2nd Malignancy Research Articles

Abstract PO4-12-02: Screening adherence for second primary malignancies in breast cancer survivors: a cross-sectional study assessing behaviors, facilitators, and barriers to enhance quality care

Abstract Background: Continuous advancements in medical care have significantly increased the life expectancy of breast cancer (BC) patients. Due to this increased lifespan, combined with genetic, hormonal and environmental factors, BC patients have an increased risk of developing a 2nd primary malignancy. Therefore, regular screening for other types of cancer is of utmost importance for comprehensive care of BC survivors (BCS). The aim of this study was to evaluate the level of compliance with screening for cervical, lung, and colorectal cancer among BCS. Additionally, the study aimed to identify the facilitators and barriers influencing cancer screening (CS) adherence. Methods: An online survey for BCS was developed to assess sociodemographic data, risk perception of developing a 2nd primary malignancy, attitudes towards CS, and compliance with CS. It was distributed through the social media of Mexican oncology-related NGOs. Results: In total, 52 BCS (median age: 44 years, range: 28-67 years) answered the survey. Most were diagnosed with stage III (38%) or II (29%) BC. The majority had completed at least high-school education (90%), had public health insurance (60%) or no insurance (25%), and reported a monthly income < 500 USD (52%). A total of 3 (6%) cases of 2nd primary malignancies were reported, including 2 cases of contralateral BC and 1 cervical carcinoma. Among 50 participants with an indication for cervical CS, 37 (74%) had a pap smear within the past 3 years. Only 7/24 (29%) eligible participants underwent colorectal CS within the last 10 years. Screening modalities included 6 colonoscopies and 1 occult blood test. The primary reason for non-compliance in both cervical and colorectal CS was the absence of a physician's recommendation, accounting for 79% and 88% of the cases, respectively. None of the participants had an indication for lung CS, thus no low-dose computed tomographies were performed for this purpose. Participants demonstrated a mean knowledge score of 72/100 (SD=19) regarding CS. Most respondents mentioned that, compared to the general population, they considered themselves to be at no/very low/low risk of developing cervical (75%), colon (73%), or lung cancer (75%). In terms of attitudes towards CS, an overwhelming majority of participants (98%) affirmed that BCS should undergo screening for other types of cancer. Most stated that, if recommended by a physician, they would agree/strongly agree (96%) to undergo screening for other neoplasms. Nearly all agreed/strongly agreed (98%) that being screened for other types of cancer would be beneficial for their own health; and agreed/strongly agreed (98%) that CS is the most effective way to approach other types of cancer. Additionally, most agreed/strongly agreed (96%) their CS would benefit their family members. On univariate analysis, no sociodemographic or clinical factors were associated with CS adherence. However, it is important to note that the study may have been underpowered to detect significant associations due to the limited sample size. Conclusion: In conclusion, even though most BCS acknowledge its importance, screening for 2nd primary malignancies in this group exhibits suboptimal rates. This study highlights the potential role that BC oncologists could play on increasing CS uptake by reminding patients of their corresponding recommendations to detect other types of cancer. Further research is crucial to enhance our understanding of the key factors influencing these outcomes and to contribute to the development of targeted strategies aimed at enhancing CS adherence. Citation Format: Fernanda Mesa-Chavez, Misael Salazar-Alejo, Cynthia Villarreal-Garza. Screening adherence for second primary malignancies in breast cancer survivors: a cross-sectional study assessing behaviors, facilitators, and barriers to enhance quality care [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-02.

Abstract PO1-16-10: BRCA mutated Male Breast Cancer, hallmarks of a distinct disease. Data from the Spanish Male Breast Cancer Registry (GEICAM/2016-04)

Abstract Background: Male breast cancer (MBC) accounts for approximately 0.25% of all male cancers and < 1% of all BCs. Its incidence is increasing by 1.1% per year. Most population studies indicate that 10-15% of MBC patients (pts) have a germline BRCA2 mutation (BRCA2 mut). Around 5-10% of BRCA2mut male carriers will develop BC at their lives. Preliminary evidence suggests that BRCA2mut MBC pts tend to have a more aggressive disease. Here we present comparative series of MBC with and without BRCA to gain insight on differences between both groups. Methods: GEICAM/2016-04 (NCT03800355) is a retrospective, observational study which includes data from MBC pts diagnosed between 2000 and 2019 throughout Spain. This analysis includes the 1st unselected 186 pts included in the study, who had BRCA1/2 genes mutational status assessed within clinical practice. BC clinical subtypes are defined: luminal (HR+, HER2-), Triple Negative (TN) (HR-, HER2-), and HER2+ (HR+ or HR-); subtype is unknown in 6% pts. Results: 186 validated pts with BRCA1/2 testing were identified, representing the 24% of pts available in the database at the cut-off date (6-Mar-2023). 36 (19%) pts had germline BRCA1/2 mut (4 pts in BRCA1, 31 pts in BRCA 2 and 1 pt in both BRCA1 and BRCA2), and 150 (81%) pts had BRCA1/2 wild type (wt) or a variant of uncertain significance (VUS)/unknown (UK). Median age at BC diagnosis was 62 (34-87) years, 98% pts were Caucasian, and the median body mass index was 27 (18-46) Kg/m2 (overweight). Prior cancer history was reported in 6% BRCA1/2mut BC pts and 11% BRCA1/2wt or vus/uk, and family history included: 56% BC, 8% ovarian cancer, and 14% prostate cancer (PC). PC as part of prior medical history, cancer family history, and 2nd non-breast primary malignancy, was most frequent in BRCA1/2wt or vus/uk pts, with no statistical differences. At first diagnosis, stages III-IV were higher in BRCA1/2mut pts (28% vs. 17%, p=0.0093). Morphologically, invasive carcinoma of no special type (NST) was the most common pattern (92% in BRCA1/2mut vs. 86% in BRCA1/2wt or vus/uk), and lobular invasive carcinoma was not reported up-to-date. Histological grade 2 was the most frequent (54%), but grade 3 was present in 17/36 BRCA1/2mut pts. 88% pts received adjuvant treatment, 7% (neo-)adjuvant, 2% neoadjuvant and 3% did not receive any systemic therapy. Breast conserving surgery was performed in 4% (5/140) BRCA1/2wt or vus/uk EBC pts, and mastectomy was performed in 55% (n=6/11) de novo metastatic pts. In the advanced setting (n=38), visceral lesions were more frequent in BRCA1/2mut pts. Additionally, 92% BRCA1/2mut pts had ≤ 3 organs involved while one third of BRCA1/2wt or vus/uk pts had ≥ 4 metastatic locations. With a median follow-up of 64 months (mo.), median iDFS and DDFS were higher, but not statistically significant, in BRCA1/2wt or vus/uk pts vs. BRCA1/2mut pts. In advanced setting, median PFS to 1L-3L do not show statistically significant differences between both groups. Regarding OS, no differences were also observed, but the median values were not reached. Further detailed information according to BRCA1/2 mutational status and BC subtypes is included in the table below. Conclusions: In this subset analysis of GEICAM/2016-04, BRCA1/2mut pts had some features of worse prognosis, with a more prevalent de novo metastatic disease. No statistically significant differences were observed in outcomes in both early-stage and advanced setting vs. BRCA1/2wt or vus/uk pts. <graphic> Citation Format: Noelia Martínez-Jáñez, Purificación Martínez, Cristina Hernando, Sabela Recalde, Alfonso Sánchez, David Morales, Marta Santisteban, Isaura Fernández, Sonia Del Barco, Esther Zamora, Vega Iranzo, Tamara Martos, Eduardo Martínez-de Dueñas, Silvia Antolin Novoa, Severina Domínguez, Paula Domínguez, Mª José Echarri, Ana Santaballa Bertrán, Xavier Mira, Andrea Blasco, Susana Bezares, Ander Urriticoechea. BRCA mutated Male Breast Cancer, hallmarks of a distinct disease. Data from the Spanish Male Breast Cancer Registry (GEICAM/2016-04) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-10.

Abstract 7250: Serial assessment of GEN2, a retroviral vector for gene transfer of an optimized thymidine kinase and GM-CSF, for genomic integration into peripheral blood mononuclear cells (PBMCs) in a Phase 1 clinical trial in adult patients with solid tumors

Abstract GEN2 is a non-replicating retroviral gene transfer vector encoding a sequence-optimized herpes simplex thymidine kinase (HSV-TK), which activates the antiherpetic pro-drug ganciclovir (GCV), resulting in chain termination during DNA replication, triggering cancer cell apoptosis and release of neoantigens (NA). GEN2 also encodes hGM-CSF, which may augment antitumor immunity by enhancing NA presentation to immune effector cells. GEN2 in combination with valganciclovir (an oral formulation of GCV) was evaluated in a dose-escalating Phase 1 clinical trial in 61 adult patients (pts) with an advanced solid tumor (NCT04313868), with serial assessment of PBMCs to detect any GEN2 integration and replication competent retrovirus (RCR). Methods: PBMCs were obtained in Cycle 1 (following 1st/3rd dose), prior to and 2 hours after Cycle 2, and thereafter at 6-month intervals for 15 years, or until death or withdrawal of consent. Digital droplet PCR (ddPCR) for psi and envelope gene sequences in extracted genomic DNA from PBMCs was used to detect vector genome integration and replication competent retrovirus (RCR), respectively. Results: All 82 samples obtained from the intravenous cohorts 1-12 were below LOD (Limit of Detection) for RCR. All results for integration were BLOQ (Below Limit of Quantitation), whereas 4 samples collected at two hours following the end of infusion were above LOD, likely resulting from non-integrated cDNA. GEN2 continues to be studied in clinical trials in adult patients with solid tumors. Per the 2020 FDA Guidance for Industry (Long Term Follow-Up After Administration of Human Gene Therapy Products), serial assessment of vector integration is mandated throughout a pt’s participation in a gene therapy clinical trial and for 15 years following the last dose. These guidance documents were originally conceived when gene therapy was developed for treatment of rare hereditary diseases in pediatric pts; however, adult pts enrolled in early-stage clinical trials for cancer typically do not have a prolonged life expectancy (BMC Cancer 2011 11:426). In the context of proper and warranted usage of pts’ blood for testing, attention should be drawn to the limited expectation for a 2nd malignancy within the lifespan of this pt population, and the absence of detectable RCR in cancer patients receiving retroviral vectors over decades. A recent review noted no evidence of RCR in 1,595 post-treatment PBMCs obtained from 60 clinical trials (Mol Ther 2023 31(3):801). Our results confirm that GEN2 also shows negligible genotoxic risk for gene therapy of cancer at doses tested to date. Citation Format: Alison L. Hannah, Noriyuki Kasahara, Li Liu, Allen Wang, Joe McNulty, Robert G. Johnson. Serial assessment of GEN2, a retroviral vector for gene transfer of an optimized thymidine kinase and GM-CSF, for genomic integration into peripheral blood mononuclear cells (PBMCs) in a Phase 1 clinical trial in adult patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7250.

Incidence of Second Primary Malignancies in Patients with AL Amyloidosis and the Impact of Disease Stage and Therapies

AL amyloidosis is a clonal disease, characterized by the production of light chains from a usually small or modest in size plasma or B-cell clone. Early mortality due to severe organ involvement is the most ominous complication, long term sequalae, associated with organ involvement resulting in end stage dysfunction occurs but other long-term complications due to therapy or immunosuppression are often neglected. The treatment of AL amyloidosis is based on the elimination of the clone with the use of chemotherapy (including high dose melphalan) or immunochemotherapy. Among patients (pts) with myeloma or other B-cell malignancies the development of 2 nd primary cancers is a well described complication, associated with longer survival, exposure to multiple drugs and long-standing immunosuppression. However, data on the incidence and risk factors for second malignancies are not available for pts with AL amyloidosis. Thus, the aim of our study was to describe the incidence and risk factors for the development of 2nd malignancies among consecutive pts with AL amyloidosis. The analysis included 417 consecutive pts, treated and followed in the Department of Clinical Therapeutics, Athens. The analysis accounted for death due to AL amyloidosis and diagnosis of 2 nd malignancy as competing events (competing risks analysis). The median age of the cohort was 65 years, 56% were females; heart, renal and liver involvement were present in 76%, 65% and 19% respectively. Per Mayo staging, 16%, 44% and 40 were stage -1, -2 and -3. Treatment, across all lines, included alkylators in 75% (mostly cyclophosphamide, melphalan was given in 21%, of which 5% as high dose), lenalidomide in 36% and daratumumab 31% while 95% had received bortezomib. The median follow up of the cohort was 56 months and the estimated median overall survival of all pts was 57 months. A second primary malignancy, after the diagnosis of AL amyloidosis, was diagnosed in 26 (6.2%) pts; these included breast (4 pts), renal (4 pts), colon (3 pts), lung (3 pts), gastric (2 pts), MDS (2 pts) and one case each from AML, ovarian, pancreatic, urothelial, sarcoma, head& neck cancers while two pts had multiple 2 nd cancers. The median age of the affected pts was 66 years and 13 (50%) were males; 29% had Mayo stage-1 disease, 52% had stage -2 and 19% stage 3 disease at initial diagnosis of AL amyloidosis. Accounting for death due to amyloidosis as a competing event, the cumulative incidence of 2nd primary malignancy was 0.7% at 2 years, 2% at 3 years, 4.5% at 4 years, 5.4% at 5 years, 7% at 6 years, 8.7% at 7 years and 10.25% at 10 years (figure 1). We then performed competing event univariate analysis to evaluate the potential association of several clinical, laboratory and treatment characteristics with the probability of developing a 2 nd malignancy. Notably, there was no increased risk of a 2 nd malignancy associated with the use of alkylators (either cyclophosphamide or melphalan), or melphalan (standard or high dose), lenalidomide or daratumumab. Since 95% of ptshad been exposed to bortezomib we could not make a meaningful analysis for this drug. Among baseline clinical characteristics, the presence of purpura or liver involvement (and with a trend for heart involvement) was associated with lower probability of diagnosis of a 2 nd malignancy, in the competing risk analysis. However, when analyzing the cumulative incidence of a 2 nd malignancy in ptswith different stages per Mayo system (1 vs 2 vs 3), the 5-year cumulative probability of death among pts with stage 1 disease per Mayo 2004, was 10.5% and the 5-year cumulative probability of 2 nd malignancy was 8.9% (the respective 5-year probabilities for Mayo stage 2 were 50.2% and 5.4% and for Mayo stage 3 were 69.7% and 3.7%). Thus, 2 nd cancers seem to affect mainly those with Mayo stage 1 discase, which also have the highest probability of long term survival. The 2 nd cancer was the cause of death in 10/26 (38%) of the affected pts. In conclusion, second primary malignancies occur in 6% of pts with AL amyloidosis, affecting mostly pts without or with early cardiac involvement who have also the longest survival probability, with a 5-year cumulative risk of 9%. Second hematologic malignancies are uncommon (0.7%). We did not find a significant correlation with the use of alkylators of other specific agents. This data emphasizes the need for screening for the most common malignancies among pts with AL amyloidosis as new therapies improve the long-term survival.

ThTP4.2 Complications Following Emergency Colorectal Cancer Resections: A single centre cohort Study

Abstract Aims Colorectal Cancer (CRC) is 3rd prevalent & 2nd lethal malignancy in UK. Emergency CRC presents < 30% cases (NBOCA 2022) & associated with high post-operative morbidity & mortality. Aim of study is to assess post-operative complications in emergency CRC resections. Methods A cohort study carried out from Jan'08 to Feb'23, post-operative surgical outcomes were evaluated in emergency CRC resections. Elective CRC resections recruited as controls. Results Conclusion Emergency CRC resections had higher ASA 3. There was a greater early post operative mortality rate, but no difference in post operative complications & anastomotic leakage. However, emergency CRC resections was associated with prolonged hospital stay (p < 0.001) & poorer survival rates (Logrank p <0.0001) (worse in perforated cancers). Emergency CRC presentations remain a challenge, accounting for 20% of all CRC’s for the last decade. Therefore, our study supports prompt diagnosis and early intervention of emergency CRC mitigate the poor survival.

Chemotherapy-free treatment with inotuzumab ozogamicin and blinatumomab for older adults with newly diagnosed, Ph-negative, CD22-positive, B-cell acute lymphoblastic leukemia: Alliance A041703.

7006 Background: Older adult patients (pts) with Philadelphia-chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) have poor survival with chemotherapy. The α-CD22 Ab-drug conjugate inotuzumab ozogamicin (InO) and α-CD19/CD3 T-cell engager blinatumomab (blina) were each superior to chemotherapy in Phase III studies in relapsed/refractory B-ALL. Because InO induces high CR rates and blina can induce durable remissions in low burden disease, we conducted a Phase II trial of induction InO then blina for older adults with newly-diagnosed (ND), Ph-, B-ALL. Methods: Eligible were pts ≥60 years old with ND, Ph-, CD22+ (≥20% of blasts) B-ALL without plan for allogeneic HCT (alloHCT). Pts with CNS leukemia or liver disease were excluded. Induction IA was InO 0.8 mg/m2 day (d) 1, 0.5 mg/m2 d8, d15 IV on a 21d cycle. Pts with adequate cytoreduction (marrow blasts by ≥50% or cellularity ≤20%) after IA went to IB if in CR/CRi (InO 0.5 mg/m2 d1, d8, d15 IV; 28d cycle) or IC if no CR/CRi (InO 0.8 mg/m2 d1, d8, d15 IV; 28d cycle). Those without cytoreduction to IA started course II blina. Pts without events in IA/B/C received course II blina CIV (9 mcg/d x 7d then 28 mcg/d x 21d; 14d break; 28 mcg/d x28d). Pts with CR/CRi to InO received 2 more 28d cycles of blina, others received 3 more. CNS prophylaxis was methotrexate 15 mg intrathecal x 8. The primary endpoint was 1-yr event-free survival (EFS) with a lower limit of a 90% CI for 1-yr EFS >10% defined as success. EFS was the time from therapy start to failure to achieve CR/CRh/CRi by end Course II, progression, relapse, or death, whichever occurred first. Results: Thirty-three eligible pts were treated (1 ineligible, 2nd malignancy). The median age was 71 years (range 60-84). Median WBC count was 3,200/mcl (range 6-38,000). Median CD22 expression was 92% (range 21-100%). Eight pts had therapy-related ALL. The cumulative CR rates through Course IA/B/C and Course II were 85% and 97%, respectively (Table). With median follow up of 22 mo, the 1-yr EFS was 75% (95% CI 61-92%). The 2-sided 90% CI was 63-89% for 1-yr EFS with lower bound above 10% indicating regimen success. Twelve pts had events: 9 relapses, 2 deaths in remission (1 after alloHCT), and 1 death without remission from respiratory failure with sinusoidal occlusion syndrome of liver. The 1-yr OS was 84% (95% CI 72-98%). Nine pts have died, 6 after relapse. Conclusions: InO induction then blina consolidation is highly active for ND, Ph-, CD22+ B-ALL. The regimen is an option for older adults and a comparator regimen for future studies. Support: U10CA180821, U10CA180882, U10CA180820 https://acknowledgments.alliancefound.org . Clinical trial information: NCT03739814 . [Table: see text]

Baseline‐PET derived metrics are the most relevant factors for risk stratification in early‐stage nonbulky HL: preliminary results of the RAFTING trial

Introduction: The efficacy of combined-modality treatment (Tx) with chemotherapy (CT) and radiotherapy (RT) in early-stage Hodgkin Lymphoma (eHL) is offset by long-term morbidity, with a cumulative incidence of 2nd primary malignancy at 40 years of 48.5% (Schaapveld 2015). The RAFTING trial (NCT Id. 04866654) is a phase-2 prospective single-cohort international study to explore the effectiveness of a risk-adapted Tx in non-bulky stage I-IIA eHL, based on the risk of CT failure (TxF) in a single-patient (p.) basis and in a personalized medicine design. Methods: p. are first stratified in 3 classes of TxF risk, depending on (a) modified EORTC criteria (m-EORTC), in which bulky is replaced by a Large Nodal Mass (LNM), defined by a longest ∅ measuring ≥5 cm in CT or PET/CT, (b) Metabolic Tumor Volume (MTV), with a SUVmax threshold method of 41% and cutoff value of 84 ml, and (c) PET-2 result (5-point scale). Tx stratification: Group 1: PET-2 neg. & low MTV p., treated either with 2 (group 1a) or 4 (group 2b) ABVD depending on no or ≥1 m-EORTC criterion presence, addressed, once in CR, to a 3-monthly cell-free tumor DNA (ctDNA) assay (CAPPSeq. Method, Spina 2018); Group 2: group 1 p. with < CR after ABVD or in “limited” relapse (LR), defined by eHL relapse in old and up to 3 new nodal areas, addressed to Involved-Node RT (INRT) and Nivolumab (N), 240 mg. i.v. twice a month for 24 doses; Group 3: PET-2+ and/or high MTV p., treated with the triplet ABVD × 4, INRT, 20 or 30 Gy (A-RxT-N). All PET/CT scans are centrally reviewed by an expert panel. The trial primary endpoint is a 3-Y PFS ≥90% in group 1 p. The secondary endpoints are: (a) Effectiveness of RxT (36 Gy) and N (same schedule of Group 3), in rescue p. with LR (b) effectiveness of the triplet A-RxT-N in high-risk (Group 3) eHL; (c) predictive value of ctDNA in detecting an impending eHL relapse after CT alone. Results: Preliminary results of risk stratification upon enrolment of the first 104/180 (58%) of the pre-planned sample size: in a per-protocol analysis, 88/104 (85%) turned out eligible and 73 stratified for risk. Non-eligibility reasons were higher HL stage, or bulky (10 p.) and early Tx stop, for p./investigator decision: (6p.). Out of 73 p. stratified, 53 (73%) were low-risk (Group 1), and 20 (27%) high risk (Group 3). Out of 53 low-risk p., 16 were in Group 1a: one of them was addressed to salvage Tx with ASCT because of an extended relapse 3 months after CT end. As many as 37 (70%) of low-risk p. belonged to Group 1b, mostly because of the presence of a LNM; two of them had a LR (entering Group 2) and started RxT-N rescue. Twenty p. (27%) had high-risk disease, most (14) for a high MTV, and a minority (6) for a positive PET-2. Updated results will be presented. The research was funded by: Polish Medical Agency ABM Ongoing Trial Keywords: Liquid biopsy, Ongoing Trials, PET-CT No conflicts of interests pertinent to the abstract.

From triple-class exposed (TCE) to penta-exposed and triple-class refractory (PE-TCR): Real-world outcomes across a spectrum of advanced relapsed or refractory multiple myeloma (RRMM) patients (Pts) in the United States.

e20011 Background: RRMM treatment (Tx) has been transformed by novel Txs including anti-CD38 monoclonal antibodies (mAbs) and 2nd/3rd generation immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs), resulting in an increasing population of TCE pts (i.e., prior exposure to ≥1 each of an IMID, a PI, and an anti-CD38 mAb). Many such pts are exposed to ≥5 drugs in these classes (i.e., “penta-exposed” PE: ≥2 IMIDs, ≥2 PIs, and an anti-CD38 mAb). Some are refractory to ≥1 drug in each class (“triple-class refractory” TCR) and some are both PE and TCR (PE-TCR). Real-world outcomes data for the spectrum of these advanced RRMM pts are limited. Methods: A US commercial insurance claims dataset (IQVIA PharMetrics Plus®) spanning 2007-20 was used to examine outcomes in pts with RRMM (≥1 prior line of therapy [LOT]) who were TCE, TCR, PE, and PE-TCR. The 1st LOT after becoming TCE or PE was defined as the “index LOT” (start date of index LOT = “index”). Subsets of TCE and PE pts who were also TCR at index were identified. To ensure complete documentation of treatment history, continuous enrollment for ≥6-mos before 1st claim with MM diagnosis was required. Outcomes assessed included Txs received, time to next Tx (TTNT), % with 2nd primary malignancy (SPM), healthcare resource use (HRU), and costs. Results: 500 TCE and 217 PE pts were identified including 228 TCR and 142 PE-TCR. Mean age across groups was 62-63 y; 39-42% were female, 40% (TCR) to 46% (PE) had prior autologous stem cell transplant; mean number of prior LOTs ranged from 3.2 (TCE ) to 4.3 (PE); 5.7% (TCR) to 8.8% (PE) had extramedullary disease at index. The no. of new TCE pts increased by ~6X from 25 in 2016 to 145 in 2020; similar increases were seen for TCR, PE, and PE-TCR. Mean post-index follow-up (mos) was 11.6 for TCE, 11.7 for TCR, 10.7 for PE, and 10.3 for PE-TCR. There was no standard Tx across cohorts; the most frequent index LOT regimens were pomalidomide (POM)+daratumumab (11% TCE), POM+carfilzomib (15% TCR), and POM+elotuzumab (7% PE and 9% PE-TCR). Kaplan-Meier median TTNT was short, ranging from 6.5 (TCR) to 11.3 mos. (TCE). TCE pts had high HRU with mean of 0.08 emergency department visit, 2.37 office/outpatient visits, 5.10 prescriptions, 0.14hospitalizations, and 1.2 days in hospital per month. Mean monthly all-cause healthcare costs (2021 $US) for TCE pts were $31,127, including $18,033 (58%) for MM medications and $10,297 (33%) for other MM-related care. Monthly HRU and costs for TCR, PE, and PE-TCR pts were similar. In TCE pts with no SPM before index date (N=291), 29 (10%) developed SPM post-index. Conclusions: Despite increasing numbers of TCE, TCR, PE, and PE-TCR pts, there is no apparent standard Tx. With current Tx, TTNT is short, HRU and costs are high, and risk of SPM is 10% (TCE). These data underscore the unmet need for new therapies in this growing population.

GCT-02. THE LONG-TERM OUTCOMES AND SEQUELAE ANALYSIS OF INTRACRANIAL GERMINOMA FROM 187 PATIENTS IN THE SINGLE INSTITUTE: NECESSITY FOR THE ADAPTATION OF RADIOTHERAPY DOSE AND VOLUME

PURPOSEWe aimed to refine the radiotherapy (RT) volume and dose determinant for disease failures and long-term sequelae in the intracranial germinoma.METHODSThe main treatment for intracranial germinoma was craniospinal RT only (n=51) during 1981–1992 and RT with upfront chemotherapy (CRT) (n=152) during 1992–2015 in Seoul National University Hospital. All 187 cases were confirmed histologically. RT fields included craniospinal, whole-ventricle (WV), whole-brain (WB), and focal radiotherapy. RT dose was dependent on the M status and combination of chemotherapy. The median follow-up duration was 115 months (range, 3–358).RESULTSThe 10-year overall and recurrence-free survival was 94.5% and 91.4%. The complete response rate after chemotherapy was 62.6%. For the patients with complete response, WV RT 16–20 Gy, and focal boost of 25–36 Gy after upfront chemotherapy showed no in-field recurrence. The causes of death were progression (n=3), 2nd malignancy (n=6), treatment-related complications (n=7), and others (n=8). For non-sellar tumors, the rate of hormonal replacement treatment was significantly related to WB RT and WB/WV RT dose ≥ 30 Gy (p=.030, and .026). After a latency of the median 20 years, ten patients (5.3%) developed 2nd malignancy. WB RT and WB/WV dose ≥ 30 Gy were significantly correlated with the 2nd malignancy (p=.024, and .004). The rate of severe neurocognitive dysfunction was significantly associated with WB/WV dose ≥ 30 Gy (p=.027).CONCLUSION: CONCLUSIONRT with or without upfront chemotherapy exhibits the excellent control rate of disease. However, the intensity and volume of RT are critical for managing treatment toxicities. Adaptation and further de-intensification of RT should be followed.

Ibrutinib Maintenance (I-M) Following Intensive Induction in Mantle Cell Lymphoma (MCL): Efficacy, Safety and Changes in Minimal Residual Disease

BACKGROUND: Ibrutinib is a BTK inhibitor approved for relapsed/refractory MCL. We evaluated the safety and efficacy of single-agent ibrutinib maintenance (I-M) following frontline chemo-immunotherapy for MCL in a multicenter phase II trial. Herein, we report preliminary results. METHODS: Patients (Pts) received I-M 560 mg daily for up to 4 years after complete/partial response (CR/PR) to frontline chemo-immunotherapy (+/- autoSCT). The 3-year PFS rate was the primary endpoint. Secondary endpoints were PR to CR conversions, median OS and toxicity. After identifying a trackable clone using archived tissue obtained at diagnosis, minimal residual disease (MRD) was measured using NGS (detection resolution of 1 cell per million; clonoSEQ®; Adaptive Biotechnologies) on peripheral blood at 4 time-points: baseline (after induction but prior to starting I-M) and then at 1, 6 and 18-24 mo(s) after initiation of I-M. RESULTS: 36 pts were enrolled between 7/2014-7/2018. Median age was 60 years (range 46-90). For induction, 17 (47%) received BR, 18 (50%) a cytarabine-containing regimen and 1 (3%) R-CHOP. Eighteen (50%) had autoSCT in CR1. Post-induction +/- autoSCT, 33 (92%) had a CR and 3 (8%) had a PR as best response respectively. One patient converted from PR to CR on I-M. Median f/u was 34.6 months. 5 (14%) pts completed the 4-year I-M course and 15 (42%) remain on I-M (median 31 cycles, range 2-52). Sixteen (44%) pts discontinued I-M early due to: treatment related adverse events (TRAEs; n=12), second malignancies considered unrelated to I-M (n=2), PD (n=1) and death of unknown cause (n=1). Three pts died, 2 deaths deemed unrelated to I-M (aspiration pneumonia, 2nd malignancy) and 1 from unknown cause; 1 pt was lost to follow-up. The most common grade ≥ 3 TRAEs during I-M were neutropenia, HTN, infection, bleeding and atrial fibrillation/flutter (Table 1). TRAEs led to permanent dose reductions in 9 (25%) pts, most commonly for neutropenia (n=3), and I-M discontinuation in 12 (33%), 6 for new onset atrial fibrillation/flutter, 1 each for myalgias, rash, pericardial effusion, mucositis, TIA, subdural hematoma/bleed. Notably, I-M was discontinued in the majority of pts with new onset atrial fibrillation/flutter though not typical of current practice. At the time of data cut-off, MRD was assessed in 21 of 36 pts at varying time points (Figure 1) with remaining samples not yet collected/analyzed. After induction but prior to I-M, 16 pts were confirmed MRD (-), 4 were MRD indeterminate and 1 was MRD (+). Four pts MRD (-) prior to I-M became MRD (+) with follow-up, 2 induced with hyperCVAD, 1 with BR and 1 with R-CHOP + autoSCT prior to I-M; 2 of these pts reverted back to MRD (-) status with ongoing I-M. Of the 2 pts with persistent MRD (+) disease, 1 had clinical progression and the other maintains radiographic CR. Post induction, all MRD indeterminate pts were MRD (-) when checked after 1 month on I-M. The pt who was MRD (+) after front-line treatment (Nordic regimen + autoSCT) remains MRD (+) after 30 cycles of I-M without clinical relapse. MRD correlations with PFS and OS have not yet been performed. CONCLUSION: I-M 560 mg daily is feasible in pts with MCL after response to frontline chemo-immunotherapy. Grade ≥ 3 rates of atrial fibrillation/flutter are consistent with ibrutinib's known safety profile. NGS-based assessments demonstrate that most pts are MRD negative after intensive induction. Longer follow-up and correlation of MRD with PFS and OS are needed to determine the clinical relevance of I-M and MRD status. Disclosures Karmali: BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Takeda: Research Funding; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Stephens:Arqule: Research Funding; Innate: Consultancy; Juno: Research Funding; Acerta: Research Funding; MingSight: Research Funding; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Beigene: Consultancy; Pharmacyclics: Consultancy; Gilead: Research Funding; Verastem: Research Funding. Winter:Norvartis: Consultancy, Other: DSMB; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: advisory board; Epizyme: Other: DSMB; Delta Fly Pharma: Consultancy; Amgen: Consultancy; CVS/Caremark: Consultancy; Ariad/Takeda: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees, Other: advisory board. Ma:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; BeiGene: Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding; Bioverativ: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Juno: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kite: Consultancy, Honoraria; TG Therapeutics: Research Funding. Petrich:AbbVie: Current equity holder in publicly-traded company; Daiichi-Sankyo: Current Employment. Hochberg:Intervention Insights: Consultancy; Leuko: Consultancy. Kuhr:Adaptive Biotechnologies: Current Employment. Gordon:Zylem Biosciences: Patents &amp; Royalties: Patents, No Royalties. Pro:Verastem Oncology: Research Funding. OffLabel Disclosure: maintenance ibrutinib after frontline therapy in MCL

Early Versus Late Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma: Long-Term Follow-up Analysis of the IFM 2009 Trial

Early Versus Late Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma: Long-Term Follow-up Analysis of the IFM 2009 Trial

Utility Of Ebus-Tbna In Diagnosis And Staging Of Lung Nodules In The Setting Of Known Second Malignancy In Veterans - A Quality Assurance Study

Abstract Introduction/Objective Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is minimally invasive procedure for diagnosis/staging/restaging of lung nodules, recommended by the National Comprehensive Cancer Network (NCCN) 2017 Clinical Practice Guidelines. Veteran patients are an elderly patient cohort with multiple comorbidities and many have existing known 2nd malignancy. It will be crucial to diagnose and appropriately stage lung nodules. Our primary aim was to assess the efficacy of EBUS-TBNA in diagnosis/nodal staging in elderly patients with known 2nd malignancy. Our secondary aim was to evaluate the safety of this procedure for veterans. Methods A retrospective search for cases of EBUS-TBNA in patients with known second malignancy was carried out in Vista/Fileman at the Corporal Michael J Crescenz VA Medical Center between the period of June 2019 to January 2020. Sites included lung, cervical lymph nodes, mediastinum and hilar region. Results Of total 93 EBUS-TBNA procedures performed; EBUS-TBNA targeted both the lung and lymph node (62 cases), lymph nodes alone (28 cases) and only lung (3 cases). Total 53 were diagnosed malignant; with primary being lung (39 cases) and pleura (2 cases); and diagnosis of new metastatic carcinomas to lung was made in (12 cases). The metastatic neoplasms included 2 urothelial carcinoma, 7 squamous carcinoma, 2 metastatic adenocarcinoma, and 1 prostatic adenocarcinoma. 32/53 (60.3%) had the history of prior extrapulmonary second malignancy. Immunohistochemical studies was able to be performed in 50/53 (94%) of malignant cases, predictive marker PD-L1 on 50/53 (94%) cases, molecular testing on 23/53(43.3%) cases and Foundation One testing (Cambridge, MA, NGS) on 11/53(20.7%) cases. In all 93 cases, there were no complications (0/93) (0%) of the procedure. Conclusion EBUS-TBNA is an efficient, cost effective and minimally invasive modality in elderly veteran patient population with multiple co-morbidities. EBUS-TBNA is successful in procuring adequate material for diagnosis, molecular and predictive marker studies; thus, it can play a crucial role in precision oncology. EBUS-TBNA plays a pivotal role diagnosing and ruling out metastatic nodal disease in veteran patient population which has a high incidence of known 2nd extrapulmonary malignancy. EBUS-TBNA is deemed safe in veterans.

Oral Fludarabine and Intravenous Rituximab (FR) for Chronic Lymphocytic Leukemia (CLL): Long Term Outcomes and Secondary Malignancies in 673 Patients Treated in British Columbia (BC)

Oral Fludarabine and Intravenous Rituximab (FR) for Chronic Lymphocytic Leukemia (CLL): Long Term Outcomes and Secondary Malignancies in 673 Patients Treated in British Columbia (BC)

Venetoclax and Ibrutinib for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) - 15-Month Safety, Response and MRD Evaluation: Third Interim Analysis from the Phase II Vision HO141 Trial

Venetoclax and Ibrutinib for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) - 15-Month Safety, Response and MRD Evaluation: Third Interim Analysis from the Phase II Vision HO141 Trial

PF472 VERY LATE REALAPSES (VLR) ≥5 YEARS AFTER INITIAL TREATMENT WITH CHEMOTHERAPY±RADIOTHERAPY (CT±RT) IN HODGKIN LYMPHOMA (HL): A JOIN STUDY ON TREATMENT STRATEGIES AND PROGNOSTIC FACTORS FOR THE OUTCOME

Background:Risk‐adapted treatment strategies have improved the long‐term outcome of patients with Hodgkin Lymphoma (HL) and traditionally the disease is considered cured after a 5‐year continuous first complete remission (CR1). However, our initial report and the recent large GHSG study have demonstrated that VLRs, occurring ≥5 years after initial treatment initiation, are a non‐negligible event. Due to the rarity of these events very few data exist describing the outcome of VLRs after CT ± RT while there is no study focusing on potential prognostic factorsAims:This study aimed to describe the treatment strategies adopted for patients with VLRs as well as their outcome and prognostic factors for Freedom From Second Progression (FF2P) and Overall Survival after failure (O2S)Methods:Cases were identified retrospectively from the databases of the 5 participating centers (4 referral centers in Greece and 1 in Northern Italy). Patients were eligible if they had remained in CR1 for ≥5 years after initial CT ± RT and had experienced VLR. Study endpoints were the estimation of FF2P and O2S and the identification of relevant prognostic factorsResults:A total of 103 patients were identified. 69% were males, 18% were ≥65 years old at relapse, 24% had relapsed &gt;15 years after the initial diagnosis, 38% had B‐symptoms, 25% extranodal disease and 30% anemia at relapse. The initial histologic subtype was nodular lymphocyte predominant in 13% of the cases, lymphocyte rich classical in 3%, nodular sclerosis (NS) in 43% and mixed cellularity in 40%. Reinduction with the same regimen was given in 24% of the cases, 6 patients (6%) received salvage RT only and 26% received salvage chemotherapy with the intention to proceed to autologous transplant (ASCT; 30% for patients &lt;65 years). The 5‐ and 10‐year FF2P was 55% and 50%, while the O2S was 78% and 55% respectively. Among 37 deaths, 21 were due to HL and 1 due to toxicity of salvage therapy, while 11 were purely attributed to 2nd malignancies and 4 to unrelated causes. Patients with and non‐nodular sclerosing classical HL histologic subtype seemed to have worse FF2P but this was not an independent prognostic factor. Reinduction with the same regimen did not significantly affect FF2P and O2S; 5/6 patients selected for salvage RT only had long‐term remission. Intention to proceed to ASCT was associated with numerically higher FF2P and O2S in patients &lt;65 years old, but the differences did not reach significance [5‐year FF2P 82% vs 56% but 10‐year rates 59% vs 56% (p = 0.57) and 10‐year O2S 84% vs 59%, (p = 0.19)]. In multivariate analysis only anemia at relapse was independent predictor of FF2P (p = 0.025) but age ≥65 (p = 0.064) and B‐symptoms at relapse (p = 0.073) entered the model with borderline significance. Both anemia and age ≥65 years at relapse were independent adverse prognostic factors for O2S (p = 0.042 and p &lt; 0.001 respectively). The presence of either anemia and/or age ≥65 years at relapse identified a subgroup comprising 41% of the whole patient population who had highly compromised 10‐year FF2P and O2S (65% vs 28% and 66% vs 35% respectively for patients, p &lt; 0.001 for both)Summary/Conclusion:The prognosis of VLRs after CT±RT for HL does not appear favorable. However, a considerable proportion of patients relapse at advanced age and also, a non‐negligible number of patients succumb to 2nd malignancies and unrelated conditions. Salvage RT may cure a small proportion of eligible patients, while ASCT should be considered despite the long duration of the initial remission. Advanced age and anemia at relapse were the most important prognostic factors in our study

Metachronous Second Primary Malignancies in Known Breast Cancer Patients on 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography-Computerized Tomography in a Tertiary Care Center.

Introduction:Breast cancer is the most common malignancy among women all over the world, which accounts to 25% of all cancers. In known cases of breast cancer, the risk of developing another denovo malignancy is more when compared to low risk groups, which might be due to common environmental risk factors, treatment induced risk factors, Genetic susceptibility for mutations, presence of cancer syndromes or better detection due to close surveillance.Objective:To study the profile of Metachronous 2nd primary malignancies suspected on 18F-FDG PET CT in known Breast cancer patients. In this Retrospective study from January 2014 to April 2018, all the consecutive patients with known Breast cancer, who were referred to Nuclear Medicine department for 18F- FDG PET CT for follow up evaluation were included. Suspected 2nd primary malignancies were correlated with Histopathological examination (HPE).Results:During the study period, a total of 233 Breast cancer patients (all are females), with a mean age of 54.2+13.4 years were studied. On 18F-FDG PET CT scan, suspicion for 2nd primary malignancy was observed in 37 patients. HPE was done in 28/37 patients at the site of suspected lesions. 15/28 were positive for second malignancy, and remaining 13/28 were either a benign pathology or a part of metastatic disease from the primary breast cancer. The sites of 2nd primary malignancies included Contralateral breast in 8/15 (53.3%), Ovary in 2/15 (13.3%), Endometrium in 2/15 (13.3%), Lung in 1/15 (6.6%), Stomach in 1/15 (6.6%) and Urinary bladder in 1/15 (6.6%) patients respectively. The incidence of metachronous 2nd primaries in breast cancer is 67.3 per 1000 breast cancer patients.Conclusion:Metachronous second primary cancers in breast cancer patients are not very rare. A high imaging suspicion on 18F-FDG PET CT helps in early detection of 2nd primary cancer, thereby facilitating early and appropriate management.

A Twenty Years Epidemiology Study of 2nd Hematological Malignancies Post to the Initial Tumor Treatment: Report from Southern China Single Cancer Group

Objective: To investigate the clinical features of 2nd hematological malignancies post to the initial cancer treatment.METHODS: A retrospective study was performed to analyze the available clinical data of 116 patients diagnosed with 2nd hematologic malignancies after treatment of various malignant tumors from June 1998 to June 2018 at Sun Yat-sen University cancer center.RESULTS: The characteristics of the 116 patients diagnosed with 2nd hematological cancer post to initial cancer treatment were indicated as following: 62 males and 54 females. The primary tumor category was grouped as (according to ICD-10 International Disease Code): i) 23 cases of head and neck malignant tumors (14 cases of nasopharyngeal carcinoma (C11), 3 cases of laryngeal carcinoma (C32), 3 cases of thyroid carcinoma (C73), 3 cases of other head and neck tumors (C00-10, 12-13), ii) 7 cases of chest malignant tumors (2 cases of esophageal cancer(C15), 4 cases of lung cancer and bronchial carcinoma (C33-34), 1 case of chest wall tumor(C49), iii) 31 cases of GI malignant tumor (7 cases of gastric cancer(C16), 7 cases of hepato-biliary cancer(C22-24), 17 cases of intestinal cancer(C18-21), iv) 17 cases of breast cancer (C50), v) 12 cases of gynecological malignancies (4 cases of ovarian cancer, 7 cases of cervical cancer, 1 case of endometrial cancer), vi) 7 cases of malignant genitourinary tumor (C61-68), vii) 15 cases of hematological malignancies (12 cases of lymphoma(C81-85), 3 cases of chronic lymphocytic leukemia(C91.101) ), viii) others: 2 cases of sarcoma (C80 03), 1 case of melanoma (C43), 1 case of glioma. The subtype of 2nd hematological malignancies were indicated as following: 33 patients with acute myeloid leukemia, 9 patients with myelodysplastic syndrome, 8 patients with acute lymphoblastic leukemia, 4 patients with chronic lymphocytic leukemia, 3 patients with chronic myeloid leukemia, and 2 patients with multiple myeloma. The rest 57 cases were non-Hodgkin's lymphoma.The median duration time for the 116 patients from starting treatment of the first tumor to the happening of the secondary hematologic tumor was 51 (range: 7-297) months, with an overall survival time 32 (range: 1-114) months. For the 50 cases diagnosed with 2nd acute leukemia and myelodysplastic syndrome, the interval period time was 33 (range: 7-167) months. The overall survival time for the 50 cases is 12 (range: 1-61) months. The 1-year and 3-year overall survival rate was 44.5% and 11.7%, respectively.Interestingly, of the patients' initial treatment options among the 50 cases, eight patients did not receive radiotherapy and chemotherapy beside surgery removal of the 1st tumor. The mean survival was 36.7 ± 12.1 months in the non-radiotherapy or non-chemotherapy group (N=8) while 12.1 ± 1.9 months in the radiotherapy and/or chemotherapy group (N=42; P = 0.032). At diagnosis of the 2nd hematological cancer of the 50 patients, i) 77% of patients had the decreased platelet count and 60% had grade III-IV platelet thrombocytopenia; ii) 82.5% of patients had elevated or decreased white blood cells count: while 40% patients had increased white blood cells >20*10^9/L, 22.5% cases had grade III-IV leukopenia; There are 72.5% patients has anemia with Hgb<9g/dL.The median duration time from the initial 1st tumor treatment to the occurrence of the 2nd non-Hodgkin's lymphoma (N=57) was 74 (range: 7-297) months, with a median survival time of 65 (range: 1-114) months. The 1-year, 3- year and 5-year overall survival rate were 85.6%, 70.5%, 56.3%, respectively. For the diagnosis of 2nd non-Hodgkin's lymphoma, 3.5% (2/57) of the patients were found by annual physicals, 61.4% (35/57) patients presented with superficial lymphadenopathy and 35.1% (20/57) cases complains of non-specific systemic symptoms: fever, night sweating, and decreased body weight.Conclusion: In general, the outcome of secondary hematological tumors is poor. However, patients who did not receive chemo- or radiotherapy during the initial tumor treatment had a longer survival than those who did. The risk factors, potentially type of chemo-agent and cumulative dosage of drugs, which may contribute to the occurrence of 2nd hematological malignancies, should be fully explored before formulating the initial tumor treatment plan. DisclosuresNo relevant conflicts of interest to declare.

Real Life Dates of Chronic Lymphocytic Leukemia (CLL) in Germany. Interim Analysis of 234 Consecutively New Diagnosed Patients in a German Epidemiological-Clinical Register

Background:Therapy studies yield important insights into clinical features and therapeutic options of CLL. However studies in Germany represent less then 20% of all CLL patients (pts); pts >75 years (yrs) are included in 3% only. Furthermore initial phases are not reflected in multicenter studies and data representing real life situation are scarce.Methods:Out of 1.443 patients consulting our center because of leucocytosis (>10 Gpt/l) between 2003/07/01 and 2018/06/30 we diagnosed CLL consecutively in 234 pts (16,2%): 143 male (m), 91 female (f). Median age at diagnosis is 71,4 yrs. Median leucocyte count is 18,0 Gpt/l. BINET - Stages are: A in 82%, B in 11% and C in 7% of pts. Diagnoses are strictly based on WHO definition: Pts with small lymphocytic lymphomas (sLL, n=11) are included but those with monoclonal lymphocytosis of unknown significance (MLUS) or monoclonal B - lymphocytoses with uncertainly flow cytometry (FC) results are excluded. Histopathology, FC and genetics have been performed by external hematological reference laboratories. All investigations followed the rules of best clinical and laboratory practice. Dates of death are given by the record sections of the involved communities (deadline 2018/06/30).To address different questions we defined 3 groups of pts: A: “collective group”, (n=234), i.e. all pts.diagnosed from 2003/07/01 to 2018/06/30. B: “epidemiological group” (n=129), i.e. pts from 3 communities (113.000 inhabitants - inc - in 2009/12/31) in close proximity referred to our center. C: “genetic features group” (n=99), i.e. pts diagnosed continuously between 2012/07/01 and 2018/06/30 with systematically performed genetics, (i.e. at least 80% of pts in this group. Genetics are: Cytogenetic (banding) n=88; FISH (del 6q21/6q, del 11q22.3, +12/+12q, del 13q14/ 13q34, del 17p13.1, 14q32) n=85. PCR (IgVH status - mutated vs. unmutated; TP53, NOTCH1, SF3B1 mutation) n=82.Results:“Collective group” (A): 7,5 years OS is 72% and 15 years OS is 33% respectively (KAPLAN-MEIER). Age of pts acts as a predominant factor for long term OS: 77% in pts < 60 yrs vs. 40% in pts ≥60 to <75 yrs vs. 16% in pts ≥75 yrs. 15 yrs OS of treated pts is 32% (n=78, median age at diagnosis: 73,3 yrs, m : f = 1,50); 15 yrs OS of untreated patients is 33% (n=146, median age at diagnosis: 71,0 yrs, m : f = 1,56). Mean time to 1st treatment was 16,0 month (0,1 to 132,6 months).“Epidemiological group” (B): Raw incidence is 7,56/105 inh. (m: 9,13, f: 6,06), age adjusted incidence is 10,3/105 inh (m: 12,5, f: 8,3), with highest rate of age between 75 to < 80 yrs. Standard incidence is calculated as 6,27/105 (BRD 1987), 4,78/105 (Europe) and 5,06/105 (USA 2000). Prevalence could be measured directly (2017-12-31): 79,1/105 inh.“Genetic features group” (C): IgVH mutation status is hypermutated in 48 pts. vs. unmutated in 39 pts. Results of FISH analyses (n = 85) are: del 6: 5,5%, del 11: 17,6%, +12: 3%, del 13q: 70,3%, del 17p: 8,8%; normal status: 13,2%. PCR revealed mutations of NOTCH1 in 7%, of SF3B1 in 10,5% and of TP53 in 8,6% of 82 pts, respectively. Combined del17p by FISH and molecular TP53 mutations at diagnosis are found in 3 of 81 pts (3,7%).Cytogenetic findings different to results of FISH and/or PCR were found in 36 of 82 pts (43,9%).Calculated 5 yrs freedom of therapy is 75% in IgVH hypermutated pts vs. 45% in unmutated pts (p = 0,0005; log rank test); calculated 5 yrs OS is 92% vs. 59% (p=0,023).Special situations in CLL: 13 of 234 pts (5,5%) have one parent or sibling with low grade NHL, mostly CLL. In contrast there is non spouse suffering of CLL / low grade NHL. Deficiency in Immunoglobuline G (Ig G < 4,0 g/l) was found in 17 of 199 pts at diagnose (8,5%), 29 pts (12,4%) were substituted with Ig G's in the Course of CLL. In 14 (6,0%) pts. we diagnosed a 2nd hematologic malignancy (3x cMPN, 1x CML, 3x MDS, 3x AML, 1x FL, 1x MCL, 1x MZL, 1x DLCBL-independent of CLL; monoclonal gammopathies are not considered). RICHTER syndrome was found in 1 case, but progression to plasmocytic/plasmoblastic disease was seen in 3 cases. Li FRAUMENI Syndrome was revealed in 1 male patient, he has been in stable disease for 13 yrs.Conclusion:CLL seems to be more frequent than yet considered. IgVH mutation status seems to be very important as a single prognostic factor concerning time of 1st therapy as well as OS. Clinical features of CLL are very different and impressing. DisclosuresBöttcher:Genentech: Research Funding; Janssen: Honoraria; AbbVie: Honoraria, Research Funding; Celgene: Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

SOLE (Study of Letrozole Extension): A phase III randomized clinical trial of continuous vs intermittent letrozole in postmenopausal women who have received 4-6 years of adjuvant endocrine therapy for lymph node-positive, early breast cancer (BC).

503 Background: In animal models of hormone receptor positive (HR+) breast cancer, acquired resistance to continued letrozole was shown to be reversed by estrogen-induced apoptosis. Sensitization to reintroduction of estrogen withdrawal by letrozole was hypothesized to improve treatment outcome. SOLE tested the hypothesis that 3 mos treatment-free intervals during extended adjuvant therapy will improve disease-free survival (DFS). Methods: SOLE enrolled 4884 postmenopausal women with HR+ lymph node-positive BC who had completed 4-6 yrs of adjuvant endocrine therapy (19% SERM, 43% AI, 38% both; stratification factor). Pts were randomly assigned to an additional 5 yrs continuous letrozole (2.5 mg daily; n = 2441) vs 5 yrs intermittent letrozole (taken for the first 9 mos of yrs 1-4, and 12 mos in yr 5; n = 2443). The primary endpoint was DFS (randomization until invasive local, regional, distant recurrence or contralateral BC; 2nd malignancy; death). Final analysis was at 665 DFS events, after 2 interim analyses. SOLE required 4800 pts for 80% power to detect a 20% DFS hazard reduction with 2-sided α = 0.05 using a stratified log rank test. Analysis is by intention-to-treat. Results: At 60 mos median follow-up, 5 yr DFS from randomization was 85.8% vs 87.5% for patients assigned intermittent vs continuous letrozole (HR = 1.08; 95% CI 0.93-1.26; P = 0.31). Similar outcome was observed for breast cancer-free interval (HR = 0.98; 95% CI 0.81-1.19), distant recurrence-free interval (HR = 0.88; 95% CI 0.71-1.09), and overall survival (HR = 0.85; 95% CI 0.68-1.07). AEs of grade &gt; 3 were reported for 43.5% vs 41.6% of pts assigned intermittent vs continuous letrozole. Overall 24% pts discontinued letrozole early in both groups. Conclusions: Among postmenopausal women with HR+ BC, extended intermittent letrozole did not improve DFS vs continuous letrozole. The similar observed outcomes and incidence of AEs provides clinically relevant information on the intermittent administration of extended letrozole for patients who could benefit from temporary treatment breaks. Clinical trial information: NCT00553410.

Reduction of Dose to the Contralateral Breast by Superflab Use in Radiation Therapy for Mammary Carcinomas

Background:Radiation therapy is an integral part of multimodality treatment for locally advanced carcinoma of breast. Radiation doses to nearby critical normal structures like heart, lungs, and contralateral breast (CLB increases risk of second malignancies. In this study, we measured doses to the CLB and studied effects of a 1 cm thickness superflap.Materials and Methods:Fifty post-mastectomy carcinoma breast patients were included in the study. Radiation therapy of 50 Gy was planned in 25 fractions, 5 days a week, using the Eclipse Treatment Planning System version 8.9.15, with a pencil beam convolution algorithm and 6 MV photon beam. Plans were transferred to a linear accelerator (Varian 2300 CD) for execution of treatment. Twenty-four CaSO4 thermoluminescent dosimeter discs (TLDs) were used for dose measurement over the CLB. The dose was measured for each patient without a superflab for ten fractions and with for another ten fractions for subsequent comparison.Results:Mean doses/fractions received by the CLB with and without a superflab? were 3.78 ± 1.29 cGy and 7.82 ± 2.62 cGy, respectively, with total dosees of 94.69 ± 32.43 cGy (1.89% of prescribed dose) and 191.14 ± 65.62 cGy (3.82% of prescribed dose). The average reduction in mean dose with a 1 cm thick superflab was 46.57 ± 17.18%, in the range of 20 to 80% and statistically significant (p < 0.001).Conclusion:Superflab? is an effective method for dose reduction to CLB. It is an easy, convenient and low time consuming method. Elucidation of any role in reduction of 2nd malignancies in CLB now needs large studies with long follow-up.