Diagnosis Of Second Malignancy Research Articles

Unraveling trajectories from aplastic anemia to hematologic malignancies: genetic and molecular insights.

Aplastic anemia (AA), characterized by hematopoietic stem cell deficiency, can evolve into different hematologic malignancies. Our understanding of the genetic basis and mechanisms of this progression remains limited. We retrospectively studied 9 acquired AA patients who later developed hematologic malignancies. Data encompassed clinical, laboratory, karyotype, and next-generation sequencing (NGS) information. We explored chromosomal alterations and mutation profiles to uncover genetic changes underlying the transition. Nine AA patients developed myelodysplastic syndrome (seven patients), acute myeloid leukemia (one patient), or chronic myelomonocytic leukemia (one patient). Among eight patients with karyotype results at secondary malignancy diagnosis, monosomy 7 was detected in three. Trisomy 1, der(1;7), del(6q), trisomy 8, and del(12p) were detected in one patient each. Among three patients with NGS results at secondary malignancy diagnosis, KMT2C mutation was detected in two patients. Acquisition of a PTPN11 mutation was observed in one patient who underwent follow-up NGS testing during progression from chronic myelomonocytic leukemia to acute myeloid leukemia. This study highlights the genetic dynamics in the progression from AA to hematologic malignancy. Monosomy 7's prevalence and the occurrence of PTPN11 mutations suggest predictive and prognostic significance. Clonal evolution underscores the complexity of disease progression.

Hematologic secondary malignancies among 102 Chinese patients with Waldenstrom’s macroglobulinemia: a single-center case experience and literature review

Waldenstrom’s macroglobulinemia (WM) is a rare and indolent B-cell lymphoma. To investigate the type and survival of hematologic secondary malignancies (SMs) in Chinese patients with WM, we retrospectively reviewed the characteristics of 102 patients with WM from February 2002 to May 2023 in our center. Four men and two women were diagnosed with hematologic SMs. Of the six patients with hematologic SMs, one was diagnosed with acute myeloid leukemia (AML), one with multiple myeloma (MM), one with myelodysplastic syndrome (MDS), one with B-cell acute lymphoblastic leukemia (B-ALL), and two with diffuse large B-cell lymphoma (DLBCL). The median age was 65.5 years (56–74 years). The median interval time between diagnosis of WM and hematologic SMs was 39.5 months (10–117 months). Among those with WM with hematologic SMs, five died and one survived. Overall survival (OS) was just 33 months (12–119 months) on median. A total of 32 patients died and 64 survived in the group of WM without hematologic SMs, and the median OS was 82 months (3–250 months). This is the first study in the Chinese population on hematologic SMs in WM. The purpose of this study was to investigate the prognosis of hematologic SMs in WM in the Chinese population, as well as to compare the population’s characteristics to those of other centers. We investigated the underlying causes further and presented a research strategy for our forthcoming investigation. We intend to investigate risk factors for SMs as well as more accessible screening methods.

Second Malignancy after Childhood AML Treatment - a Retrospective Analysis of the AML-BFM Stud

In the past decades the outcome in ped AML patients improved continuously. However, secondary malignancies seem to be a severe side-effect, affecting the quality of life in survivors. This retrospective data analysis in patients treated according to AML-BFM protocols, is focused the occurrence of secondary malignancies after AML treatment and evaluates the consequences thereof. Between 1993 - 2019 (total n=2797) 51 patients were documented with a secondary malignancy (SM) after AML treatment. 5 pat (10%) were excluded due to a lack of data concerning the SMs exact diagnosis or a clear differentiation from AMLs relapse. Patients were included if the de novo AML occurred before <18yrs. 46 pat (f=20; m=26) remained in the analysis. All pat were treated acc to the current AML-BFM protocol version at the time of their AML diagnosis and for their SM acc. to local standard of care. For AML treatment the cumulative dose of i.v.-cytarabine ranged from 41,380 to 51,380 mg/m2(median 47,380 mg/m2), i.th. cytarabine from 140 to 370 mg age and weight-depended (median 330 mg), etoposide was given constantly with 950 mg/m2 and from 2004 to 2017 anthracyclines with cumulative doses of 500 mg/m² were applied (idarubicin/mitoxantrone calculated with equivalence dosage of 1:5). Since 2004 the i.th. therapy was added with a max. dose of 70 mg prednisolone and 84 mg MTX, both depending on age and weight. The median age on initial AML was 7.3 yrs, ranged from 0.1-17.5 yrs while the median age at date of SM diagnosis was 14.4 yrs, ranged from 0.86-30.2 yrs. The median percentage of BM blasts was 61% (0 - 100%), the median WBC of 7,200/ μl (670 - 214,000/μl) and hemoglobin was 8.7 g/dl (4.6-14.2 g/dl). Acc. to the FAB classification, FAB M4/M5 (43%) was the largest group, followed by FAB M0/M1/ M2 (35%), FAB M6/M7 (6%), M3 (6%) and others (6%). In 63% of the cohort a normal karyotype was detected. Beside a single patient (2%) all others received CR during AML treatment. The median time between AML and SM was 3.6 yrs (0.6 to 19.7 years). Interestingly the median time differs between AML followed by blood cancers with 3.2 yrs (0.8- 15.2 yrs) to 8.1 yrs (0.6-19.7 yrs) for AML followed by a solid tumor. Leukemia (n=13, 28%), such as ALL (n=10) or CML (n=3), was the most frequent SM, however also secondary myelodysplastic syndromes (n=8, 17%; including RAEB and RAEB in transformation), lymphoma (n=7, 15%), head and neck tumors (n=6, 13%), skin cancer (n=3, 7%), CNS tumors (n=3, 7%) and other diagnoses (n=6, 13%) were reported. None of the patients was reported with known genetic disorders explaining the SM, but in 9 cases (20%) pre-existing diseases (malignant and non-malignant) was documented, often as multi-morbidity (e.g., heart, lung, neurological diseases). According to a median follow-up-period of 11.7 yrs (0.6-22.3 yrs) after AML diagnosis, the 5-yr-overall survival (OS) rate of the cohort was 97±2% after AML and decreases to 78±6% from the date of SM. The OS of 97±2% resulted from a single patient, which was diagnosed with the SM and died at the same day. The 5-yr-event-free-survival (EFS), defined as death by any cause, relapse (independently of AML or SM) and third malignancy, was 87±5% vs. 71±7%. Patients suffering from blood cancers as SM (n=29, 63%) had a slightly poorer outcome in comparison to solid tumor patients (n=17, 37%) with a 5-yr-OS of 79±8% vs. 88±2% (p 0.223) and 5-yr-EFS of 65±9% vs. 82±9% (p 0.097). With a cumulative incidence of 2%, SM are extremely rare after ped AML. In contrast, in the same period three times more t-AML cases were reported, therefor AML itself is the most frequent treatment-related malignancy in ped patients as previously published. The results showed a shorter period between AML followed by blood cancers than solid tumors, which suggesting either that AML and the SM are pathophysiologically related whereas solid tumors may be therapy-induced only or that hematopoiesis is more sensitive for toxic effects or shows a higher proliferation rate. Due to the very limited case numbers and lack of further genetic results to exclude e.g. predisposition syndromes, these hypotheses are speculative and cannot be proven. Based on the frequency of SM after ped AML and the outcome thereof, a further therapy intensification to improve especially the AMLs EFS is justifiable. Caused on the results and the revealed median intervals, a long-term follow up for ped AML patients into their adult life is highly recommendable to learn more about these rare events.

Second Cancers in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review by the Fondazione Italiana Linfomi.

Simple SummaryWith the presented study, the FIL researchers aimed to fill a gap in the literature regarding long-lived lymphoma patients, at least 5 years after lymphoma. These patients can develop a series of late sequelae that affect their quality of life and overall survival, in particular cardiotoxicity and secondary malignancies. This systematic review conducted by FIL researchers aimed to understand the incidence of second malignancies, consider the impact of novel therapies, and examine the best follow-up policies for their early detection. On the basis of the evidence, individualized primary risk prevention strategies are suggested, depending on the dose and volume of radiation, chemotherapy, age at treatment, and predisposing factors. When evidence was either lacking or not definitive, expert opinion was used to identify a screening schedule. Background: The increase of lymphoma patient survival led to a modification of the incidence of long-term sequelae, including second malignancies (SM). Several groups have dealt with the incidence of SM, according to the primary treatment; however, a standardized approach for the early detection and screening of SM in the population of lymphoma survivors should be implemented. Methods: A systematic review was conducted by Fondazione Italiana Linfomi (FIL), in order to define the incidence of SM, the impact of modern radiotherapy on SM risk, and the usefulness of tailored follow-up and screening strategies for early diagnosis of SM. Classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors were investigated. The MEDLINE, Embase, and Cochrane Library databases were checked for relevant reports published up to January 2020. The selection process was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: A total of 27 full-text manuscripts resulted as eligible for the analysis. The incidence of SM in cHL patients treated with ABVD was higher compared to the general population and was even higher in patients treated with intensified regimens. The risk increased over time, as well as after 10–15 years from therapy, and was augmented by radiotherapy exposure. In DLBCL, more intensive regimens (i.e., R-CHOEP or R-MegaCHOEP) vs. R-CHOP were associated with a higher SM incidence. Salvage chemotherapy and autologous stem cell transplants increased the risk of SM in both cHL and DLBCL cohorts. A lower incidence of SM, particularly of breast cancer (BC), was shown in cohorts of cHL survivors treated with reduced radiation volumes and doses (involved fields vs. extended fields), but robust trials are still lacking. Considering the advantage of a structured screening for early detection of SM, all the included studies regarded cHL survivors and screening strategy for early BC detection. Moreover, the authors discuss additional papers, to guide the early diagnosis of lung, colorectal, skin, and thyroid cancer in patients at risk due to family history, drug or RT exposure, or unhealthy lifestyles. These screening strategies all passed through patient awareness. Conclusion: A modern approach to chemotherapy and radiotherapy led to a lower risk of SM, which should be confirmed over time. Early detection of secondary cancers could be achieved through a tailored screening program, according to the individual risk profile.

Screening for second malignancies in mycosis fungoides: non‐Hodgkin lymphoma, Hodgkin lymphoma, lung cancer, bladder cancer and melanoma

Patients with mycosis fungoides (MF) are at increased risk of developing non-Hodgkin lymphoma (NHL),Hodgkin lymphoma (HL), lung cancer, bladder cancer, and melanoma. There are no guidelines for screening MF patients for second malignancies. We identified 742 patients with MF and second malignancies in the Surveillance Epidemiology and End Result-18 database. The majority of second malignancy patients were white and male, mean ages 55-67 years at diagnosis of MF, and mean age of 61-72 years at diagnosis of second malignancy. MF/NHL, MF/lung cancer, and MF/bladder, cancer tended to be diagnosed at earlier stages of the second malignancy than patients with NHL, lung cancer, or bladder cancers alone and have improved survival. There was no improvement in stage at diagnosis or survival for MF/melanoma patients. Improvements in survival in MF/NHL, MF/lung cancer, and MF/bladder cancer patients may reflect underlying biology or the importance of increased contact with the healthcare system. MF/melanoma data suggests that patients require pigmented-lesion focused skin exams. Tools for screening include regular lymph node exams, pigmented-lesion focused exams, and detailed review of systems questions. With these simple interventions, we hope to identify second malignancies sooner and potentially avoid them.

Incidence of Secondary Malignancies in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Era of Tyrosine Kinase Inhibitors (TKI)

IntroductionWith TKI therapy the survival of patients with CML-CP is approaching to that of general population. Data on the incidence of secondary malignancies in CML is conflicting given the rarity of CML and the low incidence of secondary malignancies. The aim of this study is to evaluate the incidence of secondary malignancies in patients with CML-CP in a large US-based database.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database identified 13,276 patients with newly diagnosed CML-CP during the period from 2001 to 2014. Patients who had prior history of cancer, concurrent diagnosis of other malignancies at the same diagnostic year, and patients who developed secondary leukemia after the diagnosis of CML were excluded. Cumulative incidence of secondary malignancies were estimated with the presence of competing risk of death. Standard incidence ratio (SIR) was calculated from person-years at risk divided by expected cases based on the age-adjusted incidence ratio of the 2000 U.S. standard population.ResultsOf 13,276 patients, secondary malignancies were observed in 597 patients (4%) with a median follow-up of 69 months (Table 1). The three most common secondary malignancies were male genital system 130 (22%), digestive system 124 (21%) and respiratory system, 92 (15%). The 5-year and 10-year cumulative incidence of death for all patients was 30.5% (95% confidence interval [CI], 29.6-31.4), and 41.8% (95% CI, 40.7-43.0). The 5-year and 10-year cumulative incidence of secondary malignancies were 4.4% (95% CI, 4.0-4.8), and 7.2% (95% CI, 6.6-7.9), respectively (Figure 1). Overall SIR was 1.204 (95% CI, 1.108-1.301). The increased SIRs were observed in male genital system of 1.593 (95% CI, 1.319-1.866); digestive system, 1.291 (95% CI, 1.064-1.519); skin, 1.588 (95% CI, 1.083-2.093); urinary system, 1.366 (95% CI, 1.008-1.724); and miscellaneous, 1.877 (1.033-2.721) (Figure 2). The decreased SIR was observed in breast cancer of 0.665 (95% CI, 0.479-0.852). Overall excess absolute risk was 1.714 per 1,000 person years at risk (95% CI, 0.622-2.805).ConclusionRelative incidence of overall secondary malignancies in CML-CP is slightly higher than that of general population with minimal increase in the excess absolute risk. Given the limitation of registry data, the uncertainty of use and type of TKI, and response status at the diagnosis of secondary malignancies, conclusions regarding actual risk should be cautiously interpreted. It is also at this stage not possible to determine whether any possible increased risk is associated with the diagnosis of CML-CP per se or the use of TKIs. Further analysis is needed. [Display omitted] DisclosuresKantarjian:Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding; ARIAD: Research Funding; Amgen: Research Funding; Pfizer: Research Funding; Delta-Fly Pharma: Research Funding. O'Brien:Amgen: Consultancy; Alexion: Consultancy; Celgene: Consultancy; Astellas: Consultancy; Janssen: Consultancy; Vaniam Group LLC: Consultancy; AbbVie: Consultancy; TG Therapeutics: Consultancy, Other: Research Support: Honorarium, Research Funding; GSK: Consultancy; Acerta: Other: Research Support: Honorarium, Research Funding; Gilead Sciences, Inc.: Consultancy, Other: Research Support: Honorarium, Research Funding; Regeneron: Other: Research Support: Honorarium, Research Funding; Aptose Biosciences, Inc.: Consultancy; ProNAI: Other: Research Support: Honorarium, Research Funding; Pharmacyclics: Consultancy, Other: Research Support: Honorarium, Research Funding; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding; Sunesis: Consultancy. Wierda:Emergent: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Karyopharm: Research Funding; The University of Texas MD Anderson Cancer Center: Employment; Acerta: Research Funding; Kite: Research Funding; GSK/Novartis: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Juno: Research Funding; Genentech/Roche: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding. Daver:Daiichi-Sankyo: Research Funding; Kiromic: Research Funding; Incyte Corporation: Honoraria, Research Funding; Jazz: Consultancy; Bristol-Myers Squibb Company: Consultancy, Research Funding; Otsuka America Pharmaceutical, Inc.: Consultancy; Karyopharm: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Immunogen: Research Funding; Pfizer Inc.: Consultancy, Research Funding; Sunesis Pharmaceuticals, Inc.: Consultancy, Research Funding. Takahashi:Symbio Pharmaceuticals: Consultancy. Jabbour:Bristol-Myers Squibb: Consultancy. Cortes:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Sun Pharma: Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding; ImmunoGen: Consultancy, Research Funding; ARIAD: Consultancy, Research Funding.

148P Breast cancer as second primary malignancy in cancer survivors: Experience from a Tertiary Cancer Center in India

Improvement in cancer detection and advances in treatment have resulted in an increasing number of cancer survivors. They are at risk of sequelae such as second primary malignancy (SPM) which can be due to variety of factors like genetic, environmental and pervious treatment. Being one of the most common malignancies detected in females worldwide, breast cancer presenting as SPM is increasingly reported. The patients treated in the breast cancer clinic, Department of Medical Oncology at Regional Cancer Center, a leading tertiary cancer center in South India were studied during the period January 2017 to December 2019. Among 3500 patients, 25 presented as SPM. Details of the patients were noted from the case records. Those patients with prior histologically proven breast cancer were excluded. Among the 25 patients, 24 were females and one was male. The most common primary malignancy was carcinoma thyroid (5 cases) followed by osteosarcoma and carcinoma endometrium (3 cases each).The median time interval between primary and second malignancy was 9 years (range 2-26 years). The median age at diagnosis of second malignancy was 59 years (range 39-79 years) and 76% of the patients were more than 50 years of age. Most of the patients presented with early stage disese (19 were stage 1 or 2), 6 were stage 3 and none was metastatic at presentation (9 triple negative, 9 hormone receptor+ and 7 HER2+). All patients received curative treatment based on the stage and tumor biology. In those who had received anthracyclin agents as part of their initial treatment, the same was avoided in the management of SPM. All of the HER2 positive patients received anti HER2 agents and hormone positive patients received endocrine agents based on the menopausal status. Patients who were on targeted agents were allowed to continue the same with adequate monitoring. In patients who had received radiation previously, reirradiation was given with the dose adjustments. Among the 25 patients, two progressed after initial treatment and further follow up is needed to to comment on the survival. The possibility of SPM must always be considered in the follow-up visit of cancer survivors. Tailoring of treatment may be required based on the previous therapy.

Economic Burden of Metastatic Ovarian Cancer in a Commercially Insured Population: A Retrospective Cohort Analysis.

Ovarian cancer is the tenth most common type of cancer and the fifth leading cause of cancer death among females in the United States. The majority of incident ovarian cancer cases are diagnosed in individuals aged < 65 years, but limited evidence exists regarding the economic burden of ovarian cancer in this age group. To (a) estimate the annual all-cause direct total cost of metastatic ovarian cancer and (b) compare it to the cost of individuals without cancer in the working age commercially insured U.S. We conducted a retrospective cohort analysis using the IBM MarketScan Commercial Database. Patients were included if they met the following criteria: ≥ 1 medical claim with a secondary malignancy diagnosis in the primary position between January 1, 2011, and December 31, 2015 (earliest date of diagnosis defined as the index date); aged ≥ 18 years on the index date; ≥ 12 months of continuous enrollment before the index date; ≥ 1 month of continuous enrollment after the index date; and ≥ 1 inpatient medical claim or ≥ 2 outpatient medical claims ≥ 30 days apart, with an ovarian cancer diagnosis in any claim position within 60 days before or 30 days after the index date. Patients were excluded if they had ≥ 1 medical claim with a cancer diagnosis except for ovarian cancer in any claim position during the 12-month pre-index period. Controls were randomly selected and matched to metastatic ovarian cancer patients based on age, region, index date, number of months of continuous enrollment after the index date, and propensity score. Annual all-cause direct total costs and ovarian cancer-related direct total costs were estimated and compared for each cohort by using the Kaplan-Meier sample average technique to account for censoring after the index date. 2,991 metastatic ovarian cancer patients and 2,991 matched controls were included in this study. Patients in the metastatic ovarian cancer cohort had a mean (SD) age of 54.4 (8.5) years, and controls had a mean (SD) age of 54.2 (8.4) years. The mean (95% CI) annual all-cause total costs in the 12-month post-index period were $140,124 ($134,025-$146,267) for metastatic ovarian cancer patients and $35,161 ($31,338-$39,529) for controls; the resulting mean (95% CI) difference in annual all-cause total costs was $104,964 ($99,732-$110,042). In comparison with the annual all-cause total costs, the mean (95% CI) annual ovarian cancer-related total costs in the 12-month post-index period were $86,971 ($82,349-$91,508) for metastatic ovarian cancer patients and $0 ($0-$0) for controls. Working age patients with metastatic ovarian cancer have significantly higher costs compared with those without cancer. These findings contribute to the understanding of the burden of illness in a patient population where limited evidence currently exists on the economic consequences of the disease. No outside funding supported this study. The authors have nothing to disclose. This study was presented at the 2019 International Society for Pharmacoeconomics and Outcomes Research Annual Meeting; May 18-22, 2019; New Orleans, LA.

Programmed death 1 ligand (PD-L1) in solid cancers after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Nagasaki Transplant Group.

Programmed death 1 ligand (PD-L1) is an immunomodulatory molecule expressed by cancer cells, and it has been widely demonstrated to inhibit host antitumor responses. The aim of the present study was to identify clinicopathological features associated with PD-L1 expression in the secondary solid cancers of patients after allogeneic hematopoietic stem cell transplantation. In this database of 530 patients who received allo-HSCT between 1990 and 2017, 15 developed solid cancers with a median interval of 3487days after transplantation. Three patients had 2 different solid cancers. Eighteen solid cancer cases were identified. A multivariate analysis showed that chronic graft-versus-host disease (GVHD) was associated with an increased risk of solid cancer. The presence of chronic GVHD was observed in 8 out of 18 cases at the diagnosis of secondary malignancies. PD-L1 expression levels in cancers were significantly higher in patients with active chronic GVHD than in those without chronic GVHD (P = 0.020). Five cases of cancer that developed in the involved organs of chronic GVHD showed 30% or higher PD-L1 positivity. The present results revealed distinct PD-L1 expression in the secondary solid cancers of post-transplant patients with chronic GVHD.

Second malignancy post-chemoradiation in head and neck cancer patients.

e18525 Background: There is limited data available in the literature regarding incidence and treatment of second malignancy post-chemo-radiation (CTRT) in head and neck cancer patients. Hence we planned this analysis to address this lacuna in the current literature. Methods: We have already published a randomized study of 536 head and neck cancer patients, comparing radical CTRT with weekly cisplatin with or without nimotuzumab. The database of this study was used for the current analysis. Data regarding occurrence, site, stage, treatment details and outcomes were extracted from the database. Continuous variables were expressed in terms of the median with range, while non-continuous variables were reported in percentage. Kaplan Meier method was used for estimating the overall survival (OS). Results: Out of 536 patients, 18 (3.35%) patients developed second malignancy. The most common site was head and neck (44.44%) followed by lung (27.77%), prostate, ovary, breast, gallbladder and thyroid. 16/18 (88.88%) patients developed metachronous, while 2/18 (11.11%) had synchronous second malignancy. Most of the patients (55.55%) presented with locally advanced and metastatic disease, while 44.44% of patients had early-stage disease. 8/18 (44.44%) patients received palliative treatment. Of these, 6/18 (33.33%) patients received best supportive care and 2/18 (11.11%) patients were given palliative chemotherapy and palliative radiotherapy. 10/18 (55.55%) patients received radical treatment in the form of radical surgery (22.22%), CTRT (11.11%) and radical radiotherapy (5.55%), while 16.66% patients were kept under observation only. The median OS after the diagnosis of second malignancy was 451 days (95% CI, 301.45-600.59). It was seen that median OS the diagnosis of second malignancy in the aerodigestive and non-aerodigestive system was 446 days (95% CI, 39.10 - 852.89) and 840 days (95% CI, 278.46 - 1401.53), log-rank test P-value = 0.24. Conclusions: Second malignancy is not an uncommon phenomenon in head and neck cancer patients after CTRT and if properly taken care of, the improved outcome can be expected.

Angiosarcoma — a malignant neoplasm secondary to radiotherapy for breast cancer in a female patient following breast-conserving treatment — a case report

Angiosarcoma is a rare malignant neoplasm, accounting for 1–2% of all sarcomas. The main cause of developing secondary angiosarcoma is radiotherapy. We analysed the case of a 52-year-old woman with breast cancer, who had undergone breast-conserving therapy. Four years after finishing treatment, she was diagnosed with secondary angiosarcoma in the irradiated area. The patient underwent a mastectomy. The disease relapsed six months after the operation in form of local recurrence, as well as liver and lung metastases. The patient’s condition gradually deteriorated despite treatment (chemotherapy and symptomatic management). The patient died due to cardiorespiratory failure nine months after the diagnosis of secondary malignancy.

PB1999 SECOND MALIGNANCIES IN LYMPHOMA SURVIVORS: A SINGLE CENTER EXPERIENCE

Background: Advances in the treatment of both Hodgkin's (HL) and non Hodgkin's Lymphomas (NHL) have resulted in an increasing number of long term survivors free of disease. However this patient's population is at high risk of developing late therapy related complications that can negatively affect long term survival and quality of life. Aims: Methods: In our institution the HL and aggressive NHL long term survivors are followed up in a dedicated clinic since September 2014. Here we report an update of data on second malignancies diagnosed after lymphoma resolution. We have collected retrospective data on second tumours in 587 consecutive lymphoma survivors. Results: We have analyzed data regarding 587 patients coming in our clinic from 15 September 2014 to 21 February 2019, 284 have been successfully treated for HL and 303 for NHL. Two hundred eighty six were females, 301 males; median of age at lymphoma diagnosis was 28 years for HL (range 7-84) and 46 years for NHL (range 14-83). Ninety six patients (16%) experienced a second cancer, 12 and 1 of them had respectively 2 and 3 neoplasms so we documented 110 second tumours. They were: 35 skin (32%) and 75 non cutaneous cancers (68%). Four of the cutaneous neoplasm were melanomas. The non skin neoplasm were: 21 breast, 12 gastroenteric, 10 thyroid, 8 prostatic, 2 lung, 9 bladder, 1 renal, 1 tongue, 1 testis, 2 ovarian,2 uterine, 1 laringeal, 1 meningioma, 1 myelodysplastic syndrome (MDS) with excess blasts, 1 melanoma urinary tract, 1 cutaneous marginal NHL and 1 cutaneous appendages malignant cancers. Fourteen of these tumours (3 colon, 6 breast, 2 thyroid,1 prostatic, 1 MDS and 1 ovarian) have been suspected during our annual visit or diagnosed with our program of early diagnosis of second cancers and thyroid dysfunctions. The median of time between the end of lymphoma therapy and diagnosis of second malignancy was 18 years (range 4-47), the median age of second cancer was 58 years (range 24-83). Regarding the previous therapies: 32 patients had received radiotherapies in the site of secondary tumours (33%) and 21 had more than 1 line of therapy (22%). Moreover we have documented relapse of their original lymphoma in 6 patients (1 HL and 5 NHL). Summary/Conclusion: In our Department we described a significant number of cases of second neoplasms in the lymphoma survivors population: some of these were detected by tests done for early diagnosis of late complications. These results outline the importance of continuous follow up and risk adapted plan for early diagnosis of cancers in this setting of patients that would be encouraged by both hematologist and general practitioners.

Analysis of Overall Survival in Patients With Multiple Primary Malignancies: A Single-center Experience

IntroductionMultiple primary malignancies (MPMs) are seen in ~5% of all tumors. The aim of this study was to determine the quantitative impact on overall survival (OS) and treatment choices in patients with MPMs.MethodsA retrospective analysis to determine patients with MPMs was conducted over a six-year period. Patients were defined as simultaneous MPMs if the second malignancy was discovered within 60 days of the first, and as sequential MPMs if discovered after 60 days of the first.ResultsFifty-six patients with MPMs as defined above were identified, 38 (68%) simultaneous and 18 (32%) sequential. Development of second malignancy did not affect treatment in 47 (84%) of patients. Median OS after diagnosis of first malignancy was 13.0 months (95% confidence interval (CI) 10.3-15.8 months), compared to 10.6 months (95% CI 7.1-13.9 months) after the diagnosis of second malignancy. Median OS for the simultaneous MPM group was 13.5 months (95% CI 7.1-19.9 months), compared to 3.2 months (95% CI 0.0-9.8 months) for the sequential MPM group.ConclusionsThe development of a second malignancy impacts OS and treatment decisions. Patients who developed sequential MPM performed poorer than those who developed simultaneous MPM. This was likely in part due to effects of existing treatment on performance status as well as treatment preferences when second MPM is diagnosed (as many patients opted for supportive care after second MPM). Further analysis with larger patient cohorts is necessary to ascertain the aforementioned effects of OS and treatment options with respect to tumor pathology, stage, and performance status.

Second Malignant Neoplasms in Children and Adolescents Treated for Blood Malignancies and Solid Tumors: A Single-Center Experience of 15 Years

Abstract Context: The occurrence of second malignancies is not rare in children treated for primary tumors. Objectives: The aim of this study was to investigate the occurrence and the outcomes of second malignancies in children and adolescents from a large tertiary pediatric hematology-oncology center. Materials and Methods: A retrospective study was performed looking into the characteristics and outcomes of second malignant neoplasms in children and adolescents treated for primary malignancies in a single center over a 15-year period. Results: Among 270 children and adolescents treated for hematological malignancies and solid tumors from 2000 to 2015, five cases of second malignancy were diagnosed including cancer of the parotid gland, renal cell carcinoma, Hodgkin’s lymphoma, thyroid carcinoma, and transitional liver cell carcinoma in patients previously treated for acute myeloid leukemia, glioblastoma multiforme, B-acute lymphoblastic leukemia, Langerhans cell histiocytosis, and medulloblastoma, respectively. Primary malignancies were treated with chemotherapy in all cases and four out of five patients had also received radiotherapy. Mean age at diagnosis of second malignancy was 10 years and 4 months. Overall survival after diagnosis of second malignancy was 80% at 12 months and 75% at 5 years. Conclusions: Close surveillance and long-term follow-up are mandatory for the identification of late effects in children treated for malignancy.

Real-world dosing patterns of everolimus-based lines of therapy among post-menopausal women with hormone receptor-positive and human epidermal growth factor receptor-negative (HR+/HER2-) metastatic breast cancer (mBC).

e12528 Background: This study sought to describe dosing patterns of post-menopausal women with HR+/HER2- mBC treated with everolimus during a second or later lines of therapy in the US. Methods: MarketScan Commercial and Medicare Supplemental administrative claims databases were used to select post-menopausal HR+/HER2- mBC females who initiated an everolimus-based line of therapy during 1/1/2013- 7/31/2016. The first secondary malignancy diagnosis was the index date. Patients had 6 months of continuous enrollment in their health plans pre- and post- index, and were followed until the earliest date of disenrollment, inpatient death, or end of study. A line of therapy ended at discontinuation (gap &gt;60 days in all treatment) or switch to a new treatment. Dose modification during 2L, 3L, or 4L was defined by a change in daily dose of &gt;2.5 mg compared to the prior prescription and treatment interruption was defined as a gap &gt;60 days of everolimus followed by a restart of therapy during follow-up. Results: There were 645 mBC patients with everolimus-based line(s) of therapy eligible for analysis (mean age = 61.1 [SD 11.7], mean days to treatment initiation = 33.4 [SD 65.1]). Across all lines, the majority (72.5%-80.8%) of patients were on a combination regimen with endocrine therapy and &lt;10% were on a combination regimen with chemotherapy. Among patients with valid dose data (96.2%), mean initial dose in mg was 8.6 (SD 2.6) in 2L, 8.3 (SD 2.8) in 3L and 9.1 (SD 5.9) in 4L, the majority (71.4%-79%) did not have a dose modification, and &lt;5% had a treatment interruption (Table). Conclusions: Results from this analysis of real-world data suggest that 71%-79% of patients did not experience any modification to the initial dose during an everolimus-based 2L, 3L, or 4L of therapy and less than 4% experienced a treatment interruption. [Table: see text]

Analysis of real world patient compliance to everolimus-based therapy among post-menopausal women with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC).

e12546 Background: Patient compliance, typically not captured in clinical trials, may have profound effects on treatment effectiveness. As there has been limited real-world data, the objective of this analysis was to examine compliance among HR+/HER2- mBC patients treated with everolimus as a second or later line of therapy in the US across age groups. Methods: In this retrospective cohort study, the MarketScan Commercial and Medicare Supplemental claims databases were used to select post-menopausal HR+/HER2- mBC women who initiated an everolimus-based line of therapy during 1/1/2013- 7/31/2016 study period. The first secondary malignancy diagnosis was the index date. Patients had 6 months of continuous enrollment in their health plans pre- and post- index, and were followed until the earliest of disenrollment, inpatient death, or end of study. Compliance was measured using medication possession ratio (MPR) during a second (2L), third (3L) and fourth (4L) line of therapy. MPR was defined as total days of supply of everolimus during the line of therapy divided by total duration of the line. Results: Of 645 eligible mBC patients treated with everolimus during follow-up, there were 239, 142, and 80 with a 2L, 3L, and 4L of therapy respectively. Mean age overall was 61.1 + 11.7 years and average duration of follow-up was 718.3 + 304.1 days. Across all patients the median MPR ranged during each line from 0.90-0.92 and the majority (93.8%-97.5%) were highly compliant to therapy (defined as MPR&gt;80%). These results were consistent for patients aged &lt;65 and 65+ years across a 2L, 3L, and 4L of therapy (Table). Conclusions: This study shows high compliance for everolimus-based therapy within a 2L, 3L, and 4L of therapy and this is consistent across ages. This real world data suggests good drug manageability and may provide valuable information for clinicians in selecting treatment for mBC. [Table: see text]

1096 - Incidence of secondary malignancies (SM) in patients (pts) with germ cell tumors (GCT) who received high-dose chemotherapy (HDCT): A retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) database

409Background: Little is still known about the incidence of SM in young adult pts with GCT after HDCT, owing to the rarity of the disease, and the need for long term follow-up (FUP) data registries. In Europe, the EBMT systematically collect relevant data and may provide a suitable platform for retrospective analyses. Methods: Criteria for patient selection included diagnosis of GCT, adult male gender, ≥ 2yr of FUP after the administration of HDCT. Summary statistics were used to describe pt characteristics and outcomes. χ2 tests were used to compare groups according to the length of FUP. Kaplan-Meier estimates were used to estimate overall survival (OS) since the diagnosis of SM. Log-rank test was used to compare OS in pt subgroups. Univariable Cox regression analyses examined clinical factors potentially associated with OS following SM diagnosis. Results: From 1981 to 2014, 9,153 autografts, accounting for 5,100 pts, have been registered. Of them, 1,855 had ≥ 2yr of FUP. Among the latter, a total of 56 ...

Long-Term Incidence of Secondary Malignancies after Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience

To review the emergence of secondary malignancies (SMs) in recipients of allogeneic hematopoietic cell transplantation (HCT), we documented the occurrence of SMs in 2415 allogeneic HCT recipients, ages 18 to 71, in a single center over 4 decades. SMs were seen in 209 patients, including 58 with nonmetastatic squamous cell (SCC) and basal cell carcinoma (BCC) of the skin. Cumulative incidence of SM was 6.3% at 10 years, 13.5% at 20 years, and 17.6% at 30 years post-HCT. Median age at diagnosis of SMs was 61 years (range, 21 to 85). By multivariable analysis, older age at HCT was the only independent prognostic factor for SM (HR, 1.39 for ages 41 to 55 and HR, 1.92 for age > 55 compared with age ≤ 40; P = .001). The rate of SM (excluding nonmetastatic SCC/BCC of skin) after HCT was 2.07 times higher (P = .01) compared with the general population. Overall survival (OS) after diagnosis of SM (excluding nonmetastatic SCC/BCC of skin) was 58% at 5 years and 50% at 10 years postdiagnosis. Eastern Cooperative Oncology Group (ECOG) score was the only independent predictor of OS on multivariable analysis, with over 2-fold increased risk of death for patients with an ECOG score of 1 and over 6-fold for ECOG scores of 2 to 4, compared with ECOG score 0 (P < .0001). Forty of 209 patients (19%) diagnosed with SMs subsequently developed another new malignancy. OS was 68% and 51% at 5 and 10 years, respectively. The survival of SM patients post-HCT is favorable, thus warranting diligent long-term cancer screening and standard of care treatment. ECOG status of these patients is a predominant prognostic factor.

Incidence of secondary malignancies (SM) in patients (pts) with germ cell tumors (GCT) who received high-dose chemotherapy (HDCT): A retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) database.

409 Background: Little is still known about the incidence of SM in young adult pts with GCT after HDCT, owing to the rarity of the disease, and the need for long term follow-up (FUP) data registries. In Europe, the EBMT systematically collect relevant data and may provide a suitable platform for retrospective analyses. Methods: Criteria for patient selection included diagnosis of GCT, adult male gender, ≥ 2yr of FUP after the administration of HDCT. Summary statistics were used to describe pt characteristics and outcomes. χ2 tests were used to compare groups according to the length of FUP. Kaplan-Meier estimates were used to estimate overall survival (OS) since the diagnosis of SM. Log-rank test was used to compare OS in pt subgroups. Univariable Cox regression analyses examined clinical factors potentially associated with OS following SM diagnosis. Results: From 1981 to 2014, 9,153 autografts, accounting for 5,100 pts, have been registered. Of them, 1,855 had ≥ 2yr of FUP. Among the latter, a total of 56 cases of SM were identified (3.0%). 28 (50%) had solid SM, 22 (39.3%) hematologic SM (5 had uncoded SM). Median age at first HDCT was 34 years (IQR: 30-42), median age at development of SM was 42 (37-51). 26 pts (46.4%) received single HDCT cycle, 22 (39.3%) multiple HDCT cycles (8 unknown). 31 pts had ≥ 5 yr FUP, 25 pts 2-5 yr FUP. Solid SM were developed more frequently in those with longer FUP ( ≥ 5 yrs) compared to hematologic SM (p = 0.008). Median follow-up (FUP) was 76.9 months. Univariably, the type of SM (solid vs. hematologic) was significantly associated with OS. Hematologic vs solid SM: HR: 3.49 (95%CI: 2.09-10.47, p &lt; 0.001). Median OS of pts who developed solid SM was 32.8 months compared to 7 months of those with hematologic SM. The retrospective nature of the data is the major limitation. Conclusions: The incidence of SM in GCT pts who have received HDCT is a concern. During the FUP, there seems to be a non-overlapping risk of developing solid or hematologic SM, with a significantly different prognostic impact. These data may be important to improve patient counselling and the planning of post-HDCT FUP.

Second Primary Neoplasms: A Clinico-Pathological Analysis from a Sub Himalayan Cancer Centre in India

Background: There is a lifetime risk of developing another de novo malignancy in diagnosed cancer patients. Detection of new primary has increased due to advances in both diagnostic and treatment modalities. This article aims to analyze the pattern of presentation of second primary neoplasm and to review the relevant literature. Materials and Methods: We analyzed patients presenting with histologically proven synchronous or metachronous second primaries from July 2011 to July 2016. Warren and Gate's criteria have been used to designate a case as second primary neoplasm. Various details such as age at diagnosis, sex, whether synchronous or metachronous, site, stage, histopathology, treatment were collected. Results: Over a period of 5 years total 40 cases were observed, out of which 13 were synchronous (33%) and 27 (67%) were metachronous. The median age at the diagnosis of primary malignancy was 65.5 years (range 27-84). Out of the 40 patients, 28 (70%) were males and 12 (30%) were females. The most common site of primary tumor was head and neck and genito-urinary, 11 cases each. Among the second malignancy most common site was gastrointestinal tract (11 cases), followed by genitourinary (10 cases) and lung (9 cases). Conclusion: The likelihood of diagnosis of second malignancy has increased with the advent of newer diagnostic modalities as well as increased compliance to follow up and progress in the management. Appearance of new signs and symptoms should raise a suspicion and early detection of the disease leads to appropriate management.