Amit Khanal

Second Primary Malignancies in Adults with Gastric Cancer - A US Population-Based Study.

Background Multiple studies have examined the incidence of secondary primary malignancies (SPMs) in gastric cancer patients in Europe and Asia. This retrospective review was conducted to analyze risk of SPM in patients with gastric cancer diagnosed in the United States. Methods We included adult patients diagnosed with gastric cancer from the surveillance, epidemiology, and end result (SEER) 13 database. We calculated the risk of SPMs in these patients using the multiple primary standardized incidence ratio session of SEER*stat software and performed subset analyses of SPM with regard to age, sex, radiotherapy used, and latency period. Results Among 33,720 patients, 1838 (5.45%) developed 2019 SPMs with an observed/expected (O/E) ratio of 1.11 [95% confidence interval (CI)u2009=u20091.06–1.16, pu2009<u20090.001] and an absolute excess risk of 18.16 per 10,000 population. The median time to first SPM from the time of diagnosis of gastric cancer was 46.9u2009months (range 6–239u2009months). Significant excess risk was observed for gastrointestinal malignancies [O/E ratio 1.71 (CIu2009=u20091.59–1.84, pu2009<u20090.001)], thyroid [O/E ratio 2.00 (CIu2009=u20091.37–2.8, pu2009<u20090.001)], and pancreatic cancer [O/E ratio 1.60 (CIu2009=u20091.29–21.96, pu2009<u20090.001)]. Risk of secondary melanoma, breast cancer, and prostate cancer was lower than in the general population. Conclusion The risk for SPMs is significantly increased in adults with gastric cancer compared to the general population.

The risk of secondary primary malignancy in early stage differentiated thyroid cancer: a US population-based study

protein function, encoding for an altered and non-functional isoform [12,13]. Interestingly from a clinical point of view, bsandwich mutations, such as p.V143A c.428T>C, are considered very promising targets for functional p53 rescue by generic small molecule drugs, able to restore wild-type-like activity [13]. When both alleles encode for a non-functional protein, p53 loses its function of ‘guardian of the genome’, causing high genomic instability and resistance to anticancer drugs [12]. In our case, homozygosity for p.V143A (c.428T>C) mutation could have caused tumor resistance after a prolonged response to trastuzumab. Due to the small size of the liver lesion and the ethical problem of performing a ‘clinically not required’ liver biopsy, it has not been possible to analyze the liver metastasis upfront treatment with trastuzumab. Missing this initial analysis, another hypothesis for the acquired resistance to trastuzumab could be that the mutation already existed when the metastasis first appeared, representing a more malignant subclone from the primary tumor. As regards to the expression of p53, IHC staining is usually used as a surrogate for mutational analysis in the diagnostic workup of carcinomas of multiple sites, a strong and diffuse pattern of p53 expression (greater than 60% of cells) being associated with a mutated TP53 gene in the most of cases [14]. In our case, IHC was not able to discriminate the heterozygous mutation of TP53 in the primary tumor and the homozygous mutation in the metastatic lesion, both appearing intensely positive. In conclusion, in our case, homozygosity for p.V143A c.428T>C mutation in exon5 of TP53 gene could be the cause of the acquired resistance in the course of trastuzumab therapy. Considering the difficulty to find suitable metastatic tissue specimens for molecular assessments and the uncommon presence of this mutation in gastric cancer, it could be hard to clinically verify this hypothesis, which, in our opinion, could be otherwise tested in vitro on HER2 overexpressing gastric cancer cell lines transfected with the p.V143A c.428T>C mutation.

The risk of second primary malignancy in patients with stage Ia non-small cell lung cancer: a U.S. population-based study

Abstract Background: Lung cancer is one of the most common cancers worldwide. Patients with early stage lung cancer have improved long-term survival. With the introduction of low-dose CT scan, more patients are going to be diagnosed at an early stage. However, there is limited data on the risk of second primary malignancies (SPMs) in these subsets of patients in the United States. Methods: We utilized SEER-13 (Surveillance, Epidemiology and End Results) registry to obtain Multiple Primary- Standardized Incidence Ratio and an Absolute Excess Risk between January 2004 and December 2010 for patients with Stage Ia non-small cell lung cancer. Results: The database comprised of 12,246 patients. A total of 1431 (11.68%) patients developed 1563 SPMs with an observed to expected (O/E) ratio of 2.07 (95% CIu2009=u20091.92–2.23, pu2009<u2009.001) in patients with adenocarcinoma and 2.05 (95% CIu2009=u20091.92–2.19, pu2009<u2009u2009.001) in squamous cell carcinoma group. Conclusions: This study showed an excess risk of SPMs in patients with early stage non-small cell lung cancer. We recommend a close follow-up, paying attention to concerning symptoms or examination findings and judicious use of age-appropriate cancer screening.

Second primary malignancies in gastric cancer: A U.S. population-based study.

191 Background: Risk of second primary malignancies (SPM) is not known in gastric cancer. In this population based study, we analyzed rates of SPM in gastric cancer. Methods: We selected adult (≥18 years) patients with gastric cancer as first primary malignancy diagnosed from January 1992 to December 2011 from Surveillance, Epidemiology and End Result 13 database. We used SEER*stat’s multiple primary standardized incidence ratio (MP-SIR) session to calculate the risk of SPM diagnosed 6 months after the diagnosis of index gastric cancer. Results: Among 31,818 patients with first primary gastric cancer, 1674 (5.26%) developed 1,839 SPM with observed/expected (O/E) ratio of 1.09 (95% CI = 1.05-1.15, p<0.0001) and excess risk of 16.15 per 10,000 population. The median time to first SPM from the time of diagnosis of stomach cancer was 49 months (range 6 months to 19.08 years). There was significantly increased risk of gastrointestinal malignancies [O/E ratio 1.65 (CI=1.53-1.79, p<0.001)], thyroid cancer [O/E r...