Role Of Locoregional Therapy Research Articles

Interventional Radiology Locoregional Therapies for Intrahepatic Cholangiocarcinoma.

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.

CON: Is liver organ allocation with MMaT-3 appropriate prioritization for patients with liver cancer?

CON: Is liver organ allocation with MMaT-3 appropriate prioritization for patients with liver cancer?

132TiP HCB-ONC001 ELPIS TRIAL: Omission of surgery and sentinel lymph node dissection in clinically low-risk HER2-positive breast cancer with high HER2 addiction and a complete response following standard anti-HER2-based neoadjuvant therapy

In patients with operable early HER2+ breast cancer (BC), neoadjuvant systemic treatment (NST) is a standard approach. Recent studies for dual HER2 blockage regimes revealed pathologic complete response (pCR) rates up to 75%. These data cast doubt on the role of locoregional therapy in this population. In ELPIS trial, our multidisciplinary team proposes to omit surgery and sentinel node dissection (but not radiotherapy) in 25 highly selected patients who achieve, following anti-HER2 NST, a complete response by imaging (MRI) and a negative vacuum-assisted breast biopsy (VAC) in the tumor residual bed.

Locoregional Treatments for Bridging and Downstaging HCC to Liver Transplantation.

Simple SummaryLiver transplantation is the first-line treatment for patients diagnosed with unresectable early stage hepatocellular carcinoma in the setting of cirrhosis. Patients with tumours beyond this stage may benefit from liver transplantation if their tumours are successfully downstaged. Loco-regional therapies, including ablation, trans-arterial and radiotherapeutical approaches are commonly used to treat patients before transplant, with the aim of reducing the risk of drop off from the waiting list due to tumor progression for patients within transplantation criteria as well as decreasing tumour dimension to meet acceptable criteria. In this review, current evidence on the safety, efficacy and utility of locoregional therapies as neoadjuvant therapies before liver transplantation are summarized.Liver transplantation (LT) is the first-line treatment for patients diagnosed with unresectable early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. It is well known that HCC patients within the Milan criteria (solitary tumour ≤ 5 cm or ≤3 tumours, each <3 cm) could undergo LT with excellent results. However, there is a growing tendency to enlarge inclusion criteria since the Milan criteria are nowadays considered too restrictive and may exclude patients who would benefit from LT. On the other hand, there is a persistent shortage of donor organs. In this scenario, there is consensus about the role of loco-regional therapy (LRT) during the waiting list to select patients who would benefit more from LT, reducing the risk of drop off from the waiting list as well as decreasing tumour dimension to meet acceptable criteria for LT. In this review, current evidence on the safety, efficacy and utility of LRTs as neoadjuvant therapies before LT are summarized.

Abstract PS1-50: Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis

Abstract Background: De novo metastatic breast cancer represents around 6% of breast cancer diagnoses. Retrospective data suggest that locoregional therapy (LRT) for the primary breast cancer in metastatic disease may improve outcomes. Randomized control trials (RCTs) have evaluated the role of LRT in this setting with inconsistent results. Methods: We searched PubMed to identify RCTs that compared LRT and standard systemic therapy to standard therapy alone in de novo metastatic breast cancer. The search was supplemented by a review of abstracts from key conferences. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) data were extracted for the intention to treat (ITT) population and for pre-specified subgroups defined by tumor subtype and by site of metastases. Subgroup analysis evaluated the effect of systemic treatment prior randomization to LRT. Results: Analyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was mandatory in 3 studies. Systemic treatment prior randomization showed similar results (HR=0.92 and HR=1.06 for upfront LRT and LRT following systemic treatment, respectively, p for the subgroup difference=0.72). LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72-1.29, p=0.81). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR for OS= 0.96, 95% CI 0.65-1.43, p=0.85), triple negative (HR 1.4, 95% CI 0.50-3.91, p=0.52) and human epidermal growth factor receptor 2 (HER2) positive disease (HR 0.93, 95% CI 0.68-1.28, p=0.67). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58-1.62, p=0.92) and in visceral disease (HR=1.02, 95% CI 0.77-1.35, p=0.90). Conclusions: LRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. Citation Format: Daniel Jack Reinhorn, Raz Mutai, Rinat Yerushalmi, Assaf Moore, Eitan Amir, Hadar Goldvaser. Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-50.

New insights into the pathophysiology and clinical care of rare primary liver cancers.

SummaryHepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers.

Locoregional Therapies for the Treatment of Hepatic Metastases from Breast and Gynecologic Cancers.

Breast cancer is the most common women's malignancy in the United States and is the second leading cause of cancer death. More than half of patients with breast cancer will develop hepatic metastases; this portends a poorer prognosis. In the appropriately selected patient, there does appear to be a role for curative (surgery, ablation) or palliative (intra-arterial treatments) locoregional therapy. Gynecologic malignancies are less common and metastases to the liver are most often seen in the setting of disseminated disease. The role of locoregional therapies in these patients is not well reported. The purpose of this article is to review the outcomes data of locoregional therapies in the treatment of hepatic metastases from breast and gynecologic malignancies.

Factors associated with improved outcomes for metastatic inflammatory breast cancer patients.

Controversy exists regarding the role oflocoregional therapy for stage IV inflammatory breast cancer (IBC). This study aims to determine indicators of prognosis, including primary tumor resection, for stage IV IBC patients. Using the National Cancer Data Base, female patients diagnosed 2010-2013 with unilateral a priori metastatic T4d invasive adenocarcinoma of the breast were identified. We conducted propensity score matched analysis to balance confounders of surgery versus no-surgery. Stratified log-rank test and double-robust estimation under the Cox model were used to assess the effect of surgery, and margins, on overall survival (OS) in the propensity score matched cohort. Of 1266 patients, 41% underwent surgery. In the unmatched cohort, median OS of the surgery and no-surgery groups was 36 and 20months, respectively (p<0.001). In the matched cohort (n=588), the median OS of surgery and no-surgery groups was 29 and 27months, respectively (p=0.052). Patients with negative margin surgery (p=0.024), hormone receptor-positive (p=0.019), HER2-positive disease (p<0.0001), treated with chemotherapy (p<0.0001) and hormonal therapy (p<0.0001), had better survival. Those with brain metastases had increased risk of death (p<0.0001). This study represents the largest cohort of metastatic IBC patients, and identified negative margin surgery, systemic therapy, hormone receptor and HER2-positive disease as factors associated with improved outcomes. While these findings should be interpreted cautiously, they may be used to guide further investigations into local control and quality of life in this patient population with limited treatment options.

Role of Locoregional Therapy and Predictors for Dropout in Patients with Hepatocellular Carcinoma Listed for Liver Transplantation

PurposeTo identify factors associated with removal from the liver transplantation waitlist because of death, deterioration of condition, or exceeding Milan criteria in patients with hepatocellular carcinoma (HCC), with emphasis on the role of locoregional therapy (LRT), defined as percutaneous thermal ablation and drug-eluting embolic chemoembolization, as bridge therapy. Materials and MethodsAll patients listed for liver transplant at a single institution with exception points for HCC during 2004–2012 were evaluated. The most common cause of cirrhosis was hepatitis C (68%; 121/177). Seventy-one percent (125/177) of patients underwent liver transplantation, and 83% (147/177) underwent at least 1 LRT procedure. Of the 52 patients who did not undergo liver transplantation, 31 (60%) of livers were removed because of progression of HCC. ResultsThe likelihood of transplant was higher for patients who received LRT (odds ratio [OR], 2.9; confidence interval [CI], 2.2–7.2) and lower for patients with multifocal tumors (OR, 0.25; CI, 0.12–0.52) and with larger tumors (OR, 0.94; CI, 0.90–0.98). Time on the waitlist (OR, 0.99; CI, 0.99–1.0) was not found to correlate with removal. LRT increased the likelihood of liver transplantation, specifically for patients with prolonged wait times. Patients who demonstrated complete response (CR) to LRT on the first follow-up imaging study were more likely to undergo liver transplantation. ConclusionsLRT increased the likelihood of a patient with HCC achieving liver transplant, particularly in patients facing prolonged waiting times. CR after LRT significantly increased the likelihood of liver transplantation.

Pulmonary metastasectomy for colorectal cancer: how many nodules, how many times?

Colorectal cancer (CRC) is one of the most common cancers worldwide, with 5%-15% of CRC patients eventually developing lung metastasis (LM). Despite doubts about the role of locoregional therapy in the management of systemic disease, many surgeons have performed pulmonary metastasectomy (PM) for CRC in properly selected patients. However, the use of pulmonary metastasectomy remains controversial due to the lack of randomized controlled studies. This article reviews the results of surgical treatment of pulmonary metastases for CRC, focusing on (1) current treatment guidelines and surgical techniques of PM in patients with LM from CRC; (2) outcomes of PM and its prognostic factors; and (3) controversial issues in PM, focusing on repeated metastasectomy, bilateral multiple metastases, and combined liver and lung metastasectomy.

Liver transplantation: an update 2009

In this review we focus on three challenging aspects of liver transplantation: living donor liver transplant, transplantation in HIV-positive recipients and down-staging of hepatocellular carcinoma for liver transplantation. The adult-to-adult living donor liver transplantation cohort study is providing valuable information on recipient and donor outcomes associated with living donor liver transplantation. The recipient outcomes with living donor liver transplantation are comparable to those with deceased donor liver transplantation for most diseases, but increased hepatocellular carcinoma recurrence has been reported with living donor liver transplantation. Donor morbidity is not infrequent and donor mortality remains a concern. Liver transplantation for HIV-positive recipients is associated with equivalent outcomes as HIV-negative recipients for selected recipients. Transplantation in coinfected recipients (HIV and HCV+) is associated with less favorable outcomes. Drug interaction between immunosuppression and highly active antiretroviral therapy is increasingly recognized and requires major modifications in dosing. Down-staging hepatocellular carcinoma to within transplant criteria is being used in some centers using loco-regional therapy. Waiting time after loco-regional therapy is currently the best predictor of recurrence. The role of newer chemotherapeutics is being tested as part of neoadjuvant therapy after resection or loco-regional therapy. Living donor liver transplantation is a viable strategy to increase transplantation and reduce death on the waiting list. Donor morbidity should be the subject of further efforts to minimize these risks. The increased recurrence risk with living donor liver transplantation for hepatocellular carcinoma warrants further study. Careful coordination between transplant professionals and HIV experts is necessary to monitor issues of posttransplant care of the HIV-infected recipient. The role of loco-regional therapies in down-staging patients with hepatocellular carcinoma is expanding.

The Role of Locoregional Therapy in Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is the most aggressive form of invasive breast cancer. The disease is associated with extensive local disease at the time of initial diagnosis requiring multidisciplinary treatment including neoadjuvant systemic therapy, surgery and comprehensive locoregional therapy. The clinical and pathological response to induction chemotherapy represents an important prognostic factor. IBC is otherwise associated with a high incidence of locoregional recurrence suggesting a critical role also for local modalities, particularly radiotherapy. The use of different schedules of treatment and possible combination approaches are reviewed and discussed.

E17. Update on adjuvant radiotherapy for breast cancer

Although adequate locoregional treatment improves local and regional control in early-stage breast cancer, uncertainty still exists about the role of locoregional therapy with respect to survival. To study the impact of surgery and radiotherapy on locoregional control and survival, we combined the data of three European Organisation for Research and Treatment of Cancer (EORTC) Breast Cancer Group trials including early-stage breast cancer patients with long-term follow-up. Risk ratios (RR) were estimated for locoregional recurrence and overall survival using Cox regression models. All analyses were adjusted for tumour size, nodal status, age, adjuvant radiotherapy, adjuvant chemotherapy and trial. The combined data-set consisted of 3648 patients. The median follow-up period was 11 years. 5.9% of the patients who underwent mastectomy and 10.8% of the patients who underwent breast-conserving therapy had a locoregional recurrence (P<0.0001). The risk of death after breast-conserving therapy was similar compared with mastectomy (RR 1.07, P=0.37). Adjuvant radiotherapy after mastectomy was associated with a lower risk for locoregional recurrence (RR 0.43, P<0.001) and death (RR 0.73, P=0.001). Patients with 1–3 positive nodes benefited the most from radiotherapy after mastectomy. Breast-conserving therapy was associated with an impaired locoregional control. However, breast-conserving therapy was not associated with a worse overall survival. Adjuvant radiotherapy in mastectomised patients was associated with both a significantly superior locoregional control and overall survival. The effect of adjuvant radiotherapy was most profound in patients who had 1–3 positive nodes.

Impact of locoregional treatment on the early-stage breast cancer patients: a retrospective analysis

Although adequate locoregional treatment improves local and regional control in early-stage breast cancer, uncertainty still exists about the role of locoregional therapy with respect to survival. To study the impact of surgery and radiotherapy on locoregional control and survival, we combined the data of three European Organisation for Research and Treatment of Cancer (EORTC) Breast Cancer Group trials including early-stage breast cancer patients with long-term follow-up. Risk ratios (RR) were estimated for locoregional recurrence and overall survival using Cox regression models. All analyses were adjusted for tumour size, nodal status, age, adjuvant radiotherapy, adjuvant chemotherapy and trial. The combined data-set consisted of 3648 patients. The median follow-up period was 11 years. 5.9% of the patients who underwent mastectomy and 10.8% of the patients who underwent breast-conserving therapy had a locoregional recurrence (P<0.0001). The risk of death after breast-conserving therapy was similar compared with mastectomy (RR 1.07, P=0.37). Adjuvant radiotherapy after mastectomy was associated with a lower risk for locoregional recurrence (RR 0.43, P<0.001) and death (RR 0.73, P=0.001). Patients with 1–3 positive nodes benefited the most from radiotherapy after mastectomy. Breast-conserving therapy was associated with an impaired locoregional control. However, breast-conserving therapy was not associated with a worse overall survival. Adjuvant radiotherapy in mastectomised patients was associated with both a significantly superior locoregional control and overall survival. The effect of adjuvant radiotherapy was most profound in patients who had 1–3 positive nodes.

Role of radiotherapy in small cell lung cancer

Traditionally, small cell lung cancer has been considered as a disease with early onset of distant metastases. Therefore, the role of locoregional therapy (radiotherapy or surgery) was thought to be very limited. This was supported by the first trials investigating the role of radiotherapy since there was no improvement of median survival. Recently, two meta-analyses changed this point of view: radiotherapy is essential to achieve long term survival. The possible biological explanation may be that uncontrolled distant metastases may cause the death of patients during the first months of their disease. The longer patients survive the more important local therapy becomes. Today, there is growing acceptance that adequate systemic and local therapy contributes to better treatment results of limited small cell lung cancer.