Large Population Analysis of Secondary Cancers in Pediatric Leukemia Survivors

Yavvari, Siddhartha; Makena, Yasaswi; Sukhavasi, Sahithi; Makena, Monish R.

doi:10.3390/children6120130

Cited by 12 publications

(21 citation statements)

References 25 publications

(35 reference statements)

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“…Some authors have occasionally described MEC of the head and neck that occurred after pediatric sarcoma ( 6 , 26 ), neuroblastoma ( 10 ), acute lymphoblastic leukemia ( 11 , 12 , 14 , 26 ), or acute myelocytic leukemia ( 13 ). A recent study stated that salivary gland carcinoma accounted for 7.2% of 251 cases of SMN in pediatric leukemia survivors ( 3 ), but the authors did not further clarify the cancer type. In the current study, we also noted that all secondary patients had a previous leukemia diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…Although it is rare, some authors have described mucoepidermoid carcinoma (MEC) of the head and neck as being involved in SMNs (4)(5)(6)(7)(8)(9). Whether these rare tumors could carry survival differences compared with primary MEC remains unknown, as the current evidence is limited to case reports, descriptive research, and an original study consisting of only 11 cases (3,(5)(6)(7)(10)(11)(12)(13)(14). Our hospital is one of the largest children's hospitals in China, covering ∼30 million people younger than 19 years in Henan Province.…”

Section: Introductionmentioning

confidence: 99%

“…Fortunately, the prognosis has been greatly improved because of the advent of numerous aggressive multimodality therapies, and an increasing number of long-term cancer survivors are expected. Recent evidence has reported that nearly half of nonrelapse deaths among 5-year survivors are caused by secondary malignant neoplasms (SMNs) ( 2 , 3 ), the most common explanation for cancer-caused death.…”

Section: Introductionmentioning

confidence: 99%

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Comparison Between Primary and Secondary Pediatric Mucoepidermoid Carcinoma of the Head and Neck

Shi

2020

Front. Pediatr.

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Objectives: Secondary mucoepidermoid carcinoma (MEC) of the head and neck is occasionally observed in childhood cancer survivors. The goal of this research was to compare the demographic and pathologic characteristics, as well as survival between primary and secondary MEC in children and adolescent patients. Methods: Pediatric patients (younger than 19 years old) with surgically treated MEC of the head and neck were retrospectively enrolled at the Affiliated Children's Hospital of Zhengzhou University and divided into two groups based on their cancer history. Demographic, pathologic, and survival characteristics between the two groups were compared. The main study interests were recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS). Results: The primary and secondary groups consisted of 63 and 15 patients, respectively. The two groups had similar distributions in terms of age, sex, tumor stage, neck lymph node stage, perineural invasion, lymphovascular invasion, p53, Bcl-2, proliferating cell nuclear antigen, carcinoembryonic antigen, and Ki-67 index. The 10-year RFS rates for the primary group and secondary group were 80 and 71%, respectively, and this difference was not significant (p = 0.464). The 10-year DSS rates for the primary group and secondary group were 83 and 82%, respectively, and this difference was also not significant (p = 0.649). The 10-year OS rates for the primary group and secondary group were 74 and 51%, respectively; this difference was significant (p = 0.023). Further Cox model analysis confirmed the independence of a previous cancer history (p = 0.043) in decreasing OS. Conclusions: Pediatric patients with secondary MEC exhibit similar demographic, pathologic, and molecular characteristics as primary patients but worse OS. These findings indicate that special disease management approaches might be needed for secondary patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison Between Primary and Secondary Pediatric Mucoepidermoid Carcinoma of the Head and Neck

Shi

2020

Front. Pediatr.

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“…In a recent analysis of 24,403 pediatric leukemia cases, 1.81% of the survivors developed a secondary malignancy within a time frame of 0 to 41 years (median follow-up time = 13 years). The most common secondary malignancy for leukemia survivors was secondary leukemia (23.9%), followed by thyroid cancer (18.33%), sarcoma (15.14%), astrocytoma (10.36%), lymphoma (9.56%), salivary gland carcinoma (7.17%), melanoma (4.38%), breast cancer (3.98%), followed by other less common types (12). Older estimates reported quite different prevalence of SMN t y p e s , w i t h a c u t e m y e l o g e n o u s l e u k e m i a ( A M L ) , myelodysplastic syndrome (MDS), and brain tumors as the most common ones in pediatric ALL survivors (13).…”

Section: Secondary Cancersmentioning

confidence: 99%

Long-Term Effects of Pediatric Acute Lymphoblastic Leukemia Chemotherapy: Can Recent Findings Inform Old Strategies?

2021

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During the last few decades, pediatric acute lymphoblastic leukemia (ALL) cure rates have improved significantly with rates exceeding 90%. Parallel to this remarkable improvement, there has been mounting interest in the long-term health of the survivors. Consequently, modified treatment protocols have been developed and resulted in the reduction of many adverse long-term consequences. Nevertheless, these are still substantial concerns that warrant further mitigation efforts. In the current review, pediatric-ALL survivors’ late adverse events, including secondary malignant neoplasms (SMNs), cardiac toxicity, neurotoxicity, bone toxicity, hepatic dysfunction, visual changes, obesity, impact on fertility, and neurocognitive effects have been evaluated. Throughout this review, we attempted to answer a fundamental question: can the recent molecular findings mitigate pediatric-ALL chemotherapy’s long-term sequelae on adult survivors? For SMNs, few genetic predisposition factors have been identified including TP53 and POT1 variants. Other treatment-related risk factors have been identified such as anthracyclines’ possible association with breast cancer in female survivors. Cardiotoxicity is another significant and common adverse event with some germline variants been found, albeit with conflicting evidence, to increase the risk of cardiac toxicity. For peripheral neurotoxicity, vincristine is the primary neurotoxic agent in ALL regimens. Some germline genetic variants were found to be associated with the vincristine neurotoxic effect’s vulnerability. However, these were mainly detected with acute neuropathy. Moreover, the high steroid doses and prolonged use increase bone toxicity and obesity risk with some pharmacogenetic biomarkers were associated with increased steroid sensitivity. Therefore, the role of these biomarkers in tailoring steroid choice and dose is a promising research area. Future directions in pediatric ALL treatment should consider the various opportunities provided by genomic medicine. Understanding the molecular bases underlying toxicities will classify patients into risk groups and implement a closer follow-up to those at higher risk. Pharmacogenetic-guided dosing and selecting between alternative agents have proven their efficacy in the short-term management of childhood ALL. It is the right time to think about a similar approach for the life-long consequences on survivors.

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“…We also used the ICCC3WHO variable in SEER to exclude cases that could be from a primary cancer relapse rather than second cancer developed after the treatment of primary cancer. We also used the ICCC3WHO variable to exclude patients who developed a second sarcoma after having sarcoma as their primary cancer [39].…”

Section: Seer Database Analysismentioning

confidence: 99%

Sarcoma as Second Cancer in a Childhood Cancer Survivor: Case Report, Large Population Analysis and Literature Review

et al. 2020

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The majority of pediatric patients are cured of their primary cancer with current advanced developments in pediatric cancer therapy. However, survivors often experience long-term complications from therapies for primary cancer. The delayed mortality rate has been decreasing with the effort to reduce the therapeutic exposure of patients with pediatric cancers. Our study investigates the incidence of sarcoma as second cancer in pediatric cancer survivors. We present a 9-year-old male who survived embryonal hepatoblastoma diagnosed at 22 months of age. At 4.5 years of age, he presented with a non-metastatic primitive neuroectodermal tumor (PNET) of the left submandibular area. He has no evidence of recurrence of either cancer for 51 months after finishing all chemotherapy and radiotherapy. We used the Surveillance, Epidemiology, and End Results (SEER) database to identify the current rate of second sarcomas in pediatric cancer survivors. Our literature review and large population analysis emphasize the impact of sarcoma as a second malignancy and provide help to physicians caring for pediatric cancer survivors.

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Large Population Analysis of Secondary Cancers in Pediatric Leukemia Survivors

Cited by 12 publications

References 25 publications

Comparison Between Primary and Secondary Pediatric Mucoepidermoid Carcinoma of the Head and Neck

Comparison Between Primary and Secondary Pediatric Mucoepidermoid Carcinoma of the Head and Neck

Long-Term Effects of Pediatric Acute Lymphoblastic Leukemia Chemotherapy: Can Recent Findings Inform Old Strategies?

Sarcoma as Second Cancer in a Childhood Cancer Survivor: Case Report, Large Population Analysis and Literature Review

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