Risk of second malignancy in patients with ovarian clear cell carcinoma

ObjectiveOvarian clear cell carcinoma has unique clinical and molecular features compared with other epithelial ovarian cancer histologies. Our objective was to describe the incidence of second primary malignancy in patients with ovarian clear cell carcinoma.MethodsRetrospective cohort study of patients with ovarian clear cell carcinoma at two tertiary academic centers in Toronto, Canada between May 1995 and June 2017. Demographic, histopathologic, treatment, and survival details were obtained from chart review and a provincial cancer registry. We excluded patients with histologies other than pure ovarian clear cell carcinoma (such as mixed clear cell histology), and those who did not have their post-operative follow-up at these institutions.ResultsOf 209 patients with ovarian clear cell carcinoma, 54 patients developed a second primary malignancy (25.8%), of whom six developed two second primary malignancies. Second primary malignancies included: breast (13), skin (9), gastrointestinal tract (9), other gynecologic malignancies (8), thyroid (6), lymphoma (3), head and neck (4), urologic (4), and lung (4). Eighteen second primary malignancies occurred before the index ovarian clear cell carcinoma, 35 after ovarian clear cell carcinoma, and 7 were diagnosed concurrently. Two patients with second primary malignancies were diagnosed with Lynch syndrome. Smoking and radiation therapy were associated with an increased risk of second primary malignancy on multivariable analysis (OR 3.69, 95% CI 1.54 to 9.07, p=0.004; OR 4.39, 95% CI 1.88 to 10.6, p=0.0008, respectively). However, for patients developing second primary malignancies after ovarian clear cell carcinoma, radiation therapy was not found to be a significant risk factor (p=0.17). There was no significant difference in progression-free survival (p=0.85) or overall survival (p=0.38) between those with second primary malignancy and those without.ConclusionPatients with ovarian clear cell carcinoma are at increased risk of second primary malignancies, most frequently non-Lynch related. A subset of patients with ovarian clear cell carcinoma may harbor mutations rendering them susceptible to second primary malignancies. Our results may have implications for counseling and consideration for second primary malignancy screening.

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Mutation associated with Fanconi anemia pathway may increase patients’ second primary malignancy risk: Results from somatic and germline testing of clear cell papillary renal cell carcinoma

European Urology ◽

10.1016/s0302-2838(21)01088-5 ◽

2021 ◽

Vol 79 ◽

pp. S980

Author(s):

X. Tian ◽

A. Aihetaimujiang ◽

Y.Y. Qu ◽

H.L. Zhang ◽

D.W. Ye

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Fanconi Anemia ◽

Renal Cell ◽

Clear Cell ◽

Papillary Renal Cell Carcinoma ◽

Second Primary ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Germline Testing

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The risk of second primary cancers in clear cell and papillary renal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.446 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 446-446 ◽

Cited By ~ 1

Author(s):

Muhammad Saad Hamid ◽

Raji Shameem ◽

Rishi Jain ◽

Kevin M. Sullivan

Keyword(s):

Thyroid Cancer ◽

Solid Tumors ◽

Clear Cell ◽

Latency Period ◽

Initial Diagnosis ◽

Second Primary ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Second Primary Cancers ◽

Increased Risk

446 Background: Renal cell carcinoma (RCC) survivors have an increased risk of developing second primary cancers. We sought to determine the role of RCC tumor histology for the risk of developing second primary solid tumors. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect RCC cases diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The two most common RCC histological subtypes were included; clear cell and papillary. The latency exclusion period from the date of diagnosis was 60 months. We investigated for the effect of latency period after initial diagnosis (5-10 years and >10 years) that may increase the risk for a second primary cancer. Results: A total of 2,669 patients with an initial diagnosis of RCC (clear cell: 2,368, papillary: 301) that developed second primary cancers were included in our analysis. There was a significantly increased risk of thyroid cancer (SIR: 2.30, p<0.05), prostate cancer (SIR: 1.12, p<0.05) and “all solid tumors” (SIR: 1.14, p<0.05) in clear cell RCC cases. Regarding latency period, thyroid cancer (SIR: 2.87, p<0.05) risk was increased in the 5-10 years latency period, but not in the >10 years latency period. Overall, in patients diagnosed with papillary RCC, tumors of the prostate (SIR: 1.30, p<0.05), lung (SIR: 1.78, p<0.05) and pancreas (SIR: 2.70, p<0.05) were increased. Exclusively in the 5-10 years latency period, the risk for developing lung cancer (SIR: 1.90, p<0.05) was significant. Conclusions: RCC histology may impact the risk for developing specific second primary solid tumors.

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Second Primary Malignancies in Chronic Lymphocytic Leukaemia; Skin, Solid Organ, Haematological, and Richter's Syndrome

10.1101/2021.11.22.21266332 ◽

2021 ◽

Author(s):

Yandong Shen ◽

Luke Coyle ◽

Ian Kerridge ◽

William Stevenson ◽

Christopher Arthur ◽

...

Keyword(s):

Chronic Lymphocytic Leukaemia ◽

Cell Carcinoma ◽

Lymphocytic Leukaemia ◽

High Rate ◽

Second Primary ◽

Solid Organ ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Second Primary Malignancies ◽

Richter’S Syndrome

Chronic lymphocytic leukaemia (CLL) is invariably accompanied by some degree of immune failure. CLL patients have a high rate of second primary malignancy (SPM) compared to the general population. We comprehensively documented the incidence of all forms of SPM including skin cancer (SC), solid organ malignancy (SOM), second haematological malignancy (SHM), and separately Richter's Syndrome (RS) across all therapy eras. Among the 517 CLL/SLL patients, the overall incidence of SPMs with competing risks were SC 31.07%, SOM 25.99%, SHM 5.19% and RS 7.55%. Melanoma accounted for 30.3% of SC. Squamous cell carcinoma (SCC), including 8 metastatic SCCs, was 1.8 times more than basal cell carcinoma (BCC), a reversal of the typical BCC:SCC ratio. The most common SOM were prostate (6.4%) and breast (4.5%). SHM included 7 acute myeloid leukaemia and 5 myelodysplasia of which 8 were therapy-related. SPMs are a major health burden with 44.9% of CLL patients with at least one, and apart from SC, associated with significantly reduced overall survival. Dramatic improvements in CLL treatment and survival have occurred with immunochemotherapy and targeted therapies but mitigating SPM burden will be important to sustain further progress.

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Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy

Pathology & Oncology Research ◽

10.3389/pore.2021.1609809 ◽

2021 ◽

Vol 27 ◽

Author(s):

Xi Tian ◽

Wen-Hao Xu ◽

Jun-Long Wu ◽

Hua-Lei Gan ◽

Hong-Kai Wang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Papillary Renal Cell Carcinoma ◽

Second Primary ◽

Published Data ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Germline Variants

Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified, TCEB1 (3/18) and VHL (3/18) variants occurred at the highest frequencies. Germline mutation detection showed that nine variants associated with Fanconi anemia (VAFAs) pathway (FANCA, 6/18; FANCI, 3/18) were identified in 18 ccpRCC patients. Among ccpRCC patients with VAFAs, five out of eight patients had second primary malignancy or family history of cancer. Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.

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