Second Primary Tumors Research Articles

Craniofacial second primary tumors in patients with germline retinoblastoma previously treated with external beam radiotherapy: A retrospective institutional analysis.

The long-term survival of germline retinoblastoma patients is decreased due to the risk of second primary tumors (SPTs) that occur years after the diagnosis of retinoblastoma. This risk is related to genetic predisposition and other factors, such as the treatment of retinoblastoma by external beam radiotherapy (EBRT). We studied the incidence, risk factors, and prognosis of specific craniofacial SPTs developed within the margins of radiation field in a cohort of 209 patients with germline retinoblastoma treated with EBRT at our institution between 1977 and 2010. Clinical characteristics, survival, incidence, and histology of craniofacial SPTs were recorded. Fifty-three of the 209 patients developed 60 distinct craniofacial SPTs in irradiated field with a median time from EBRT of 16.9 years (4-35) and a median follow-up of 24.8 years (5.3-40). Osteosarcoma (33.3%) and undifferentiated sarcoma (23.3%) were the more prevalent histological entities. Benign tumors (16.7%) also occurred. The cumulative incidence of craniofacial SPTs reached 32.6% at 35 years after EBRT, and the median survival after diagnosis was five years. In our series, irradiation under 12 months of age, bilateral EBRT, or previous treatment of retinoblastoma with chemotherapy did not significantly increase the risk of craniofacial SPTs. This work presents a strong argument to avoid EBRT in the management of retinoblastoma and emphasizes the high risk and poor prognosis of specific craniofacial SPTs. This study also points to the question of the need and benefits of special programs for early detection of craniofacial SPTs in survivors of irradiated germline retinoblastoma.

Identification of second primary tumors from lung metastases in patients with esophageal squamous cell carcinoma using whole-exome sequencing.

Esophageal squamous cell carcinoma (ESCC) patients with a synchronous or metachronous lung tumor can be diagnosed with lung metastasis (LM) or a second primary tumor (SPT), but the accurate discrimination between LM and SPT remains a clinical dilemma. This study aimed to investigate the feasibility of using the whole-exome sequencing (WES) technique to distinguish SPT from LM.Methods: We performed WES on 40 tumors from 14 patients, including 12 patients with double squamous cell carcinomas (SCCs) of the esophagus and lung (lymph node metastases were sequenced as internal controls) diagnosed as LM according to pathological information and 2 patients with paired primary ESCC and non-lung metastases examined as external controls.Results: Shared genomic profiles between esophageal (T) and lung (D) tumors were observed in 7 patients, suggesting their clonal relatedness, thus indicating that the lung tumors of these patients should be LM. However, distinct genomic profiles between T and D tumors were observed in the other 5 patients, suggesting the possibility of SPTs that were likely formed through independent multifocal oncogenesis.Conclusions: Our data demonstrate the limitations and insufficiency of clinicopathological criteria and that WES could be useful in understanding the clonal relationships of multiple SCCs.

Notch Intracellular Domain (NICD) Expression and Clinical Manifestations of Second Primary Tumor at Esophagus in Patients with Head and Neck Squamous Cell Carcinoma.

IntroductionSecond primary tumor (SPT) is a major factor that affects the survival of head and neck squamous cell carcinoma (HNSCC) patients, and the esophagus is a common site. Detection of SPT is essential for optimal HNSCC treatment planning and follow-up. Mutation of the NOTCH1 gene is common in head and neck cancer. However, details relating to Notch signaling and clinical outcomes among different primary tumors are still inconclusive. This study aimed to identify the role of the Notch signaling pathway in HNSCC, and to compare NOTCH1 expression in HNSCC compared between those with and without SPT at esophagus while focusing on the Notch intracellular domain (NICD).MethodsTwenty-three cases of esophageal SPT and 47 non-SPT controls that were treated at Siriraj Hospital during 2006–2017 were included. Patient information and clinical outcomes were analyzed. NICD expression demonstrated by immunohistochemistry technique in formalin-fixed paraffin-embedded specimens was studied.ResultsMean age of SPT and non-SPT was 55.13 and 62.09 years, respectively, and 94.3% of patients were male. Regarding SPT detection, 82.6% were synchronous and 17.4% were metachronous. There was significantly more active smoking among SPT than among non-SPT (87.0% vs 51.1%, p=0.01). Active alcohol use was also significantly greater among SPT than among non-SPT (87.0% vs 61.7%; p=0.04). Hypopharynx was the most common primary tumor site among SPT. Three-year and 5-year survival among SPT patients was 38.0% and 25.3%, respectively. NICD expression was absent in 52.2% of SPT, and in 53.3% of non-SPT. NICD expression intensity was mostly weak or moderate.ConclusionActive smoking and alcohol use were found to be significantly associated with SPT development. A high percentage of NICD inactivation was noted in HNSCC with no significant difference between groups. The Notch signaling pathway is involved in HNSCC tumorigenesis, but may not be a suitable molecular marker for SPT development.

The risk of second primary tumors in head and neck cancer: A systematic review.

Second primary tumors (SPTs) are a common cause of reduced life expectancy in patients treated for head and neck cancer (HNC). This phenomenon forms an area to be addressed during posttreatment follow-up. We conducted a systematic review of literature following PRISMA guidelines, from 1979 to 2019, to investigate incidence of SPTs, synchronous, and metachronous, in HNC population. Our review includes data of 456 130 patients from 61 articles. With a minimum follow-up of 22 months, mean incidence of SPTs was 13.2% (95% CI: 11.56-14.84): 5.3% (95% CI: 4.24-6.36) for synchronous SPTs and 9.4% (95% CI: 7.9-10.9) for metachronous SPTs. The most frequent site for SPTs was head and neck area, followed by the lungs and esophagus. Although with wide variations between studies, the rate of SPTs in HNC patients is high. Given the impact in the prognosis, we must develop strategies for the early diagnosis of SPTs.

Association Between Gastrointestinal Stromal Tumors and Other Malignancies: It Is Only a Matter of Time ? A Case Series and an Overview of Systematic Reviews.

Little is known about the sporadic coincidence of gastrointestinal stromal tumors (GISTs) with second primary tumors (SPTs). The aim of this study is to clarify if there is a clinicopathologic correlation responsible for the synchronous or metachronous occurrence of SPTs in GIST patients. We carried out a single-center, retrospective analysis on patients with GISTs surgically treated at our institution from January 2019 to June 2019. Two groups of patients were identified: isolated GIST (group A) and GIST associated with SPT (group B). A meta-review was conducted with the aim to examine the published systematic reviews that included studies assessing the SPT risk in GIST patients. Thirty-nine patients were surgically treated for GIST during the study period, with seven (17.9%) of them having other SPTs. SPTs were most frequent in the colon. Group A patients had a lower mean age at initial diagnosis (56.8 ± 15.2 vs. 73.4 ± 16.6, P = 0.012). No statistically significant difference was found between the two groups in terms of tumor location, mitotic index, Ki-67 expression, risk classification, and imatinib therapy. The overview showed that the cumulative prevalence rate of SPTs ranged from 9.3 to 18.0%. SPTs were more frequent in the gastrointestinal tract (37.9-95.0%), followed by the genitourinary tract. GIST patients under our care experienced a 17.9% overall risk of developing SPTs with different histology. When comparing patients with isolated GIST and patients with GIST and SPT, age was the only variable significantly related to the development of other neoplasms. However, the potential non-random association and causal relationship between GISTs and SPTs remain to be investigated.

Gene targets of sulforaphane in head and neck squamous cell carcinoma.

Patients who have undergone curative‑intent therapy for head and neck squamous cell carcinoma (HNSCC) exhibit a high rate of development of second primary tumors (SPTs), which are frequently lethal. A chemoprevention strategy that prevents SPTs would have a major impact on patient outcomes. Sulforaphane, a naturally‑occurring compound derived from cruciferous vegetables exhibits chemopreventive activity against HNSCC in a preclinical model. The effects of sulforaphane are considered to be mediated, in large part, through increased protein expression of the transcription factor nuclear factor erythroid 2‑related factor 2 (NRF2). Development of sulforaphane chemoprevention for HNSCC would benefit from the identification of robust biomarkers of sulforaphane activity in HNSCC cells and normal mucosal epithelial cells. The present study revealed that sulforaphane potently induces multiple oxidative stress‑associated genes at the RNA and protein levels, in HNSCC cells and Het‑1A cells, a non‑tumorigenic mucosal epithelial cell line. In the present analysis, HMOX1 and HSPA1A were identified as the most highly upregulated genes following sulforaphane treatment, suggesting their potential value as biomarkers to guide clinical trials. Sulforaphane induction of HMOX1 and HSPA1A was validated invivo in murine tissues. Furthermore, the impact of sulforaphane treatment of HNSCC cells on the expression levels of natural killer group 2D (NKG2D) and DNAX accessory molecule‑1 (DNAM‑1) ligands, which are activators of natural killer (NK) cells, was examined. NRF2‑dependent upregulation of the NKG2D ligand MICA/B was observed. However, only one of the six HNSCC cell lines studied exhibited enhanced sensitivity to NK cell‑mediated killing following sulforaphane treatment, suggesting that this may not be a general mechanism of sulforaphane chemopreventive activity in HNSCC. In summary, the present study identified robust biomarkers of sulforaphane activity in HNSCC and normal tissues, supporting their application in the development of sulforaphane chemoprevention approaches for HNSCC.

GR01.05 Site of Oligometastases

GR01.05 Site of Oligometastases

Thymoma appearing 9 years after the resection of squamous cell carcinoma of the lip: A case report of triple primary tumors and literature review.

The occurrence of second primary tumor (SPT)following malignancy treatment is common. In patients with head and neck (H&N) cancer, SPTs principally occur in the H&N region, lungs or esophagus. Therefore, patient follow-up after cancer treatment is important in order to detect recurrence, metastasis and new primary tumors. However, no standard guidelines on lifelong follow-up imaging are available. Herein, we report a patient who presented with three metachronous primary tumors-squamous cell carcinoma (SCC) of the tongue, SCC of the lip and type A thymoma. The third tumor was incidentally detected during follow-up using contrast-enhanced computed tomography (CT) 9 years following resection of the second tumor. To the best of our knowledge, this specific combination of metachronous tumors has not yet been reported. Based on the literature review, we observed that thymoma occurs following H&N cancer treatment. Therefore, to ensure that the presence of subsequent thymomas is not overlooked, we suggest regular lifelong follow-up using contrast-enhanced CT in patients who had previously been diagnosed with H&N cancer. The literature review revealed that thymomas occur in patients with H&N cancer and should be detected at the earliest convenience.

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature.

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

Clinical benefits from endoscopy screening of esophageal second primary tumor for head and neck cancer patients: Analysis of a hospital-based registry

ObjectivesEsophageal second primary tumors (SPTs) in head and neck cancer (HNC) patients is not uncommon. The impact of image-enhanced endoscopy (IEE) screening for esophageal SPT on the outcome of HNC patients has not been well clarified. Methods and methodsPatients with malignancies of the head and neck region and esophagus were recruited from a hospital-based cancer registry between July 2000–December 2016. IEE screening included magnifying endoscopy with narrow-band imaging and chromoendoscopy with Lugol's solution. Biopsied specimens with revised Vienna classification categories 1 and 2 were defined as group I, and those with categories 3 to 5 were defined as group II. The Kaplan-Meier estimate and Cox regression model were used for survival analysis. ResultsTotally 1577 HNC and 501 esophageal cancer patients were enrolled. The 5-year overall survival (OS) rates of stage I/II HNC, stage III/IV HNC and esophageal cancer patients were 58%, 29%, and 8%, respectively (p < 0.01). The 5-year OS rate of HNC patients with negative IEE results was higher than that of HNC patients without IEE screening, followed by IEE screening groups I, II and esophageal cancer patients (44% vs. 39% vs. 35% vs. 11% vs. 8%, respectively, p for trend <0.01). Among advanced HNC patients, those who received IEE screening had a trend of better prognosis than those without screening (5-year OS rate of 31% vs. 28%, p = 0.17). ConclusionsIEE screening for esophageal SPTs is helpful in risk stratification and prognosis prediction for HNC patients. Routine IEE screening is recommended in HNC patients.

Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

Locoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. To assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. This multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. Patients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. The primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. A total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P = .48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). This study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. ClinicalTrials.gov identifier: NCT01345669.

Risk of second primary neoplasia in patients with oropharyngeal carcinoma: Role of HPV status in the outcome.

e17544 Background: Patients with HPV-positive oropharyngeal cancer (OPC) have better prognosis and a lower risk of appearance of second primary neoplasm (SPN) than HPV-negative OPC patients. The aim of our study was to analyze the risk of developing SPN in a large group of patients with OPC according to HPV status in the primary tumor and its relationship with toxic habits. Methods: This study includes patients from a prospective data-base: 484 OPC patients were treated from 1991 to 2017 for which the HPV DNA positivity was evaluated by PCR in available tumor specimens. HPV DNA positive samples were further tested for HPV E6*I mRNA detection and/or p16INK4a immunohistochemistry. The mean follow-up of patients included in the study was 4.9 years (SD 5.1 years). We estimated the incidence of SPN in all cancer sites and in cancer sites related to tobacco and alcohol consumption according to the HPV status in the primary tumor. Results: Ninety-nine (20.5%) out of 484 OPCs included in the study were HPV-related. During the follow-up period, 127 patients with HPV-negative tumors (33.0%) and 19 patients with HPV-positive tumors (19.2%) had a SPN. Considering only the tobacco/alcohol-related SPNs, 106 of the patients with HPV-negative tumors (27.5%), and 12 patients with HPV-positive tumors (12.1%) had a tobacco/alcohol-related SPN (P &lt; 0.0001). Five-year and 10-year SPN-free survival for HPV-negative versus HPV-positive OPC patients was 61.0% versus 81.5%, and 37.6% versus 73.8%, respectively (P &lt; 0.001). When restricting the analyses to tobacco/alcohol-related SPNs, the corresponding survival rates were 66.6% versus 86.8% and 45.9% versus 83.5% for 5-year and 10-year survival rates, respectively (P &lt; 0.0001). The frequency of tobacco/alcohol-related SPNs occurrence throughout the follow-up period for patients with HPV-negative OPC was 27.5%, for patients with HPV-positive tumors with a previous history of severe tobacco and/or alcohol use was 21.4%, and for patients with HPV-positive tumors without a history of severe tobacco and/or alcohol consumption it was 8.5% (P &lt; 0.0001). Conclusions: HPV status and previous toxic habits might allow classifying patients regarding the risk of tobacco/alcohol-related SPNs. HPV-related OPC patients without previous history of severe tobacco and/or alcohol use have a significant low risk of SPN development, particularly in those locations related to tobacco use or alcohol consumption

Incidence of second primary neoplasms among cancer survivors in the United States, 2000 through 2015.

1586 Background: The number of cancer survivors in the United States is projected to exceed 20 million by 2024. Survivors are at risk of developing a second primary neoplasm (SPN) – a leading cause of survivor death. We described the risk of developing a SPN among survivors of common cancers (smoking-related vs non-smoking-related) in the United States. Methods: We identified patients aged ≥18 years who were diagnosed with a primary cancer from the 10 sites with highest survival rates and stratified as smoking-related (urinary bladder, kidney &amp; renal pelvis, uterine cervix, oral cavity &amp; pharynx, and colon &amp; rectum) and non-smoking related (prostate, thyroid, breast, corpus &amp; uterus, and non-Hodgkin lymphoma) from Surveillance, Epidemiology, and End Results (2000-2015). SPN was defined as the first subsequent primary cancer occurring ≥2 months after first cancer diagnosis. Excess SPN risk was quantified using standardized incidence ratios (SIRs) stratified by sex. Results: A cohort of 2,908,349 patients (50.1% female) was identified and 260,267 (9.0%) developed SPN (7.6% of females and 10.3% of males). All index cancer sites were associated with a significant increase in SPN risk for females and males (except prostate cancer). Index smoking-related cancers (SIR range 1.20 – 2.17 for females and 1.12 – 1.91 for males) had higher increased risk of SPN than non-smoking-related cancers (SIR range 1.08 – 1.39 for females and 0.55 – 1.38 for males) relative to the general population. Conclusions: Nearly 10% of cancer survivors developed an SPN, and those with smoking-related cancers had higher risk. Given the increasing number of cancer survivors and importance of SPN as a cause of cancer death, these findings can improve secondary prevention and surveillance guidelines. [Table: see text]

Neuroendocrine neoplasms of gastrointestinal tract and secondary primary synchronous tumors: A systematic review of case reports. Casualty or causality?

BackgroundNeuroendocrine neoplasms (NENs) can arise in most of the epithelial organs of the body and are not a rare condition in the gastrointestinal tract (GIT). The presence of NENs in GIT associated with other secondary primary malignancies (SPM) has been considered an exotic event. This study aims to describe the case reports of NENs accompanied by synchronous primary tumors.Methods and findingsWe performed a systematic literature search of the databases Scopus, PubMed, Scielo and LILACS to identify case reports that described the presence of NENs in GIT with SPM. 78 case reports were included. The mean of age of the cases was 60.2 years. 60% were male. 95.4% were NENs G1. 17 cases of NENs had metastasis. 80% of SPM were recognized in the GIT (36% in stomach, 27% in large intestine, 11.2% in small intestine, and 5.6% in esophagus). The most common type of SPM was adenocarcinoma (49.4%), followed by GIST (13.5%), other NENs in different GIT segment (7.9%), lymphoma (6.8%), and squamous cell carcinoma (4.5%). The most common tumor in GIT was adenocarcinoma (97.6%) and the presence of adenocarcinoma in the same segment of GIT was found in 68.4% of the cases. Association between adenocarcinomas and NENs in GIT (p:<0.0001) and adenocarcinoma and tumor in the same segment of GIT location were observed (p<0.001).ConclusionThese results demonstrate that NENs with SPM are not a rare condition. Several theories have been proposed to explain this association; one of these is the ability of NENs to generate synchronous tumors by autocrine and paracrine effect. We observed an association between adenocarcinomas and NENs in the same segment of GIT.

Early detection of esophageal second primary tumors using Lugol chromoendoscopy in patients with head and neck cancer: A systematic review and meta-analysis.

BackgroundEarly detection of esophageal secondary primary tumors (SPTs) in head and neck squamous cell carcinoma (HNSCC) patients could increase patient survival. The purpose of this study was to determine the diagnostic yield of esophageal SPTs using Lugol chromoendoscopy.MethodsA systematic review of all available databases was performed to find all Lugol chromoendoscopy screening studies.ResultsFifteen studies with a total of 3386 patients were included. The average yield of esophageal‐SPTs in patients with HNSCC was 15%. The prevalence was the highest for patients with an index hypopharyngeal (28%) or oropharyngeal (14%) tumor. The esophageal‐SPTs were classified as high‐grade dysplasia in 49% of the cases and as invasive carcinoma's in 51%.ConclusionOur results show that 15% of the patients with HNSCC that underwent Lugol chromoendoscopy were diagnosed with an esophageal‐SPT. Based on these results there is enough evidence to perform Lugol chromoendoscopy, especially in an Asian patient population.

Combined Extraskeletal Chondrosarcoma of Left Orbit : A Rare Second Primary Tumor of Retinoblastoma Survivor A Case Report

Retinoblastoma, a rare eye malignant tumor of childhood, is generally responsive to chemotherapy or radiation therapy, but the survivors have high risk to development of second primary tumors (SPTs) due to genetic susceptibility and/or prior radiation therapy. The SPTs predominantly occured among heritable form of Retinoblastoma and show worse prognosis than Retinoblastoma itself. A 13 years old girl underwent enucleation to remove tumor mass within her left orbit. This tumor initially appeared 4 years after the patient undergoing right bulbar enucleation and receiving chemotherapy due to Retinoblastoma in her right eye. Clinical and radiologic examination suspected the left one as a late presentation of bilateral Retinoblastoma, but microscopic examination revealed a combined Extraskeletal Chondrosarcoma. The histologic type of this SPT is rare, so does it occurance at younger age and in a survivor with unilateral Retinoblastoma wihout a history of radiation therapy. The treatment of choice is combine surgery and chemo/radiation therapy, and the prognosis is poor.

Risk of second primary neoplasm and mortality in childhood cancer survivors based on a national registry database

ObjectiveAlthough overall childhood cancer survival has improved, survivors may still have an elevated risk for second primary neoplasm (SPN) and excess mortality. The aim of the current study was to estimate the risks for SPN and mortality in childhood cancer survivors in Israel as compared to the general population. MethodsAll children aged 0–19 diagnosed with primary neoplasm between 1980–2007 who survived at least 5 years following diagnosis were included in the study. Follow-up continued until December 31st, 2013, or diagnosis of SPN, or death due to any cause (the earliest of these events). Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated. Cox proportional hazards regression was employed to assess predictors of SPN and mortality. ResultsThe cohort consisted of 6637 childhood cancer survivors. A total of 244 all-site SPN cases were observed. Compared to the general population, the risks for SPN and for mortality were significantly increased (SIR = 5.48; 95%CI: 4.82–6.22 and SMR = 13.99; 95%CI = 12.54–15.56, respectively). Factors predicting SPN were sex (female), older age at first diagnosis, and initial cancer diagnosis (lymphomas). Factors predicting mortality were older age at first diagnosis, initial cancer diagnosis (myeloproliferative diseases) and earlier years, according to calendar period of initial diagnosis. ConclusionsAlthough 5-year childhood cancer survival is high, survivors are at elevated risk for SPN and mortality, and the risks are associated with baseline characteristics of the patients. The increased risks should be considered when planning treatment, follow-up and surveillance of the survivors.

Complex treatment of locally advanced squamous cell carcinoma of the parotid gland and secondary primary melanoma

Primary squamous cell carcinoma of the parotid gland accounts for 0.35% up to 9.8% of all parotid malignancies. In advanced stages, the gold standard is wide excision, lymphadenectomy and postoperative radiotherapy. Furthermore, head and neck cancers have an increased risk of secondary primary tumors development. Case report: A 82-year-old male underwent subtotal parotidectomy with facial nerve preservation for right parotid squamous cell carcinoma, in another department. Due to incomplete resection, 4 months later he presented with locoregional recurrence and cutaneous invasion. The patient underwent total parotidectomy en bloc with facial nerve, part of the external auditory meatus, posterior belly of digastric and part of sternocleidomastoid muscle with modified radical neck dissection, levels I-V. The defect was closed with ipsilateral pectoralis major myocutaneous flap, followed by a temporary lateral tarsorrhaphy after two months. The patient underwent adjuvant radiotherapy. One year after surgery, functional and aesthetic impairment of the facial nerve palsy were corrected: the lower face deficit by an orthodromic temporalis tendon transfer; lagophthalmos by lid loading with gold-weight. Postoperative outcome was satisfactory for the patient, with 3 years of postoperative evolution with no recurrence or metastasis. Concomitantly, the patient developed pT1a secondary primary melanoma on the skin island of the flap, which was excised. Conclusion: Patients with locoregional advanced parotid squamous cell carcinoma can benefit from wide excision with neck dissection and postoperative radiotherapy. When the facial nerve cannot be preserved, facial asymmetry can be improved through reanimation procedures. Secondary primary malignancies require proper treatment concomitantly with index tumor follow-up.

Synchronous and antecedent malignancies in patients with papillary thyroid carcinoma

Objective. This study aimed to evaluate concurrently detected second primary malignancy in the patients who underwent surgery for papillary thyroid carcinoma. Methods. In this study, we retrospectively analyzed the files of the patients who underwent surgery for papillary thyroid carcinoma between 2000-2017. A total number of 601 patients with papillary thyroid carcinoma were evaluated. Among these patients, 48 patients were found to have secondary primary tumors. Preoperative and postoperative laboratory examination findings of the patients were retrospectively recorded. Results. Among 601 patients with papillary thyroid cancer evaluated with respect to radiation exposure, the second primary tumor with breast cancer was found to be the most common tumor. Renal cell carcinoma, malignant melanoma and stomach cancer were found to be more frequent when evaluated regardless of radiation effect. Furthermore, when molecular genetic results were evaluated, BRAF mutation rate was found to be more frequent than in other secondary tumors, especially in patients with renal cell carcinoma. Conclusions. The importance of epidemiological and experimental studies of multiple cancers is obvious. Although it is known that the impact of radiation is considerable among the ones with concurrence of breast cancer and papillary thyroid carcinoma, we suggest that further studies on common molecular genetic characteristics and development of targeted treatment for detected molecules are required in the patients with renal cell carcinoma in whom papillary thyroid carcinoma is diagnosed regardless of radiation effect.

Risk, pattern and survival impact of second primary tumors in patients with nasopharyngeal carcinoma following definitive intensity‐modulated radiotherapy

Second primary tumor (SPT) is a serious late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). We evaluated the incidence, pattern, risk factors and survival impact of SPT in NPC patients following definitive intensity-modulated radiotherapy (IMRT). A retrospective review of 780 consecutive IMRT-treated NPC patients between February 2003 and September 2011 was conducted. Cumulative SPT incidence and overall survival after SPT diagnosis were estimated. Associations between clinical characteristics and SPT risk were analyzed. Standardized incidence ratios (SIR) were calculated using age, gender and calendar-year-specific cancer incidences from the Hong Kong Cancer Registry. At a median follow-up of 7.5 years, 51 SPTs (6.7%) were identified, 22 (43.1%) of which occurred within previous radiotherapy fields. Tongue cancers (31.8%) and sarcomas of the head and neck (31.8%) were the most common in-field SPTs. Age [hazard ratio (HR), 1.051; 95% confidence interval (CI), 1.025-1.078] and smoking status (HR, 1.755; 95% CI, 1.002-3.075) were independent risk factors associated with SPT development. Median overall survival after SPT diagnosis was 2.9 years. There was an 84% increase in cancer risk (SIR, 1.84; 95% CI, 1.37-2.42) compared with the general population. Significant excess risks were observed for sarcoma, tongue, oropharyngeal, prostate and liver cancer. Excess risks were higher beyond 5 years of follow-up. Substantial risk of SPT, especially for in-field sarcoma and tongue cancers, exists after definitive IMRT for NPC. SPT severely negates longevity of NPC survivors. High awareness and careful surveillance is warranted for this late lethal complication.