End Of First-line Treatment Research Articles

ATRT-06. PEDIATRIC INI1-NEGATIVE ATYPICAL TERATOID RHABDOID TUMORS TREATED WITH TAZEMETOSTAT AS MAINTENANCE THERAPY IN THE RELAPSE SETTING: AN ITALIAN SINGLE-CENTRE EXPERIENCE

Abstract BACKGROUND Rhabdoid tumors are aggressive malignancies, primarily affecting children ≤3 years. Common sites of primary localization are kidney, central nervous system (atypical teratoid rhabdoid tumor -AT/RT-) or soft tissues. Although high-dose chemotherapy (HD-CT) with radiotherapy (RT) has significantly increased EFS and OS rates, more than 50% of patients diagnosed with AT/RT still die of tumor progression. METHODS From February 2021 to January 2024 three patients with AT/RT were treated with tazemetostat after first-line treatment (complete resection, CT, RT). RESULTS At diagnosis, patient 1 presented with a lesion in the lamina quadrigemina and a renal mass; patient 2 and 3 with a lesion in the posterior cranial fossa. Median age at diagnosis was 8 months (3-34 months). Patient 1 died due to the progression of the disease (OS 24 months); patient 2 ended treatment with tazemetostat on December 2023; for patient 3 the treatment is still ongoing. Patient 1 started tazemetostat at the end of first-line treatment, as maintenance therapy. Before starting treatment with tazemetostat, patient 2 performed a re-irradiation on the tumor bed; patient 3 performed surgery and then RT on a new-onset spinal lesion. Median time of treatment with tazemetostat was 9 months (6-12 months). Patient 1 showed an EFS of 9 months. EFS of patients 2 and 3 has exceeded this timepoint. For patient 2 the treatment is ongoing (in total 6 months of treatment), with a complete response of the disease (CR); patient 3 ended treatment after 12 months, with a CR. Tazemetostat was overall well tolerated. CONCLUSIONS Despite the small number of patients, we feel able to state that the use of tazemetostat as a single agent in the relapse setting could represent a therapeutic promise as maintenance therapy. Future studies with a larger number of patients are needed to confirm this hypothesis.

Evaluation of total tumor volume reduction ratio in initially unresectable colorectal liver metastases after first-line systemic treatment

PurposeTotal tumor volume (TTV) may play an essential role in the estimation of tumor burden. This study is aimed to investigate the clinical value of the reduction ratio of TTV as a valuable indicator of clinical outcomes in patients with colorectal liver metastases (CRLM). MethodsA total of 240 initially unresectable CRLM patients who underwent first-line systemic treatment were enrolled in this study. TTV at baseline and at the end of first-line treatment were assessed using a three-dimensional reconstruction system according to CT or MRI images. Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). ResultsA total of 212 (88.3%) patients achieved tumor regression with a median reduction ratio of TTV of 86.0%. An increasing reduction ratio of TTV was associated with a gradually ascending successful conversion outcome. Patients with a reduction ratio >86.0% had better survival than those with a reduction ratio 0–86.0% or <0 (5-year overall survival (OS) rates, 64.4% vs. 44.9% vs. 23.5%, P < 0.001; 5-year progression-free survival (PFS) rates, 36.3% vs. 28.2% vs. 6.5%, P < 0.001). Multivariate analysis indicated that the reduction ratio of TTV ≤ 86.0% (OR [95%CI]: 4.956 [2.654–9.253], P < 0.001) was an independent factor for conversion failure outcome. Cox analyses revealed that the reduction ratio of TTV ≤ 86.0% was an independent factor for both unfavorable OS (HR [95%CI]: 2.216 [1.332–3.688], P = 0.002) and PFS (HR [95%CI]: 2.023 [1.376–2.974], P < 0.001). ConclusionsThe reduction ratio of TTV was an effective indicator for conversion outcome and long-term prognosis in patients with initially unresectable CRLM after first-line systemic treatment.

FDG PET/CT Maximum Tumor Dissemination to Predict Recurrence in Patients with Diffuse Large B-Cell Lymphoma.

We investigated the prognostic value of maximum tumor dissemination (Dmax), the distance between malignant lesions that were farthest apart, as assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and other clinical factors in patients with diffuse large B-cell lymphoma (DLBCL).We investigated the prognostic value of maximum tumor dissemination (Dmax), the distance between malignant lesions that were farthest apart, as assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and other clinical factors in patients with diffuse large B-cell lymphoma (DLBCL). Patients who underwent FDG PET/CT for initial staging and treatment response evaluation of DLBCL were reviewed retrospectively. Baseline Dmax, maximum standardized uptake value, total summation of all metabolic tumor volumes (tMTV), and total summation of all total lesion glycolysis (tTLG) were measured. The treatment response was evaluated at the interim and end of first-line treatment (EOT) using the Deauville score (DS). FDG PET/CT parameters and other clinical factors including sex, age, serum lactate dehydrogenase (LDH) level, stage, performance status, and the International Prognostic Index (IPI) were analyzed to identify factors prognostic of the time to progression (TTP) and disease-specific survival (DSS). A total of 63 patients were included. Univariate survival analysis identified Dmax (> 275mm), tMTV (> 180mL), tTLG (> 1300), interim DS (≥ 4), and EOT DS (≥ 4) as significant predictors of poor TTP. Serum LDH level (> 640IU/L), IPI (≥ 4), tMTV (> 180mL), tTLG (> 1300), interim DS (≥ 4), and EOT DS (≥ 4) were significant predictors of DSS. After multivariate survival analysis, Dmax (P = 0.008) and EOT DS (P = 0.005) were independent predictors of TTP. EOT DS was an independent predictor of DSS (P = 0.029). Dmax at the time of diagnosis and the EOT response assessed by FDG PET/CT provide useful prognostic information additive to the IPI in patients with DLBCL.

P1074: PRIMARY REFRACTORY HODGKIN’S LYMPHOMA: A MOROCCAN MONOCENTRIC RETROSPECTIVE STUDY

Background: Primary refractory Hodgkin’s lymphoma (PRHL)is defined as disease progression during initial first-line therapy or early relapse of less than 3 months [1], this entity is a therapeutic challenge for hematologists, as the response rate to second-line therapy remains lower (51% vs. 83%, P < 0.0001)[2] Aims: Compare different parameters between patients with PRHL and patients with non-PRHL to reveal factors that could predict the primary refractory character of our patients. Evaluate the evolution in terms of therapeutic response and survival of our patients with PRHL compared to non-PRHL Methods: This is a monocentric retrospective descriptive study that collected all the files of patients followed for Hodgkin Lymphoma at the clinical hematology department of the Military Hospital of Instruction Mohammed V in Rabat between January 2010 and December 2020. Their epidemiological, clinical and prognostic characteristics were recorded, and the efficacy and tolerance of the therapies used were evaluated. We used the t-student, Mann-Whitney, χ2 tests (or Fisher’s exact test) to compare the differences between PRHL and non-PRHL patients. To assess the difference in survival between the two groups, we used the Log-rank test on Kaplan-Meier survival curves.Treatment outcomes were measured in terms of response rate, overall survival (OS) and progression-free survival (PFS). Statistical analyses were performed using JAMOVI software (version 1.6) Results: Classical Hodgkin lymphoma was diagnosed in 122 patients. 27 patients were primary refractory (22.1%). Our comparison between the group of PRHL and non-PRHL patients in terms of age, sex, time to consultation, performance status (PS) score, clinical signs at admission, histological subtype, presence of Bulky mass on chest X-ray, the Ann Arbor stage and the prognostic risk group did not show any significant difference, which makes the identification of primary refractory patients in pre-therapy a difficult challenge. In our serie 83(68%) patients were re-evaluated at 2 courses by PET-Scan (Positron Emission Tomography, 45(54.3%) patients were in Complete Remission (CR), 34(41%) in Partial Remission (PR). Comparing PRHL and non-PRHL patients according to the response at 2 courses, a highly significant difference was observed (p=0.001). Using a univariate logistic regression model, we found that a PR at 2 courses was more likely to be PRHL than a complete response (OR= 4.95; CI95% [1.55-15.78]; p=0.007). At the end of first-line treatment, 77.1% of all patients achieved complete remission, 11.5% achieved partial response, 1 patient had a stable response and 10.6% were in progression. The overall response at the end of treatment for PRHL patients was 44.4% vs 93.6% for the non-PRHL group (p<0.001). 10.7% of patients relapsed within a median of 23 months. With a median follow-up of 65.5 months, the OS and PFS of all patients at 5 years were 91.2% and 90.6% respectively. Comparing primary refractory and non-refractory patients, the OS at 5 years was 73% [56.2-94.8] vs 96.5% [92.7-100] (p<0.0001) (Figure 1). Image:Summary/Conclusion: Primary refractory Hodgkin’s lymphoma remains a form with a poor prognosis, the overall 5-year survival of this form in our series is 73% compared to 96.5% for the non-PRHL patients. PET-2 may be a predictive step for this form, studies are needed to identify the place of immunotherapy in the management of these patients

150P Monitoring of PD-L1 expression on circulating immune cells of patients with small cell lung cancer (SCLC) receiving first-line treatment: Prognostic implications

PD-L1 expression has been reported on tumor-infiltrating immune cells in SCLC tissue, however its prognostic role is not clear as yet. We herein assessed the incidence and clinical value of PD-L1 expression on immune cells circulating in the peripheral blood (PB) of SCLC patients receiving first-line treatment. PB was obtained from 34 SCLC patients (limited-stage: n=7; extensive-stage: n=27) at baseline and at the end of first-line treatment, consisting of chemotherapy alone (n=18) or in combination with atezolizumab (n=16). Peripheral blood mononuclear cell (PBMC) cytospins were immunofluorescently stained for dapi/PD-L1 (Clone: E1L3N) and PD-L1 expression was quantified on 1.000 randomly selected intact PBMCs/per sample via the Ariol microscopy system. PD-L1positive PBMCs were identified in 70.6% and 73.5% of patients at baseline and post treatment, respectively, while PD-L1high PBMCs in 17.6% and 26.5%, respectively. In 23.5% of patients, PD-L1high PBMCs were detected in the post-treatment sample only (in 31.3% and 16.7% of patients treated with chemoimmunotherapy as compared to chemotherapy alone, respectively; p=0.429). The detection of PD-L1high PBMCs in the post-treatment sample only was associated with disease progression in the brain (in 38.5% versus 0% of patients with and without brain progression, respectively; p=0.009). Kaplan Meier analysis showed that patients harboring PD-L1high PBMCs post-treatment only, had numerically reduced progression free survival (median PFS: 5.3 versus 6.7 months; p=0.089) and overall survival (median OS: 8.4 versus 15.8 months; p=0.152). In addition, patients treated with chemoimmunotherapy and post-treatment only PD-L1high PBMCs, had significantly shorter OS (8.4 versus 15.7 months; p=0.007). PD-L1 is frequently expressed on PBMCs of SCLC patients receiving first-line treatment. The detection of PD-L1high PBMCs post-treatment might be associated with disease progression in the brain and worse survival measures. To further delineate its role, PD-L1 expression on PBMCs is currently being investigated in a larger SCLC patient cohort.

Prognostic evaluation value of (18)F-FDG PET-CT in Hodgkin's lymphoma after treatment

Objective: To investigate the prognostic value of (18)F-fluorodeoxygen-D-glucose-positron emission tomography /computerized tomography ((18)F-FDG-PET-CT) in Hodgkin's lymphoma (HL) at the end of first-line treatment (PET-end), by comparing the ratio of maximum standardized uptake value (SUV(max)) of lesion and liver SUV (rLL), SUV(max) reduction between baseline PET (PET-0) and PET-end (ΔSUV(max)), and Deauville 5-point scale (5-PS). Methods: Patients with HL newly treated in our hospital from August 2006 to December 2015 were retrospectively analyzed. All the patients enrolled in the study underwent post-treatment FDG PET-CT. The rLL and ΔSUV(max) were calculated, and all the cases were scored using Deauville 5-PS. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point value, and survival curves according to different PET-CT assessment methods were estimated using the Kaplan-Meier analysis. The prognostic efficacy of different PET-CT assessment methods was compared, and DeLong test was used to verify it. Kaplan-Meier method and multivariate analysis using the Cox proportional hazards model were performed to analyze the potential independent risk factors. Results: There were 5 patients progressed within a 3-year follow-up. In the three PET-CT assessment methods, the predictive value of rLL and Deauville 5-PS were significant effective. ROC analysis for rLL as a progression predictor showed an optimal cut-point of 1.29. Deauville 5-PS=4 and rLL=1.29 showed the best prognostic accuracy. The sensitivity of rLL and Deauville 5-PS were both 80.0%, and the specificity of each was 98.0% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of rLL were 66.7% and 98.7%, while the PPV and NPV of 5-PS were 44.4% and 98.7%. The 3-years progression-free survival (PFS) rates of rLL≥1.29 group and rLL<1.29 group were 33.3% and 98.7%, with significant difference (P<0.001). The 3-years PFS rates of post-treatment Deauville 5-PS<4 group and Deauville 5-PS≥4 group were 98.7% and 55.6%, with significant difference (P<0.001). The prognostic evaluation efficacy of rLL was positively correlated with that of Deauville 5-PS (r=0.75, P<0.05). Area under curves (AUC) of rLL and Deauville 5-PS were 0.93 (95%CI: 0.825-1.000) and 0.91 (95%CI: 0.757-1.000), respectively. DeLong test showed the significant difference between the two methods (P<0.05). The univariate analysis results showed that clinical baseline stage, post-treatment rLL and Deauville 5-PS were associated with the prognoses of HL patients (P<0.05). The multivariate analysis results showed that post-treatment rLL and Deauville 5-PS were independent prognostic factors of HL (P<0.05). Conclusions: The rLL and Deauville 5-PS are potential prognostic factors for HL response assessment. The new semi-quantitative method rLL has methodological advantages over visual analysis, and it is a good supplement for Deauville 5-PS. rLL can improve prognostic evaluation accuracy of PET-CT and is useful to early identify patients with HL at a high risk of relapsing after first-line treatment.

NP-109: Improving long-term quality of life for patients living with multiple myeloma: a service evaluation

<h3>Background</h3> Multiple myeloma (MM) is an incurable malignancy of the bone marrow. With improving survivorship patients are developing late effects and long-term consequences due to the treatments, alongside the disease itself. The 2017 guidance for screening and management of late and long-term consequences does not suggest where in the MM pathway this screening should be. <h3>Methods</h3> A quantitative, formative service evaluation using audit of the current screening and a correlational design, using one-way MANOVA evaluating the effect the stage of pathway has on symptom burden and distress. Symptom burden is assessed using the palliative outcome score MY-POS and distress using the distress thermometer. <h3>Results</h3> Patients (N=60) are currently frequently screened for adjusted calcium (96%), urea and electrolytes (96%), liver function tests (90%) and blood pressure (62%). LH/FSH (0%), testosterone (10%), oestrogen (0%), T-SAT (30%), Vitamin D (15%) and BNP (3%) are least likely to be screened. Completed questionnaires (N=223) demonstrated that frequently reported symptoms were pain (76.2%), weakness or lack of energy (86.1%), drowsiness (69.1%), poor mobility (70.1%) and tingling in the hands and feet (65.5%). Distress is perceived higher by those patients on treatment (M=4.01, SD=2.486). Higher levels of distress were demonstrated by patients post first line (M=3.33, SD=2.446) and post third line (M=4.6, SD=2.510). MANOVA analysis demonstrated an effect on overall wellbeing of the patients in relation to position in the treatment pathway (F=13.35, p=<0.005) <h3>Discussion</h3> Screening and management of late effects and long-term consequence can improve quality of life. This evaluation has demonstrated the need for formal screening and management of these complications from diagnosis. Evaluation of symptoms and distress in the pathway has demonstrated that assessment at diagnosis, at the end of first line treatment or one year after starting a continuous treatment and repeated annually from when patients start third line treatment will improve QOL.

TREATMENT AND OUTCOMES OF PATIENTS WITH POST‐TRANSPLANT LYMPHOPROLIFERATIVE DISORDER: A SINGLE CENTRE EXPERIENCE

Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially severe complication that takes place after solid (SOT) or allogeneic hematopoietic stem cell transplant (HSCT). To date, its treatment is not standardised, and choice of therapy depends on histology and clinical presentation. We report the results of a 10 years (yrs) single-centre retrospective study assessing presentation, treatment patterns and outcomes of patients with PTLD. Methods: Patients ≥18 yrs diagnosed with a PTLD between 2011 and 2020 were identified in our medical records database. Primary endpoints were 2 yrs progression-free survival (PFS), overall survival (OS), and relapse incidence (RI) estimated with Kaplan-Meier and comparison between HSCT and SOT group. Secondary endpoints were the overall response rate (ORR) and complete response rate (CRR) at the end of first line treatment. Exploratory univariate analysis for OS, PFS were investigated using Cox regression model. Results: A total of 38 patients were included. Patient's characteristics and treatment strategies are presented in Table 1. HCST patients present a significantly higher prevalence of early onset PTLD (90% in HCST group vs 0% in SOT group), positive EBER immunostaining (100% vs 22%) and detectable Epstein Bar Virus (EBV) viremia (100% vs 28%), higher LDH (95% vs 66%), IPI score 3-5 (50% vs 33%), with a remarkable higher use of single agent Rituximab as first line therapy in HSCT patients (65% vs 11%). 2 yrs PFS was 54% (95%CI 36-73%) for the entire cohort, 42% (95%CI 16-67%) for HSCT and 67% (95%CI 41-92) for SOT; p-value 0.23. 2 yrs OS was 53% (95%CI 41-66%) for the entire cohort, 42% (95% CI 16-67%) for HSCT and 65% (95% CI 39-91) for SOT; p-value 0.22. 2 yrs RI was 9% (95% CI: 0-21%) for the entire cohort, 0% for HSCT and 14% (95% CI 0-33%) for SOT; p-value 0.26. ORR and CRR were similar with 82% (75% for HSCT, 89% for SOT, p-value 0.41) at the end of first line treatment. High IPI score (3-5) demonstrated worse outcome for PFS (HR: 2.5, 95%CI 0.95-6.65, p-value 0.063) and OS (HR: 2.4, 95%CI 0.92-6.48, p-value 0.07). A total of 17 patients died during follow-up: 7 during first line treatment of PTLD complication and multiorgan failure (5 in the HSCT group, 2 in the SOT group; p-value 0.41); 2 following PTLD relapse after first CR (0 in the HSCT group, 2 in the SOT group; p-value 0.22). Conclusion: This study highlights the clinical and therapeutic heterogeneity of PTLD. We observe a worse 2 yrs PFS and OS in patients with high IPI score. CRR after first line treatment is almost 90% in the SOT group, with a 2 yrs OS of 53%, consistent with previous studies (Trappe et al, JCO 2017). The higher mortality observed in the HSCT group suggests that serious treatment-related toxicities remain main challenges in this fragile patient population. New tools to guide therapeutic approaches in PTLD patients are warranted. Keywords: Lymphoid Cancers - Other No conflicts of interests pertinent to the abstract.

Association of Albumin-Bilirubin Grade and Sequential Treatment with Standard Systemic Therapies for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study Using a Japanese Administrative Database.

BackgroundEvidence about the relationship between albumin-bilirubin (ALBI) grade and sequential systemic therapy for advanced hepatocellular carcinoma in real-world Japanese clinical practice is limited.ObjectiveThe objective of this study was to investigate ALBI grades and sequential treatment for advanced hepatocellular carcinoma in Japanese clinical practice.MethodsWe conducted a retrospective cohort study using a Japanese hospital-based administration database to assess treatment sequence in patients with confirmed advanced hepatocellular carcinoma and first prescription (index line) of lenvatinib (July 2014–June 2019; N = 1558) or sorafenib (July 2014–June 2016 [sorafenib-A; N = 1511] or June 2017–June 2019 [sorafenib-B; N = 1276]). Transition to subsequent line was assessed in patients who completed the index line without transarterial chemoembolization. The ALBI grade and sequential treatment relationships were analyzed in patients with baseline and/or end of index line ALBI scores.ResultsTransition to a subsequent line was low (sorafenib-A [n = 1320]: 12.6%; sorafenib-B [n = 1049]: 40.7%; lenvatinib [n = 786]: 27.2%). In patients with baseline ALBI data (combined cohorts; n = 385), overall treatment duration was shorter in those with baseline ALBI grade 2b or 3 vs grade 1 or 2a (median: 7.1, 6.7, 4.5, and 3.0 months for grades 1, 2a, 2b, and 3, respectively). In patients with baseline and end of index line ALBI data (combined cohorts; n = 222), ALBI grade worsened during index line regardless of baseline grade. Of these patients in the sorafenib-B or lenvatinib cohorts who completed the index line without transarterial chemoembolization (n = 120), transition to a subsequent line was higher with the end of index line grade 1/2a (66.7/68.4%) than with grade 2b/3 (34.0/11.1%).ConclusionsAdequate liver function, indicated by ALBI grade, at the start and end of first-line treatment is associated with successful sequential therapy in Japanese clinical practice.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00245-8.

Oxaliplatin rechallenge in metastatic colorectal cancer patients with clinically significant oxaliplatin-induced peripheral neurotoxicity.

We investigated whether rechallenge with oxaliplatin (OXA) can worsen the pre-existing oxaliplatin-induced peripheral neurotoxicity (OXAIPN) in metastatic colorectal cancer (mCRC) patients. Patients previously treated with OXA, having clinically significant grade 1 or 2 OXAIPN were assessed, after receiving rechallenge with OXA, using the clinical version of the Total Neuropathy Score (TNSc). Peripheral neuropathy was assessed at the end of first OXA exposure and at completion of OXA rechallenge. The first line OXA-based chemotherapy was completed at least 9 months earlier (OXA-free interval). We studied 25 mCRC patients, 14 males and 11 females, with a median age of 63 (35-77) years. After their first exposure to OXA-based chemotherapy, 9 (36%) patients developed grade 1 OXAIPN and 16 patients grade 2 (64%) neurotoxicity. OXA reintroduction with a median of 10 (8-14) cycles led to grade 1 OXAIPN in two patients (8%), grade 2 in 19 patients (76%), and grade 3 neuropathy in 4 (16%) patients Worsening of pre-existing OXAIPN was documented in seven (28%) patients and was significantly associated with higher OXA delivered cumulative dose (P < .001). Median TNSc scores following treatment (10; range 4-18) were significantly increased (P < .001), when compared to the scores recorded at the end of first line treatment (8; range 2-12). Rechallenging OXA appears to relatively worsen the severity of existing OXAIPN. However, the majority of rechallenged patients developed a clinically significant (grade 2) OXAIPN, rather than treatment-emergent grade 3. As such, OXA rechallenge might be a feasible option in patients previously having OXAIPN.

Study of Treatment Complications in Oncology / Hematology Patients: Protocol for a Prospective and Interventional Cohort Study from the Pasca Program

Introduction In France, cancer incidence is increasing, reaching approximately 400,000 new cases in 2017. Thanks to diagnostic and therapeutic advances, net survival at 5 years is improving, with a corollary increase in the number of survivors. Among survivors, 44% have a poor quality of life due to the more or less late onset of treatment-related complications. Despite the objectives of the 2014-2019 national cancer plan considering the latest therapeutic advances, very few initiatives integrating systematic, early detection and management of complications exist in France. Methods and analysis PASCA (Care pathways through cancer) is a single-arm, interdisciplinary, prospective, interventional, cohort study. During a period of 24 months, it is intended to include 858 adults aged 18 to 65 years with non-Hodgkin and Hodgkin lymphoma, acute myeloid leukemia, testicular germ cell tumor, non-metastatic invasive breast cancer, soft tissue sarcoma, osteosarcoma or Ewing's sarcoma at Centre Leon Berard (Lyon, France). The program consists on exhaustive identification of 22 complications at 1 month, 6 months, 24 months and 60 months after the end of first line treatment: social precariousness, return-to-work issues, cognitive problems, anxiety and depression disorders, chronic fatigue, physical deconditioning, overweight/obesity, chronic pain, dermatological disorders, gastrointestinal disorders, sexual disorders, hypogonadism, premature ovarian failure, osteoporosis, chronic kidney failure, heart failure, coronary heart disease, respiratory failure, hypothyroidism, lymphedema, modifiable risk factors associated with the occurrence of secondary cancers. Each identification will give rise to management, which consists of referring the patient to a healthcare professional belonging to the network of dedicated healthcare professionals at the regional level. The course of action to be followed will be defined using decision trees based on international, national or learned society recommendations. Referral outside Centre Leon Berard will be made to a specialist doctor, a health professional from the paramedical field or the patient's general practitioner who will confirm the diagnosis and initiate patient management and follow-up. These patients will also benefit from their usual follow-up in the context of their initial malignancy. Each study visit will include a search for clinical signs using questionnaires, an assay of 12 biological parameters, a urine test strip, 5 tests evaluating physical deconditioning and an electrocardiogram. The weight, height, waist circumference, blood pressure will also be measured. Primary outcome will be the incidence of the 22 complications, measured at 1 month, 6 months, 24 months and 60 months after the end of intensive chemotherapy treatment. Ethics and dissemination The study protocol was approved by the French ethics committee (Comité de protection des personnes Ile de France IV), the study database is currently being declared and registered to the Commission Nationale de l'Informatique et des Libertés (CNIL) and the study on ClinicalTrials.gov. The results will be disseminated to patients and in peer-reviewed journals and academic conferences. Strengths and limitations of this study This study is based on a previous feasibility study with 52 patients recruited in onco-hematology, which demonstrated the feasibility of the intervention and the existence of patient management needs.(1) The study design does not include a comparator arm, as the objective of the study is to provide a comprehensive picture of treatment-related complications, especially those that appear over the long term. Due to the lack of recent data concerning some complications, sample size was calculated empirically on the basis of the active queue of patients at the Centre Leon Berard. References Michallet M, Sobh M, Buono R, Poirey S, Pascu I, Nicolas-Virelizier E, et al. Personalised Follow-up Program after Acute Phase of Treatment in Oncology/Hematology Patients Towards Early Intervention, Better Care and Quality of Life Improvement: Results from Pasca Pilot Study. Blood. 13 nov 2019;134(Supplement_1):5817-5817. Disclosures Nicolini: Sun Pharma Ltd: Consultancy; Incyte: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

Eligibility for Second-line Therapy in Patients With Advanced Hepatocellular Carcinoma: A Population-based Study.

With an increasing number of systemic therapy options for hepatocellular carcinoma (HCC), optimal sequencing is an important consideration. There remains limited real-world data about the eligibility of patients for second-line therapies in advanced HCC. We characterized real-world eligibility and use of second-line therapies post sorafenib. We identified all patients with advanced HCC who received ≥1 cycle of first-line sorafenib between January 1, 2014 and December 31, 2017 in British Columbia, Canada. All patients were Child-Pugh class A for initiation of sorafenib. Baseline characteristics and clinical outcomes were reviewed. Eligibility for second-line therapy was determined using the RESORCE and CELESTIAL study entry criteria. Of 144 patients with advanced HCC who received ≥1 cycle of first-line sorafenib, median age was 65.3 years (range, 32.2 to 83.4 y) and 85% were male. Median duration of sorafenib was 2.6 months. Twelve patients (8%) received second-line treatment but 37 patients (26%) were eligible for second-line therapies based on inclusion criteria from recent registration trials. Primary reasons for ineligibility included ECOG ≥2 (58%), and deterioration to Child-Pugh status B (28%). On Cox regression, improved survival was associated with better ECOG and recurrent disease after initial locoregional therapy. Eligibility for second-line treatment was associated with improved median overall survival from end of first-line treatment (8.5 vs. 5.1 mo; P<0.01). Only a minority of real-world patients with advanced HCC were eligible for second-line therapies based on trial criteria. Given the high rate of attrition, improved first-line treatment options are urgently needed.

Eligibility for second-line therapy in patients with advanced hepatocellular carcinoma (aHCC): A BC Cancer population-based study.

491 Background: Evidence supporting second-line therapies has become available for aHCC, including regorafenib, cabozantinib, ramucirumab, and nivolumab. The optimal second-line treatment regimen is unknown, and there remains limited real-world data about the eligibility of patients for second-line therapies in aHCC. We aimed to characterize the real-world eligibility and use of second-line therapies post sorafenib. Methods: We identified all patients with aHCC who received ≥1 cycle of first-line sorafenib between January 1, 2014 and December 31, 2017 across 6 centers in British Columbia (BC), Canada. All patients were required to be Child-Pugh class A for initiation of sorafenib in BC. Baseline characteristics and clinical outcomes were reviewed. Eligibility for second-line therapy was determined using the RESORCE and CELESTIAL study entry criteria. Results: Of 144 patients with advanced HCC who received ≥1 cycle of first-line sorafenib, median age was 65.3 years (range 32.2-83.4) and 85% were male. Median duration of sorafenib was 2.6 months. 12 patients (8%) went on to receive second-line treatment. 37 patients (26%) were deemed eligible for second-line systemic therapy. Primary reasons for ineligibility included ECOG ≥2 (58%), and deterioration to Child-Pugh status B (28%). On Cox regression, improved survival was associated with better ECOG and recurrent disease. (Table). Kaplan-Meier analysis demonstrated that eligibility for second-line treatment was associated with improved median overall survival from end of first-line treatment (8.5 vs. 5.1 months; p&lt;0.01). Conclusions: Only a minority of real-world patients with aHCC were eligible for second-line therapies based on second-line trial criteria. Given the high-rate of attrition, improved first-line treatment options are urgently needed. [Table: see text]

Survivorship Care Planning in Gynecologic Oncology—Perspectives From Patients, Caregivers, and Health Care Providers

(Abstracted from J Cancer Surviv 2018; https://doi.org/10.1007/s11764-018-0713-9) Survivors of gynecological cancer experience a significant level of disease- and treatment-related symptoms after the end of first-line treatment that persist and greatly impact their long-term quality of life. Fear of cancer recurrence is a significant and overwhelming psychological concern among women who survive.

Clinical Impact of Post-Progression Survival on Overall Survival in Elderly Patients with Non-Small-Cell Lung Cancer Harboring Sensitive EGFR Mutations Treated with First-Line EGFR Tyrosine Kinase Inhibitors

Background/Aims: More than 50% of patients with lung cancer are aged > 65 years, and non-small-cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer among both elderly and adult patients. Subsequent therapies confound the capability to discern the effect of first-line chemotherapy on overall survival (OS). Therefore, using individual-level data, our study aimed to determine the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS after first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in elderly patients with NSCLC harboring sensitive EGFR mutations. Methods: Between April 2008 and December 2015, we analyzed 68 elderly patients with NSCLC harboring sensitive EGFR mutations and treated with first-line EGFR-TKI. The relationships of PFS and PPS with OS were analyzed at an individual level. Results: Linear regression analysis showed that PPS was more closely associated with OS (R² = 0.54) than PFS was (R² = 0.48). Best response at first-line treatment, performance status at the end of first-line treatment, and administration of EGFR-TKI rechallenge were significantly correlated with PPS. Conclusions: PPS has a stronger impact on OS than PFS does in elderly patients with NSCLC harboring sensitive EGFR mutations and treated with first-line EGFR-TKI. These results indicate that OS in this patient population may be influenced by treatments subsequent to first-line chemotherapy; however, this remains to be verified in prospective studies.

Molecular remission at the end of treatment is a necessary goal for a good outcome in ELN favorable-risk acute myeloid leukemia: a real-life analysis on 201 patients by the Rete Ematologica Lombarda network

Favorable acute myeloid leukemia (AML) patients (pts.) demonstrate a relatively good outcome with standard induction; thus, pts. are generally not addressed to allogeneic transplant in first remission. However, it is not clear if also in a real-life setting, the outcome is homogeneous in the different favorable molecular groups and which are the parameters significantly associated to an increased relapse risk, useful to suggest the need of an intensified approach. In order to clarify this point, we collected clinical data on consecutive unselected AML pts. assigned to favorable category (modified ELN 2010 due to the inclusion of double-mutated CEBPA-positive cases), diagnosed and treated in six centers of the Italian network Rete Ematologica Lombarda (REL) from 2007 to 2015. We assessed response (CR, mCR), relapse rate (CIR), and outcome (OS, DFS) after first-line treatment. A total of 201 pts. was studied and the analysis was performed globally and in each molecular group: t(8;21)(q22;q22)/RUNX1-RUNX1T1 (30 pts., 14.9%), inv. (16)(p13q22) or t(16;16)(p13q22)/CBFB-MIH11 (35 pts., 17.4%), normal karyotype and mutated NPM1 and negative FLT3-ITD (116 pts., 57.7%) or double-mutated CEBPA (CEBPAdm) (20 pts., 10%). Complete remission (CR) was obtained in 188 pts. (93.5%), molecular CR (mCR) in 114 (67.5%); After a median follow-up of 2.4years, cumulative incidence of relapse (CIR) was documented in 78 of 188 responding pts. (41%) after a median time of 11.3months. CIR was higher in the CBFB-MIH11 group, in pts. achieving only a hematological response without mCR (72.1 vs 28.1%, p < 0.001), in older pts. and it resulted independently associated with a lower median cytarabine cumulative dose (CCD). Median OS was not reached: after 5years it was 66.3%, and median DFS was 5.3years, both without difference among groups. Molecular CR reached at any time, during or after the end of first-line treatment, was significantly associated with better DFS, and in particular, mCR assessed at the end of treatment was confirmed in multivariate analysis as an independent prognostic factor both for DFS and OS. In conclusion, the present study confirms in a real-life context the overall good prognosis of favorable-risk AML; the achievement of any molecular negativity during first-line treatment, particularly when assessed at the end of treatment, is associated with lower relapse and better survival. Increasing age at diagnosis has a negative prognostic impact, while CCD higher than 18g/sqm is associated with better outcome.

High-dose chemotherapy and peripheral hematopoietic stem cell transplantation in relapsed/refractory Hodgkin’s lymphoma

High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin's lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. All patients ≥15 years old with relapsed/refractory Hodgkin's lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. HDCT and ASCT for relapsed/refractory Hodgkin's lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.

Refractory diffuse large B-cell lymphoma after first-line immuno-CT: Treatment options and outcomes.

In the rituximab era, one-third of diffuse large B-cell lymphoma patients experience relapse/refractory disease after first-line anthracycline-based immunochemotherapy. Optimal management remains an unmet medical need. The aim of this study was to report the outcomes of a cohort of refractory patients according to their patterns of refractoriness and the type of salvage option. We performed a retrospective analysis, which included 104 diffuse large B-cell lymphoma patients treated at Lyon Sud University Hospital (2002-2017) who presented with refractory disease. Refractoriness was defined as progressive/stable disease during first-line treatment (primary refractory, N=47), a partial response after the end of first-line treatment that required subsequent treatment (residual disease, N=19), or relapse within 1year of diagnosis after an initial complete response (CR) (early relapse, N=38). The 2-year overall survival (OS) rates for primary refractory, early relapse, and residual disease patients were 27%, 25%, and 52%, respectively, while the event-free survival rates for those groups were 13%, 13%, and 42%, respectively. In a univariate analysis, lactate dehydrogenase level, Ann Arbor stage, poor performance status, high age-adjusted International Prognostic Index score, and age>65years were associated with shorter OS. The use of rituximab and platinum-based chemo during the first salvage treatment was associated with prolonged OS. In a multivariate analysis, age (HR:2.06) and rituximab use (HR:0.54) were associated with OS. Among patients <65years who achieved a CR, autologous stem-cell transplant was associated with higher 2-year OS (90% vs 74%, P=0.10). Patients who were treated with a targeted therapy in the context of a clinical trial after second-line treatment had a higher 2-year OS (34% vs 19%, P=0.06). In conclusion, patients with primary refractory disease or early relapse have very poor outcomes but may benefit from rituximab retreatment during the first salvage treatment.

Abstract 1129: Sigma receptors: Novel targets for the treatment of highly malignant tumors

Abstract Introduction. More than 7 million patients are diagnosed with cancer every year, and approximately 24 million new cases of cancer will probably be registered by 2035. Over the past decades, numerous cancer targets have been identified and, despite promising results in this field, the discovery of novel targeted therapies is still a largely unmet need. Sigma receptors (SRs), more highly expressed in tumor cells than in normal cells, have aroused the interest of the scientific community because of increasing evidence of their involvement in proliferation and survival signaling pathways of cancer cells. Glioblastoma (GBM) and pancreatic cancer (PCa) are two of the most aggressive and lethal solid tumors. GBM patients usually relapse within 7-10 months of the end of first-line treatment with median survival of about 14.6 months while PCa is the fourth most fatal cancer in both men and women, with median survival of 6-12 months. Little or no improvement in prognosis has been obtained over the past 20 years. Thus, new approaches to the treatment of both tumors are urgently needed. In the present work, 3D GBM primary cultures endowed with stemness features and PCa cell lines were used to evaluate the antitumor activity of a dual S1R and S2R ligand RC-106, a novel sigma receptor modulator. Methods. RC-106 tissue distribution studies were performed in mice. PCa cell lines were assessed by cytotoxic assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay). Molecular analyses were performed by qRT-PCR and Western blot. Apoptosis and cell cycle were analyzed by flow cytometry. GBM primary cultures were isolated from surgical tumor samples. A rotatory cell culture system (RCCS) was used to obtain 3D cell cultures. Growth and morphology of the colonies were monitored by open-source AnaSP and ReViSP software tools. Molecular analyses were performed by flow cytometry and qRT-PCR. 3D cell viability was measured using CellTiter-Glo® 3D Cell Viability Assay. Apoptosis and cell cycle were analyzed by flow cytometry. Results. RC-106 preferentially accumulate in mice pancreas and brain after intravenous administration, supporting the use of sigma receptor modulators as a novel therapy for these tumors. Treatment with RC-106 strongly inhibited cell proliferation and survival regardless of the type of cancer investigated. 25 μM of the drug impaired the in vitro clonogenic ability of tumor cells, an effect lasting for up to 42 days, the longest time tested. RC-106 also led to the induction of substantial apoptosis mediated by caspase 3 and 9 activation, and to a modulation of the Akt pathway. Furthermore, treatment with RC-106 significantly reduced the growth of human GBM and PCa spheroids. Conclusions. (RC-106) represents the hit compound of a new class of dual-action ligands targeting S1R and S2R potentially useful for the treatment of cancer disease. Citation Format: Michela Cortesi, Sara Pignatta, Simona Collina, Andrea Rocca, Alice Zamagni, Chiara Arienti, Michele Zanoni, Luigino Tosatto, Daniela Bartolini, Evandro Nigrisoli, Annamaria Marra, Marta Rui, Anna Tesei. Sigma receptors: Novel targets for the treatment of highly malignant tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1129. doi:10.1158/1538-7445.AM2017-1129

Chemotherapy for ovarian cancer in the Netherlands: a population-based study on treatment patterns and outcomes.

Information on treatment patterns for ovarian cancer (OC) is limited. The aim of this study was to describe current patterns of chemotherapy and other systemic treatments for OC in the Netherlands and evaluate survival outcomes following subsequent lines of treatment. Data from the Eindhoven Cancer Registry, including on newly diagnosed cancer patients, were linked to the PHARMO Database Network, including information on in- and out-patient drug use. Patients diagnosed with OC between January 2000 and December 2010 were selected. An algorithm was used to identify separate lines of treatment. Data were studied descriptively. Detailed data on systemic drug use were available for 261 patients (17%) with OC. In first-line treatment, 87% of the patients (227/261) received platinum-based chemotherapy. Of the 161 patients receiving second-line treatment, 101 patients (63%) received platinum-based chemotherapy. In third line, this was 51% (53/103). The median number of treatment lines received by patients was two (interquartile range 1-3), and eight or more lines of chemotherapy were identified for 12 patients. Median survival from diagnosis onwards was 47months from the end of first-line treatment, median survival was 32months, and from the end of second-line treatment, it was 14months. Predominantly beyond second-line treatment, there is much variety in treatment patterns with chemotherapy for OC. Although uncertainty remains regarding the desirability of this observed treatment variation, there seems a need for detailed clinical guidance, assuring that physicians can properly choose the most suitable treatment for each patient.