Risk Of Second Malignancies Research Articles

Hematopoiesis and immune reconstitution after CD19 directed chimeric antigen receptor T-cells (CAR-T): A comprehensive review on incidence, risk factors and current management.

Impaired function of hematopoiesis after treatment with chimeric antigen T-cells (CAR-T) is a frequent finding and can interest a wide range of patients, regardless of age and underlying disease. Trilinear cytopenias, as well as hypogammaglobulinemia, B-cell aplasia, and T-cell impairment, can severely affect the infectious risk of CAR-T recipients, as well as their quality of life. In this review, we provide an overview of defects in hematopoiesis after CAR-T, starting with a summary of different definitions and thresholds. We then move to summarize the main pathogenetic mechanisms of cytopenias, and we offer insight into cytomorphological aspects, the role of clonal hematopoiesis, and the risk of secondary myeloid malignancies. Subsequently, we expose the major findings and reports on T-cell and B-cell quantitative and functional impairment after CAR-T. Finally, we provide an overview of current recommendations and leading experiences regarding the management of cytopenias and defective B- and T-cell function.

Lenalidomide-associated B-cell ALL: clinical and pathologic correlates and sensitivity to lenalidomide withdrawal.

Lenalidomide is an effective component of induction and maintenance therapy for multiple myeloma, though with a risk of secondary malignancies, including acute lymphoblastic leukemia (ALL). In contrast to therapy-related myeloid neoplasia, lenalidomide-associated lymphoblastic neoplasia remains poorly characterized. We conducted a dual institution retrospective study of 32 ALL cases that arose after lenalidomide maintenance (all B-lineage, 31/32 BCR::ABL-negative). B-cell ALL (B-ALL) was diagnosed at median 54months (range, 5-119) after first exposure to lenalidomide and after median 42months of cumulative lenalidomide exposure (range, 2-114). High incidence of TP53 mutations (9/19 evaluable cases) and low hypodiploidy (8/26 patients) were identified. Despite median age of 65 years and poor-risk B-ALL features observed in the cohort, rates of complete response (CR) or CR with incomplete hematologic recovery were high (25/28 patients receiving treatment). Median event-free survival was 35.4months among treated patients (not reached among those undergoing allogeneic hematopoietic cell transplantation [HCT]). Sixteen patients remain alive without evidence of B-ALL after HCT or extended maintenance therapy. We also describe regression of B-ALL or immature B-cell populations with B-ALL immunophenotype after lenalidomide discontinuation in 5 patients, suggesting lenalidomide may drive leukemic progression even after initiation of lymphoblastic neoplasia and that lenalidomide withdrawal alone may be an appropriate first-line intervention in selected patients. Monitoring for early B-ALL-like proliferations may offer opportunities for lenalidomide withdrawal to prevent progression. Established combination chemotherapy regimens, newer surface antigen-targeted approaches, and allogeneic HCT are effective in many patients with lenalidomide-associated B-ALL and should be offered to medically fit patients.

Observation vs. radiotherapy in primary mediastinal B-cell lymphoma patients with complete response to standard immunochemotherapy: The IELSG37 randomized trial.

LBA7505 Background: Primary mediastinal B-cell lymphoma (PMBCL) has a good prognosis if remission is rapidly achieved with dose‐intensive immunochemotherapy. In these patients mediastinal radiotherapy (RT) may consolidate responses; however, it increases the risk of second malignancies and coronary or valvular heart disease. The IELSG37 trial was planned with a non-inferiority design to test whether RT can be omitted in patients who achieve a complete metabolic response (CMR) after immunochemotherapy. Methods: Patients with newly diagnosed PMBCL were eligible. Initial rituximab and anthracycline-based therapy was chosen according to local practice. CMR was defined, upon central review of positron emission computed tomography (PET/CT) scans, as Deauville score 1 to 3, according to the Lugano classification. Responding patients were randomized to observation (OBS) or consolidation RT (30 Gy). Randomization was stratified on gender, chemotherapy regimen, country, and PET/CT score. The primary endpoint was progression-free survival (PFS) after randomization. The sample size (540 patients to enrol, and 376 to randomize) was calculated assuming a 30-month PFS probability of 0.85 in both arms, with alpha at 0.05, 80% power and a hazard ratio (HR) of 1.77 as non-inferiority margin. Results: At a median follow-up of 30 months, the number of observed events was considerably lower than expected, hence, the Independent Data Monitoring Committee (IDMC) of the trial recommended to complete the planned total accrual without increasing the study size or duration. The primary endpoint analysis was performed, according to the IDMC recommendation, with ≥80% of patients having a minimum follow-up of 30 months. 545 patients (209 men, 336 women) were enrolled. Induction immunochemotherapy was completed and response assessed in 530 patients, 268 of them (50.6%) achieved a CMR and were randomly allocated to OBS (n = 132) or RT (n = 136). The PFS at 30 months was 98.5% (95%CI, 94.3 – 99.6) in the RT arm and 96.2% (95%CI, 91.1-98.4) in the OBS arm (P = 0.278). The estimated relative effect of radiotherapy vs observation in terms of hazard ratio (HR) was 0.47 (0.12-1.89) without adjustments and 0.79 (0.19-3.31) after stratification for the variables used for randomization. At 30 months the absolute risk reduction from RT was 2.3% (-1.5 to 6.2) unadjusted, and 0.8% (-3.0 to 8.3) with stratified HR. The number needed to treat is high (43 patients, unadjusted, and 126 after stratification). The 5-year overall survival was 99% in both arms. Longer follow-up is needed to examine late toxicity. Conclusions: This study is the largest prospective study of PMBCL ever conducted and although the event rate did not reach the assumed level, its evidence supports the omission of RT in patients achieving a CMR after immunochemotherapy.

Outcomes of myeloid malignancies in patients previously treated with PARP inhibitors for solid malignancies: A single institution experience.

e19000 Background: Treatment with Poly(ADP-ribose) Polymerase proteins (PARP) has improved the survival of patients (pts) with solid malignancies harboring a homologous recombination deficiency (HRD). The association between PARP inhibitors (PARPi) and the development of myeloid neoplasms post cytotoxic therapy (MN-pCT) has been reported. We aim to describe the characteristics and outcomes of pts who develop MN-pCT after treatment with PARPi. Methods: Pts treated with PARPi at a single institution from July 2014 to August 2022, who developed MN-pCT (AML, MDS or CMML), were retrospectively evaluated. Diagnosis of MN-pCT was defined according to the 5th edition of the WHO criteria. Clinical and demographic characteristics along with cytogenetics and molecular features were analyzed. HRD was assessed by NGS on peripheral blood with a 13-gene panel. Results: 1462 pts were treated with PARPi at MDACC. Of these, 15 (1%) developed MN-pCT. These include 9 (60%) with MDS, 5 (34%) with AML, and 1 (7%) with B/Myeloid Mixed-Phenotype Acute Leukemia (MPAL). The median age was 62 (46-74) years and 14 (93%) were female. The most frequently used PARPi was olaparib in 9 (60%) pts. All pts had also previously received platinum-based agents and taxanes. Pts with 19 different solid tumors were included; 11 (85%) had active concomitant solid tumors at the time of MN-pCT. The median time from PARPi treatment to myeloid neoplasm (TTM) was 20.7 months (9.3-39.9). Cytogenetics and molecular features were available in 14 pts (93%). Eight (57%) had complex karyotype. The median number of mutations were 2 (0-4). TP53mut was present in 9 (64%) pts with a median VAF 47.3% (11.9-76.6%) of whom 6 (67%) were biallelic. The ORR to antileukemic therapy was 66% (n = 8): 3 (38%) had CR, 2 (25%) had PR, 2 (25%) had mCR with HI and 1 (13%) had isolated HI. The patient with B/myeloid MPAL was not evaluable for response. Of the responders, 7 (88%) pts relapsed at a median of 2.8 months (1.5-4.2). The median OS and EFS on the whole cohort were 7.8 (3.2-12.4) and 5.3 (3.8-6.7) months respectively. Conclusions: Development of MN-pCT in pts treated with PARPi is rare but most outcomes are very poor. Prospective analysis to evaluate pts at higher risk of developing MN-pCT is warranted in order to select pts who might benefit from novel therapies without increasing the risk of secondary myeloid malignancies. [Table: see text]

Secondary primary malignancy risk by ER, PR, and HER-2 status in post-menopausal women with breast cancer: A population-based analysis.

1050 Background: Breast cancer is the most commonly diagnosed cancer and second leading cause of death due to cancer in women in the United States. We aimed to determine site specific incidence of SPMs in post-menopausal women with primary BC using data from the US Surveillance, Epidemiology, and End Results (SEER-17) cancer registries. Methods: We retrospectively analyzed post-menopausal women aged 45 or older with a first primary breast cancer diagnosis between 2000 and 2019, excluding those aged 45 or younger or with non-breast cancers as their first malignancy. We defined SPMs as second malignancies occurring at least 6 months after the initial breast cancer diagnosis and calculated standardized incidence ratios (SIRs) and absolute excess risk (AER) using SEER*Stat. Statistical significance was determined using p-values <0.05 and a 95% CI assuming a Poisson distribution of SPM incidence. Results: Among 774,965 post-menopausal women ≥45 years old with primary breast cancer, 10.8% developed SPMs, with significantly increased risk compared to the general population (SIR=1.14, 95% CI=1.13-1.15, p<0.05), particularly for solid tumors (SIR=1.16, 95% CI=1.15-1.16, p<0.05) and certain malignancies including salivary gland (SIR=1.77), thyroid (SIR=1.56), endocrine system (SIR=1.56), and hematological malignancies such as ALL, ANLL, and AML (SIR>1.70). Women aged 45-59 and Black women had the highest risk for all malignancies. PR receptor-positive women had higher risk for thyroid SPMs, while PR-negative women had higher risk for SPMs in female genitalia, bones and joints, and hematological malignancies. HER-positive and triple-positive (HER ER PR) women had higher risk for thyroid and hematological SPMs, while triple-negative women had higher risk for ALL, ANLL, and AML. Conclusions: This study found that 11% of post-menopausal women with primary BC develop SPMs, with thyroid cancer being the most common. Black and older women (45-59 years) had a higher risk of developing SPMs. [Table: see text]

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Patients (pts) with cHL with slow early response (SER) to initial chemotherapy (chemo) have a high risk of relapse. Current treatments such as chemo dose intensification and radiotherapy (RT) can increase the risk of secondary malignancies and cause long-term toxicity. KEYNOTE-667 (NCT03407144) is an open-label, phase 2 study being conducted to evaluate pembrolizumab (pembro) plus chemo in pts with cHL and SER to front-line chemo. We present results of an interim analysis of pts with high-risk cHL and SER (group 2). Methods: Pts eligible for group 2 were aged 3–17 (children) or 18–25 y (young adults) with newly diagnosed high-risk (stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB) cHL. Pts in group 2 received induction therapy with 2 cycles of vincristine, etoposide, prednisone/prednisolone, and doxorubicin (OEPA). Response was then assessed by PET/MRI/CT. Pts with rapid early response to OEPA received nonstudy therapy and pts with SER to OEPA (Deauville score, 4/5) received consolidation with 4 cycles of cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28) plus pembro 2 mg/kg up to 200 mg IV Q3W (3–17 y) or 200 mg IV Q3W (18–25 y). After consolidation, pts with PET positivity (Deauville score, 4/5 at late response assessment [LRA]) received involved-site RT (28.8 Gy) to late PET-positive residua. RT was omitted in pts with PET negativity. All pts with SER continued to receive pembro Q3W for 17 doses. The primary end point was ORR in pts with SER by blinded independent central review (BICR) per Cheson 2007 International Working Group criteria. Secondary end points included PET negativity at LRA and safety. Results: 49 pts with high-risk cHL with SER to OEPA were included in group 2. The median age was 15 y (range, 6–22), 24 pts (49%) had bulky disease, and 31 (63%) had Ann Arbor stage IV disease. At data cutoff (2 September 2022), the median follow-up was 15.3 mo (range, 3.2–30.5); 22 pts (45%) had completed treatment and 24 (49%) were ongoing on consolidation/maintenance. Median time on pembrolizumab was 10.4 mo (range, 0.5–11.8). 42 pts (86%) had an LRA, of whom 27 (64%) were PET negative by BICR (30 pts [71%] were PET negative by investigator review). Adverse events (AEs) occurred in 42 pts (86%), with grade 3/4 AEs in 13 pts (27%). Serious AEs were reported in 7 pts (14%). No pts died because of an AE. Treatment-related AEs occurred in 30 pts (61%), with grade 3/4 treatment-related AEs in 6 pts (12%). 4 pts (8%) had immune-mediated AEs: 2 grade 1 hypothyroidism and 2 grade 2 hypothyroidism. Conclusions: The results showed that pembro plus COPDAC-28 consolidation had manageable safety and promising efficacy in children and young adults with high-risk cHL and SER to front-line chemo. 64% of pts with a LRA had a PET-negative response and were spared RT. These findings suggest that adding pembro to COPDAC-28 consolidation may augment responses in this high-risk cHL population. Encore Abstract - previously submitted to ASCO 2023 and EHA 2023 The research was funded by: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Keywords: Hodgkin lymphoma, immunotherapy Conflicts of interests pertinent to the abstract L. Vinti Consultant or advisory role: Amgen, Clinigen Research funding: Merck, Sharp & Dohme Educational grants: Takeda, Neon Other remuneration: Amgen, Takeda F. Fagioli Employment or leadership position: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi Consultant Or Advisory Role: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi Honoraria: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi Educational Grants: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi Other Remuneration: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi D. Plaza Lopez de Sabando Research funding: MERCK J. Landman-Parker Research funding: BMS, MSD J. Shen Employment or leadership position: Merck P. Pillai Employment or leadership position: Merck Stock ownership: Merck P. Marinello Employment or leadership position: Merck Stock ownership: Merck C. Mauz-Koerholz Consultant or advisory role: MSD Research funding: MSD

Long-Term Risk of Subsequent Malignant Neoplasms Among Childhood and Adolescent Lymphoma Survivors (1975-2013): A Population-Based Predictive Nomogram.

Studies are needed to assess risk factors pertinent to the incidence of secondary malignancies among childhood and adolescent lymphoma survivors. We aimed to identify risk factors pertinent to the incidence of secondary malignancies and subsequently establish a clinically practical predictive nomogram. A total of 5561 patients who were diagnosed with primary lymphoma below the age of 20 years between 1975 and 2013 and survived for at least 5 years were identified. Standardized incidence ratio (SIR) and excess risk (ER) analysis were performed by sex, age, and year when primary lymphoma was diagnosed, sites and types of primary lymphoma, and therapy strategies. Univariable and multivariable logistic regression were used to identify independent risk factors for adolescent and childhood lymphoma-related secondary malignancies. Based on 5 factors (age, time from lymphoma diagnosis, gender, lymphoma type, and therapy), a nomogram for predicting the risk of a secondary malignancy for patients with childhood and adolescent primary lymphoma was established. Among 5561 lymphoma survivors, 424 developed a secondary malignancy. Females (SIR = 5.34, 95% CI, 4.73-5.99; ER = 50.58) exhibited a higher SIR and ER than males (SIR = 3.28, 95% CI, 2.76-3.87; ER = 15.53). Blacks were at a higher risk than Caucasians or others. Nodular lymphocyte-predominant Hodgkin lymphoma survivors exhibited typically high SIR (13.13, 95% CI, 6-24.92) and ER (54.79) among all lymphoma classifications. Lymphoma survivors who underwent radiotherapy, whether they received chemotherapy or not, had typically higher SIR and ER. Among all types of secondary malignancies, "bone and joint neoplasms" (SIR = 11.07, 95% CI, 5.52-19.81) and "soft tissue neoplasms" (SIR = 12.27, 95% CI, 7.59-18.76) presented significantly high SIR whereas "breast cancer" and "endocrine cancer" associated with higher ER. The median diagnosis age of secondary malignancies was 36 years old, and the median time interval between the diagnosis of two malignancies was 23 years. A nomogram was constructed to predict the risk of secondary malignancies in patients diagnosed with primary lymphoma before 20 years of age. After internal validation, the AUC and C-index of the nomogram are 0.804 and 0.804, respectively. The established nomogram provides a convenient and reliable tool for predicting the risk of a secondary malignancy among childhood and adolescent lymphoma survivors, concluding significant concern for lymphoma survivors with high-risk estimates.

Cancer Control, Toxicity, and Secondary Malignancy Risks of Proton Radiation Therapy for Stage I-IIB Testicular Seminoma

This study's objective was to report cancer control and toxicity outcomes after proton radiation therapy (RT) in testicular seminoma and to compare secondary malignancy (SMN) risks with photon-based treatment alternatives. Consecutive patients with stage I-IIB testicular seminoma treated with proton RT at a single institution were retrospectively analyzed. Kaplan-Meier estimates for disease-free and overall survival were computed. Toxicities were scored using Common Terminology Criteria for Adverse Events version 5.0. Photon comparison plans, including 3-dimensional conformal RT (3D-CRT) and intensity modulated RT (IMRT)/volumetric arc therapy (VMAT), were created for each patient. Dosimetric parameters and SMN risk predictions for different in-field organs-at-risk were compared between the techniques. Excess absolute SMN risks were estimated with organ equivalent dose modeling. Twenty-four patients were included (median age, 38.5 years). The majority of patients had stage II disease (IIA, 12 [50.0%]; IIB, 11 [45.8%]; IA, 1 [4.2%]). Seven (29.2%) and 17 (70.8%) patients had de novo and recurrent disease, respectively (de novo/recurrent: IA, 1/0; IIA, 4/8; IIB, 2/9). Most acute toxicities were mild (grade 1 [G1], 79.2%; G2, 12.5%) with G1 nausea being most common (70.8%). No serious events (G3-5) occurred. With a median follow-up time of 3 years (interquartile range, 2.1-3.6 years), 3-year disease-free and overall survival rates were 90.9% (95% confidence interval,68.1%-97.6%) and 100% (95% confidence interval, 100%-100%), respectively. There were no documented late toxicities in the follow-up period, including worsening serial creatinine levels suggestive of early nephrotoxicity. Proton RT had significant reductions in mean organ-at-risk doses to the kidneys, stomach, colon, liver, bladder, and body compared with both 3D-CRT and IMRT/VMAT. Proton RT had significantly lower SMN risk predictions compared with 3D-CRT and IMRT/VMAT. Cancer control and toxicity outcomes using proton RT in stage I-IIB testicular seminoma are consistent with existing photon-based RT literature. However, proton RT may be associated with significantly lower SMN risks.

Overview and Recent Advances in 18F-FDG PET/CT for Evaluation of Pediatric Lymphoma

Pediatric lymphoma is the third most common childhood cancer, representing 15% of all pediatric malignancies. Evaluation of the extent of disease with imaging is essential for appropriate risk stratification and treatment planning, and has evolved extensively over the past several decades. At present, PET/CT plays a key role in the diagnostic evaluation of these patients, particularly for staging, treatment planning, and therapy response assessment. The vast majority of pediatric lymphomas are FDG avid and as a result, FDG PET/CT has a higher sensitivity for detecting sites of disease compared to conventional imaging modalities, as well as a higher sensitivity for detecting focal bone marrow lesions compared to standard bone marrow biopsy of the iliac crest. PET/CT can be used to identify early responders, helping to minimize overtreatment with intensive chemotherapy and radiotherapy, thereby reducing the risk of secondary malignancies and cardiovascular complications. Conversely, PET/CT can identify patients with an inadequate metabolic response during treatment, who can then benefit from earlier treatment intensification. A negative interim or end of treatment FDG PET/CT is highly predictive for a complete remission, although positive PET/CT scans, particularly at end of treatment, have a lower PPV and must be interpreted cautiously. Nevertheless, PET/CT is more accurate than conventional imaging alone, as well as in the case of conflicting results, such as residual lymph node enlargement and soft tissue lesions that can that can persist despite resolution of the underlying malignancy. For these reasons, FDG PET/CT has been incorporated into the standard diagnostic procedures for lymphoma staging and treatment response evaluation, using the visual Deauville 5-point scale and Lugano classification. In the future, innovations in low-dose ultrafast total-body PET/CT, increased use of PET/MR and incorporation of quantitative parameters from PET such as total metabolic tumor volume may allow even more precise prediction of response and personalized therapy while minimizing radiation exposure and adverse effects and complications of treatment.

PO-2019 Does VMAT increase the risk of secondary malignancies after radiotherapy of left-breast cancer?

PO-2019 Does VMAT increase the risk of secondary malignancies after radiotherapy of left-breast cancer?

A tale of multiple primaries: Primary neuroendocrine carcinoma, vaginal vault and renal cell carcinoma in a 52 years old female

Cancer patients have 15-25% higher risk of second malignancy compared to general population. We hereby describe an extremely unusual case of 52-years-old-female with Neuroendocrine Carcinoma (NEC) of vaginal vault developing 4

Characteristics of Patients With Second Primary Lung Cancer Following Breast Cancer: A Retrospective Descriptive Study

BackgroundBreast cancer (BC) is the most common noncutaneous malignancy in women and survivors are at an increased risk for secondary malignancy with lung cancer (LC) being the most common. There are few studies that have explored the clinicopathological specifics of LC in BC survivors. MethodsIn this single-institution, retrospective study, we identified BC survivors who subsequently developed LC, examined their breast and LC clinical and pathological characteristics and compared them to the general BC and LC population as published in the literature. ResultsIn our study, we found the following associations that could be meaningful: an association between receiving radiation (RT) and LC (including a statistically significant P = .03 chance of ipsilateral LC after BC treatment with RT), a higher incidence and amount of smoking and LC, high BRCA positivity (78.9%) in the few patients who had germline testing, and a higher incidence of EGFR mutations in NSCLC after BC (60.9%) as well as an earlier stage of NSCLC disease. ConclusionTreatments such as RT, genetic factors such as BRCA mutations, and tobacco use may increase the risk of developing LC amongst BC survivors. Exploring this further can potentially lead to better risk stratification through modified low-dose CT chest screening protocols to catch LCs earlier and ultimately improve outcomes. Past studies have shown that BC survivors who are subsequently diagnosed with NSCLC may have improved OS compared with primary NSCLC and our study showed a high incidence of EGFR mutated NSCLC, which also suggest both improved prognosis and a different molecular profile of NSCLC, which warrants further investigation. Lastly, BC survivors who subsequently are diagnosed with NSCLC had earlier stage disease in our study, perhaps a result of surveillance, highlighting the importance of close monitoring of BC survivors.

473 Clinical characteristics and risk of second malignancies of extramammary paget’s disease patients in Canada and Japan

473 Clinical characteristics and risk of second malignancies of extramammary paget’s disease patients in Canada and Japan

Greetings From the Editor of Clinical Thyroidology

Clinical ThyroidologyVol. 35, No. 4 Greetings from the EditorFree AccessGreetings From the Editor of Clinical ThyroidologyPublished Online:11 Apr 2023https://doi.org/10.1089/ct.2023;35.129-130AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Our editorial team is thrilled to share this month's issue of Clinical Thyroidology, which provides an in-depth look at recent studies spanning the topics of thyroid laboratory testing, thyroid disease and pregnancy, pediatric thyroidology, thyroid nodules, and thyroid cancer.The issue begins with a review by Drs. Sawan Vijay Rupani and Anupam Kotwal of a study on the use of age- and sex-specific thyroid function test ranges to more appropriately diagnose subclinical thyroid dysfunction. Moving to the topic of thyroid and pregnancy, Drs. Ricardo Villela and Ricardo Correa summarize a study examining the role of thyroid autoantibodies on thyroid function in women during preconception and gestation. Relatedly, Drs. Sofie Bliddal and Ulla Feldt-Rasmussen provide their perspective on a study reporting the challenges of antithyroid drug use in women with Graves’ disease during pregnancy. Our pediatric thyroidologist editorial board member, Dr. Gary Francis, wraps up this first group of papers with his summary on a study of macro-thyrotropin in the consideration of congenital hypothyroidism.Moving on to thyroid nodules and thyroid cancer, Drs. George Taylor and Lindsay Kuo discuss a study assessing the accuracy of the Bethesda cytopathologic reporting system in indeterminate thyroid lesions. On the provocative topic of cancer prevention, Dr. Joanna Klubo-Gwiezdzinska reviews a study that tackles this question by studying a healthy lifestyle. Drs. David Toro-Tobon and Omar El Kawkgi then discuss a Korean population-based epidemiologic study on the risk of secondary malignancies associated with radioactive iodine treatment for thyroid cancer. The topic of postoperative serum calcitonin levels as a predictor of medullary thyroid cancer behavior is discussed in a study reviewed by Dr. Christopher Rowe. For all patients with a diagnosis of thyroid cancer, the potential unexpected effects of initial treatment are important to consider. Dr. Jie Liu reviews a study that surveyed thyroid cancer patients to assess changes in quality-of-life measures associated with their treatment. Relatedly, Drs. Erivelto Volpi and Leonardo Rangel summarize a study reporting the risk of hypoparathyroidism and impacts on quality of life among thyroid cancer survivors. Finally, Drs. Eric Walser and Jesse Pasternak share their perspective on a study examining the role of same-day discharge with patients undergoing thyroid surgery.We remain active on our various social media channels, and I invite our readers to further engage with us there. In these channels, we recap the featured highlights from each month's issue and discuss other topics related to the latest clinical thyroid literature. All are welcome to join us at:Twitter:https://twitter.com/clinicalthyroid(@clinicalthyroid)Facebook:https://www.facebook.com/ThyroidAssociationLinkedIn:https://www.linkedin.com/company/american-thyroid-associationYoutube:https://www.youtube.com/user/thyroidorgI also thank the editorial board of Clinical Thyroidology for the Public [CTFP] (https://www.thyroid.org/patient-thyroid-information/ct-for-patients), as led by Dr. Alan Farwell, for their work in providing short summaries of our Clinical Thyroidology articles each month. These quicker reads are helpful to patients and to the general public who are interested in learning more about recently published studies in the clinical thyroid literature.We will continue to provide reviews, commentaries, editorials, and perspectives of the most relevant clinical thyroid studies from the published literature. Guidelines for submitting Letters to the Editor and select Guest Editorials that cover timely and innovative aspects of clinical thyroid disease management may be found at https://home.liebertpub.com/publications/clinical-thyroidologyand174/623/for-authors.Thank you again for your interest in Clinical Thyroidology. Please feel free to send me any questions or comments at clinicalthyroidology@thyroid.org.Warmest regards,Angela M. Leung, MD, MScEditor-in-Chief, Clinical ThyroidologyFiguresReferencesRelatedDetails Volume 35Issue 4Apr 2023 Information© Copyright 2023, Mary Ann Liebert, Inc.To cite this article:Greetings From the Editor of Clinical Thyroidology.Clinical Thyroidology.Apr 2023.129-130.http://doi.org/10.1089/ct.2023;35.129-130Published in Volume: 35 Issue 4: April 11, 2023PDF download

CLO23-056: Risk of Second Malignancy Among Non-Metastatic Seminoma Patients Treated With Radiation Therapy and Chemotherapy in Manitoba

"CLO23-056: Risk of Second Malignancy Among Non-Metastatic Seminoma Patients Treated With Radiation Therapy and Chemotherapy in Manitoba" published on 31 Mar 2023 by National Comprehensive Cancer Network.

CLO23-066: Risk of Secondary Malignancies After Platinum-Based Chemotherapy in Testicular Seminoma Patients: A Population-Based Study

"CLO23-066: Risk of Secondary Malignancies After Platinum-Based Chemotherapy in Testicular Seminoma Patients: A Population-Based Study" published on 31 Mar 2023 by National Comprehensive Cancer Network.

Diagnosis and Treatment of Peripheral and Cranial Nerve Tumors with Expert Recommendations: An EUropean Network for RAre CANcers (EURACAN) Initiative.

The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively.

Risk of Secondary Malignancies in Hematopoietic Stem Cell Transplantation Recipients: A Nationwide Population-Based Study in Taiwan

The improvement of survival after hematopoietic stem cell transplantation has brought about a need to evaluate long-term complications, for instance, secondary malignancies. The risk of subsequent malignancies after hematopoietic stem cell transplantation must be clarified in a large population. To estimate the risk of secondary malignancies in hematopoietic stem cell transplantation survivors and compare it with the risk in patients without hematopoietic stem cell transplantation history. We conducted a population-based retrospective cohort study of 3,059 hematopoietic stem cell transplantation recipients from the National Health Insurance Research Database of Taiwan, containing 1,378 autologous, 1,641 allogeneic, and 40 cord blood stem cell transplantation recipients between 2000 and 2013. A control group of 12,236 patients without an hematopoietic stem cell transplantation history was identified. The covariates included age, sex, comorbidities, stem cell source, facility level of care, and history of total body irradiation. Comorbidities were estimated by the revised Charlson comorbidity index, and a higher score suggested more severe comorbidity. Adjusted hazard ratios were determined by adjusting for age, sex, comorbidity, and facility level of care. Overall, hematopoietic stem cell transplantation recipients had a higher risk of secondary malignancies with an adjusted hazard ratios of 1.348 (p = 0.017). Being male and female (adjusted hazard ratios 1.395, p = 0.009 and adjusted hazard ratios 1.291, p = 0.042, respectively) and pre-hematopoietic stem cell transplantation total body irradiation (adjusted hazard ratios 1.591, p < 0.001) were correlated with a high risk of secondary malignancies. Among the subsequent neoplasms, bone cancer showed the highest risk (adjusted hazard ratios 27.899, p < 0.001), followed by laryngeal (adjusted hazard ratios 6.643, p < 0.001), kidney (adjusted hazard ratios 5.580, p < 0.001), esophageal, pancreatic, thyroid (adjusted hazard ratios 1.993, p < 0.001), and skin (adjusted hazard ratios 1.992, p < 0.001) cancers. The median follow-up duration was 2.16 years in the hematopoietic stem cell transplantation group and 2.57 years in the control group, and the overall median follow-up duration was 2.21 years. Medical practitioners should be aware of the high risk of secondary malignancies in hematopoietic stem cell transplantation recipients later in life. These recipients should be informed about the importance of regular follow-up and photoprotective measures. Lifelong surveillance is recommended.

Second malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea.

Patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF), are known to have an increased risk of second malignancies (SMs). Hydroxyurea (HU) is a guideline-recommended cytoreductive therapy for patients at high risk for MPNs. Controversy exists as to whether HU use is associated with a higher risk of SMs, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We conducted a retrospective cohort study of older patients diagnosed with MPN (age ≥66 years) between 2010 and 2017 and included the data in the Surveillance, Epidemiology, and End Results Medicare-linked database. Multivariable competing risk analyses adjusting for patient characteristics were used to assess the impact of HU on the development of SM. We identified 4023 patients (1688 with PV, 1976 with ET, and 359 with MF) with a median age of 77 (interquartile range [IQR], 71-83) years at the time of MPN diagnosis. After a median follow-up of 3.25 (IQR, 2.10-5.00) years, 489 patients developed an SM (346 solid, 73 lymphoid, and 70 myeloid malignancies). The cumulative incidence probability of SM was 19.88% (95% confidence interval [CI], 17.16%-22.75%) among 2683 HU users and 22.31% (95% CI, 17.51%-27.47%) among 1340 nonusers, respectively (Gray's test, P< .01). We did not identify significant differences in the incidence of solid or hematologic SMs, including AML/MDS (hazard ratio, 1.33; 95% CI, 0.77-2.29; P= .30), between HU users and nonusers. Our results suggest that the use of HU does not increase the risk of SM in older patients with MPN.

Abstract PD14-09: PD14-09 The effect of timing of TP53 genetic testing on treatment and outcomes among women with Li-Fraumeni syndrome and breast cancer

Abstract Background: Li-Fraumeni syndrome (LFS) is a pan-cancer predisposition syndrome caused by pathogenic germline TP53 variants. Breast cancer (BC) is the most prevalent tumor in women with LFS. The risk of secondary malignancies, including multiple primary BCs, other LFS-related cancers, radiation-induced sarcomas, and local recurrences are important clinical concerns in the LFS setting. The diagnosis of LFS may influence treatment decisions and outcomes. Methods: In this international multicenter study, we analyzed women with pathogenic or likely pathogenic germline TP53 variants and BC (DCIS or invasive breast carcinoma) diagnosed 2002-2022 from three retrospective LFS cohorts (Dana Farber Cancer Institute, USA; Institut Gustave Roussy, France; Hospital Sírio-Libanês, Brazil). We excluded carriers of TP53 unconfirmed possibly mosaic variants, carriers of a 2nd pathogenic variant in another BC susceptibility gene, and those with missing data related to timing of genetic testing (TGT) or date of 1st BC diagnosis (dx). The overall cohort was divided in two groups: genetic testing before or at 1st BC dx (group A) and those with testing ≥1 year after 1st BC dx (group B). In cases with synchronous bilateral BC, we included the tumor of higher risk of recurrence (invasive, higher stage, more aggressive tumor biology) and excluded the other. The chi-square test was used to measure the association between TGT and other categorical variables. Results: 209 patients (pts) met criteria for this analysis. The median age of 1st BC dx was 35 years (IQR, 31-42). BC was the 1st cancer dx in 87.5% of the pts. Among 1st breast tumors, 38 were DCIS, 147 were early-stage BC (61 I, 49 II, 37 III) and 7 stage IV (17 missing). There were no differences between groups A and B regarding staging at dx. Missense TP53 variants were the most common type of germline mutation (n=154, 73.6%), with 60.4% (n=93) in the DNA-binding domain and 38.9% (n=60) in the tetramerization domain. Median follow-up from 1st BC dx was 6 years (IQR, 3-10). 53.1% of pts (n=111) underwent TP53 germline testing only after 1st BC dx. Family history of BC &amp;lt; 50 and non-BC malignancy prior to or synchronous with 1st BC dx were not associated with TGT (p=0.3 and p=0.2, respectively). 35.4% of pts developed a second primary BC (25 ipsilateral; 49 contralateral). Among pts without synchronous bilateral BC or metastatic BC at dx, 97 pts underwent contralateral risk reducing mastectomy (CRRM), 56.7% (55/97) as part of treatment surgery for the 1st BC. CRRM uptake was associated with TGT (A 70.3% vs B 41.6%, p=0.001). Of 194 pts with detailed data on surgical treatment (1st BC), 146 underwent mastectomies and 48 breast conserving surgery (BCS). Group A had more mastectomies (79.5% vs 61.2%, p=0.001) and less radiation therapy (10.2% vs 45.9%, p&amp;lt; 0.001). Among the irradiated pts, 9.8% (n=5) developed sarcomas in the irradiated field. Thirty-eight pts had BC recurrence: 21 loco-regional (A 6 vs B 15, p&amp;lt; 0.05), mostly in-breast, and 17 distant relapses. There was a significant statistical association between TGT and type of BC surgery (p=0.001), radiation-therapy (p&amp;lt; 0.001), CRRM uptake (p=0.001) and local relapses (p&amp;lt; 0.05). Conclusion: This analysis of BC in our sizable cohort of LFS patients with treatment data confirms that, timing of genetic testing affects some treatment options and outcomes, including surgical procedures and use or avoidance of radiation. These decisions appear to influence the risk of local recurrence or additional primary BC and radiation-induced sarcoma. Recognition of germline TP53 variants in breast cancer patients as part of genetic testing at diagnosis appears to have implications for treatment options and outcomes. Citation Format: Renata Sandoval, Michele Bottosso, Natalia Polidorio, Brittany Bychkovsky, Benjamin Verret, Alessandra Gennari, Sophie Hyman, Maria Isabel Achatz, Olivier Caron, Fabrice Andre, Judy Garber. PD14-09 The effect of timing of TP53 genetic testing on treatment and outcomes among women with Li-Fraumeni syndrome and breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD14-09.