Locoregional Treatment In Patients Research Articles

Locoregional Treatment in Patients With Metastatic Cervical Cancer: Benefit of Dose Escalation Strategies

The objective of this work was to examine the benefit of an intensive locoregional treatment including an image guided adaptive brachytherapy (IGABT) among patients with cervical cancer and extrapelvic extension. Medical records of consecutive patients with a metastatic cervical cancer and receiving external beam radiation therapy and IGABT boost in Gustave Roussy Institute as part of their first line of treatment were examined. Depending on tumor sites, patients received pelvic ± para-aortic external beam radiation therapy. For those with visceral or supradiaphragmatic lymph node metastases, chemoradiation was delivered after usually 3 cycles of chemotherapy. All patients received a brachytherapy boost, guided by magnetic resonance imaging and aimed at increasing the dose to the high-risk clinical target volume (CTVHR). Local control (LC), patient overall survival (OS), progression-free survival, and radiation therapy-related side effects were examined, and prognostic factors were searched. One hundred sixty-four patients were included; 76.2% had para-aortic lymph node extension without distant metastasis (N2) and 23.8% had distant metastatic sites (M1). There was not a statistically significant difference in survival between both groups. With a median follow-up of 36 months, OS, progression-free survival, and LC at 3 years were 55.5% (95% CI, 48%-64%), 40.6% (95% CI, 38%-54%), and 90% (95% CI, 85%-96%), respectively. In multivariate analysis, a D90CTVHR dose ≥80 Gy was significant for better OS (hazard ratio, 0.96; 95% CI, 0.94-0.98; P < .001). Most toxicities were mild to moderate, with 2% grade 3 late urinary toxicity, 7% late grade 2 vaginal sequelae, and 1 grade 3 proctitis. During follow-up, rectovaginal fistula occurred in 2 patients without local relapse. IGABT permits dose escalation and high LC rates for patients with cervical cancer and extrapelvic extension. Dose/effect relationships for survival were shown. Because of high frequency of distant events, systemic intensification should be tested more specifically among these patients.

¿Está indicada la irradiación del tumor primario en el estadio IV?

De-novo metastatic breast cancer is a rare entity, occurring in 3–10% of cases. The most common treatment for these patients is systemic therapy (chemotherapy, hormonal therapy, targeted therapies, and combinations of these). The subgroup of patients with oligometastatic disease and low systemic disease burden may benefit more from adding a locoregional treatment. This literature review aims to analyze the benefits and disadvantages of locoregional treatment in patients with de-novo oligometastatic breast cancer. Retrospective series report that this subgroup of patients may benefit from locoregional treatment, despite presenting with metastatic disease, by improving overall survival and local control. Additionally, several retrospective series have shown that locoregional treatment with surgery, surgery and adjuvant radiotherapy, or exclusive radiotherapy present similar results in local control. Therefore, exclusive radiotherapy may be a viable alternative in these patients. In recent years, attempts have been made to demonstrate the trend of retrospective series in prospective trials. These studies have shown great heterogeneity. Some with positive results in improving overall survival and others with negative results, but not statistically significant. The main limitation of retrospective series is the selection bias, which could explain the differences in the results obtained. For this reason, locoregional treatment in these patients should be approached by multidisciplinary teams on an individualized basis, with greater consideration for oligometastatic patients.

MRI-based radiomics model and nomogram for predicting the outcome of locoregional treatment in patients with hepatocellular carcinoma

BackgroundPrediction of locoregional treatment response is important for further therapeutic strategy in patients with hepatocellular carcinoma. This study aimed to investigate the role of MRI-based radiomics and nomogram for predicting the outcome of locoregional treatment in patients with hepatocellular carcinoma.MethodsThe initial postoperative MRI after locoregional treatment in 100 patients with hepatocellular carcinoma was retrospectively analysed. The outcome was evaluated according to mRECIST at 6 months. We delineated the tumour volume of interest on arterial phase, portal venous phase and T2WI. The radiomics features were selected by using the independent sample t test or nonparametric Mann‒Whitney U test and the least absolute shrinkage and selection operator. The clinical variables were selected by using univariate analysis and multivariate analysis. The radiomics model and combined model were constructed via multivariate logistic regression analysis. A nomogram was constructed that incorporated the Rad score and selected clinical variables.ResultsFifty patients had an objective response, and fifty patients had a nonresponse. Nine radiomics features in the arterial phase were selected, but none of the portal venous phase or T2WI radiomics features were predictive of the treatment response. The best radiomics model showed an AUC of 0.833. Two clinical variables (hCRP and therapy method) were selected. The AUC of the combined model was 0.867. There was no significant difference in the AUC between the combined model and the best radiomics model (P = 0.573). Decision curve analysis demonstrated the nomogram has satisfactory predictive value.ConclusionsMRI-based radiomics analysis may serve as a promising and noninvasive tool to predict outcome of locoregional treatment in HCC patients, which will facilitate the individualized follow-up and further therapeutic strategies guidance.

Neoadjuvant and Adjuvant Systemic Therapies in Loco-Regional Treatments for Hepatocellular Carcinoma: Are We at the Dawn of a New Era?

Despite maximizing techniques and patient selection, liver resection and ablation for HCC are still associated with high rates of recurrence. To date, HCC is the only cancer with no proven adjuvant or neoadjuvant therapy used in association to potentially curative treatment. Perioperative combination treatments are urgently needed to reduce recurrence rates and improve overall survival. Immunotherapy has demonstrated encouraging results in the setting of adjuvant and neoadjuvant treatments for non-hepatic malignancies. Conclusive data are not yet available in the context of liver neoplasms. However, growing evidence suggests that immunotherapy, and in particular immune checkpoint inhibitors, could represent the cornerstone of an epochal change in the treatment of HCC, improving recurrence rates and overall survival through combination treatments. Furthermore, the identification of predictive biomarkers of treatment response could drive the management of HCC into the era of a precision medicine. The purpose of this review is to analyze the state of the art in the setting of adjuvant and neoadjuvant therapies for HCC in association with loco-regional treatments in patients not eligible for liver transplantation and to hypothesize future scenarios.

Prognostic biomarkers in and selection of surgical patients with hepatocellular carcinoma.

Prognostic biomarkers in and selection of surgical patients with hepatocellular carcinoma.

The Role of Primary Surgery in De Novo Metastatic Breast Carcinoma.

Approximately 6-10% of all breast carcinoma is metastatic at diagnosis, termed de novo metastatic breast carcinoma (dnMBC). Systemic therapy remains the first line of treatment in dnMBC, but there is growing evidence that adjuvant locoregional treatment (LRT) of the primary tumor increases progression-free and overall survival (OS). Although selection bias may exist, real-world data from nearly half a million patients show that patients are undergoing primary tumor removal because of the survival benefit. The main question for the advocates for LRT in this patient population is not whether primary surgery is beneficial in dnMBC patients, but rather who is a good candidate for it. Oligometastatic disease (OMD) is a distinct subset of dnMBC that affects a limited number of organs. A better OS can be achieved with LRT in breast cancer patients, especially in those with OMD, bone only, or favorable subtypes. Though there is currently no consensus among breast care specialists on how to treat dnMBC patients, primary surgery for dnMBC should be taken into consideration for a subset of patients following an extensive multidisciplinary discussion.

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.

Abstract MS2-2: Can genomic risk be used to tailor radiation therapy?

Abstract Radiation therapy (RT) reduces any-recurrence risks and breast cancer related mortality after mastectomy for node positive disease and after breast conserving surgery. The relative risk reduction is partially independent from patient, tumour and treatment related factors, while the absolute benefit depends to a large extent on the absolute risks without RT. Of note is an important interaction between systemic and locoregional treatments. The continuous improvements in outcomes after breast cancer diagnosis led to a quest for treatment de-escalation. In this, the decreased extent of axillary surgery led to an increased proportion of patients eligible for nodal RT. While most data concerning prognostic and predictive value of genomic data is related to metastatic disease and to systemic treatments, more recently also RT evolves from the “one-size fits all” to a much more “tailor-made approach”. Optimally, current tailoring of locoregional treatments involves decreasing volumes and extensiveness, maintaining treatment focus mainly at high-risk areas, while de-escalating treatment to low-risk areas. The multidisciplinary aspects call for integration of predictive and prognostic tools and looking into optimally combining less of both systemic and locoregional treatments to optimise tumour control while sparing normal tissues.Not only distant but also locoregional recurrences risks depend on the intrinsic tumour phenotype, which can be expressed by the genomic profile. Several post-hoc evaluations of datasets derived from prospective studies showed that the genomic profile score can assist in predicting locoregional recurrence risks (and thereby indirectly the possible benefits of RT) or, with more scarce data, the interaction between the genomically predicted risk and the risk reduction obtained by RT. Currently, several trials are evaluating further de-escalation of locoregional treatments in patients with favourable intrinsic tumour types. Of interest in patients with intrinsic high-risk tumour types is the response to primary systemic therapy, with trials ongoing to de-escalate both axillary and local management after a favourable tumour response. Preclinical data suggests that immunogenic cell death, mediated through activation of tumour infiltrating lymphocytes (TIL’s) might contribute to the efficacy of RT. However, high TIL’s levels are seen in only 10% of breast cancers, more commonly in basal-like- and Her2-enriched subtypes. The mechanism behind this association with TIL’s remain unclear. Of particular interest seems the recently validated genomic adjusted radiation dose (GARD), aimed to personalise RT dose prescription based on the biological effect rather than merely on physical dose. GARD combines a gene expression assay, assuming pan-tissue biological networks of radiosensitivity and radioresistance, with a linear quadratic model for estimation of total radiation dose in tissues. Up to now, clinical utility remains to be confirmed, preferably by integrating GARD in prospective clinical research. Summary: at present no validated biomarkers can reliably predict the benefit derived from RT at the individual patient’s level, with current evidence not yet robust enough to guide decision making. Available data are mainly based on retrospective analyses of older trials, necessitating prospective validation in contemporary cohorts. Research is ongoing to personalise RT using biological factors including gene expression profiles. Projects to identify genetic variants associated with susceptibility to radiotoxicity are required to proceed to a more personalised indication/target volume/dose approach for our patients. In the meantime, we should avoid jeopardising the impressive improvements obtained in the outcomes after breast cancer diagnosis by precipitated treatment de-escalating based on beliefs and assumptions. Citation Format: PMP Poortmans. Can genomic risk be used to tailor radiation therapy? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr MS2-2.

Abstract P3-19-13: Radiation oncology treatment planning in breast cancer patients undergoing lumpectomy with and without oncoplastic reconstruction

Abstract Background Breast conserving surgery (BCS) followed by whole breast irradiation with a tumor bed boost is a common approach for locoregional treatment of patients with breast cancer. While tumor bed boost improves local control, it is also associated with increased risk of fibrosis and fat necrosis. Oncoplastic reconstruction is being increasingly employed to improve cosmesis and symmetry with the contralateral breast following partial mastectomy. The extensive rearrangement of breast tissue during oncoplastic reconstruction has the potential to increase tumor bed volume, thereby increasing the volume of breast receiving a higher dose of radiation. In this study, we aimed to elucidate the current rise in use of oncoplastic reconstruction following breast-conserving surgery in patients with breast cancer and its impact on the volume of tumor bed as contoured by attending radiation oncologists at the time of radiation treatment planning. Methods A retrospective chart review of 331 women, who underwent breast conserving surgery at our institution between Jan 2020 and March 2021 for treatment of breast cancer was conducted. Patient demographics and tumor characteristics, including clinical and pathological staging, tumor receptor status, and tumor histology were recorded. Treatment-related information such as type of oncoplastic reconstruction where applicable, receipt of systemic therapy, dose and fractionation of radiation therapy, treatment technique and volume of tumor bed defined at the time of radiation treatment planning were collected. Results The median age of the cohort was 61, and 54.7% of patients received oncoplastic reconstruction. A plastic surgeon was involved in reconstruction in 22.8% of patients. Complex tissue advancement closure was the most common oncoplastic reconstruction employed in this cohort. A two-tailed T-test assuming unequal variances demonstrated that oncoplastic reconstruction was associated with a contoured tumor bed that was on average almost 10 mL larger (35.5 vs. 26.6 mL, p &amp;lt; 0.02). Conclusion Over half of patients receiving breast conserving surgery at our institution underwent oncoplastic reconstruction. The rate of oncoplastic reconstruction in this cohort was significantly higher than historic rates reported in the literature, likely reflecting an exponential growth in adoption of this approach in the United States. Use of oncoplastic reconstruction was associated with larger tumor bed volume at the time of radiation treatment. Although tumor bed boost improves local control, it also increases risk of fibrosis and fat necrosis. Therefore, further studies are needed to determine if larger volume of tumor bed irradiated in patients receiving oncoplastic reconstruction is associated with decline in long term cosmetic outcomes due to fibrosis and fat necrosis. Increased multi-disciplinary communication and collaboration between surgical oncologists, reconstructive surgeons and radiation oncologists is necessary to address the competing interests between breast reconstruction and irradiation following breast conserving surgery in patients undergoing breast conserving surgery for treatment of breast cancer. Citation Format: Brian Ko-Hung Lue, Ev Kakadiaris, Prasanna Alluri, M.D. Radiation oncology treatment planning in breast cancer patients undergoing lumpectomy with and without oncoplastic reconstruction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-13.

The role of surgery on locoregional treatment of patients with breast cancer newly diagnosed with ipsilateral supraclavicular lymph node metastasis.

Radiotherapy is a practical locoregional treatment approach for women with breast cancer who show ipsilateral supraclavicular lymph node metastasis (ISLNM) on diagnosis. However, there is controversy around the role of supraclavicular lymph node dissection. Therefore, we aimed to study the significance of supraclavicular surgery based on radiotherapy. We retrospectively reviewed the data of 142 patients with breast cancer who presented with isolated ISLNM and received radiotherapy between the years 2000 and 2016. We also defined the effect of surgery on locoregional treatment of these patients by analyzing the prognostic factors for recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). We observed that, of the 142 patients, 104 who received radiotherapy underwent supraclavicular lymph node dissection. Also, among the study group, the progesterone receptor (PR) status (P = 0.044) and the number of axillary lymph nodes (ALNs) involved (P = 0.002) were significant independent predictors of RFS. Also, tumor size (P = 0.007), PR (P < 0.001), and number of ALNs (P < 0.001) were independent predictors of DMFS and were statistically significant. Also, PR was an independent prognostic factor of OS (P = 0.033), whereas the supraclavicular surgery was not an independent prognostic factor for RFS, DMFS, and OS. Furthermore, our study focused on 92 patients with negative estrogen receptors (ERs). The result showed that supraclavicular surgery was statistically significant for RFS (P = 0.023); no significant differences in DMFS and OS were found between patients who received supraclavicular surgery and those who did not. Radiotherapy may be the primary locoregional treatment approach for patients with breast cancer who present with newly diagnosed ISLNM. Additionally, supraclavicular surgery may be more appropriate for patients with negative ER who received radiotherapy.

Hepatic Artery Infusion Chemotherapy Using Fluorouracil, Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score–Matching Analysis

PurposeTo compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with a modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) regimen with that of transarterial chemoembolization as a locoregional treatment for patients with locally advanced hepatocellular carcinoma (HCC). MethodsThis retrospective study included adult patients with locally advanced HCC who received first-line treatment with either HAIC-mFOLFOX or conventional transarterial chemoembolization monotherapy from January 2015 to December 2016. The outcomes, including tumor response rates, evaluated via imaging assessment using the modified response evaluation criteria in solid tumors; overall survival; progression-free survival; and safety, were compared. The propensity score–matching methodology was used to reduce the influence of confounding factors on the outcomes. ResultsThe study included 131 patients with locally advanced HCC who underwent transarterial chemoembolization and 101 who received HAIC-mFOLFOX as initial treatment. After propensity score matching (n = 67 in each group), patients who received HAIC-mFOLFOX had a higher objective response rate (43.3% vs 13.4%, P = .001), longer median overall survival (13.9 vs 6.0 months, P < .001), and longer median progression-free survival (6.4 vs 2.8 months, P = .001) than those who underwent transarterial chemoembolization. The survival benefit with HAIC-mFOLFOX was strengthened in patients with HCC with vascular invasion (hazard ratio: 0.379; 95% confidence interval: 0.237–0.607). HAIC-mFOLFOX was associated with lower incidences of severe adverse events (8.9% vs 22.9%) and liver toxicity than transarterial chemoembolization. ConclusionsCompared with transarterial chemoembolization, HAIC-mFOLFOX is a potentially safer and more effective locoregional therapy for patients with locally advanced HCC.

An observational retrospective analysis of the main metastatic site and corresponding locoregional treatment as a prognostic factor in metastatic gastric cancer.

Despite novel drugs, the prognosis for patients with metastatic gastric cancer remains poor. In rare instances, locoregional therapies are used in addition to standard chemotherapy in patients with oligometastatic involvement. This type of approach has not been supported by solid published evidence. The aim of the present retrospective study was to assess the prognostic impact of factors such as metastatic site, tumour histology and locoregional treatment in patients with metastatic gastric cancer. A total of 184 patients with metastatic gastric or gastroesophageal junction adenocarcinoma who received at least one line of palliative therapy with doublet or triplet chemotherapy were enrolled in the current analysis. Median overall survival (OS) was 8.32 months (95% CI, 7.02–9.41) and median progression-free survival (PFS) was 4.16 months (95% CI, 3.24–5.08). Lung metastases vs. other sites of metastatic involvement [hazard ratio (HR), 0.27; P=0.0133] and intestinal histology (HR, 0.48; P=0.08) were significantly associated with an improved OS. Improved PFS was also observed (HR, 0.49; P=0.10 and HR, 0.72; P=0.08 for lung metastases and intestinal histology, respectively). Second line chemotherapy and locoregional treatment of metastases (surgery or radiotherapy) were associated with improved OS (HR, 0.52; P<0.0001 and HR, 0.35; P<0.0001, respectively). Multivariate analysis confirmed an independent prognostic role for OS only for locoregional treatment, second line treatment and intestinal histology. The present results suggested that the presence of lung metastases alone was not a relevant prognostic factor and was influenced by the availability of further lines of treatment or by locoregional treatments. Locoregional treatments in patients with oligometastatic disease should be offered as they allow prolonged survival in patients with otherwise relatively short life expectancy.

Systemic therapy with a loco-regional treatment in patients with locally advanced pancreatic cancer: The SMART study.

TPS445 Background: Pancreatic cancer is a major cause of cancer-related death. About 40% of patients with pancreatic cancer present with locally advanced disease and are not candidates for curative surgery. Most patients are treated with chemotherapy with a limited life expectancy. The role of local treatment such as radiation is not well defined. Other conventional ablative therapies, such as thermal or cryoablation have limited role due to the risk of collateral damage to the adjacent structures. Irreversible electroporation (IRE) is a novel non-thermal ablation technology that does not cause injury to nearby blood vessels, ducts, and bowel and has the potential to provide longer disease control and thereby better overall survival. We hypothesized that addition of IRE to combination chemotherapy in patients with locally advanced pancreatic cancer will improve their outcomes, and patients with undetectable 12-week post IRE circulating tumor cell DNA will have better prognoses. Methods: It is a prospective, multicenter, single-arm phase II study. The primary objective is to determine 12-month PFS rate of patients with locally advanced pancreatic cancer who are treated with combination chemotherapy and IRE. Secondary objectives include identification of prognostic and predictive biomarkers, 24-months survival rate, quality of life of subjects, as well as cost-effectiveness and complication rates of IRE. Based on the assumption that treatment with IRE and chemotherapy would result in doubling of PFS versus chemotherapy alone a sample of n = 27 of patients with locally advanced pancreatic adenocarcinoma is estimated. Eligible patients will be recruited at the two major cancer centers in Saskatchewan. All IRE-eligible patients will receive 12 weeks of induction combination chemotherapy and will undergo IRE if there is no disease progression. An additional 12 weeks of chemotherapy will be recommended. Patients who are not eligible for IRE will receive chemotherapy at the discretion of treating oncologist until disease progression or until they become eligible for IRE. Circulating tumor DNA and a panel of genes will be examined using next-generation sequencing for their correlation with prognosis. Quality of life will be assessed, and cost-effectiveness analysis of IRE will be performed.The results of this study will be used to develop a future multicenter, national phase III trial. Clinical trial information: NCT04276857.

Diagnosis and locoregional treatment of patients with breast cancer during the COVID-19 pandemic

We are facing a pandemic that is going to affect a significant part of the population. At the end of April in the world there are about 3,000,000 cases, with 205,000 deaths and 860,000 patients recovered.The response to this pandemic has in many cases led to a significant change in the daily work of caring for cancer patients, the good results of which depend largely on time-adjusted protocols and multidisciplinary treatments.We present a review of local, surgical and radiotherapy treatment together with authors’ recommendations made from personal experience on ways to act in the diagnosis and surgical treatment of breast cancer during the COVID-19 pandemic.The multidisciplinary Breast Committees must continue to meet weekly in videoconference format. All surgical actions and irradiations must be carried out with maximum safety for both the patients and the participating teams. Hypofractionation in radiation therapy should be the standard treatment. Sometimes it is recommended to apply a primary systemic treatment or even a primary irradiation. Great coordination between the surgical and oncology teams, both medical and radiotherapeutic, is essential.

Systemic Therapy With a Loco-regional Treatment in Patients With Locally Advanced Pancreatic Cancer

Systemic Therapy With a Loco-regional Treatment in Patients With Locally Advanced Pancreatic Cancer

Abstract P1-20-01: Primary surgery in patients with de novo stage IV BC; finalizing the protocol MF07-01 randomized clinical trial

Abstract Background. The MF07-01 trial is a multicenter randomized study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone in de novo Stage IV breast cancer (BC) patients. Aim: To evaluate and finalize the survival data of LRT in patients with the diagnosis of de novo Stage IV BC. Methods. At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. Continuous and categorical variable differences between LRT and ST groups were analyzed using t-test and Chi-square test, respectively. Overall survival (OS) and 5-year survival rates were compared using Kaplan-Meier log-rank tests. Univariate and multivariate Cox models were used to estimate hazard ratios, and logistic regession model used to estimate odds ratio. Results. During more than 10 years follow-up, 23% of patients in LRT group and 8% of patients in ST group were alive. Median survival was 46 months for LRT (n=134) and 35 months for ST (n=131) [HR:0.71, 95%CI;0.59-0.86, p=0.0004]. Solitary bone metastasis patients’ median survival was 14 months longer in LRT group comparing ST group [HR:0.55, 95%CI; 0.35-0.86, p=0.008]; 16% of solitary bone metastasis patients in the LRT group were alive, but all patients died in the ST group. Patients younger than 55 lived longer compared the patients older than 55 [HR:0.67, 95%CI; 0.52-0.87, p=0.002], and 26% of hormone receptor positive patients were still alive in the LRT group comparing 10% in the ST group [HR:0.71, 95%CI; 0.58-0.88, p=0.002]. Regarding the patients who lived at least 5 years since randomization, LRT (p=0.003), hormone receptor positivity (p=0.004), Triple negative status (p=0.02), hormonotherapy (p=0.0001), bisphosphonates usage (p=0.03), and 2 or more organ metastases (p=0.004) were associated with OS in univariant analyses. However, in the multivariate model with significant baseline and clinical characteristics only LRT [OR= 1.58, p=0.03] was found to be significantly related with over 5 years of survival. Conclusion. In the current analysis, patients at the diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 58% higher chance to live at least 5 years compared to the patients who received only ST. Longer follow-up of the study discloses that LRT should be presented to patients when discussing treatment options. ClinicalTrials.gov identifier number is NCT00557986 Citation Format: Atilla Soran, Vahit Ozmen, Serdar Ozbas, Hasan Karanlik, Mahmut Muslumanoglu, Abdullah Igci, Zafer Canturk, Zafer Utkan, Cihangir Ozaslan, Turkkan Evrensel, Cihan Uras, Erol Aksaz, Aykut Soyder, Umit Ugurlu, Cavit Col, Neslihan Cabioglu, Ergun Erdem, Gunay Gurleyik, Efe Sezgin. Primary surgery in patients with de novo stage IV BC; finalizing the protocol MF07-01 randomized clinical trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-01.

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.

310PD - The importance of primary surgery in patients with de novo stage IV BC surviving at least 5 years: Protocol MF07-01 randomized clinical trial

BackgroundThe MF07-01 trial is a multicenter randomized study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone in de novo stage IV breast cancer (BC) patients. The aim of this study is to evaluate the importance of LRT in patients who lived at least 5 years after the diagnosis of de novo Stage IV BC. MethodsAt initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. Continuous and categorical variable differences between LRT and ST groups were analyzed using t-test and Chi-square test, respectively. Overall survival (OS) and 5-year survival rates were compared using Kaplan-Meier log-rank tests. Univariate and multivariate Cox models were used to estimate hazard ratios. ResultsDuring 124 months of follow-up, 26% of patients in LRT group and 11% of patients in ST group remained alive. Median survival was 46 months for LRT (n=134) and 35.5 months for ST (n=132) [HR:0.65, 95%CI;0.49-0.85, p=0.002]. Solitary bone metastasis patients’ median survival was 14.5 months longer in the LRT group compared with the ST group [HR:0.53, 95%CI; 0.29-0.98, p=0.04]; 22% of solitary bone metastasis patients in the LRT group and 5% in the ST group were alive. Regarding the patients who lived at least 5 years since randomization, LRT (p=0.004), hormone receptor positivity (p=0.007), hormonotherapy (p=0.0001), bisphosphonates usage (p=0.02), T2 tumor (p=0.0008) and 2 or more organ metastases (p=0.007) were associated with OS in univariate analysis, and in a multivariate Cox proportional model with a significant baseline and clinical characteristics, LRT [OR=1.75, p=0.05)], bisphosphonates usage [OR=1.93, p=0.05), T2 tumor [OR=3.5, p=0.003), and 2 or more organ metastases [OR=0.48, p=0.03] were found to be significantly related with OS. ConclusionsIn the current analysis, patients at the diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 75% higher chance to live at least 5 years compared with the patients who received only ST. Longer follow-up of the study discloses that LRT should be presented to the patient when discussing treatment options. Clinical trial identificationNCT00557986. Legal entity responsible for the studyTurkish Federation of Breast Diseases Societies. FundingTurkish Federation of Breast Diseases Societies. DisclosureAll authors have declared no conflicts of interest.

EUS-guided radiofrequency ablation as an alternative to surgery for pancreatic neuroendocrine neoplasms: Who should we treat?

Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors, but their incidental diagnosis has significantly increased due to the widespread use of imaging studies. Therefore, most PanNENs are now diagnosed when completely asymptomatic and in early stages. PanNENs are classified according to their grade (Ki-67 index) and can be functional (F-) or nonfunctional (NF-) depending on the presence or absence of a clinical, hormonal hypersecretion syndrome. The mainstay treatment of PanNENs is a surgery that is mostly curative but also associated with significant short- and long-term adverse events. Therefore, less invasive alternative locoregional treatment modalities are warranted. Recently, few case reports and two case series have described EUS-guided radiofrequency ablation (EUS-RFA) for the treatment of patients with both F-PanNENs and NF-PanNENs. If for F-PanNENs EUS-RFA can very easily become the standard of care, for NF-PanNENEs it is still controversial how to select patients for EUS-RFA. A balance between overtreatment (i.e., RFA/surgery in patients who will not progress) and undertreatment (locoregional treatments in patients with undetected metastases) needs to be found based on solid data. The decision should also take into account patients’ comorbidity and risk of postoperative death, life expectancy, tumor location, risk of postoperative fistula and postoperative morbidity, and risk of long-term exocrine and/or endocrine insufficiency. To answer the important question on which a patient should be treated with EUS-RFA, properly designed studies to evaluate the efficacy of this treatment in large cohorts of patients with NF-PanNENs and to establish prognostic factors associated with treatment response are urgently needed.

Management of Occult Breast Cancer with Axillary Involvement

Occult breast cancer (OBC), which is defined as clinically recognizable axillary metastatic carcinoma from an undetectable primary breast tumor, accounts for less than 1% of all patients who present with breast cancer (BC). Although criticized for high false positive rate (FPR) in routine BC diagnosis, the role of magnetic resonance imaging (MRI) is crucial in the diagnosis of OBC. The standard treatment for OBC, initially, was blind modified radical mastectomy, but one third of patients who undergo blind mastectomy, will have no histopathological findings of carcinoma. Current evidence supports the use of whole breast radiotherapy (WBRT) and axillary nodes clearance (ANC) as the locoregional treatment for patients with OBC. Management of the axilla does not differ from that of patients with BC with clinically palpable axillary lymph nodes (LNs) and ANC, which remains the gold standard, should be used for staging and loco-regional control. Neo-adjuvant chemotherapy (NACT) could reduce ANC by 43%, and for patients who undergo NACT with complete radiological response, a more conservative surgical approach, with a minimum of 3 sentinel lymph node biopsies (SLNBs), together with targeted dissection of the involved LNs could be considered as an option. This offers adequate staging and loco-regional control, combined with significantly less comorbidities than ANC. Overall, the prognosis of OBC is equal to or better than that of other BCs with metastasis to the axillary LNs. Progesterone receptor (PR) expression should be taken into account when evaluating the prognosis of OBC because PR-positive patients achieve better overall survival and have a lower risk of local recurrence. Surveillance should include breast MRI and mammography.