P. Della Vigna

Best choice of central venous insertion site for the prevention of catheter-related complications in adult patients who need cancer therapy: a randomized trial

BACKGROUND Central venous access is extensively used in oncology, though practical information from randomized trials on the most convenient insertion modality and site is unavailable. METHODS Four hundred and three patients eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City, UT), through a percutaneous landmark access to the internal jugular, a ultrasound (US)-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Early and late complications were prospectively recorded until removal of the device, patients death or ending of the study. RESULTS Four hundred and one patients (99.9%) were assessable: 132 with the internal jugular, 136 with the subclavian and 133 with the cephalic vein access. The median follow-up was 356.5 days (range 0-1087). No differences were found for early complication rate in the three groups {internal jugular: 0% [95% confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%), cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had significantly lower failures (e.g. failed attempts to place the catheter in agreement with the original arm of randomization, P = 0.001). Infections occurred in one, three and one patients (internal jugular, subclavian and cephalic access, respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11 patients (P = 0.272). CONCLUSIONS Central venous insertion modality and sites had no impact on either early or late complication rates, but US-guided subclavian insertion showed the lowest proportion of failures.

Should liver metastases of breast cancer be biopsied to improve treatment choice

BACKGROUND Currently, the acquisition of tissue from metastatic deposits is not recommended as a routine practice. Our aim was to evaluate the discordance rate of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) receptor status between primary tumor and liver metastases and its potential impact on treatment choice. PATIENTS AND METHODS We retrospectively analyzed a database including 1250 ultrasound-guided liver biopsies carried out at the European Institute of Oncology from August 1999 to March 2009. ER, PgR, and HER2 status were determined by immunohistochemistry and/or FISH. Differences between proportions were evaluated using Fishers exact test. RESULTS We identified 255 consecutive patients with matched primary and liver tissue samples. Changes in ER status were observed in 37 of 255 patients (14.5%). Changes in PgR status were observed in 124 of 255 patients (48.6%). Changes in HER2 status were observed in 24 of 172 assessable patients (13.9%). We observed a discordance in receptor status (ER, PgR, and HER2) between primary tumor and liver metastases, which led to change in therapy for 31 of 255 of patients (12.1%). CONCLUSIONS Biopsy of metastases for reassessment of biological features should be considered in all patients, when safe and easy to carry out, since it is likely to impact treatment choice.

High-intensity focused ultrasound (HIFU) in patients with solid malignancies: evaluation of feasibility, local tumour response and clinical results.

PurposeThe purpose of this study was to evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of solid tumours without damaging the surrounding structures.Materials and methodsA specific written informed consent was obtained from every patient before treatment. From September 2008 to April 2009, 22 patients with 29 lesions were treated: nine patients with liver and/or soft-tissue metastases from colorectal carcinoma (CRC), six with pancreatic solid lesions, three with liver and/or bone metastases from breast cancer, one with osteosarcoma, one with muscle metastasis from lung cancer, one with iliac metastasis from multiple myeloma and one with abdominal liposarcoma. The mean diameter of tumours was 4.2 cm. All patients were evaluated 1 day, 1 month and 3 months after HIFU treatment by multidetector computed tomography (MDCT), positron-emission tomography (PET)-CT and clinical evaluation. The treatment time and adverse events were recorded.ResultsAll patients had one treatment. Average treatment and sonication times were, respectively, 162.7 and 37.4 min. PET-CT or/and MDCT showed complete response in 11/13 liver metastases; all bone, soft-tissue and pancreatic lesions were palliated in symptoms, with complete response to PET-CT, MDCT or magnetic resonance imaging (MRI); the liposarcoma was almost completely ablated at MRI. Local oedema was observed in three patients. No other side effects were observed. All patients were discharged 1–3 days after treatment.ConclusionsAccording to our preliminary experience in a small number of patients, we conclude that HIFU ablation is a safe and feasible technique for locoregional treatment and is effective in pain control.RiassuntoObiettivoL’obiettivo di questo studio è stato quello di valutare la sicurezza e l’efficacia dell’applicazione degli ultrasuoni focalizzati ad elevata intensità (USgHIFU) nell’ablazione terapeutica di tumori solidi senza danneggiare le strutture circostanti.Materiali e metodiUno specifico consenso informato scritto è stato ottenuto da tutti i pazienti prima del trattamento. Da settembre 2008 ad aprile 2009 sono stati trattati 22 pazienti con 29 lesioni: 9 pazienti con metastasi epatiche e/o dei tessuti molli da carcinoma del colon retto (CRC), sei pazienti con lesioni solide del pancreas, tre con metastasi epatiche e/o ossee da tumore mammario, uno con osteosarcoma, uno con metastasi muscolare da tumore del polmone, uno con lesione iliaca da mieloma multiplo ed uno con liposarcoma addominale. Il diametro medio era di 4,2 cm. Tutti i pazienti sono stati valutati ad 1 giorno, 1 mese e a 3 mesi di distanza dal trattamento HIFU con tomografia computerizzata multidetettore (MDCT), tomografia computerizzata con tomografia ad emissione di positroni (PET-CT) e valutazione clinica. La durata del trattamento e gli eventi avversi sono stati registrati.RisultatiTutti i pazienti sono stati trattati in una unica sessione. Il tempo medio di trattamento e di sonazione sono stati di 162,7 e 37,4 minuti, rispettivamente. PET-CT e/o MDCT hanno mostrato risposta completa in 11/13 metastasi epatiche; tutte le lesioni ossee, dei tessuti molli e le lesioni pancreatiche sono state palliate nei sintomi, con risposta completa all’esame PET-CT, MDCT o risonanza magnetica (RM); il liposarcoma ha mostrato una ablazione quasi completa all’esame RM. Edema locale è stato osservato in tre pazienti senza ulteriori eventi avversi. Tutti i pazienti sono stati dimessi da 1 a 3 giorni dopo il trattamento.ConclusioniSecondo la nostra esperienza preliminare da un limitato numero di pazienti, l’ablazione USgHIFU può essere considerata una metodica sicura e fattibile in assenza di alternative terapeutiche locoregionali e valida per il controllo del dolore.

Treatments for colorectal liver metastases: A new focus on a familiar concept

A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and its the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival. Better tumor response rates with modern systemic therapy mean that more unresectable patients are now down-staged for radical resection following conversion therapy but for other patients, additional procedures are needed. In multiple unilobar disease, when the projected remnant liver is <30% of the total liver, portal embolization or selective-internal-radiation-therapy (SIRT) can induce hypertrophy of the healthy liver, leading to resectability. In multiple bilobar disease, in situ destruction of non-resectable lesions by minimally invasive techniques may be associated with liver resection to achieve potential curative intent. Other palliative liver-directed approaches, such as SIRT or intra-hepatic chemotherapy (HAI), which are associated with higher response rates, may also have role in down-staging patients for resection. Until recently, such technologies have not been validated in prospective controlled trials. However in the light of new Phase 3 data for SIRT as well as for HAI combined with modern therapies or radiofrequency ablation in the first- and second-line setting, the clinical value of these treatments needs to be re-appraised.

Contrast-enhanced ultrasonography in the follow-up of patients with hepatic metastases from breast carcinoma

Purpose.Oncological treatment planning relies on the evaluation of treatment response, which is defined by the change in size of measurable lesions. The purpose of this study was to evaluate the use of contrast-enhanced ultrasound (CEUS) to obtain a precise measurement of hepatic metastases in breast cancer patients with fatty-liver disease.Materials and methods.Twelve consecutive patients with 25 liver metastases from breast cancer and fatty liver disease, as defined by US criteria, were enrolled in this prospective study. All patients underwent conventional US, CEUS and multidetector computed tomography (MDCT), used as the gold standard for measuring the maximum diameter of lesions. Agreement between US, CEUS and MDCT measurements was analysed using Altman-Bland plots; 95% confidence limits were calculated for the difference among means.Results.Mean diameter as measured by MDCT was 26.2 mm (range 11–83). US allowed measurement of 20/25 lesions. In 15 lesions, CEUS measurements were more accurate than those obtained by US. The difference among means was 1.1 mm with a 95% confidence interval (–9.2, 11.4) for US measurements and 0.6 mm with a 95% confidence interval (–2.0, 3.1) for CEUS.Conclusions.Our preliminary data show that CEUS can be used to obtain more accurate measurements than conventional US for the follow-up of patients with metastases in fatty liver.

A FOLFIRI-induced complete tumor response in a patient with FOLFOX-refractory metastatic duodenal adenocarcinoma

1Division of New Drugs Development and Clinical Pharmacology, European Institute of Oncology Ripamonti 435 Milan, Italy, 2Department of Pathology, European Institute of Oncology Ripamonti 435 Milan, Italy, 3Division of Abdomino-Pelvic Surgery, European Institute of Oncology Ripamonti 435 Milan, Italy, 4Division of Gynecology, European Institute of Oncology Ripamonti 435 Milan, Italy, 5Division of Nuclear Medicine, European Institute of Oncology Ripamonti 435 Milan, Italy and 5Divison of Radiology, European Institute of Oncology Ripamonti 435 Milan, Italy

Interventional oncology in the elderly: Complications and early response in liver and kidney malignancies

OBJECTIVES The complication rate, loco-regional responses and length of hospital stay were analyzed in patients with liver and kidney cancer older than 70years treated with interventional oncology procedures. The findings from the older population were compared with the younger patients (<70years) to detect any difference not related to chance. MATERIALS AND METHODS Prospectively collected data on patients who underwent hepatic artery embolization (with or without radiofrequency ablation) and kidney radiofrequency ablation were retrospectively analyzed. Complication rates, loco-regional responses and length of hospital stay for patients older and younger than 70 were compared. RESULTS 163 patients were treated, 66 (40.5%) older and 97 (59.5%) younger than 70years. The complication rate in patients older than 70 was 4.5% (3/66 pts) versus 3.1% (3/97 pts) (p=0.69) in the younger age-group. The complication rates for the liver embolization group, liver embolization plus radiofrequency and kidney radiofrequency group were 2/90 pts (2.2%), 2/42 pts (4.8%) and 2/31 pts (6.5%), respectively (p=0.46). Median hospital stay was three nights in both older and younger patients. Response rates were not significantly influenced by age. CONCLUSION Liver embolization with or without radiofrequency and renal radiofrequency are safe and effective in older patients. Age alone should not be considered a contraindication to treatment in carefully selected patients.

Ultrasuoni focalizzati ad elevata intensità (HIFU) in pazienti con tumori solidi. Valutazione della fattibilità, della risposta locale e dei risultati clinici

PurposeThe purpose of this study was to evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of solid tumours without damaging the surrounding structures.Materials and methodsA specific written informed consent was obtained from every patient before treatment. From September 2008 to April 2009, 22 patients with 29 lesions were treated: nine patients with liver and/or soft-tissue metastases from colorectal carcinoma (CRC), six with pancreatic solid lesions, three with liver and/or bone metastases from breast cancer, one with osteosarcoma, one with muscle metastasis from lung cancer, one with iliac metastasis from multiple myeloma and one with abdominal liposarcoma. The mean diameter of tumours was 4.2 cm. All patients were evaluated 1 day, 1 month and 3 months after HIFU treatment by multidetector computed tomography (MDCT), positron-emission tomography (PET)-CT and clinical evaluation. The treatment time and adverse events were recorded.ResultsAll patients had one treatment. Average treatment and sonication times were, respectively, 162.7 and 37.4 min. PET-CT or/and MDCT showed complete response in 11/13 liver metastases; all bone, soft-tissue and pancreatic lesions were palliated in symptoms, with complete response to PET-CT, MDCT or magnetic resonance imaging (MRI); the liposarcoma was almost completely ablated at MRI. Local oedema was observed in three patients. No other side effects were observed. All patients were discharged 1–3 days after treatment.ConclusionsAccording to our preliminary experience in a small number of patients, we conclude that HIFU ablation is a safe and feasible technique for locoregional treatment and is effective in pain control.RiassuntoObiettivoL’obiettivo di questo studio è stato quello di valutare la sicurezza e l’efficacia dell’applicazione degli ultrasuoni focalizzati ad elevata intensità (USgHIFU) nell’ablazione terapeutica di tumori solidi senza danneggiare le strutture circostanti.Materiali e metodiUno specifico consenso informato scritto è stato ottenuto da tutti i pazienti prima del trattamento. Da settembre 2008 ad aprile 2009 sono stati trattati 22 pazienti con 29 lesioni: 9 pazienti con metastasi epatiche e/o dei tessuti molli da carcinoma del colon retto (CRC), sei pazienti con lesioni solide del pancreas, tre con metastasi epatiche e/o ossee da tumore mammario, uno con osteosarcoma, uno con metastasi muscolare da tumore del polmone, uno con lesione iliaca da mieloma multiplo ed uno con liposarcoma addominale. Il diametro medio era di 4,2 cm. Tutti i pazienti sono stati valutati ad 1 giorno, 1 mese e a 3 mesi di distanza dal trattamento HIFU con tomografia computerizzata multidetettore (MDCT), tomografia computerizzata con tomografia ad emissione di positroni (PET-CT) e valutazione clinica. La durata del trattamento e gli eventi avversi sono stati registrati.RisultatiTutti i pazienti sono stati trattati in una unica sessione. Il tempo medio di trattamento e di sonazione sono stati di 162,7 e 37,4 minuti, rispettivamente. PET-CT e/o MDCT hanno mostrato risposta completa in 11/13 metastasi epatiche; tutte le lesioni ossee, dei tessuti molli e le lesioni pancreatiche sono state palliate nei sintomi, con risposta completa all’esame PET-CT, MDCT o risonanza magnetica (RM); il liposarcoma ha mostrato una ablazione quasi completa all’esame RM. Edema locale è stato osservato in tre pazienti senza ulteriori eventi avversi. Tutti i pazienti sono stati dimessi da 1 a 3 giorni dopo il trattamento.ConclusioniSecondo la nostra esperienza preliminare da un limitato numero di pazienti, l’ablazione USgHIFU può essere considerata una metodica sicura e fattibile in assenza di alternative terapeutiche locoregionali e valida per il controllo del dolore.

High-intensity focused ultrasound (HIFU) in patients with solid malignancies: evaluation of feasibility, local tumour response and clinical results@@@Ultrasuoni focalizzati ad elevata intensità (HIFU) in pazienti con tumori solidi. Valutazione della fattibilità, della risposta locale e dei risultati clinici

PurposeThe purpose of this study was to evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of solid tumours without damaging the surrounding structures.Materials and methodsA specific written informed consent was obtained from every patient before treatment. From September 2008 to April 2009, 22 patients with 29 lesions were treated: nine patients with liver and/or soft-tissue metastases from colorectal carcinoma (CRC), six with pancreatic solid lesions, three with liver and/or bone metastases from breast cancer, one with osteosarcoma, one with muscle metastasis from lung cancer, one with iliac metastasis from multiple myeloma and one with abdominal liposarcoma. The mean diameter of tumours was 4.2 cm. All patients were evaluated 1 day, 1 month and 3 months after HIFU treatment by multidetector computed tomography (MDCT), positron-emission tomography (PET)-CT and clinical evaluation. The treatment time and adverse events were recorded.ResultsAll patients had one treatment. Average treatment and sonication times were, respectively, 162.7 and 37.4 min. PET-CT or/and MDCT showed complete response in 11/13 liver metastases; all bone, soft-tissue and pancreatic lesions were palliated in symptoms, with complete response to PET-CT, MDCT or magnetic resonance imaging (MRI); the liposarcoma was almost completely ablated at MRI. Local oedema was observed in three patients. No other side effects were observed. All patients were discharged 1–3 days after treatment.ConclusionsAccording to our preliminary experience in a small number of patients, we conclude that HIFU ablation is a safe and feasible technique for locoregional treatment and is effective in pain control.RiassuntoObiettivoL’obiettivo di questo studio è stato quello di valutare la sicurezza e l’efficacia dell’applicazione degli ultrasuoni focalizzati ad elevata intensità (USgHIFU) nell’ablazione terapeutica di tumori solidi senza danneggiare le strutture circostanti.Materiali e metodiUno specifico consenso informato scritto è stato ottenuto da tutti i pazienti prima del trattamento. Da settembre 2008 ad aprile 2009 sono stati trattati 22 pazienti con 29 lesioni: 9 pazienti con metastasi epatiche e/o dei tessuti molli da carcinoma del colon retto (CRC), sei pazienti con lesioni solide del pancreas, tre con metastasi epatiche e/o ossee da tumore mammario, uno con osteosarcoma, uno con metastasi muscolare da tumore del polmone, uno con lesione iliaca da mieloma multiplo ed uno con liposarcoma addominale. Il diametro medio era di 4,2 cm. Tutti i pazienti sono stati valutati ad 1 giorno, 1 mese e a 3 mesi di distanza dal trattamento HIFU con tomografia computerizzata multidetettore (MDCT), tomografia computerizzata con tomografia ad emissione di positroni (PET-CT) e valutazione clinica. La durata del trattamento e gli eventi avversi sono stati registrati.RisultatiTutti i pazienti sono stati trattati in una unica sessione. Il tempo medio di trattamento e di sonazione sono stati di 162,7 e 37,4 minuti, rispettivamente. PET-CT e/o MDCT hanno mostrato risposta completa in 11/13 metastasi epatiche; tutte le lesioni ossee, dei tessuti molli e le lesioni pancreatiche sono state palliate nei sintomi, con risposta completa all’esame PET-CT, MDCT o risonanza magnetica (RM); il liposarcoma ha mostrato una ablazione quasi completa all’esame RM. Edema locale è stato osservato in tre pazienti senza ulteriori eventi avversi. Tutti i pazienti sono stati dimessi da 1 a 3 giorni dopo il trattamento.ConclusioniSecondo la nostra esperienza preliminare da un limitato numero di pazienti, l’ablazione USgHIFU può essere considerata una metodica sicura e fattibile in assenza di alternative terapeutiche locoregionali e valida per il controllo del dolore.

Should Liver Metastases of Breast Cancer Be Biopsied To Improve Treatment Choice

CRA1008 Background: Decision making on systemic treatment of women with metastatic breast cancer is based on features like estrogen receptor (ER), progesterone receptor (PgR), and HER2 status assessed on the primary tumor. We evaluated the concordance of receptor status between primary tumor and liver metastases (mts) and its impact on treatment choice. METHODS We retrospectively analyzed a database including ultrasound guided liver biopsies performed from 1995 to 2008. All tissue samples, both from primary tumor and liver mts, were analyzed for ER, PgR and HER2 status. Clinical and biological data were obtained from medical charts. Differences between proportions were evaluated using the Pearson chi-square test. RESULTS We identified 255 consecutive patients (pts) with matched primary and liver tissue samples. Median time from primary diagnosis to liver biopsy was 3.4 years (range 0-18.3 years). Changes in ER status were observed in 41/255 pts (16.0%). 16/58 pts (27.6%) changed from ER-negative to ER-positive and 25/197 pts (12.7%) changed from ER-positive to ER-negative (p=0.0066). Changes in PgR status were observed in 76/255 pts (29.8%). 18/91 pts (19.8%) changed from PgR-negative to -positive and 58/164 pts (64.6%) from PgR-positive to PgR-negative (p <0.0001). 12/52 pts (23.1%) changed from ER- and PgR-negative to ER- or PgR-positive (group A) and 27/203 pts (13.3%) changed from ER- or PgR-positive to ER- and PgR-negative (group B) (p=0.087). In the group A the treatment of 4/12 pts (33.3%) was changed after biopsy: 2/4 started endocrine treatment (HT) and 2/4 stopped it. In group B the treatment of 18/27 pts (66.6%) was changed after biopsy: 17/18 stopped HT. Changes in HER2 status were observed in 22/167 pts (13.1%): 6/116 pts (5.1%) changed from HER2-negative to HER2-positive and 16/51 pts (31.4%) changed from HER2-positive to negative (p≤0.0001). In this group pts started and/or stopped a trastuzumab containing treatment after biopsy. CONCLUSIONS There was a discordance in receptor status between primary tumor and liver mts, which led to change in therapy for 48/255 of pts (18.8%). Biopsy of metastases for reassessment of biological features should be considered in all pts when safe and easy to perform, since it is likely to impact treatment choice. No significant financial relationships to disclose.