Patterns Of Relapse In Patients Research Articles

Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study.

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

(Neo)adjuvant approaches in lung cancer—paving the road to a cure

SummaryImmune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of metastatic non-small-cell lung cancer (NSCLC). During the past few years the focus of research has shifted toward examining these therapies in patients with early-stage NSCLC to improve long-term overall survival and cure rates. As recurrence rates are high and the relapse pattern in patients with completely resected early-stage NSCLC is predominantly systemic, high expectations rest on the integration of ICI therapy in their treatment approach. A large number of studies with adjuvant or neo-adjuvant ICI are ongoing. The first data from phase III studies have demonstrated improvements in disease-free survival and pathologic remissions, but overall survival data are mostly immature. Additionally, targeted therapies have also been explored in early-stage NSCLC. The first very promising results are available from EGFR-mutant and ALK-translocated NSCLC and have already changed our clinical practice for some patient subgroups. This review discusses the most recent results of phase III trials in the neoadjuvant, perioperative, and adjuvant setting for ICI and targeted therapies in early-stage resectable NSCLC.

Patterns of Relapse in Patients with Locally Advanced Cervical Cancer after Image Guided Brachytherapy

Patterns of Relapse in Patients with Locally Advanced Cervical Cancer after Image Guided Brachytherapy

Bridging Radiotherapy for Patients with Limited (<5 Disease Sites) Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma Prior to CAR T-Cell Therapy

Purpose The predominant pattern of relapse for patients with B-cell non-Hodgkin lymphoma (NHL) who undergo anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) involves sites previously involved by NHL. Bridging radiotherapy (BRT) has shown to be an effective bridging treatment with excellent local control rates. Our previous work defined limited/oligometastatic lymphoma as disease involving <5 sites. This study is the first to report on the role of BRT for patients with limited (<5 involved sites) disease prior to CART. Methods Following Institutional Review Board approval, a retrospective review from 2018 to 2023 across 3 Mayo Clinic sites (Arizona, Florida, and Minnesota) was performed and identified 139 patients with relapsed/refractory (r/r) B-cell NHL without bone marrow involvement who received CART and had <5 disease sites prior to leukapheresis. Ann Arbor staging was used to define the number of involved disease sites. An involved disease site included the Ann Arbor anatomical lymph node region(s) harboring the pathological lymph node(s) or any extranodal lesion. Bridging treatment (radiation and/or systemic therapy) was defined as treatment administered between leukapheresis and CART infusion. The primary endpoint was event-free survival (EFS),defined from CART infusion to any disease progression or initiation of post-CART consolidative/salvage therapy. Secondary endpoints included progression -free survival (PFS),defined from CART infusion to any disease progression, and overall survival (OS), defined from CART infusion to death. Results Prior to CART infusion, 44 (32%) patients received BRT and 95 (68%) did not. Bridging systemic therapy was given to 5 (11%) and 34 (36%) patients in the BRT and no BRT groups, respectively (p=0.003). The median number of involved disease sites prior to leukapheresis was 2 (range: 1-4). There was no significant difference in the baseline characteristics prior to CART infusion between the BRT and no BRT groups, except for extranodal involvement that was more common in the BRT group (Table 1). The median equivalent 2 Gy dose was 27 Gy (Interquartile range 23-34), and the most common BRT regimen was 20 Gy in 5 fractions. Among the 44 BRT patients, 34 received radiation to all visible PET-avid disease sites, and 10 received radiation to some but not all disease sites. The median follow-up was 20 months. The rate of grade ≥2 cytokine release syndrome was 41% in both groups (p=0.99). The rate of grade ≥2 immune effector cell-associated neurotoxicity syndrome was 21% and 37% in the BRT and no BRT groups, respectively (p=0.059). There were no observed grade ≥3 BRT-related toxicities. Objective response rate by PET 5 point scale was higher in the BRT group (93% versus 79%; p=0.036). Crude rates of progression were 30% in BRT and 55% in no BRT patients, with 9/13 (69%) and 43/52 (83%) patients relapsing in pre-existing sites of disease present prior to CART infusion in the BRT and no BRT group, respectively. Seven (16%) BRT patients relapsed in the radiation field. The 2-year EFS was 50% in the BRT group and 39% in the no BRT group (p=0.01). The 2-year PFS was 55% in the BRT group and 45% in the no BRT group (p=0.017). The 2-year OS was 55% in the BRT group and 62% in the no BRT group (p=0.7). Intriguingly, patients who received BRT to all visible PET-avid disease sites (n=34) had further improvement in 2-year EFS (67% vs 39%, p=0.003) and 2-year PFS (71% vs 46%, p=0.008) compared to no BRT or patients who received BRT to some but not all visible disease sites (n=105). Nine patients (2 in BRT and 7 in no BRT groups) received consolidative radiotherapy for day 30 residual disease with only one patient subsequently experiencing progression. Twenty-five patients (6 in BRT and 19 in no BRT groups) received salvage/palliative RT for post-CART relapsed disease. Thirty-seven (39%) patients in the no BRT group remained without disease progression and did not receive radiation in the bridging, consolidative or salvage/palliative setting. Conclusion Bridging radiotherapy prior to CART infusion for patients with limited (<5 involved disease sites) r/r NHL appears to improve response rate, EFS, and PFS without causing significant toxicities. Approximately one third of patients who do not receive BRT will require subsequent post-CART radiation, and another third will remain free of radiation and disease progression.

Patterns of Relapse in Patients with Acute Myeloid Leukemia (AML) Treated with Venetoclax-Containing Regimens

Background: Advances in next generation sequencing (NGS) technologies and better insight into the biology of acute myeloid leukemia (AML) have demonstrated the heterogeneity of the disease and its polyclonal nature at the time of diagnosis. While targeted therapies have improved remission rates and significantly improved outcomes, relapses are frequent and tend to arise from resistant sub-clones with genomic profiles and sensitivities that are often different from the dominant clone at initial diagnosis. While the use of targeted therapy at initial diagnosis may effectively control the dominant clone, the backbone chemotherapy in combination may be important in controlling the myriad of sub-clones that may be present. Methods: We hypothesized that the type of chemotherapy used in combination with the BCL2 inhibitor venetoclax (ven) may influence the pattern of relapses (including genomic profile) in patients with AML treated with different regimens. We retrospectively reviewed patients treated in three clinical trials of frontline ven in combination with chemotherapy-cladribine (clad) + LDAC + ven, CLIA + ven, and FLAG-IDA + ven-who had documented relapsed disease at any time. All patients had undergone karyotype and NGS based mutation testing at baseline and at time of relapse. We analyzed the baseline characteristics, karyotypes, and mutational profiles at baseline and at the time of relapse as well as outcomes of these patients. Results: We retrospectively reviewed 34 newly diagnosed patients who were treated on three prospective clinical trials including frontline ven and experienced a relapse: clad + LDAC + ven (N=19); CLIA + ven (N=7); and FLAG-IDA + ven (N=8). The median ages of these patients were 68 yrs (range, 57-80), 43 (23-61), and 39 (20-63), respectively. The median durations of response for these relapsing patients on each of the trials were 4.80, 8.05, and 7.61 months, respectively. 5.3%, 0%, and 75% of patients who relapsed from each of the three groups, respectively, had undergone prior allogeneic SCT. The baseline and relapsing mutation frequencies for the patients from each of the trials are summarized in Table 1. The most prevalent mutations present in patients who relapsed after frontline clad + LDAC + ven were TP53 (32%) and TET2 (26%); on CLIA + ven, DNMT3A (57%) and TET2 (43%); on FLAG-IDA + ven, TP53 (50%) and DNMT3A (38%). In the three cohorts, among all newly acquired mutations (n=41), the highest incidences were observed in RUNX1 (22%), DNMT3A (17%), TET2 (10%), and SMC3 (10%) (Table 1). The relapsed clad + LDAC + ven cohort developed the greatest variety of intermediate- and unfavorable-risk cytogenetic abnormalities upon relapse, and of the 42% of patients (n=8) with new abnormalities, -7/7q- was most frequently observed at 38% (n=3). Among all newly acquired cytogenetic abnormalities at relapse among the three cohorts, 55% (n=6) acquired -7/7q-, making this the most frequent cytogenetic abnormality acquired upon relapse in these patients. Conclusions: Among patients with relapsed AML after treatment with 3 frontline ven-containing regimens, we observed varying profiles. Mutational profiles exhibiting previously undetected aberrancies in RUNX1, DNMT3A, TET2, and SMC3 were most frequently observed at the time of relapse. Meanwhile, the most frequent karyotypic changes observed at the time of relapse were the acquisition -7/7q among patients, with the greatest number of acquisitions occurring among the clad + LDAC + ven cohort. Further analysis of the patterns of genomic changes at the time of relapse, including after treatment with hypomethylating agents and ven, can inform treatment decisions, maintenance strategies, and can improve patient outcomes

Pathological complete response, long-term outcomes, and recurrence patterns in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy

BackgroundThe interest in HER2-low breast cancer (BC) has increased in recent years with the development of novel anti-HER2 antibody–drug conjugates. Here, we investigated the clinical outcomes and relapse patterns of patients with HER2-low or -zero BCs in an Asian population. MethodsWe retrospectively identified HER2-low or -zero BC patients with stage I–III tumours who were treated with neoadjuvant chemotherapy and underwent curative surgery, between 2014 and 2018 at Asan Medical Center, Seoul, Korea. ResultsA total of 818 and 754 HER2-zero and HER2-low BC patients, respectively, were consecutively included in this analysis. The HER2-low group had more hormone receptor [HR]-positive patients (81% versus 56%, P < 0.001). The HER2-zero group had a higher proportion of patients who achieved pathological complete response (pCR) (14.7% versus 9.8%, P = 0.003); however, no significant differences of pCR rate by HER2 status were identified in the HR-positive (P = 0.4) and HR-negative groups (P = 0.3) when analysed separately. The HER2-low BC cases had higher 5-year overall survival (OS) and disease-free survival (DFS) rates (P < 0.001 for OS; P = 0.002 for DFS); however, no differences were observed in terms of OS and DFS by HER2 status in the HR-positive group (P = 0.21 for OS and P = 0.66 for DFS). ConclusionsOur current findings do not support that HER2-low BC had different biology and clinical features compared to HER2-zero BC in patients who treated with neoadjuvant chemotherapy. However, the prognostic impact of HER2-low status in BC remains controversial; thus warranting further research.

Next-generation sequencing-based analysis to assess the pattern of relapse in patients with Philadelphia-positive acute lymphoblastic leukemia.

In this study, we performed serial monitoring using targeted DNA sequencing to identify genetic alterations in adults with Philadelphia-positive acute lymphoblastic leukemia (Ph-ALL). Deep sequencing was performed by targeting the coding regions of 45 genes with recurrent driver mutations and 1129 single nucleotide polymorphism sites. Of the 43 patients that we examined, at least one case of genetic alterations was detected in 38 (88%) of the 43 patients at diagnosis (somatic mutations in 10 patients [23%] and copy number aberrations [CNA] in 36 patients [84%]).The most frequently detected CNA lesions were in IKZF1 (n=25, 58%) and the most frequently mutated gene was SETD2 (n=5). At least one genetic abnormality (loss, gain, or persistence) was observed in all the samples obtained at relapse that were available for analysis (n=15), compared with the samples obtained at diagnosis (disappearance of any previously detected genetic alterations: 11 patients [73%]; new genetic abnormalities: nine patients [60%]; and persistent genetic abnormalities: eight patients [53%]]. The most frequently deleted lesions were in IKZF1 (n=9, 60%), and the most frequently mutated gene was ABL1 (eight patients, 53%). Our data indicate that leukemic progression may be associated with complex genetic alterations in Ph-ALL during the course of treatment.

193P Pathologic complete response, long-term outcomes, and recurrence patterns in HER2-low vs HER2-zero breast cancer after neoadjuvant chemotherapy

The HER2-low classification (immunohistochemistry [IHC] 1+ or IHC2+ and in situ hybridization–negative) is a new breast cancer (BC) category, established with the introduction of novel anti-HER2 antibody-drug conjugates. We investigated the characteristics, clinical outcomes, and relapse patterns of patients with HER2-low and HER2-zero (IHC 0) BC in an Asian population.

Patterns of relapse after immunotherapy in patients with high-risk neuroblastoma.

10043 Background: While the addition of anti-GD2 immunotherapy led to improvement in outcomes in patients on the Children’s Oncology Group (COG) ANBL0032 study, relapse remains a concern. Prior studies demonstrated the prognostic importance of time to first relapse, however, the effect of immunotherapy on timing and patterns of relapse in neuroblastoma (NBL) have yet to be evaluated. The purpose of this exploratory analysis was to describe the impact of immunotherapy on patterns of relapse in patients with high-risk NBL, including a descriptive comparison of sites of relapse based on post-consolidation treatment received [dinutuximab with cytokines and isotretinoin (DIN) vs isotretinoin alone (ISO)]. Methods: A retrospective, descriptive analysis of patients on ANBL0032 was performed, including patients randomized to DIN or ISO and those non-randomly assigned to DIN after ISO arm closure. Pt characteristics including age, stage, MYCN amplification status, tumor grade, mitosis-karyorrhexis index (MKI) and ploidy were summarized descriptively and relapse sites were tabulated. For DIN patients who subsequently relapsed, overall survival (OS) was calculated starting from the time of first relapse after enrollment on ANBL0032 (“post-relapse OS”). Kaplan-Meier OS curves were generated based on site of relapse. Results: The analytic cohort included 1,431 (DIN = 1,327; ISO = 104) patients. Among DIN patients, 492 relapsed, many in &gt; 1 site. In the randomized cohort (n = 248), 122 relapsed (DIN = 68/144; ISO = 54/104). The frequencies (DIN; ISO) by site of relapse in the randomized cohort were: bone (53%; 54%), CNS (16%; 11%), lymph node (13%; 17%), abdominal (10%; 17%), paraspinal (6%; 2%), liver (3%; 4%), other soft tissue (22%; 7%). A higher proportion of ISO patients had marrow relapse (29.4% DIN; 48.2% ISO); however, the proportion of DIN patients with lung relapses appeared higher (9% vs 2%). Among all relapsed patients, the proportion with bone relapse did not appear to differ between treatment groups, regardless of MYCN status. Among patients with MYCN amplified disease, the proportion with marrow relapse did not appear to differ based on treatment [21/149 (14.1%) DIN; 3/20 (15.0%) ISO]; however, among patients with MYCN non-amplified disease, the proportion with marrow relapse appeared higher in the ISO group [16/23; 69.6%] vs the DIN group [52/193 (26.9%)]. Conclusions: In this exploratory analysis of patients on COG ANBL0032, the pattern for site of relapse appears to differ between patients treated with DIN vs ISO. While immunotherapy remains the treatment of choice in this population, the findings from this retrospective exploratory analysis warrant further investigation to decrease the risk for post-immunotherapy relapse. Clinical trial information: NCT00026312.

Patterns of Relapse in Patients with Well Differentiated Thyroid Cancer (Single Institutional Experience)

Patterns of Relapse in Patients with Well Differentiated Thyroid Cancer (Single Institutional Experience)

Changes in the Relapse Pattern and Prognosis of Glioblastoma After Approval of First-Line Bevacizumab: A Single-Center Retrospective Study

Controversies exist regarding the aggressive recurrence of glioblastoma after bevacizumab treatment. We analyzed the clinical impact of bevacizumab approval in Japan by evaluating the clinical course and relapse pattern in patients with glioblastoma. We included 100 patients with IDH-wild-type glioblastoma from September 2006 to February 2018 in our institution. The patients were classified into the pre-bevacizumab (n= 51) and post-bevacizumab (n= 49) groups. Overall, progression-free, deterioration-free, and postprogression survivals were compared. We analyzed the relapse pattern of 72 patients, whose radiographic progressions were evaluated. Significant improvement in progression-free (pre-bevacizumab, 7.5 months; post-bevacizumab, 9.9 months; P= 0.0153) and deterioration-free (pre-bevacizumab, 8.5 months; post-bevacizumab, 13.8 months; P= 0.0046) survivals was seen. These survival prolongations were strongly correlated (r: 0.91, P < 0.0001). The nonenhancing tumor pattern was novel in the post-bevacizumab era (5 of 33). The presence of a nonenhancing tumor did not indicate poor postprogression survival (hazard ratio: 0.82 [0.26-2.62], P= 0.7377). The rate of early focal recurrence was significantly lower (P=0.0155) in the post-bevacizumab (4 of 33) than in the pre-bevacizumab (18 of 39) era. There was a significant decrease in early focal recurrence after approval of bevacizumab in patients with unresectable tumors (P= 0.0110). The treatment era was significantly correlated with a decreased rate of early focal recurrence (P= 0.0021, univariate analysis; P= 0.0144, multivariate analysis). Approval of first-line bevacizumab in Japan for unresectable tumors may prevent early progression and clinical deterioration of glioblastoma without worsening the clinical course after relapse.

Pattern of relapse in patients with stage IB1 cervical cancer after radical hysterectomy as primary treatment. Minimally invasive surgery vs. open approach. Systematic review and meta-analysis.

BackgroundAfter the LACC trial, the SUCCOR study, and other studies, we know that patients who have undergone minimally invasive surgery for cervical cancer have worse outcomes, but today, we do not know if the surgical approach can be a reason to change the pattern of relapses on these patients. We evaluated the relapse pattern in patients with stage IB1 cervical cancer (FIGO, 2009) who underwent radical hysterectomy with different surgical approaches. MethodsA systematic review of literature was performed in PubMed, Cochrane Library, Clinicaltrials.gov, and Web of science. Inclusion criteria were prospective or retrospective comparative studies of different surgical approaches that described patterns or locations of relapse in patients with stage IB1 cervical cancer. Heterogeneity was assessed by calculating I2. ResultsThe research resulted in 782 eligible citations from January 2010 to October 2020. After filtering, nine articles that met all inclusion criteria were analyzed, comprising data from 1663 patients who underwent radical hysterectomy for IB1 cervical cancer, and the incidence of relapse was 10.6%. When we compared the pattern of relapse (local, distant, and both) of each group (open surgery and minimally invasive surgery), we did not see statistically significant differences, (OR 0.963; 95% CI, 0.602–1.541; p = 0.898), (OR 0.788; 95% CI, 0.467–1.330; p = 0.542), and (OR 0.683; 95% CI, 0.331–1.407; p = 0.630), respectively. ConclusionThere are no differences in patterns of relapse across surgical approaches in patients with stage IB1 cervical cancer undergoing radical hysterectomy as primary treatment.

Prognostic Implications of Epilepsy Onset Age According to Relapse Pattern in Patients with Four-Year Remission.

A total of 472 epilepsy patients with a 4-year remission period were divided into 10-year age groups according to age of onset. The relapse patterns during at least 3 years of follow-up were classified as early relapse (ER), late relapse (LR), and seizure-free (SF). The remission probability and multiplicity of prognostic factors were evaluated using univariate and multivariate multinomial logistic analyses. The weighted risk score based on odd ratios (ORs) was used for comparisons of the relative risk of relapse between groups. The group with onset in their 20s had the lowest remission probability among the groups. The risks of relapse in the LR patients and the relative weighted risk score of ER patients in the group with onset in their 20s were 3.11 and 19.44, respectively, which was the highest risk among the age groups. Patients without remission within 1 year had the highest relapse risk, with an OR of 7.18 in ER patients. The OR of relapse in patients with >10 generalized tonic–clonic (GTC) seizures was the second most important prognostic factor in LR patients. The distinct risk and corresponding prognostic factors in LR and ER patients reflected inherent differences between these relapse patterns.

Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab.

Blinatumomab is a CD19/CD3 bispecific T-cell engager (BiTE) antibody that simultaneously binds CD19 on the surface of B-cells and CD3 on the surface of T-cells, resulting in tumor cell lysis. It is approved for the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and in patients with minimal residual disease after intensive induction chemotherapy. Relapse patterns after treatment with blinatumomab have not been well characterized. We reviewed patients treated with blinatumomab with relapsed, refractory or minimal residual disease-positive B-ALL from 1 December 2014 to 31 December 2018 at a single academic medical center. Patient demographics, blast percentage prior to blinatumomab initiation, prior lines of therapy, blinatumomab treatment duration, sites of relapse, progression free survival, and overall survival were collected. A total of 20 patients were identified. Four (20%) patients developed extramedullary relapse following blinatumomab. The median time from treatment initiation to extramedullary relapse was 179 days (range 47-241). Sites of extramedullary relapse included the pancreas, adrenal gland, kidneys, liver, parotid gland, and brain. Extramedullary relapse occurs frequently following treatment of B-ALL with blinatumomab. Further studies aimed at preventing extramedullary relapse following blinatumomab treatment are warranted.

Abstract P3-08-04: Impact of ER-positivity on time and pattern of relapse in early-stage breast cancer patients

Abstract Background: While it is well recognized that ER positivity is predictive of response to endocrine therapy for patients with early-stage breast cancer (EBC), the method to assess ER level has evolved over time. The applicability of early trial data to clinical practice using contemporary methods of assessment is unclear. Clinical trials of hormone therapy, which inform clinical practice, do not correlate the ER level of positivity to the magnitude of benefit. Given that most newly diagnosed EBCs are ER positive, it is important to determine if the level of ER positivity as determined by current IHC methodology and scoring systems affect the frequency, time and pattern of relapse in patients with low, moderate or high ER positivity. Methods: The BC Cancer Breast Cancer Outcomes Unit (BCOU) database was utilized to identify patients with EBC referred to BC Cancer from 2005-2014. Baseline clinical, pathological and treatment criteria were compiled. Patients were divided into 3 groups, defined as “ER low” (Allred 3-4 OR IHC 1), “ER moderate” (Allred 5-6 OR IHC 2) or “ER high” (Allred 7-8 OR IHC 3). Event-free survival (EFS) was compared across the 3 groups using Kaplan-Meier survival curves in univariate and multivariate models. Key secondary endpoints included breast-cancer specific survival (BCSS) and overall survival (OS). Additional secondary endpoints included local-regional free survival (LRFS) and distant-disease-free survival (DDFS) and sites of relapse. Results: A total of 14,260 patients met the inclusion criteria consisting of 492 (3.5%) ER low, 1,088 (7.7%) ER moderate and 12,613 (88.9%) ER high patients. Median age was 55yrs (24-91) in the ER low, 53yrs (23-92) in the ER moderate and 61yrs (22-99) in the ER high groups (p&amp;lt;0.001). A total of 66.1%, 69.6% and 76.8% had stage I or IIa cancers in the ER low, moderate and high groups, respectively (p&amp;lt;0.001). Overall, grade 3 was present in 78.0%, 42.8% and 23.7% of patients in the ER low, moderate and high groups, respectively (p&amp;lt;0.001). HER2 positivity was present in 34.1% of the ER low, 24.1% of the ER moderate and 8.5% of the ER high groups (p&amp;lt;0.001). Systemic treatment received consisted of chemotherapy with subsequent hormone therapy in 76.4% of the ER low, 61.1% of the ER moderate and 34.4% of the ER high patients, whereas the rest received hormone therapy alone. Median follow-up was 7.4 yrs. 5-year EFS was 80% (95% CI 76, 84) in the ER low group, 87% (85, 89) in the ER moderate group and 89% in the ER high group (88, 90) in univariate analysis; p=0.004. This remained statistically significant in multivariate analysis when comparing the ER high to the ER low and moderate groups; p=0.01. 10-year EFS was 75% (70, 80) in the ER low, 77% (74, 79) in the ER moderate and 77% (76, 78) in the ER high groups; p=0.004. 5-year BCSS was 89% (86, 92), 94% (93, 95) and 97% (96, 98) in the ER low, moderate and high groups, respectively; p&amp;lt;0.0001. 5-year OS was 85% (82, 88), 91% (89, 93) and 93% (92, 94) for the ER low, moderate and high groups, respectively; p=0.03. Local recurrences were more frequent in ER low patients, as opposed to the ER moderate or high groups; p&amp;lt;0.001. Distant relapses were also more frequent in the ER low group when compared to the ER moderate and high groups; p&amp;lt;0.001. Distant sites of recurrence were also significantly different amongst groups (p=0.091), although absolute differences were small. Conclusions: The level of ER positivity was significantly associated with all survival parameters in a real-world setting. This large series highlights the importance of the ER level as a predictive and prognostic marker for patients with EBC. Patterns of relapse including the timing of recurrence will be also described. Research on the optimal treatment and duration of therapy for patients with low to moderate ER positivity is needed to improve outcomes and further define the impact of endocrine therapy for the ER low group. Citation Format: Nathalie LeVasseur, Kaylie-Anne Willemsma, Caroline Lohrisch, Lovedeep Gondara, Caroline Speers, Christine Simmons, Alan Nichol, Karen Gelmon. Impact of ER-positivity on time and pattern of relapse in early-stage breast cancer patients [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 P3-08-04.

Current status of immune checkpoint inhibition in early-stage NSCLC.

Immune checkpoint inhibition (ICI) immunotherapy has revolutionized the approach to metastatic non-small-cell lung cancer (NSCLC). In particular, antibodies blocking the inhibitory immune checkpoints programmed death 1 (PD-1) and its ligand (PD-L1) are associated with higher response rates, improved overall survival and better tolerability as compared with conventional cytotoxic chemotherapy. Recently, ICI has moved from the second-line to the first-line setting for many patients with non-oncogene-addicted NSCLC, either alone or in combination with chemotherapy. The next logical step is to examine this therapy in patients with non-metastatic NSCLC to improve long-term overall survival and cure rates. For patients with unresectable stage III NSCLC, ICI with durvalumab after concurrent chemoradiotherapy has brought a major improvement in 2-year progression-free and overall survival, which holds promise for an improved cure rate. As the relapse pattern in patients with completely resected early-stage NSCLC is predominantly systemic, high expectations rest on the integration of ICI therapy in their treatment approach. A large number of studies with adjuvant or neo-adjuvant ICI are ongoing and will be discussed here. The advent of stereotactic ablative radiotherapy has brought a valid alternative treatment of patients unfit for or not willing to undergo surgery. Data on combining systemic therapy and stereotactic ablative radiotherapy are virtually non-existent, but there is a strong biological rationale to combine radiotherapy and ICI therapy. Early findings in small feasibility studies are promising and now need to be explored in well-designed phase III trials.

L1CAM as a Negative Prognostic Factor in Endometrioid Endometrial Adenocarcinoma FIGO Stage IA-IB.

In this study, we aimed to investigate how positivity for L1 cell adhesion molecule (L1CAM) was associated with outcome and relapse pattern in patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IA-IB endometrial cancer. This retrospective study included 358 patients who underwent surgical treatment for endometrial carcinoma. Tumor samples from 312 patients (87.2%) were available for L1CAM analysis by immunohistochemistry. Of the 312 tumor samples analyzed, 93 (29.8%) were L1CAM-positive. L1CAM positivity was significantly more common in grade 3 compared to grade 1-2 carcinomas (p=0.02). Patients with L1CAM positivity more commonly experienced disease progression. Distant metastasis was significantly associated with L1CAM positivity (p=0.01). Progression-free interval and overall survival did not significantly differ between L1CAM-positive and L1CAM-negative cases. L1CAM is a promising independent prognostic marker associated with aggressive tumor behavior and recurrence risk, but not with overall survival.

Patterns of Relapse After Salvage Autologous Stem Cell Transplant for Hodgkin's Lymphoma: Should Sites of Relapse Relative to Initially Involved Sites Be Used to Guide Indications for Peri-Transplant Radiation Therapy

PurposeWe aimed to assess patterns of relapse in patients undergoing salvage autologous stem cell transplant (ASCT) for relapsed Hodgkin lymphoma in the modern era with the hypothesis that patients who suffer a relapse at initially involved sites are at increased risks of relapse post-ASCT that may help guide the application of peri-transplant radiation therapy. Methods and MaterialsA retrospective review was conducted of 38 patients undergoing ASCT between 2002 and 2017 for relapsed or refractory Hodgkin lymphoma. The site of relapse at the time of ASCT and subsequent relapses were compared with sites of the initial involvement at the time of diagnosis using follow-up imaging (most commonly positron emission computed tomography). Relapse and overall survival rates were calculated from the date of ASCT using the Kaplan-Meier method with a multivariate analysis, completed using a Cox multivariate analysis. ResultsThe median follow-up time was 38 months (interquartile range, 18-66 months). Twenty-two patients (58%) suffered a relapse after ASCT at a median time to relapse of 9.1 months (interquartile range, 2.9-12.3 months) with a 5-year risk of relapse of 58% (95% confidence interval [CI], 41%-75%). On univariate analysis, relapse at an initially involved site was significant for higher rates of relapse at 71% at 5-years (95% CI, 52%-90%) compared with relapse at initially uninvolved sites at 30% (95% CI, 2%-58%; P = .05). The relapse rate was also significantly higher in patients age <30 years at the time of diagnosis at 80% (95% CI, 59%-100%) compared with 40% (95% CI, 18%-62%) at 5 years in patients aged >30 years (P < .01). On multivariate analysis, relapse at initially involved sites was significant for higher rates of relapse (hazard ratio: 8.3; 95% CI, 1.2-57.4; P = .03). ConclusionsRelapses at initially involved sites may potentially increase the risk of relapse after ASCT. Additional studies are needed to clarify whether this should be used as an additional factor to guide recommendations for peri-transplant radiation therapy.

Patterns of Relapse after Salvage Autologous Hematopoietic Cell Transplantation for Hodgkin’s Lymphoma: Should Sites of Relapse Relative to Initially Involved Sites Be Used to Guide Indications for Peritransplant Radiation Therapy

The utilization of radiotherapy (RT) in the upfront management of Hodgkin’s Lymphoma (HL) is declining in favor of chemotherapy alone favoring patterns of relapse towards initially involved sites. For patients suffering relapsed/refractory HL, autologous Hematopoietic Cell Transplantation (auto-HCT) is the preferred method of salvage therapy, where-in the role of peritransplant RT is controversial and based primarily on data formulated in subsets receiving RT as a component of upfront therapy. We aimed to assess patterns of relapse in patients undergoing salvage auto-HCT for relapsed HL with the hypothesis that patients suffering relapse at initially involved sites are at increased risks of relapse post-auto-HCT that may help guide the application of peritransplant RT. A retrospective review of 41 patients undergoing auto-HCT from 2002-2017 for relapsed or refractory HL. Three patient received peritransplant RT to a median dose of 32.5Gy. Site of relapse at time of auto-HCT and subsequent relapse were compared to sites of involvement at diagnosis using follow-up imaging (PET/CT). Relapse and overall survival were calculated from the date of auto-HCT using the Kaplan Meier method with multivariate analysis completed using Cox multivariate analysis. The median follow-up was 39 months for all patients [Interquartile Range (IQR): 18-68 months] and 48 months for surviving patients (IQR: 29-84 months). Median age at auto-HCT was 35 years (IQR: 26-50 years), stage at relapse was I-II in 49%. For upfront therapy, 81% of patients received chemotherapy alone, predominately with ABVD to a median of 6 cycles. Twenty-three patients (56%) suffered relapse following auto-HCT at a median time to relapse of 8.8 months (IQR: 3.2-12.3) with a 5-year risk of relapse of 56% (95%CI: 40-72%). Of those patients with relapse, 37% were in sites involved prior to auto-HCT, of which 86% were similarly involved at initial diagnosis and only 8% of which had RT as a part of upfront therapy. On univariate analysis, there was no difference in relapse after auto-HCT by refractory versus relapsed HL, B-symptoms at diagnosis, use of RT as part of upfront therapy or peritransplant, age at diagnosis or relapse, response to salvage chemotherapy prior to auto-HCT or stage at diagnosis or relapse. However, pre-auto-HCT relapse at an initially involved site trended toward significance for higher rates of relapse post-auto-HCT at 68% at 5-years (95%CI: 49-87%) compared to relapse at initially uninvolved sites 30% (95%CI: 8-58%), p =0.06. By multivariate analysis, initial sites of disease were more likely to be involved at relapse after auto-HCT, HR 5.85 95%CI 1.10-31.0, p =0.04. Post-auto-HCT relapse of HL are likely to occur early in initially involved sites of disease and site of relapse at an initially involved site represent an area where additional studies are needed to clarify the role of peritransplant RT.

Class I hysterectomy in stage Ia2-Ib1 cervical cancer.

IntroductionDuring the last 3 decades, the standard treatment for stage Ia2-Ib1 cervical cancer has been Piver-Rutledge class II or III radical hysterectomy. However, this surgery is associated with a high rate of urologic morbidity.AimTo determine the efficacy of class I radical hysterectomy compared with class III radical hysterectomy in terms of morbidity, overall survival, and patterns of relapse in patients with Ia2-Ib1 cervical cancer undergoing primary surgery.Material and methodsA total of 101 patients with stage Ia2-Ib1 cervical cancer < 2 cm were randomized to class I and class III hysterectomy groups. Clinical, pathologic, and follow-up data were prospectively collected. Univariate analysis was carried out. Of the total patients, 45 were randomized to class I surgery and 56 to class III surgery. No significant differences were observed in terms of pathologic findings or adjuvant treatment (p > 0.05). The morbidity rates were higher after class III surgery.ResultsThe difference in recurrence rate between the class I and class III groups was not statistically significant (p > 0.05). The 5-year overall survival rate was 93% and 91%, respectively (p > 0.05). There were no significant differences in terms of recurrence rate or overall survival among patients with stage Ia2-Ib1 cervical cancer < 2 cm who underwent class I or radical (class III) hysterectomy. Morbidity was proportional to the extent of radicality.ConclusionsThese data confirm the need for reducing surgical radicality in the treatment of patients with early cervical cancer, by tailoring the extent of resection according to the extent of disease.