oncology. To assess an adequate therapeutic approach we analysed 513 surgeries performed on 453 patients between 1980 and 2005 and reviewed the literature.The most significant factor is the histology of the primary tumour. A biopsy is mandatory to confirm the diagnosis in an unknown primary tumour, especially in cases of solitary lesions. Pulmonary carcinoma has an unfavourable prognosis compared to breast and renal cell carcinoma patients. Radical resection in isolated metastatic disease in renal cell carcinoma reduces the risk of local recurrence and even may result in a long progression-free survival. In breast cancer osseous and visceral dissemination is the most decisive factor for prognosis. An interdisciplinary approach is mandatory in every patient.

Thyroid Metastases of Renal Cell Carcinoma: Clinical Course in 45 Patients Undergoing Surgery. Assessment of Factors Affecting Patients' Survival

Metastases of renal cell carcinoma (RCC) to the thyroid gland are uncommon. There is no clear consensus regarding the role of surgery in metastatic disease to the thyroid since most clinical studies include small numbers of patients. Also, risk factors associated with disease progression following thyroidectomy are not yet defined. We examined the determinants of the outcome in patients undergoing surgery for thyroid metastases of RCC. The medical records of 45 patients undergoing resection of thyroid metastases of RCC at 15 institutions in Germany and Austria were reviewed retrospectively. The outcome parameters assessed were overall survival and tumor-related survival. Factors associated with disease progression following thyroid surgery have been calculated. The overall 5-year survival rate following thyroid metastasectomy was 51%. Nineteen patients died during the study: 14 of disseminated disease and 5 of non-tumor-related causes. In the multivariate analysis, the prognosis was significantly worse in patients older than > or = 70 years and in patients who had undergone nephrectomy for metastases in the contralateral kidney during the course of the disease. Nine patients developed a thyroid recurrence following surgery. No local disease relapse occurred if resection margins were documented to be free of the tumor. Of the 45 patients with thyroid metastases, 14 (31%) developed pancreatic metastases during the course of disease. Ten of these patients also underwent pancreatic surgery with a 5-year survival rate of 43% in this subgroup. The overall survival of patients undergoing thyroidectomy for metastases of RCC is affected rather by general health status than by tumor-related factors. There is a significant coincidence of thyroid and pancreatic metastases of RCC.

Multidisciplinary Teams in the Management of Rectal Cancer

A myriad of advances in the treatment of rectal cancer have been achieved over the last few decades. The introduction of total mesorectal excision (TME) has resulted in significant improvements in local recurrence. Surgical education on the technique has made it the standard of care. Radiation and chemotherapy combined with TME have improved results even further with stage II and III cancers. Sphincter-sparing techniques, reservoir procedures, local treatment advances, minimally invasive techniques, surgery for metastatic disease, newer chemotherapies, and extended resections for locally advanced and recurrent lesions, have all benefited the patient with rectal cancer. The goal and responsibility of colorectal surgeons treating rectal cancer patients is to understand and coordinate the wide variety of modalities available to optimize survival, minimize morbidity, and maximize quality of life for those with this difficult problem. Coordination of specialists in this time of evolution in rectal cancer treatment becomes more important than ever. Here the authors briefly review the role of the multidisciplinary team, discuss a model multidisciplinary team approach and look at evidence supporting team use as we begin this issue devoted to the multidisciplinary management of rectal cancer.

Liver: surgical planning

Hepatic surgery for primary malignant disease, either hepatocellular or cholangiocarcinoma, is performed with curative intent, whereas surgery for metastatic disease, either functional endocrine metastases or isolated colorectal metastases, is essentially palliative, aiming to increase duration of survival and quality of life. Patient selection is dependent upon clinical and imaging criteria. The aim of imaging is to define site, size, and multiplicity of tumor in relation to segmental anatomy, vessels and ducts and evaluate for extrahepatic metastatic disease. A multimodality approach employing sonography, CT, MRI and MRCP, and isotope imaging is used as appropriate in each circumstance. The ultimate goal of imaging is to provide a surgeon with anatomic information that will result in a resection with negative free margin or a decision to use resection, ablation, or chemoembolization techniques alone or in concert for best potential outcomes.

Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I–II study

A phase I-II multicenter trial was conducted to define the maximal tolerated dose and describe the activity of an OCFL combination using oxaliplatin (OHP), irinotecan (CPT-11) and 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (CRC). CRC patients not pretreated with palliative chemotherapy, with performance status < or =1 and adequate haematological, kidney and liver function, were eligible. Treatment consisted in weekly 24-h infusion 5-FU (2300 mg/m(2))/LV (30 mg) and alternating OHP (70-85 mg/m(2), days 1 and 15) and CPT-11 (80-140 mg/m(2), days 8 and 22) repeated every 5 weeks. OHP and CPT-11 were escalated in cohorts of three to six patients. Thirty patients received a median of five cycles. Dose-limiting toxicity occurred at dose level 3, and the recommended dose was OHP 70 mg/m(2), CPT-11 100 mg/m(2), LV 30 mg and 5-FU 2300 mg/m(2)/24 h. Grade > or =3 toxicities were diarrhea 23%, neutropenia 20%, fatigue 7%, and neurologic 7%. Two febrile neutropenia episodes (one fatal) were recorded. Among 28 patients with measurable disease (90%), we observed two complete and 20 partial responses; overall RR was 78% (95% CI, 59% to 92%). Median time to progression and overall survival were 9.5 and 25.4 months, respectively. Seven patients underwent liver metastases resection. OCFL is an overall well tolerated regimen with very high efficacy, which makes it most suitable for tumour control before surgery of metastatic disease.

Cancer du rein – Actualités — Diagnostics et thérapeutiques

In this paper we review the recent advances for the diagnosis and the management of renal cell carcinoma. Urine tests, genetics and modification of the TNM system help for the diagnosis. Multifocality and microvascular venous invasion are interesting prognostic factors. Recent prospective studies gave important informations on lymph node dissection and the role of surgery in metastatic disease. New surgical tools are in development and new approaches in medical treatment too.

Surgery in metastatic testicular cancer.

Surgery in advanced testicular tumors is an integral part of the multimodality treatment. However, the indications for surgery in testis cancer have changed over the last 10 years. Patients with advanced seminoma only rarely will need surgery after chemotherapy whereas patients with advanced non-seminoma need to undergo the resection of residual disease in most of the cases. Surgery in metastatic disease may even be beneficial for patients with recurrent tumors, patients with persisting marker elevations during chemotherapy, or patients with late relapse of the disease. In view of late relapse, the extent and completeness of the primary resection is an important issue and, therefore, surgery should be performed in specialized centers. Most of the procedures are technically demanding and, therefore, individualized perioperative precautions are necessary to reduce morbidity of surgery. Nevertheless, in individual cases nerve-sparing techniques and laparoscopic approaches may be applicable to reduce surgery-related morbidity. This review will update the current indications and recommendations for post-chemotherapy surgery in advanced testis cancer.

Epitrochlear lymph nodes as a site of melanoma metastasis.

The incidence of epitrochlear lymph node metastasis for patients with melanomas on the hand or forearm is disputed, and management guidelines for these nodes are unclear. The records of 13,139 consecutive melanoma patients were reviewed to document the incidence of metastatic disease in epitrochlear nodes. The frequency of direct lymphatic drainage to epitrochlear nodes was determined for 109 patients with melanomas of the distal upper limb who had undergone preoperative lymphoscintigraphy. Nine of 801 patients (1.1%) with upper limb primary melanomas developed metastatic disease in an epitrochlear node, and one other patient with an occult primary tumor did so. Six of these ten patients underwent elective axillary node dissection at the time of surgery for epitrochlear node disease, and three were found to have metastatic disease in an axillary node. Epitrochlear node metastasis occurred in only two of 83 (2.4%) patients with upper extremity melanoma who underwent therapeutic axillary dissection. Of the 109 patients who underwent lymphoscintigraphy, four (3.7%) demonstrated lymphatic drainage to an epitrochlear node. Epitrochlear nodal involvement from melanoma of the distal upper extremity is rare, and routine epitrochlear node clearance at the time of either elective or therapeutic axillary dissection for upper extremity melanoma is not indicated. However, it is desirable to perform an axillary dissection whenever surgery for metastatic disease in an epitrochlear node is performed.

Point of View: Factors Influencing Wound Healing After Surgery for Metastatic Disease of the Spine

Point of View: Factors Influencing Wound Healing After Surgery for Metastatic Disease of the Spine

334 - Surgery for metastatic disease

334 - Surgery for metastatic disease

Renal cell carcinoma.

The behavior of renal cell carcinoma remains one of the most unpredictable of the genitourinary neoplasms. Once this disease has spread beyond the confines of the kidney, it is extremely difficult to control. This year, emphasis has focused on the characteristic cytogenetic and chromosomal changes that are seen in this tumor that help to explain partially its enigmatic behavior. Immunotherapy remains the mainstay of nonsurgical therapy. Recent studies have examined the efficacy of using combinations of interferons, interleukin-2, or specific subpopulations of lymphoid cells to control metastatic renal cell carcinoma. The role of surgery in metastatic disease, tumor extending into the vena cava, and parenchyma-sparing operations continues to be examined. This review examines the most recent literature on each of these aspects in the treatment of this difficult and challenging tumor.

Anti‐tumor effects of interferon in mice injected with interferonsensitive and interferon‐resistant friend leukemia cells. VI. Adjuvant therapy after surgery in the inhibition of liver and spleen metastases

Adult DBA/2 mice were injected s.c. with the highly malignant, interferon-resistant 3C18 line of Friend erythroleukemia cells (FLC). Eight or 9 days after established s.c. tumors had developed, the primary tumor was excised and mice were treated i.p. with either mouse interferon alpha/beta or a control preparation. At the time of surgery, mice already had tumor cells in the liver. All control-treated mice died in the ensuing 2 weeks with extensive tumor metastases in the liver and spleen. Interferon treatment resulted in an inhibition of the development of liver and spleen metastases and a markedly increased survival time. We conclude that interferon alpha/beta is effective as adjuvant therapy after surgery for metastatic disease in mice.