Local Therapy Group Research Articles

402. BRAIN METASTASES FROM ESOPHAGEAL CANCER AFTER MULTIMODAL TREATMENT: EARLY DETECTION AND AGGRESSIVE LOCAL TREATMENT CAN LEAD TO BETTER OUTCOMES

Abstract Background International guidelines do not recommend imaging investigations to rule out the presence of BM (brain metastases) during clinical staging or follow-up in patients with oesophageal cancer. Patients with single or up to three BM can be considered oligometastatic: in our study we analysed patients with BM focusing on the management and outcomes of BM. Methods We retrospectively identified patients who underwent surgical resection for oesophageal adenocarcinoma or squamous cell carcinoma from 2006 to 2022 in our Upper GI division and subsequently developed brain metastasis (BM). Starting from January 2018, a brain CT scan was added to the routine follow-up procedures in our centre. We divided patients in two groups based on the treatment received for BM: local therapy group treated with surgery and/or stereotactic body radiation therapy/stereotactic radiosurgery (SBRT/SRS) versus no local therapy group treated with chemotherapy or whole brain radiotherapy (WBRT). Results 34 patients developed BM (three didn’t receive treatment); 23 patients in local therapy versus 8 in no local therapy group. Median overall survival (OS, from BM diagnosis to patient’s death or last follow-up) in local therapy group was 14.52 months whereas in no-local therapy 3.41 months, p<0.001. At univariable analysis predictors of OS were pathological stage, pathological response, GI-GPA score, number of metastases, treatment. In multivariable analysis, only pathological stage was statistically significative. We diagnosed 17 BM recurrence before 2018 (17 patients of 355, 4,7%) and 17 after 2018 with introduction of routine brain CT (17 of 217, 7.8%). Conclusion BM from oesophageal cancer benefit from local aggressive treatment in terms of overall survival and to apply a local treatment is necessary that BM are diagnosed early. The introduction of brain CT scan during follow up may have improved the detection rate of BM and therefore in our opinion routine brain CT scan could be necessary.

Additional local therapy before disease progression for EGFR-mutated advanced lung cancer: a systematic review and meta-analysis.

International guidelines recommend the use of local therapy (LT) to limited progression in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). However, the use of LT before disease progression has not been extensively analyzed. This meta-analysis evaluates the efficacy and safety of administering additional LT in conjunction with first-line EGFR-tyrosine kinase inhibitors (TKIs) before disease progression in patients with EGFR-mutated advanced NSCLC. We systematically searched PubMed, Embase, and the Cochrane Library for studies published up until May 31, 2023. The LT group consisted of patients who received first-line EGFR-TKIs in conjunction with additional LT, while the TKI group comprised participants treated with first-line EGFR-TKIs alone. Studies comparing the survival outcomes of the LT and TKI groups were included in this analysis. The primary outcomes were progression-free survival (PFS) and overall survival (OS). This review was registered on PROSPERO (registration number CRD42023439913). Among the 11 investigated studies covering 1,313 patients, the LT modalities included radiotherapy, surgery, and ablation therapy, which accounted for 91%, 27%, and 27% of the studies, respectively. The pooled hazard ratios of median PFS and OS were 0.34 [95% confidence interval (CI): 0.22-0.53; P<0.001] and 0.42 (95% CI: 0.36-0.48; P<0.001), respectively, which indicated significant benefits for the LT group compared to the TKI group. There was no significant difference between the LT and TKI groups (P=0.473) regarding the incidence of grade 3 or higher adverse events. This study suggests that the strategic use of additional LT before disease progression is a promising approach for the treatment of EGFR-mutated advanced NSCLC.

Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT

BackgroundThe third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can penetrate blood–brain barrier and are effective for brain metastases (BMs). There is no consensus on the optimal sequence of local therapy (LT) and EGFR-TKIs for symptomatic BM patients because patients suffering neurological symptoms were not enrolled in most clinical trials.MethodsNon-small cell lung cancer (NSCLC) patients with EGFR mutation (EGFRm) and symptomatic BM receiving first-line osimertinib and aumolertinib from two medical centers were collected. All participants were allocated into the third-generation EGFR-TKIs (TKIs) group and the upfront LT (uLT) plus third-generation EGFR-TKIs (TKIs + uLT) group. Demographic data, survival outcomes, treatment failure patterns, and adverse events were evaluated between the two groups. We also conducted subgroup analyses to explore the impact of BM number on survival outcomes.Results86 patients were enrolled, 44 in the TKIs group and 42 in the TKIs + uLT group. There were no significant differences in the short-term response between the groups. TKIs + uLT was associated with significantly longer overall survival (OS) (43 vs. 28 months; hazard ratio [HR], 0.36, 95% confidence interval [CI], 0.17–0.77; p = .011). No differences in progression-free survival (PFS), intracranial PFS (iPFS), failure patterns, or safety were observed. In subgroup analyses of oligo-BM patients, TKIs + uLT could prolong OS (43 vs. 31 months; HR 0.22; 95% CI 0.05–0.92; p = .015).ConclusionsEGFRm NSCLC patients with symptomatic BM might benefit from uLT, particularly oligo-BM patients. However, larger prospective cohort studies should be carried out to confirm the responses of the TKIs + uLT scheme.

Optimal Treatment Strategy for Oligo-Recurrence Lung Cancer Patients with Driver Mutations.

The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. Therefore, we aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. Among 2152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated, focusing on their post-recurrence therapies and prognoses. The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701-2.912; log-rank, p = 0.324) and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459-1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can cure the recurrence and can delay the start of administration of molecular targeted therapies.

Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial

The efficacy of local therapy for patients with oligometastatic oesophageal squamous cell carcinoma is unclear. We aimed to assess the efficacy of local plus systemic therapy compared with systemic therapy alone in patients with oligometastatic oesophageal squamous cell carcinoma. The ESO-Shanghai 13 trial was a randomised, open-label, multicentre, phase 2 trial. Patients (aged ≥18 years) were recruited from six hospitals in China with histological confirmation of oligometastatic oesophageal squamous cell carcinoma with a controlled primary tumour and one to four metastatic lesions. Eligible patients were randomly assigned via a computer-generated schedule in a 1:1 ratio to receive either systemic therapy alone (ie, systemic therapy only group) or combined systemic and local therapy (ie, systemic and local therapy group). The systemic therapy regimens in both groups were at the discretion of the investigator and included chemotherapy alone, anti-PD-1 antibodies alone, or chemotherapy plus anti-PD-1 antibodies. Local therapy-radiotherapy, surgery, or thermal ablation-was delivered to all metastatic lesions for patients in the systemic and local therapy group. Randomisation was balanced dynamically on three factors: the number of disease sites, the lines of systemic therapy, and the location of the metastases. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, defined as the time from randomisation to progression or death from any cause in the intention-to-treat population. The safety population included all patients who had undergone random assignment and at least one of the intended therapies. This trial is registered with ClinicalTrials.gov, NCT03904927. The trial is ongoing but closed to new participants. 116 patients were screened for enrolment between March 5, 2019, and Sept 16, 2021, and 104 patients who met the eligibility criteria were randomly assigned to the systemic and local therapy group (n=53) or the systemic therapy only group (n=51). 20 (38%) patients in the systemic plus local therapy group and 23 (45%) patients in the systemic therapy only group received anti-PD-1 antibody-based systemic therapy; three patients in the systemic and local therapy group did not receive systemic therapy. At a median follow-up of 30·5 months (IQR 24·7-37·8), median progression-free survival was 15·3 months (95% CI 10·1-20·5) in the systemic and local therapy group versus 6·4 months (5·2-7·6) in the systemic therapy only group (stratified hazard ratio 0·26 [95% CI 0·16-0·42]; stratified log rank p<0·0001). Grade 1-2 acute oesophagitis was more common in the systemic and local therapy group than in the systemic therapy only group (10 [19%] vs one [2%] patients; p=0·036). The number of patients who had grade 3 or worse treatment-related adverse events was similar between groups (25 [47%] vs 21 [41%]; p=0·538), with the most common adverse events being leukocytopenia (17 [32%] vs 18 [35%]) and neutropenia (19 [36%] vs 20 [39%]). Treatment-related deaths occurred in two patients in the systemic and local therapy group and one patient in the systemic therapy only group. The addition of local treatment for metastases could significantly improve progression-free survival among patients with oligometastatic oesophageal squamous cell carcinoma being treated with systemic therapy. Our findings suggest that combining local and systemic therapy could be a treatment option for patients with oligometastatic oesophageal squamous cell carcinoma, but further support from phase 3 trials is required. Science and Technology Commission of Shanghai Municipality, National Nature Science Foundation of China, and Shanghai Municipal Health Commission. For the Chinese translation of the abstract see Supplementary Materials section.

Comparing the role of different treatment modalities in locoregionally advanced olfactory neuroblastoma: The 20-year clinical experience of a single institution.

The clinical value of different treatment modalities, especially systemic chemotherapy (CT) in patients with locoregionally advanced olfactory neuroblastoma (LA ONB) remains unclear. Patients with LA ONB from 2000 to 2020 at our center were collected retrospectively. The entire cohort was divided into combined systemic and local therapy (CSLT) versus local therapy (LT) groups (grouping method 1), and the same cohort was divided into neoadjuvant chemotherapy (NAC) versus non-NAC groups (grouping method 2). CSLT group included patients treated with CT + LT. LT group included patients treated with surgery (SG), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or any combination of the above methods. LT group was further divided into mono-modality local therapy (MOLT) group and multi-modality local therapy (MULT) group. MOLT group included patients treated with RT alone or SG alone. MULT group included patients treated with SG + RT/CCRT, or CCRT alone. NAC group included patients treated with NAC + LT ± adjuvant chemotherapy (ADC). Non-NAC group included patients who received LT ± ADC. A total of 111 patients with LA ONB were included. The median follow-up was 80.2 months (range, 2.1-254.9). The 5- and 10-year OS rates were 70.2% and 61.3%, respectively. In univariate analysis, patients treated with NAC (n = 43) had significantly better overall survival (OS) compared with those without NAC (n = 68) (p = 0.041). Patients in MULT group (n = 45) had significantly improved OS (p = 0.004) and PFS (p = 0.003) compared with those in MOLT group (n = 15). Multivariate analysis identified NAC and CSLT (n = 51) were independent prognostic factors for superior OS (p = 0.020, p = 0.046). Our study suggested that CSLT, especially a combination of NAC and LT, improved the survival of patients with LA ONB. Multiple treatment modalities yielded better PFS and OS compared to single-modality treatment.

Comparing the role of different treatment modalities in locoregionally advanced olfactory neuroblastoma: The 20-year clinical experience of a single institution.

e18055 Background: There are few studies on different treatment modalities, especially systemic chemotherapy (CT) for locoregionally advanced olfactory neuroblastoma (LA ONB) with only a few small-sample studies reported. We retrospectively analyzed the treatment patterns and explored the factors affecting the prognosis of patients with LA ONB at our center over the past 20 years in the present study. Methods: LA ONB patients from 2000 to 2020 at our center were collected retrospectively. The entire cohort was divided into combined systemic and local therapy (CSLT) vs. local therapy (LT) groups (grouping method 1), and the same cohort was divided into neoadjuvant chemotherapy (NAC) vs. non-NAC groups (grouping method 2). CSLT group included patients treated with CT + LT. LT group included patients treated with surgery (SG), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or any combination of the above methods. LT group was further divided into mono-modality local therapy (MOLT) group and multi-modality local therapy (MULT) group. MOLT group included patients treated with RT alone or SG alone. MULT group included patients treated with SG + RT/CCRT, or CCRT alone. NAC group included patients treated with NAC + LT ± adjuvant chemotherapy (ADC). Non-NAC group included patients who received LT ± ADC. Results: A total of 111 patients with LA ONB were included. The median age was 40 (range, 10–82) years old. The median follow-up duration for the entire cohort was 80.2 (range, 2.1-254.9) months, while 88.5 (range, 4.0-240.7) months for the CSLT group, 77.2 (range, 2.1-254.9) months for the LT group, 86.0 (range, 4.0-240.7) months for the NAC group, and 78.7 (range, 2.1-254.9) months for the non-NAC group. Thirty-five patients (31.5%) died, among which 30 patients died of tumor progression, 3 patients died of other diseases, and 2 patients’ causes of death were not available. The estimated 5-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates for the entire cohort (n = 111) were 70.2%, 53.1%, 73.6%, and 74.1%, respectively. The estimated 10-year OS, PFS, LRFS, and DMFS rates were 61.3%, 37.7%, 60.1%, and 68.0%, respectively. In univariate analysis, patients treated with NAC (n = 43) had significantly better overall survival (OS) compared with those without NAC (n = 68) ( P = 0.041). Patients in MULT group (n = 45) had significantly improved OS ( P = 0.004) and PFS ( P = 0.003) compared with those in MOLT group (n = 15). Multivariate analysis identified NAC and CSLT (n = 51) were independent prognostic factors for superior OS ( P = 0.020; P = 0.046). Conclusions: Our study suggested that CSLT, especially a combination of NAC and LT, improved the survival of patients with LA ONB. Multiple treatment modalities yielded better PFS and OS compared to single modality treatment.

Abstract 2105: Implications of metastatic stage at presentation in docetaxel naïve metastatic castrate resistant prostate cancer

Abstract Background: Studies on metastatic hormone sensitive prostate cancer have shown that metachronous presentation has a better prognosis compared to synchronous disease. However, it remains unknown if such association is pertinent in metastatic castrate resistant prostate cancer (mCRPC). We performed a secondary analysis of ACIS study to determine if the response to dual androgen receptor axis-targeted therapy (ARAT) in in docetaxel naïve metastatic castrate resistant prostate cancer (mCRPC) varies based on M-stage at diagnosis and if prior local therapy plays an effect modifying role in the association of M-stage at presentation with survival. Patients and Methods: In this phase III randomized controlled trial, mCRPC patients with no prior exposure to androgen biosynthesis signaling inhibitors were randomly assigned to either apalutamide or placebo combined with abiraterone and prednisone. Cox regression models were applied for radiographic progression-free survival (rPFS), overall survival (OS) with interaction terms between M-stage and treatment regimen. Multivariable Cox regression analyses were performed to determine the adjusted association of M-stage with rPFS and OS after considering the effect modification by prior local therapy (LT). Results: Among 972 evaluable patients -432 had M0, 334 had M1 at diagnosis while M-stage was unknown in 206. We did not find any statistically significant heterogeneity of treatment effect on rPFS (interaction p=0.13; HR for placebo in M0 group: 1.42 [1.13-1.79]; M1/unknown group: 1.11 [0.90-1.37]), and OS (interaction p=0.87; HR for placebo in M0 group: 1.02 [0.81-1.29], and M1/unknown group: 1.00 [0.82-1.23]) based on M-stage at diagnosis. There was no significant association of M-stage with rPFS (HR for LT group: 1.08 [0.84-1.40], HR for no LT: 0.91 [0.67-1.24]) and OS (HR for LT: 1.04 [0.81-1.33] and no LT: 0.95 [0.70-1.29]) with no significant heterogeneity depending on receipt of LT (interaction p-value of 0.94 and 0.93, respectively). Conclusion: We did not find a statistically significant heterogeneity in efficacy of dual ARAT based on synchronous versus metachronous presentation. M-stage was not found to be a predictor for rPFS and OS after considering effect modification by prior LT. Citation Format: Shawn Malone, Christopher Wallis, Scott Morgan, Amar Kishan, Amy Tu Trinh Le, Julia Malone, Yilun Sun, Daniel Spratt, Fred Saad, Soumyajit Roy. Implications of metastatic stage at presentation in docetaxel naïve metastatic castrate resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2105.

Characterization of Central Nervous System Clinico-Genomic Outcomes in ALK-Positive Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Alectinib

IntroductionHighly effective brain-penetrant ALK-targeted tyrosine kinase inhibitors (TKIs) have been developed for the management of NSCLC patients with brain metastases (BM). Local therapy (LT) such as SRS or therapeutic craniotomy is increasingly being deferred for such patients. Herein we report detailed patient- and lesion-level intracranial outcomes and co-mutational genomic profiles from a cohort of NSCLC patients with BM treated with alectinib, with or without LT. MethodsWe retrospectively reviewed ALK fusion-positive NSCLC patients with BMs who received alectinib at the diagnosis of BM from 1/2012 and 5/2021. Outcome variables included intracranial progression-free survival (iPFS), overall survival (OS), duration of TKI therapy, and CNS response rates. Genomic characteristics from tumor specimens were assessed with MSK-IMPACT, a next-generation sequencing (NGS)-based genomic profiling assay. ResultsA total of 38 patients with 114 CNS lesions were included. Twelve of these patients also received contemporaneous LT (SRS, WBRT, or surgical resection). Maximal BM diameter in the TKI + LT group was greater (p < 0.003) but despite this difference, iPFS (TKI only, HR 1.21, 95 % CI 0.51–2.89; p = 0.66) and OS (TKI only, HR 5.99, 95 % CI 0.77–46.6; p = 0.052) were similar between groups and trended towards more favorable outcomes with the addition of LT. SMARCA4 co-alterations were associated with inferior OS (HR 8.76, 1.74–44.2; p = 0.009). ConclusionsOur study demonstrated that patients with ALK fusion-positive NSCLC treated with TKI + LT had larger BM and higher likelihood of pre-treatment neurologic symptoms. Despite these differences, iPFS was similar between groups. Results should be interpreted with caution as our study was limited by an underpowered sample size. SMARCA4 co-alterations were associated with inferior OS and these findings warrant further investigation.

Locoregional recurrence after nephrectomy for localized renal cell carcinoma: Feasibility and outcomes of different treatment modalities.

Locoregional recurrence after nephrectomy for localized renal cell carcinoma (RCC) is rare with diverse manifestations. The selection criteria and efficacy of different treatments are unanswered. The objective was to compare different treatment modalities and present data on stereotactic body radiotherapy (SBRT) for recurrent RCC. Patients with locoregional recurrence after nephrectomy without distant metastasis were identified from institutional big data intelligence platform between 2001 and 2020. Patients receiving local therapy (surgery or SBRT) or systemic therapy alone (targeted therapy or PD-1 inhibitors) were divided into two groups. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method, Cox regression model. Patients were matched with propensity score matching. Among 106 patients, 33 (31.1%) received systemic therapy alone and 73 (68.9%) received local therapy. Local therapy was surgery in 34 patients (32.1%) and SBRT in 39 (36.8%) patients. Patients treated with systemic therapy alone had more non-clear cell type (p=0.044), more advanced T stage (p=0.006), higher number (p=0.043) but smaller size of lesions (p=0.042). Patients receiving local therapy had significantly longer PFS than systemic therapy (19.7 vs. 7.5months, p=0.001). After matching, the PFS in the local therapy group remained higher (23.9 vs. 7.5months, p=0.001). The 2-year OS of the local therapy group and systemic therapy group was 91.6% and 71.8%, respectively (p=0.084). Local therapy was associated with better PFS (HR 0.37; p=0.0003) and OS (HR 0.23; p=0.002) in multivariate analysis. Grade 2 or higher toxicities related to local therapy occurred in nine patients. Local therapy could delay disease progression compared with systemic therapy alone. SBRT is safe and effective for locally recurrent RCC.

Efficacy of local therapy to metastatic foci in nasopharyngeal carcinoma: large-cohort strictly-matched retrospective study.

Background:Studies of local therapy (LT) to metastatic foci from nasopharyngeal carcinoma (NPC) are inconsistent and controversial. Here, we aimed to explore the survival benefit of LT directed at metastatic foci from NPC.Methods:A retrospective analysis was conducted in NPC patients with liver, lung, and/or bone metastases. The postmetastatic overall survival (OS) rate was analyzed using the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox hazard model. Subgroup analyses evaluating the effect of LT were performed for prespecified covariates. Propensity score matching was applied to homogenize the compared arms.Results:Overall, 2041 of 2962 patients were eligible for analysis. At a median follow-up of 43.4 months, the 5-year OS improved by an absolute difference of 14.6%, from 46.2% in the LT group versus 31.6% in the non-LT group, which led to a hazard ratio of 0.634 for death (p < 0.001). Matched-pair analyses confirmed that LT was associated with improved OS (p = 0.003), and the survival benefits of LT remained consistent in the subcohorts of liver and lung metastasis (p = 0.009 and p = 0.007, respectively) but not of bone metastasis (BoM; p = 0.614). Radiotherapy was predominantly used for BoM and biological effective dose (BED) >60 Gy was found to yield more survival benefit than that of BED ⩽ 60 Gy.Conclusions:The addition of LT directed at metastasis has demonstrated an improvement to OS compared with non-LT group in the present matched-pair study, especially for patients with liver and/or lung metastases.

The Effect of Local Therapy on Brain Metastasis of Renal Cell Carcinoma

We compared brain metastasis of renal cell carcinoma (RCC) in patients who received tyrosine kinase inhibitors (TKIs) ; 17 received local therapy, while 16 did not. The median survival rate was 19 months in the local therapy group and 11 months in the tyrosine kinase inhibitor alone group, showing no significant difference (p＝0.52). Symptoms such as paralysis, headache, and dysarthria occurred due to brain metastasis. These symptoms improved in 8 out of 10 patients in the local therapy group. There were no cases of grade 3 or higher complications due to local therapy. Although local therapy did not prolong the overall survival, an improvement in symptoms was observed, suggesting that it is acceptable as palliative treatment.

Evaluation of local aggressive lung therapy versus systemic therapy in oligometastatic non-small cell lung cancer: a systematic review and meta-analysis.

BackgroundPrevious studies have shown the feasibility and effectiveness of local aggressive thoracic therapy (surgery and radiotherapy) for oligometastatic non-small cell lung cancer compared with systemic therapy, but with small sample. This study aims to perform a pooled analysis to explore whether LT could improve outcomes of oligometastatic patients with non-small cell lung cancer.MethodsProtocol of present study was registered on PROSPERO as number: CRD42021233095. PubMed, Embase and Web of knowledge were searched, and eligible studies investigating local therapy for non-small cell lung cancer with 1–5 metastases regardless of organs were included. Linear regression between survival and clinical characteristics were conducted. Hazard ratios of survival and adverse effects were merged. Pooled survival curves were carried out.ResultsThree randomized controlled trials and 5 cohort studies enrolling 499 patients were included. There was a trend that median overall survival declined with the increasing proportion of N2–3 positive patients in local therapy group, but with no statistical difference (P=0.09, R2=0.98). Undergoing local therapy for oligometastatic non-small cell lung cancer achieved reduction of 47% and 60% in the risk of death and cancer progression (P<0.001), respectively. In subgroup analysis, patients receiving local therapy including surgery showed hazard ratio of 0.33 on progression-free survival and 0.55 of these excluding surgery. Patients receiving consolidative local therapy (local therapy after systemic therapy) obtained hazard ratios 0.33 and 0.45 on progression-free and overall survival vs. systemic therapy, respectively. Hazard ratios of those receiving upfront local therapy (local therapy first) were 0.62 and 0.68 on progression-free and overall survival vs. systemic therapy. Pooled survival analysis showed median overall and progression-free survival of local therapy (21.6 and 14 months) group were both longer than systemic one (14.3 and 6.5 months). Odds ratio of adverse effects were no difference between 2 groups (P=0.16).ConclusionsLocal aggressive thoracic therapy could prolong 7 months overall and progression-free survival compared with systemic therapy in patients with oligometastatic non-small cell lung cancer. Consolidative local therapy might be a more favorable choice of local therapy. Benefits of local therapy for N2–3 positive patients should explored further.

Efficacy of local therapy for oligoprogressive disease after programmed cell death 1 blockade in advanced non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non‐small‐cell lung cancer (NSCLC); however, the vast majority of patients eventually develop progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD‐1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty‐eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option.

Optimal Sequence of Local and EGFR-TKI Therapy for EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases Stratified by Number of Brain Metastases

It is unclear whether local therapy (LT) or epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) should take precedence for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases (BMs). The number of BMs is important in the choice of LT, including whole-brain radiation therapy, stereotactic radiosurgery, and surgery. We retrospectively evaluated cases of EGFR-mutant non-small cell lung cancer with BMs from a single site. Patients were divided into 2 groups based on upfront therapy-EGFR-TKI (TKI) or LTs-and subsequently stratified by the number of BMs. Among 176 patients, 61% received upfront EGFR-TKI, and 39% received upfront LT. The number of patients with 1 to 4 BMs was similar (56% vs 52%; P=.61). All patients with 1 to 4 BMs in the LT group, except for surgical cases, received stereotactic radiosurgery (n=31). Among those with ≥5 BMs, most (n=27; 82%) received whole-brain radiation therapy. There was no significant difference in OS between LT and TKI groups (median overall survival, 28 vs 23months; hazard ratio, 0.75; 95% confidence interval, 0.52-1.07). In patients with 1 to 4 BMs, the LT group showed significantly better OS compared with the TKI group (median overall survival, 35 vs 23months; hazard ratio, 0.54; 95% confidence interval, 0.32-0.90). There was no difference in OS between the LT and TKI groups for patients with ≥5 BMs. Multivariable analysis showed that upfront LT yielded significantly better OS for patients with 1 to 4 BMs. Upfront LT followed by EGFR-TKI is more effective than upfront EGFR-TKI for the survival of untreated patients harboring EGFR mutations with 1 to 4 BMs.

Role of liver-directed local tumor therapy in the management of hepatocellular carcinoma with extrahepatic metastases: a SEER database analysis

ABSTRACTBackground: This study assessed the prognostic impact of the liver-directed local tumor therapy in the management of hepatocellular carcinoma (HCC) with extrahepatic metastases.Methods: Metastatic HCC patients diagnosed between 2004 and 2013 were identified from the SEER (Surveillance, Epidemiology, and End Results) database. Propensity-matched analysis was performed considering baseline characteristics (age, gender, race, histology, TNM stage, site of metastases, fibrosis score and alpha fetoprotein).Results: A total of 2529 patients were identified. The median age was 65 years, and 151 patients received liver-directed local treatment (either surgical treatment or local destructive treatment). Both before and after propensity score matching, cancer-specific and overall survival (p < 0.0001 for all) were better in the liver-directed local therapy group. When the overall survival was stratified by the type of local treatment (surgical resection versus destructive treatment), both types of treatment improved overall survival (p < 0.0001 for both). In multivariate analysis of the matched population, the only factor correlated with better survival receiving is local therapy (p < 0.0001).Conclusion: This analysis suggests that liver-directed local treatment may play a role -in addition to systemic treatment- in the management of selected patients with metastatic HCC. Further prospective randomized controlled trials are needed to confirm or deny this hypothesis.

Memory and Spatial Cognition in Breast Cancer Patients Undergoing Adjuvant Endocrine Therapy

Introduction: It is generally accepted that estrogens play a protective role in cognitive function. Therefore, it can be expected that subtotal estrogen deprivation following aromatase inhibition will alter cognitive performance. Methods: In a cross-sectional study we investigated 80 postmenopausal women with breast cancer. Memory and spatial cognition were compared across 4 treatment groups: tamoxifen only (TAM, n = 22), aromatase inhibitor only (AI, n = 22), TAM followed by AI (‘SWITCH group', n = 15), and patients with local therapy (LT) only (surgery and radiation, n = 21). Duration of the 2 endocrine monotherapy arms prior to the assessment ranged from 1 to 3 years. The ‘SWITCH group' received 2-3 years TAM followed by at least 1 year and at most 3 years of AI. Memory and spatial cognition were investigated as planned comparisons. Investigations of processing speed, attention, executive function, visuoconstruction and self-perception of memory were exploratory. Results: With regard to general memory, AI patients performed significantly worse than the LT group (p = 0.013). Significant differences in verbal memory did not remain significant after p-value correction for multiple testing. We found no significant differences concerning spatial cognition between the groups. Conclusion: AI treatment alone significantly impairs general memory compared to the LT group.

Local salvage therapy for late (≥2 years) metastatic and local relapse of renal cell cancer is a potentially curative treatment irrespective of the site of recurrence

ObjectiveThe primary treatment approach to locoregional renal cell carcinoma (RCC) is surgical resection. Most relapses occur within the first 2 years but some patients experience late recurrences. Surgical resection of oligometastatic disease may be considered a curative option for relapsed RCC. However, limited data are available of long-term follow-up of late relapse regarding treatment choice. Patients and methodsWe identified 104 patients with RCC from our database, who relapsed after≥2 years from resection of their primary tumor. Median age at primary diagnosis was 61 years and sex distribution was F:M = 40:64. Histology was clear cell, n = 103 and papillary, n = 1. Sites of relapse were local, n = 14 (13.4%); lung only, n = 25 (24.0%); or extrapulmonary, n = 65 (62.5%). Treatment at first relapse was local therapy (LT) in n = 60 (57.7%) patients, of these, n = 55 patients had surgery done and n = 5 patients had underwent radiotherapy. Systemic therapy was used in n = 9 (8.7%) patients. Overall, 35 patients received best supportive care (33.7%). ResultsWe found a median overall survival (OS) of 49.8 months (95% CI: 29.3–70.2) and a progression-free survival (PFS) of 21.6 months (95% CI: 12.6–30.5) for all patients. Patients receiving LT had a median OS of 99.9 months (95% CI: 77.2–122.6) and a PFS of 31.1 months (95% CI: 21.5–40.7). Patients treated with systemic therapy, in turn, had an OS of 21.1 months (95% CI: 8.4–33.8) and a PFS of 4 months (95% CI: 1.0–6.2). Patients who received best supportive care had an OS of 10 months (95% CI: 1.3–18.7). This difference was highly significant (log rank for PFS: P<0.001; log rank for OS: P<0.003). Subgroup analysis of the LT group showed a superior outcome for local relapses (OS: not reached, PFS: 61.4mo [95% CI: 28.5–9.2]) compared to visceral relapses (OS: 35.5mo [95% CI: 17.9–53.1], PFS: 21.1mo [95% CI: 19.2–22.9]). ConclusionLocal salvage therapy should be considered the first therapeutic option in late relapse of RCC irrespective of the site of relapse.

Prognostic impact of different chemotherapy strategies on small cell esophageal carcinoma

To investigate the prognostic impact of different chemotherapy strategies on small cell esophageal carcinoma (SCEC). The clinical data of 62 patients with histologically confirmed SCEC treated in our department between January 2006 and April 2011 were retrospectively analyzed. There were 39 patients with limited stage (LS) and 23 patients with extensive stage (ES) SCEC according to the Veterans Administration Lung Study Group staging system. Cox's hazard regression model was used to determine the prognostic factors, and Chi-square test was used to detect the difference of frequencies among different groups. Kaplan-Meier and log-rank analyses were used to estimate and compare the survival rates. The chemotherapy combined with local therapy group was significantly better than chemotherapy alone group in median survival time (MST) (20.8 vs. 7.6 months, P<0.05). The MST was 18.0 months and the 1-, 2-, and 3-year overall survival rates (OS) were 68.8%, 38.6%, and 20.9%, respectively, for all the 62 patients. Etoposide plus cisplatin or carboplatin (EP/CP) did not result in significantly longer MST, compared with that of the cases treated by other combination chemotherapy (P>0.05, for either LS or ES cases). Multivariate analysis showed that the VALSG stage, the number of chemotherapy cycles (≥ 4), and treatment modality are independent prognostic factors (P<0.05). SCEC is a tumor characterized by high malignancy and poor prognosis. Chemotherapy combined with local therapy is an effective treatment for SCEC, and appropriate chemotherapy cycles (≥ 4) may improve the survival time. EP/CP, as commonly used multidrug chemotherapy regimen, is not superior to other combination chemotherapy.

Effect of sequential chemotherapy and gefitinib on survival outcome in advanced NSCLC with acquired gefitinib resistance.

e19085 Background: As one of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), gefitinib has been proven to be highly effective for patients with advanced NSCLC. However, almost all patients who experienced remarkable improvement eventually develop acquired resistance. There are no approved therapies after disease progression on gefitinib. Subsequent therapeutic modalities are needed. Methods: From September 2007 to July 2012, 74 patients with pathologically confirmed advanced NSCLC who had had disease control with gefitinib more than 6 months were retrospectively reviewed. After acquired resistance to gefitinib, 38 (51%) patients received systemic chemotherapy and sequential gefitinib, 14 (20%) received local treatment and continued gefitinib, and 22 (29%) received best supportive care (BSC) only.Our objective was to assess the survival outcome of different subsequent therapy after acquired resistance to gefitinib. Results: In chemotherapy group, Patients achieved higher response rate and disease control rate, respectively 39% and 82%. The median overall survival (OS) and progression free survival (PFS) from the time of gefetinib resistance in the subsequent chemotherapy group (13.9 m and 5.2 m, respectively) were longer than the local therapy group (7.1 m and 3.1 m, respectively) and the BSC group (3.7 m and 1.1 m, respectively; P &lt; .01). Furthermore, we found that patients who accepted subsequent therapy and continued gefitinib at the same time got better PFS and OS. Local therapy and in combination with continuation of gefitinib treatment could prolong time from local progress to distant metastasis. Conclusions: Subsequent therapy, especially sequential chemotherapy and gefitinib could bring gefetinib resistance NSCLC better survival outcome. Local therapy could also be a reasonable choice for local progress or metastasis patients during gefitinib treatment.