Cementoplasty of metastases of the proximal femur: is it a safe palliative option?

PURPOSE: Percutaneous cementoplasty has proved very effective for the palliation of pain from bone metastases. However, several studies argue that it should be contraindicated for metastases that are located in the proximal femur because of inadequate bone consolidation. The aim of this study was to evaluate the risk factors for fracture despite performing cementoplasty for metastases of the proximal femur. METHODS: We retrospectively analyzed all consecutive patients who underwent cementoplasty for metastases of the proximal femur who had a high risk for fracture (N = 21) from June 2003 to October 2010. Cementoplasty was performed for preventive consolidation as well as for pain palliation in 16 patients. The risk factors studied were the patient characteristics, the Mirels score, the maximal size and cortical involvement of the lesion, and a history of a previous fracture of the lesser trochanter. RESULTS: The 1-year pathologic fracture rate was 40.6% (seven fractures). The risk of fracture was significantly higher for cortical involvement greater than 30 mm (n = 7/11 vs n = 0/10; P = .0005) and a history of a previous fracture of the lesser trochanter (n = 3/3 vs 4/18; P = .0009). CONCLUSIONS: Percutaneous cementoplasty can be considered for patients with metastases of the proximal femur under certain conditions: cortical involvement less than 30 mm and no history of a fracture of the lesser trochanter. Otherwise, the risk of fracture is too high, and cementoplasty is contraindicated.

Analysis of morbidity and clinical implications of laparoscopic para-aortic lymphadenectomy in a continuous series of 98 patients with advanced-stage cervical cancer and negative PET-CT imaging in the para-aortic area.

BACKGROUND: Laparoscopic para-aortic lymphadenectomy (PAL) is being used increasingly to stage patients with locally advanced cervical cancer (LACC) and to define radiation field limits before chemoradiation therapy (CRT). This study aimed to define clinical implications, review complications, and determine whether surgical complications delayed the start of CRT. METHODS: We retrospectively reviewed a continuous series of patients with LACC, with no positive para-aortic (PA) nodes on positron emission tomography-computed tomography (PET-CT) and who had undergone a primary laparoscopic PAL. RESULTS: From November 2007 to June 2010, 98 patients with LACC underwent pretherapeutic PAL. Two patients did not undergo PAL: extensive carcinomatosis was discovered in one case and a technical problem arose in the other. No perioperative complications occurred. Seven patients had a lymphocyst requiring an imaging-guided (or laparoscopic) puncture. Eight patients (8.4%, which corresponds to the false-negative PET-CT rate) had metastatic disease within PA lymph nodes. In cases of suspicious pelvic nodes on PET-CT, the risk for PA nodal disease was greater (24.0% versus 2.9%). When patients with and without surgical morbidity were compared, the median delay to the start of treatment was not significantly different (15 days; range, 3-49 days versus 18 days; range, 3-42 days). CONCLUSIONS: The morbidity of laparoscopic PAL was limited and the completion of treatment was not delayed when complications occurred. Nevertheless, if PET-CT of the pelvic area is negative, the interest in staging PAL could be discussed because the risk for PA nodal disease is very low.

Irinotecan as first-line chemotherapy in patients with advanced hepatocellular carcinoma: a multicenter phase II study with dose adjustment according to baseline serum bilirubin level.

This study assessed the clinical activity and safety of irinotecan (CPT-11) in patients with advanced hepatocellular carcinoma (HCC) using dose adjustment according to baseline serum bilirubin level. Patients with advanced HCC received CPT-11 at a dose of 350 mg/m(2) when total bilirubin level was 1.5 times upper limit of normal (ULN) (group A), or 200 mg/m(2) when total bilirubin level was between 1.51 and 3 ULN (group B). No objective response, one minor response and 12 disease stabilizations were observed in the 29 patients (group A, 23; group B, 6) enrolled. Median time to progression and overall survival were 3.1 months (95% confidence interval [CI]: 2.0-4.0) and 7.4 months (95% CI: 3.9-12.0), respectively. Grade 3-4 adverse events (mostly neutropenia [47%], anaemia [24%], and diarrhoea [17%]) were more frequent in group A (74%) than in group B (33%) (P = 0.086). This study found favourable toxicity profile using dosage adjustment to the baseline total bilirubin level in patients with bilirubin level comprised between 1.51 and 3 ULN. However, the antitumour activity of single agent CPT-11 was not significant in advanced HCC.

A role for adjuvant RFA in managing hepatic metastases from gastrointestinal stromal tumors (GIST) after treatment with targeted systemic therapy using kinase inhibitors.

PURPOSE: This study was designed to assess the role of radiofrequency ablation (RFA) in the multimodality management of gastrointestinal stromal tumors (GIST) in patients undergoing targeted tyrosine kinase inhibitor therapy (TKI) for liver metastases. METHODS: Outcomes of 17 patients who underwent liver RFA for 27 metastatic GIST after TKI therapy, from January 2004 to March 2012, were retrospectively analyzed. Mean maximum tumor diameter was 2.5 ± 1 cm (range 0.9-4.5 cm). In seven patients (group A), RFA of all residual tumors was performed, with curative intent, and TKI therapy was discontinued. In five patients (group B), RFA of all residual tumors was performed upon achieving the best morphological response with TKI therapy, which was maintained after RFA. In another five patients (group C), RFA was performed on individual liver metastases which were progressive under TKI therapy. RESULTS: All 27 targeted tumors were completely ablated, without local recurrence during the mean follow-up period of 49 months. No major complications occurred. Two minor complications were reported (11 %). Only two patients (both in group C) died at 20 and 48 months. Two-year progression-free survival (PFS) after RFA was 29 % in group A, 75 % in group B, and 20 % in group C. CONCLUSIONS: RFA in patients, previously treated with TKI, is feasible and safe. Our data suggest that RFA is a useful therapeutic option in patients with metastatic GIST and should be performed at the time of best clinical response with patient maintained under TKI after the procedure.

Are G3 ENETS neuroendocrine neoplasms heterogeneous?

The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.

Intervention in gastro-enteropancreatic neuroendocrine tumours.

Neuroendocrine tumours require dedicated interventions to control their capacity to secrete hormones but also, antitumour growth strategies. Recommendations for early interventions in NET include the management of hormone-related symptoms and poorly differentiated neuroendocrine carcinomas. In contrast, prognostic heterogeneity is a key feature of well differentiated NET that complexified the antitumour strategy whatever the stage in this subgroup of tumour. In this review, timely therapeutic interventions to control hormone-related symptoms and tumour growth in GEP NET patients are discussed. The necessity of controlling hormone-related symptoms as the first step of any strategy affects also the tumour growth control strategy. In the absence of cure at the metastatic stage, progresses are expected in the recognition of well differentiated NET subgroups that display either excellent or poor prognosis.

[Pelvic perfusion for localy advanced tumors]. / La perfusion pelvienne sous circulation extracorporelle dans les tumeurs pelviennes localement évoluées.

Isolated pelvic perfusion (IPP) is a method of intra-arterial local-regional treatment using a simplified balloon occlusion technique. It achieved high-dose drug concentration in pelvis with the minimal adverse effects. Recently, this approach was improved with the use of a pressure-suit placed above the level of aortic and caval stop-flow. A better ratio between pelvic and systemic compartments was achieved. This stop-flow technique with low dose TNF-alpha and melphalan has shown promise in palliation of resectability of advanced cancer in patients not amenable to treatment with conventional chemo radiation in a comparable proportion to those obtained with isolated limb perfusions. A randomized study will start soon.

Biliary tract neoplasms: update 2003.

PURPOSE OF REVIEW: Biliary tract neoplasm is one of the most aggressive malignancies, with a very poor prognosis. Most cancers of the biliary tract will have grown beyond the limits of curative resection by the time they become clinically evident. This reality has fostered therapeutic nihilism, and most physicians and surgeons, in their pessimism, have to run ambitious trials evaluating new diagnostic tools and therapeutic techniques in this disease. RECENT FINDINGS: Advances in imaging over the period of the last 5 years now allow for earlier diagnosis and better surgical planning. Recent improvements in operative technique have substantially improved the outlook of patients with this cancer. Palliative management of obstructive disease recently has been improved with the advent of photodynamic therapy. Among the different drugs tested in this disease, gemcitabine seems to have the best efficacy:toxicity ratio. However, efficacy results remain disappointing, and combination schedules need to be developed to improve the results. Among them, the gemcitabine-oxaliplatin combination seems to be one of the most promising schedules. Biological studies, especially those evaluating mutation-independent activation of the Hedgehog pathway, have provided interesting information on the carcinogenesis of this rare tumor. Furthermore, these results bring us the opportunity of development of future targeted therapies in biliary tract cancer. SUMMARY: Biliary tract neoplasm remains one of the most aggressive malignancies. However, as for other gastrointestinal malignancies, biological studies and diagnostic and therapeutic improvements have provided interesting results that could lead to a major improvement in the prognosis of this disease.