Role Of Locoregional Treatment Research Articles

Should Locoregional Treatment be Performed in de novo Metastatic Breast Cancer? A Retrospective Single-centre Experience

Purpose: De novo metastatic breast cancer (DMBC) represents approximately 6% of patients with breast cancer [1]. The role of locoregional treatment (LRT) remains controversial, with conflicting trial evidence [2–4]. Palliative systemic therapy remains the mainstay of treatment. We report the impact of different LRTs on breast cancer survival in this heterogeneous disease.

Prognostic factors and the role of locoregional treatment in patients with distantly metastatic hypopharyngeal cancer: a retrospective cohort study based on SEER database.

There is increasing evidence that locoregional treatment (LRT, surgery or/and radiotherapy) for the primary tumor can improve survival in some cancers with systemic dissemination. This study aimed to investigate the survival benefit of LRT and prognostic factors in patients with hypopharyngeal cancer with distant metastasis. A retrospective population-based analysis was performed using the Surveillance, Epidemiology, and End Results database. Cox regression analysis was used to account for the imbalance of baseline covariates. The Kaplan-Meier method, log-rank test, and competing risk analysis were used to compare survival outcomes between treatment patterns. Four hundred and sixty-three eligible patients were included in the analysis with a median overall survival of 7 months. LRT plus systemic therapy was the most common treatment modality (47%) and was associated with the most prolonged survival compared with other treatment methods (log-rank test, P<0.001). In multivariate analysis, bone metastasis, liver metastasis, and treatment were identified as independent prognostic factors for survival. Patients receiving LRT and systemic therapy had a 35% reduced risk of death compared with patients receiving systemic therapy (HR =0.65, 95% CI: 0.39-0.92, P=0.028). Further subgroup analysis and competing risk analysis also confirmed this survival trend favoring LRT and systemic therapy. Interestingly, interaction analysis revealed that only age variable affected the treatment effect and younger patients (<65 years) were more likely to benefit from LRT plus systemic therapy. Our results suggest that bone metastasis, liver metastasis, and treatment were prognostic factors for the survival of patients with metastatic hypopharyngeal cancer. Patients with distant metastasis are often treated with systemic therapy for a palliative intention. In our work, LRT plus systemic therapy was associated with improved survival compared with systemic therapy alone in selected patients. Particularly, patients younger than 65 years may be the potential subpopulation that can benefit from LRT with improved survival.

Locoregional Therapy for the Primary Tumour in Women with a De Novo Diagnosis of Metastatic Breast Cancer

The role of locoregional treatment (LRT) in the setting of metastatic breast cancer (MBC) is widely debated due to conflicting results on the impact on outcomes. This review provides a brief overview and evaluation of current evidence. The majority of retrospective studies suggest LRT provides some survival benefit, but it is not known exactly which subgroup of patients would benefit the most. The significant concerns about inherent biases associated with these studies make interpretation of results challenging. Recent data from prospective clinical trials are conflicting and suggest that adding LRT to treatment regimens makes no difference to health-related quality of life. Based on the limited high-quality evidence, there is uncertainty that LRT improves outcomes in patients with MBC, and it should not become standard clinical practice. Further prospective research focused on whether subsets of patients benefit from LRT is required.

Abstract PS1-42: Locoregional treatment in de novo metastatic breast cancer: An overview of the current evidence

Abstract Background: Patients presenting with de novo metastatic breast cancer (dnMBC) is considered incurable but treatable. Despite the advances in systemic therapies, the role of locoregional treatment (LRT, primary tumor surgery and/or radiotherapy) for dnMBC remains controversial. Aim: To review and discuss the present evidence of surgery- and radiation-based treatment strategies for dnMBC. Settings and design: A systematic review and meta-analysis of the literature were carried out. Methods: We did a systematic review and meta-analysis of observational studies and randomised controlled trials (RCTs) published from database inception to Feb 28, 2020, which reported on survival outcomes of LRT in patients with dnMBC. Studies were identified by searches in PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. The review and meta-analysis were conducted to assess the effect of LRT on overall survival (OS). Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, and subgroup analyses. All statistical analyses were performed with Stata 16.0. Findings: Data on 714 patients in 3 RCTs and 173476 patients in 39 observational studies were included. In total 174190 patients, 76711 patients (44.04 %) underwent LRT ± systemic therapy, and 97479 patients (55.96 %) received systemic therapy alone (STA). Observational data showed LRT significantly improved overall survival (HR=0.63; 95%CI, 0.57 to 0.69, P&amp;lt;0.001, I2=96.3%). The subgroup analysis found a favorable impact on survival in both patients undergoing surgery plus radiotherapy and surgery. However, the pooled outcomes of prospective trials suggested a 19.0% reduction in mortality which was not statistically significant (HR=0.81; 95% CI, 0.57 to 1.14, P=0.06, I2=64.4%). Interpretation: Due to the paucity of RCTs exploring LRT in patients with dnMBC, this was a meta-analysis which included retrospective and prospective data; both sets provide a complete picture of the effect. However, withstanding for retrospective bias, separate analyses was conducted to specifically examine the prospective trials. Findings from observational studies and RCTs associated with LRT and OS in these patients were inconsistent. Given the retrospective nature of observational studies, its results cannot be used as level I evidence to support LRT in patients with dnMBC. As level I evidence, prospective data suggest that the relationship between the LRT and survival benefit in these patients could not be causal. Although these trials have been criticized due to systemic therapy protocols which differ from standard modern treatments, they continue to provide important data. Ongoing well-designed prospective studies, including ECOG 2108 trial, are awaiting mature data. Conclusions: Based on the results of current level I evidence, LRT should not be part of routine clinical practice in patients with dnMBC but might be performed in specific patients. Key words: Locoregional treatment; De novo metastatic breast cancer; Systematic review; Meta-analysis Citation Format: Ren Chongxi. Locoregional treatment in de novo metastatic breast cancer: An overview of the current evidence [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 PS1-42.

The role of loco-regional treatment in long-term quality of life in de novo stage IV breast cancer patients: protocol MF07-01Q.

Since more solid evidence has emerged supporting the effectiveness of loco-regional treatment (LRT), clinicians consider LRT a treatment option for selected de novo stage IV breast cancer (BC) patients. This is the first report on long-term quality of life (QoL) in a cohort of patients who were randomized to receive either LRT and then systemic treatment (ST) or ST alone in the protocol MF07-01. We aimed to evaluate QoL in patients living at least 3years since randomization using scores from the SF-12 health survey. SF-12 (V2) forms were completed during visits of patients who were living 36months after the randomization. We first calculated PCS-12 (Physical Health Composite Scale) and MCS-12 (Mental Health Composite Scale) scores from de novo stage IV BC patients and compared them with the scores of patients diagnosed with stage I-III BC who lived more than 3years. Further, PCS-12 and MCS-12 scores were compared between the LRT and ST groups with de novo stage IV BC. Additionally, general health, physical functioning, role functioning, bodily pain, vitality, mental health, and social functioning were evaluated and compared between the groups. Considering age-related changes in QoL, we also compared PCS-12 and MCS-12 scores of patients below or above 55 and 65years of age. Responses to four additional questions (compare your physical health, mental health, daily activities, and energy currently vs. at diagnosis of BC) were recorded, considering cultural differences. There were 81 patients in this analysis; 68% of patients (n= 55) had LRT, and 32% (n= 26) received ST. General health was good or very good in 62% (n= 34) in the LRT group and 66% (n= 17) in the ST-only group (p= 0.63). Mean PCS-12 score was 40.8+1.6, and mean MCS-12 score was 43.4+2.0 (p= 0.34 and p= 0.54, respectively). PCS-12 and MCS-12 score difference was lower than that of the general Turkish population (PCS-12 = 49.3+12.8 and MCS-12 = 46.8+13.0) and stage I-III BC patients (PCS-12 = 51.1 ± 0.5, MCS-12 = 45.7 ± 0.6). PCS-12 and MCS-12 scores were similar between the LRT and ST-only groups in patients younger and older than 55 and 65, but QoL scores were much better in stage I-III BC patients younger than 65 when compared to the scores of those with de novo stage IV BC. Although treatment with or without LRT did not affect physical health, mental health, daily activities, and energy at 3years vs. at diagnosis of BC in de novo stage IV BC patients (p> 0.05), these variables were significantly better in stage I-III BC patients (p< 0.001). The current MF07-01Q study demonstrates that patient who had LRT has similar physical and mental health outcomes compared to ST only in a cohort of patients who lived longer than 3years. Trial registration This study is registered on clinicaltrials.gov with identifier number NCT00557986.

Oligometastatic colorectal cancer: prognosis, role of locoregional treatments and impact of first-line chemotherapy—a pooled analysis of TRIBE and TRIBE2 studies by Gruppo Oncologico del Nord Ovest

BackgroundOligometastatic disease (OMD) identifies tumours with limited metastatic spread. OMD definition is not univocal and no data from clinical trials are available about the prognostic effect of OMD in metastatic colorectal cancer (mCRC), the impact of locoregional treatments (LRTs) and the effect of chemotherapy intensification in these patients. The role of tumour burden (TB) in driving therapeutic choices is also debated. Patients and methodsWe performed a pooled analysis of phase III TRIBE and TRIBE2 studies comparing FOLFOXIRI/bevacizumab (bev) to doublets (FOLFOX or FOLFIRI)/bev. Patients were grouped in OMD versus non-OMD based on the European Society for Medical Oncology definition. Among patients with OMD, those with OMD/low TB were compared with all the others. ResultsOf 1187 patients enrolled, 1096 were classified as OMD (N = 312 [28%]) or non-OMD (N = 784 [72%]). Among patients with OMD, 126 (40%) were OMD/low TB. OMD was associated with longer progression-free survival (14.0 versus 10.1 months; p < 0.01) and overall survival (38.2 versus 22.0 months; p < 0.01). These results were confirmed in multivariable models. The benefit provided by FOLFOXIRI/bev compared with doublets/bev did not differ in accordance with OMD and TB (p for interaction >0.05). Patients with OMD underwent LRTs more frequently (p < 0.01) and those with OMD/low TB had higher chance to undergo LRTs after the first progression (p < 0.01). ConclusionsOMD is a positive prognostic factor in mCRC. The benefit from the upfront treatment intensification is independent of the metastatic spread extent and TB. LRTs should be highly considered in these patients, mainly during the first-line therapy but also at later stages of treatment history in selected cases.

Oligometastatic colorectal cancer: Prognostic implications of tumor load, role of locoregional treatments, and of first-line therapy intensification—A pooled analysis of TRIBE and TRIBE2 studies by GONO.

12 Background: According to the ESMO guidelines a metastatic spread involving up to 2 or occasionally 3 sites with 5 or sometimes more metastases (mts) is defined as oligometastatic disease (OMD) and the possibility to offer locoregional treatments (LRTs) should be carefully considered. Tumor load and treatment’s objective (cytoreduction vs disease control) are included among factors affecting the choice of the intensity of the upfront chemotherapy (CT). Nevertheless, no data from clinical trials adopting this definition are currently available, so that the prognostic effect of tumor load, the impact of LRTs and the magnitude of benefit from the CT-intensification in OMD remain unclear. Here we assess the effect of FOLFOXIRI/bev compared to doublets (FOLFOX or FOLFIRI)/bev and the impact of LRTs according to tumor load (OMD vs non-OMD) in a pooled analysis of two randomized phase III studies (TRIBE and TRIBE2). Methods: Subgroup analyses for ORR, PFS and OS were performed according to tumor load at baseline. OMD was defined as up to 5 mts, up to 3 mts in one organ, up to 3 affected organs, mts size ≤ 3 cm, absence of ascites and peritoneal, bone and central nervous system mts. Results: Among 1187 patients (pts) enrolled, 1158 were classifiable: 126 as OMD (11%) and 1032 as non-OMD (89%). Pts with OMD had longer PFS (14.3 vs 10.5 months (mos); p &lt; 0.01) and OS (44.3 vs 24.0 mos; p &lt; 0.01) compared with those with non-OMD. These results were confirmed in multivariable models (p &lt; 0.01). Also among pts who underwent LRTs with curative intent during first line (N = 202), those with OMD at baseline (N = 35) reported longer OS than those with non-OMD (59.6 vs 50.6 mos; p = 0.04). The benefit provided by FOLFOXIRI/bev compared to doublets/bev was confirmed in the OMD subgroup with no interaction effect between treatment arm and tumor load in terms of ORR, PFS and OS (p for interaction = 0.10, 0.58 and 0.23, respectively). Conclusions: OMD is confirmed as a positive prognostic factor and is associated with a higher magnitude of long-term benefit from LRTs than non-OMD. The positive impact of the intensification of the upfront CT is independent of tumor load.

Role of Locoregional Treatment in De Novo Stage IV Breast Cancer.

It is estimated that approximately 154000 women in the United States have stage IV breast cancer (BC). A subset of this group has metastatic disease at presentation, known as de novo stage IV disease. De novo stage IV BC accounts for approximately 6% of all BC diagnoses in the United States. Traditionally, stage IV BC patients are treated with primary systemic therapy with a palliative intent reserving possible locoregional treatment (LRT) as last resort. There has been a lot of interest in the role of LRT in de novo stage IV BC for the past decade with mixed conclusions. Although this review is not intended to be a comprehensive overview of all literature regarding this topic to date, we will review the recent findings in literature focusing on the studies with larger sample sizes to investigate the role of LRT in de novo stage IV BC.

Spatial distribution of malignant transformation in patients with low-grade glioma

BackgroundMalignant transformation represents the natural evolution of diffuse low-grade gliomas (LGG). This is a catastrophic event, causing neurocognitive symptoms, intensified treatment and premature death. However, little is known concerning the spatial distribution of malignant transformation in patients with LGG.Materials and methodsPatients histopathological diagnosed with LGG and subsequent radiological malignant transformation were identified from two different institutions. We evaluated the spatial distribution of malignant transformation with (1) visual inspection and (2) segmentations of longitudinal tumor volumes. In (1) a radiological transformation site < 2 cm from the tumor on preceding MRI was defined local transformation. In (2) overlap with pretreatment volume after importation into a common space was defined as local transformation. With a centroid model we explored if there were particular patterns of transformations within relevant subgroups.ResultsWe included 43 patients in the clinical evaluation, and 36 patients had MRIs scans available for longitudinal segmentations. Prior to malignant transformation, residual radiological tumor volumes were > 10 ml in 93% of patients. The transformation site was considered local in 91% of patients by clinical assessment. Patients treated with radiotherapy prior to transformation had somewhat lower rate of local transformations (83%). Based upon the segmentations, the transformation was local in 92%. We did not observe any particular pattern of transformations in examined molecular subgroups.ConclusionMalignant transformation occurs locally and within the T2w hyperintensities in most patients. Although LGG is an infiltrating disease, this data conceptually strengthens the role of loco-regional treatments in patients with LGG.

Role of Locoregional Treatment in Vulvar Cancer With Pelvic Lymph Node Metastases: Time to Reconsider FIGO Staging?

Vulvar cancer with pelvic nodal involvement is considered metastatic (M1) disease per AJCC staging. The role of definitive therapy and its resulting impact on survival have not been defined. Patients with pelvic lymph node-positive vulvar cancer diagnosed in 2009 through 2015 were evaluated from the National Cancer Database. Patients with known distant metastatic disease were excluded. Logistic regression was used to evaluate use of surgery and radiation therapy (RT). Overall survival (OS) was evaluated with log-rank test and Cox proportional hazards modeling (multivariate analysis [MVA]). A 2-month conditional landmark analysis was performed. A total of 1,304 women met the inclusion criteria. Median follow-up was 38 months for survivors. Chemotherapy, RT, and surgery were used in 54%, 74%, and 62% of patients, respectively. Surgery was associated with prolonged OS (hazard ratio [HR], 0.58; P<.001) but had multiple significant differences in baseline characteristics compared with nonsurgical patients. In patients managed nonsurgically, RT was associated with prolonged OS (HR, 0.66; P=.019) in MVA. In patients undergoing surgery, RT was associated with better OS (3-year OS, 55% vs 48%; P=.033). Factors predicting use of RT were identified. MVA revealed that RT was associated with prolonged OS (HR, 0.75; P=.004). In this cohort of women with vulvar cancer and positive pelvic lymph nodes, use of RT was associated with prolonged survival in those who did not undergo surgery. Surgery followed by adjuvant RT was associated with prolonged survival compared with surgery alone.

A prognostic scoring model for survival after locoregional therapy in de novo stage IV breast cancer.

The role of locoregional treatment (LRT) remains controversial in de novo stage IV breast cancer (BC). We sought to analyze the role of LRT and prognostic factors of overall survival (OS) in de novo stage IV BC patients treated with LRT utilizing the National Cancer Data Base (NCDB). The objective of the current study is to create and internally validate a prognostic scoring model to predict the long-term OS for de novo stage IV BC patients treated with LRT. We included de novo stage IV BC patients reported to NCDB between 2004 and 2015. Patients were divided into LRT and no-LRT subsets. We randomized LRT subset to training and validation cohorts. In the training cohort, a seventeen-point prognostic scoring system was developed based on the hazard ratios calculated using Cox-proportional method. We stratified both training and validation cohorts into two "groups" [group 1 (0-7 points) and group 2 (7-17 points)]. Kaplan-Meier method and log-rank test were used to compare OS between the two groups. Our prognostic score was validated internally by comparing the OS between the respective groups in both the training and validation cohorts. Among 67,978 patients, LRT subset (21,200) had better median OS as compared to that of no-LRT (45 vs. 24 months; p < 0.0001). The group 1 and group 2 in the training cohort showed a significant difference in the 3-year OS (p < 0.0001) (68 vs. 26%). On internal validation, comparable OS was seen between the respective groups in each cohort (p = 0.77). Our prognostic scoring system will help oncologists to predict the prognosis in de novo stage IV BC patients treated with LRT. Although firm treatment-related conclusions cannot be made due to the retrospective nature of the study, LRT appears to be associated with a better OS in specific subgroups.

Locoregional Treatment of the Primary Tumor Shows Survival Benefit in De Novo Stage IV Breast Cancer

Although systemic therapy is a mainstay of treatment for metastatic breast cancer, the role of locoregional treatment (LRT) of the primary tumor for an overall survival advantage is still unclear. The aim of this study was to assess the clinical outcomes of patients with de novo stage IV breast cancer after undergoing LRT of the primary site. From January 2006 to November 2013, a total of 245 patients diagnosed with de novo stage IV breast cancer at Yonsei University Health System were included. Among them, LRT of primary tumor (+ systemic therapy) was performed in 86 patients (35%) (Surgery only : n = 28, surgery + radiotherapy (RT) : n = 47, RT only : n = 11). The remaining 155 patients (63%) received systemic therapies (chemotherapy and/or hormone therapy), while 4 patients (2%) received no treatment. For surgery type, 87% (n = 66) received mastectomy, and 12% (n = 9) received breast-conserving surgery (BCS). Local recurrence-free survival (LRFS) and overall survival (OS) were investigated, and propensity score matching method was used to balance groups. The median follow-up duration was 40 months (Range, 13 days to 124 months). The 5-year LRFS and OS rates were 27% and 50%, respectively. Total of 188 patients (77%) experienced recurrence, while local recurrence rate was 45% (LRT group 12% vs. no LRT group 47%, p <0.001) and systemic recurrence rate was 95% (LRT group 69% vs. no LRT group 76%, p=0.248). Advanced T stage (T4), liver or brain metastasis, ≥5 metastatic sites, no hormone therapy, and LRT(-) were considered significant adverse factors for LRFS, while T4 stage, no hormone therapy, and LRT(-) were considered significant for OS. LRT group demonstrated favorable outcome (5-year LRFS: 55% and 5-year OS: 71%), especially when surgery was performed. Even after matching the baseline characteristics, survival rates were still significantly higher in LRT group than no LRT group (5-year LRFS 55% vs. 22%, p<0.001, 5-year OS 71% vs. 43%, p<0.001). Furthermore, LRT (especially surgery) was an important good prognostic factor in patients with <T4 stage tumors, no liver or brain metastasis, and <5 metastatic sites in subgroup analysis. For the type of surgery, BCS + RT was not inferior to other LRTs, although more patients with early stage tumors or ≤2 sites, without lung/liver/distant lymph node metastasis, were included. For the role of post-mastectomy RT, treatment results were higher (5-year LRFS 61% vs. 50%, OS 74% vs. 68%) with RT in selected T/N stage (≥N2, ≥T3, or T2N1) of patients. LRT including RT, together with systemic therapies, is an important option in selected de novo stage IV breast cancer patients, especially when the burden of the tumor is low. Furthermore, BCS + RT would be a possible substitute for mastectomy without compromising oncologic outcome in early stage metastatic breast cancer. Post-mastectomy RT should be re-evaluated in light of the advances in systemic therapy, with improving survival in stage IV disease.

Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial

The role of locoregional treatment in women with metastatic breast cancer at first presentation is unclear. Preclinical evidence suggests that such treatment might help the growth of metastatic disease, whereas many retrospective analyses in clinical cohorts have suggested a favourable effect of locoregional treatment in these patients. We aimed to compare the effect of locoregional treatment with no treatment on outcome in women with metastatic breast cancer at initial presentation. In this open-label, randomised controlled trial, we recruited previously untreated patients (≤65 years of age with an estimated remaining life expectancy of at least 1 year) presenting with de-novo metastatic breast cancer from Tata Memorial Centre, Mumbai, India. Patients were randomly assigned (1:1) to receive locoregional treatment directed at their primary breast tumour and axillary lymph nodes, or no locoregional treatment, by a computer-generated block randomisation sequence (block size of four). Randomisation was stratified by site of distant metastases, number of metastatic lesions, and hormone receptor status. Patients with resectable primary tumour in the breast that could be treated with endocrine therapy were randomly assigned upfront, whereas those with an unresectable primary tumour were planned for chemotherapy before randomisation. Of the patients who had chemotherapy before randomisation, we randomly assigned patients who had an objective tumour response after six to eight cycles of chemotherapy. The primary endpoint was overall survival analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT00193778. Between Feb 7, 2005, and Jan 18, 2013, of the 716 women presenting with de-novo metastatic breast cancer, we randomly assigned 350 patients: 173 to locoregional treatment and 177 to no locoregional treatment. At data cut-off of Nov 1, 2013, median follow-up was 23 months (IQR 12·2-38·7) with 235 deaths (locoregional treatment n=118, no locoregional treatment n=117). Median overall survival was 19·2 months (95% CI 15·98-22·46) in the locoregional treatment group and 20·5 months (16·96-23·98) in the no-locoregional treatment group (HR 1·04, 95% CI 0·81-1·34; p=0·79), and the corresponding 2-year overall survival was 41·9% (95% CI 33·9-49·7) in the locoregional treatment group and 43·0% (35·2-50·8) in the no locoregional treatment group. The only adverse event noted was wound infection related to surgery in one patient in the locoregional treatment group. There is no evidence to suggest that locoregional treatment of the primary tumour affects overall survival in patients with metastatic breast cancer at initial presentation who have responded to front-line chemotherapy, and this procedure should not be part of routine practice.

Recurrence of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: Is there a role for locoregional treatment?

329 Background: The majority of patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma (PDA) will face recurrence. While other types of metastatic tumors are often treated with loco-regional therapy, this approach is rarely applied to metastatic PDA. We examined recurrence patterns of PDA and the potential application of loco-regional treatment. Methods: Evaluation of a prospective database of patients undergoing pancreaticoduodenctomy at an academic institution by a single surgeon. Patients: Pancreaticoduodenectomy for PDA was performed in 95 patients between 2002 and 2012. Margin status was R0 in 88 (93%) and R1 in the remainder. Results: Overall median survival was 27 months and 1 and 3 year survival was 68% and 41%. Known recurrence occurred in 44 of 64 patients (69%) at a median of 20.9 months, while the status of 31 patients was unknown. The most common site of initial recurrence was liver (n=19, median 9.2 months post-surgery), followed by local recurrence (n=15; median 18.7 months) and lung (n=5; median 5.2 months). Patients with R0 margin vs R1 recurred at a median 21 vs 5 months. In our series, 6 patients (5/6 treated in the last 2 years) underwent loco-regional treatment of recurrent disease, including liver resection (n=2), stereotactic radiotherapy (n=2), hepatic ablation (n=1) or radioembolization (n=1). All 6 patients treated with loco-regional therapy are alive at a median of 15.6 months after recurrence and a median of 25.3 months since initial surgery. Conclusions: The initial site of recurrent PDA after pancreaticoduodenectomy is usually liver, and the major risk factor for recurrence is the margin status at resection. Loco-regional modalities for the treatment of recurrent PDA hold promise in select patients. The tendency to utilize loco-regional therapy for recurrent PDA is increasing and warrants continued consideration.

Abstract S2-02: Surgical removal of primary tumor and axillary lymph nodes in women with metastatic breast cancer at first presentation: A randomized controlled trial

Abstract BACKGROUND: The role of loco-regional treatment, in women with metastatic breast cancer (MBC) at first presentation, is debatable. Preclinical evidence suggests that such treatment may facilitate growth of metastatic disease. On the other hand, many retrospective analyses in clinical cohorts have suggested favorable impact of loco-regional treatment in these patients. However, these results are likely to be influenced by selection bias. We conducted a prospective randomized controlled trial to assess the impact of loco-regional treatment on outcome in women with metastatic breast cancer at initial diagnosis. [NCT00193778] METHODS: Women with metastatic breast cancer at initial diagnosis and planned to be treated with anthracycline based chemotherapy (CT) were registered for the study. Those who had objective tumor response after 6 cycles of CT were randomized to one of the following arms: ‘LRT’ (loco-regional treatment) or ‘No-LRT’ (no loco-regional treatment). Patients were stratified by endocrine receptor (ER) status, site of metastases (visceral Vs bone Vs both) and number of metastatic lesions (&amp;lt; 3 Vs &amp;gt; 3). Women in LRT arm received surgery (breast conservation or mastectomy plus axillary lymph node dissection) followed by radiation therapy (RT), as per standard adjuvant guidelines. Women in No-LRT arm were followed up without surgery and RT. Both groups received standard endocrine therapy after last cycle of chemotherapy, if indicated. They were regularly followed up with clinical evaluation. Appropriate imaging was performed within 6 months after randomization and thereafter as clinically indicated. The primary endpoint was overall survival (OS). RESULTS: Between Feb 2005 and Jan 2013, 350 women were randomized, 173 in LRT and 177 in No-LRT arm. The data cutoff was in May 2013. The two arms were balanced with respect to age, clinical tumor size, HER2 receptor status and stratification factors. Eight (5.8%) patients in the LRT arm did not undergo loco-regional therapy while 19 (10.7%) patients in the No-LRT arm underwent surgical removal of primary tumor because of palliative reasons. The median follow-up was 17 months and 218 deaths (LRT = 111/173, No-LRT = 107/177) had been recorded at data cutoff. The median OS in LRT and No-LRT arms were 18.8 and 20.5 months (HR = 1.07, 95%CI = 0.82-1.40, p = 0.60) and the corresponding 2-year OS were 40.8% and 43.3%, respectively. After adjusting for age, ER status, HER2 receptor status, site of metastases and number of metastatic lesions in a Cox regression model, there was no significant difference in OS between LRT and No-LRT arms (HR = 1.00, 95%CI = 0.76-1.33, p = 0.98). There was no interaction between the effect of LRT and covariates in the model. CONCLUSIONS: Loco-regional treatment of the primary tumor and axillary nodes has no impact on OS in patients diagnosed with MBC at initial presentation, who have responded to frontline chemotherapy. We were unable to identify any subgroups that are likely to benefit from LRT. Such treatment should be reserved for women who need it for palliative reasons. Detailed analysis will be presented at the Symposium. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S2-02.

Recurrence of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: Is there a role for loco-regional treatment?

Recurrence of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: Is there a role for loco-regional treatment?