Waiting-Time and Quality of Care Deserved to Patients with Early Stage Hepatocellular Carcinoma Undergoing RFA Treatment
Maurizio Soresi, Anna Licata, Lydia Giannitrapani, Giuseppe Montalto
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Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy
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Several factors contribute to poor prognosis: the presence of a coexisting liver cirrhosis which limits responsiveness to systemic chemotherapy, the frequent association with comorbidities, the often delay of diagnosis. In this respect, to reduce diagnosis delay, international scientific societies such as the European Association for the Study of the Liver (EASL), the Japan Society of Hepa-tology (JSH) and the American Association for the Study of Liver Diseases (AASLD) proposed screening schedules for patients at risk of developing hepatocellular carcinoma.</p><p id="p0015" class="elsevierStylePara elsevierViewall">The study of Brahmania M, <span class="elsevierStyleItalic">et al</span>. focuses attention on a particular aspect not reported in the literature: the relationship between the time between diagnosis and therapy and its impact on survival.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">2</span></a> The authors analyze this issue by using Radio Frequency Ablation (RFA) therapy, which actually represents one of the most widespread ablative methods in the world, having replaced the alcoholization technique, in most liver tumors. Its indication is for T1 and T2 tumors where resection may be used as well, but the selection of treatment modality depends on the underlying liver function, the degree of portal hypertension, the tumor site more than on the oncologic stage of the tumor. Therefore, while therapeutic options are limited for patients who presents with an advanced liver disease and/or advanced tumor stages, multiple options exist for those presenting with well-compensated cirrhosis and smaller, potentially resectable tumors. Several studies have shown that RFA for early stage HCC has similar survival rates to surgical management at 3 and 5 years, around 90% and 70%, respectively. Anyway, a Cochrane systematic review performed by Weis et al. on the treatment for early-stage HCC in patients with Child's A or B class cirrhosis concluded that the total number of included patients was too low to reach a firm conclusion.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">3</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">The impact of wait times on survival for patients with cancer undergoing therapy is an ongoing issue in Canada's publically funded healthcare system, where the study of Brahmania et al. was conducted. The effects of increased waiting time can generally be associated with worse clinical outcomes, negative impact on survival and a poorer quality of life. This depends on a variety of factors especially the invasiveness of the neoplasia, but also the extension of the disease at diagnosis. Tumors that are diagnosed with delay, because they may have late warning signs, they benefit less of a shorter waiting time between diagnosis and therapy. Studies on colon, pancreas, uterine cervix, stomach and lung cancer have reported an unclear relationship between waiting time and survival.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">4-9</span></a> Others, on the other hand, melanoma, rectal, breast and bladder cancer have reported a negative effect of treatment delay on survival.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">4,10-13</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">HCC is certainly a symptomatic and biologically aggressive neoplasm, it is therefore understandable why rapidity of treatment is essential. However, despite these assumptions the authors point that in Ontario it is not always possible to intervene early and to maintain the 28-waiting days standard for other malignancies.</p><p id="p0030" class="elsevierStylePara elsevierViewall">The authors in their study propose to evaluate whether wait times for RFA were associated with residual tumor, tumor recurrence, need for liver transplantation, or death.</p><p id="p0035" class="elsevierStylePara elsevierViewall">Although the study of Brahmania et al is retrospective, results are interesting because the problem of diagnostic delay in HCC is extremely real, overall in areas with high incidence of HBV and HCV related chronic liver disease. From the retrospective analysis of 219 patients with HCC in BCLC 0-1 stage, with a cancer size between 2.1 and 4 cm, sufficient liver function (median of MELD 8.7, Child-Pugh score of < 10), with different etiologies (predominantly HCV) they found that the median time from HCC diagnosis to RFA treatment was 96 days, and further, that each 30-day incremental in wait time was associated with an increased risk of residual tumor as well as death. Thus, as has been recently reported by Johnson P et al in a large study on HCC, the variation in survival is largely accounted for stage at diagnosis, which in turn is related to the intensity of surveillance programs and the consequent variation in therapeutic options.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">14</span></a> In addition, the data on tumor residue are interesting, and coincide with the recent results of Radunz S, <span class="elsevierStyleItalic">et al.</span> which has recently demonstrated, with histopathological analysis on HCC samples from livers transplanted for HCC following Yttrium-90 radio-em-bolization bridging treatment, as the complete necrosis of explanted specimens has a trend towards a lower risk of tumor recurrence.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">15</span></a></p><p id="p0040" class="elsevierStylePara elsevierViewall">Probably the long wait time between diagnosis and therapy of this study, as the same authors suggest, is due to the fact that it is conducted in a quaternary center which is referral for a large number of patients and where the multi-disciplinary approach to therapeutic choices creates the “snowball” effect responsible for delayed treatment.</p><p id="p0045" class="elsevierStylePara elsevierViewall">Treating early HCC depends, not only on a multidisci-plinary approach (hepatologist, oncologist, interventional radiologist) but also on the resources available at the hospital. We report the same experience of Brahmania, <span class="elsevierStyleItalic">et al.</span>, which despite physicians try to organize the RFA treatment of HCC as soon as possible, the possibility of a delay due to delayed presentation of the case to the multidisci-plinary cancer conference, scheduling consultation with radiologist, and finally the availability of the appropriate instrumentation is the actual rule.</p><p id="p0050" class="elsevierStylePara elsevierViewall">Another key point that should be addressed is the necessity of finding predictors (clinical and/or biological) of the behavior, in terms of aggressiveness, of the cancer in the single patient. From a clinical point of view, it has been recently described an index of liver dysfunction in HCC, based solely on albumin and bilirubin levels, called ALBI grade, that has been validated as a novel biomarker of liver functional reserve and successfully used as predictor of patient overall survival after surgical resection, tran-sarterial chemoembolization and sorafenib. Prospective studies, however, are needed in subjects with the indication to RFA treatment.</p><p id="p0055" class="elsevierStylePara elsevierViewall">Serum markers have also been studied, in particular Alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-c-carboxy prothrombin (DCP) are well-known markers for HCC.</p><p id="p0060" class="elsevierStylePara elsevierViewall">Recently, the status of these three positive tumor markers was considered as a prognostic factor for HCC patients treated with hepatic resection (HR) or RFA.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">16</span></a> In fact when adding to traditional histological prognostic factors, like microvascular invasion and tumor differentiation, the positive expression of the three HCC markers, survival rates of patients who underwent HR and RFA when treating single nodular HCC < 5 cm, were differently influenced.</p><p id="p0065" class="elsevierStylePara elsevierViewall">In summary, in the era of the new antiviral treatments which are changing the etiological scenario of chronic liver diseases, attention should be placed on advanced and personalized surveillance programs for HCC to finally improve quality of care deserved to patients. However, wait time references for curative intent treatment of early HCCs have not yet been developed. In this study the authors report an initial attainable measure of a wait time target not to be greater than 60 days as death rates increased from 6.7% to 28.1% after this period. Anyway, further investigations are warranted to confirm these data on prospective case studies.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-07-31" "fechaAceptado" => "2017-07-31" "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0010" "etiqueta" => "1." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 0 | 2 |
| 2024 October | 9 | 8 | 17 |
| 2024 September | 6 | 3 | 9 |
| 2024 August | 7 | 2 | 9 |
| 2024 July | 5 | 1 | 6 |
| 2024 June | 4 | 0 | 4 |
| 2024 May | 4 | 3 | 7 |
| 2024 April | 9 | 6 | 15 |
| 2024 March | 12 | 2 | 14 |
| 2024 February | 5 | 4 | 9 |
| 2024 January | 9 | 5 | 14 |
| 2023 December | 2 | 3 | 5 |
| 2023 November | 10 | 4 | 14 |
| 2023 October | 8 | 6 | 14 |
| 2023 September | 5 | 2 | 7 |
| 2023 August | 5 | 3 | 8 |
| 2023 July | 5 | 2 | 7 |
| 2023 June | 13 | 5 | 18 |
| 2023 May | 29 | 6 | 35 |
| 2023 April | 47 | 2 | 49 |
| 2023 March | 35 | 4 | 39 |
| 2023 February | 17 | 4 | 21 |
| 2023 January | 20 | 0 | 20 |
| 2022 December | 36 | 5 | 41 |
| 2022 November | 16 | 5 | 21 |
| 2022 October | 9 | 3 | 12 |
| 2022 September | 6 | 7 | 13 |
| 2022 August | 4 | 7 | 11 |
| 2022 July | 9 | 7 | 16 |
| 2022 June | 9 | 9 | 18 |
| 2022 May | 7 | 7 | 14 |
| 2022 April | 4 | 9 | 13 |
| 2022 March | 9 | 7 | 16 |
| 2022 February | 7 | 4 | 11 |
| 2022 January | 11 | 5 | 16 |
| 2021 December | 5 | 9 | 14 |
| 2021 November | 10 | 7 | 17 |
| 2021 October | 10 | 5 | 15 |
| 2021 September | 6 | 8 | 14 |
| 2021 August | 5 | 7 | 12 |
| 2021 July | 6 | 6 | 12 |
| 2021 June | 9 | 9 | 18 |
| 2021 May | 9 | 5 | 14 |
| 2021 April | 9 | 12 | 21 |
| 2021 March | 7 | 14 | 21 |
| 2021 February | 4 | 7 | 11 |
| 2021 January | 2 | 7 | 9 |
| 2020 December | 4 | 3 | 7 |
| 2020 November | 5 | 3 | 8 |
| 2020 October | 2 | 1 | 3 |
| 2020 September | 3 | 7 | 10 |
| 2020 August | 3 | 4 | 7 |
| 2020 July | 2 | 6 | 8 |
| 2020 June | 2 | 1 | 3 |
| 2020 May | 2 | 6 | 8 |
| 2020 April | 1 | 2 | 3 |
| 2020 March | 2 | 3 | 5 |
| 2020 February | 5 | 4 | 9 |
| 2020 January | 3 | 3 | 6 |
| 2019 December | 5 | 7 | 12 |
| 2019 November | 1 | 2 | 3 |
| 2019 October | 1 | 7 | 8 |
| 2019 September | 2 | 2 | 4 |
| 2019 August | 1 | 0 | 1 |
| 2019 July | 1 | 1 | 2 |
| 2019 June | 9 | 9 | 18 |
| 2019 May | 2 | 4 | 6 |
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