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Objective: This report details the experience of a patient who developed a second primary glioblastoma (GB), offering insights into the treatment process and reviewing relevant literature., Case Presentation: A male patient, who was diagnosed with medulloblastoma at age 9, received treatment with cobalt-60 craniospinal irradiation (CSI) (36 Gy/20 fractions) and a tumor bed boost (total of 56 Gy). After 32 years, at age 41, an MRI revealed a space-occupying mass in the left cerebellar hemisphere. Surgical resection was performed, and postoperative pathology confirmed a diagnosis of radiation-induced glioblastoma (RIGB). Given the history of irradiation and the current tolerability of brainstem doses, proton beam therapy (PBT) combined with Temozolomide (75 mg/m 2 ) was chosen. The treatment plan included 60 Gy on the gross tumor bed and 54 Gy on the clinical target volume, delivered in 30 fractions. The patient underwent regular follow-up and achieved a complete response., Clinical Discussion: For childhood cancer survivors, the development of a second primary tumor significantly impacts prognosis. RIGB is a rare form of secondary tumor with distinct molecular characteristics compared to primary GB and recurrent secondary GB. Molecular markers such as IDH and MGMT status can help differentiate between primary GB, recurrent secondary GB, and radiation-induced secondary GB in patients with a history of prior radiation therapy. Surgical resection remains a primary treatment option, while PBT is preferred for postoperative treatment due to its superior protection of normal tissues and the ability to deliver high-dose irradiation., Conclusion: RIGB is a rare second primary tumor that requires strategic molecular profiling and individualized management. Proton beam therapy provides effective high-dose irradiation in the postoperative phase and is the preferred treatment option for such cases., (© 2024. The Author(s).)

Ambiguity exists over treatment and surveillance strategies after endoscopic submucosal dissection (ESD) for esophageal squamous cell neoplasia (ESCN) with unfavorable histologic features. This study investigated the long-term outcomes of ESD in high-risk ESCN patients. We retrospectively included early ESCN patients treated with ESD at two medical centers in Taiwan between August 2010 and December 2023. Demographic, endoscopic and pathological data were collected. Among 146 patients (mean age 59.17 years) with 183 lesions, 73 (50%) had a history of head and neck cancer (HNC). En bloc and R0 resections were achieved in 100% and 95.6% of the lesions, respectively. The 5-year overall survival (OS), disease-specific survival (DSS) and local recurrence rates were 42.7%, 94.7% and 11%. R0 resections were significantly associated with recurrence in a univariate analysis (HR: 0.19, 95% CI: 0.06-0.66, p = 0.008). Alcohol abstinence was independently associated with lower recurrence (HR: 0.34, 95% CI: 0.16-0.73, p = 0.006). Patients with pT1a-MM (muscularis mucosa invasion) had comparable OS ( p = 0.82), DSS ( p = 0.617) and recurrence ( p = 0.63) rates to those with pT1a-EP/LPM (epithelium/lamina propria invasion). The long-term outcomes of ESCN patients after ESD for expanded indications were satisfactory. ESD could be considered in selected ESCN patients involving the muscularis mucosa, notably among high-risk HNC patients.

Objectives: In the presented study, the occurrence rates of second primary oral carcinomas and their prognostic relevance were analyzed., Materials and Methods: All patients with surgically treated oral squamous cell carcinomas within the years 2010 and 2022 in our department were included in this retrospective cohort study. Two groups were designed including patients with second primary carcinomas and patients with local tumor recurrences. Occurrence rates, tumor stages and applied therapies were assessed. Primary outcome was overall survival in dependence of the index tumor. Secondary outcomes were overall survival in dependence of local recurrences or second primary tumors., Results: An overall number of 908 patients was included in the analysis. 98 patients (10.8%) developed a second primary oral squamous cell carcinoma. Patients with second primary tumors presented significantly (p < 0.001) better overall survival in dependence of the index tumor compared to patients suffering from local recurrences. There was no significant difference in overall survival (p = 0.4) in dependence of the date of second primary tumor or local recurrence. Patients with second primary tumors were more likely to receive surgery-based therapy compared to patients with local recurrences who more frequently received definitive radiotherapy., Conclusion: Our data indicates different clinical courses in terms of therapy and survival of patients suffering from second primary tumors compared to patients with local tumor recurrences. This may be due to a more aggressive biology of local recurrences and earlier detection of second primaries due to oncological follow-up of the index tumor., Clinical Relevance: The differentiation of local tumor recurrences and second primary tumors is of clinical relevance, as applicable therapies and resulting prognosis may differ significantly., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic exposure to persistent organic pollutants (POPs) is suspected to contribute to the onset of breast cancer, but the impact on the evolution of patients after diagnosis is unclear. We aimed to analyze the contribution of long-term exposure to five POPs to overall mortality, cancer recurrence, metastasis, and development of second primary tumors over a global follow-up of 10 years after surgery in breast cancer patients in a cohort study. Between 2012 and 2014, a total of 112 newly diagnosed breast cancer patients were recruited from a public hospital in Granada, Southern Spain. Historical exposure to POPs was estimated by analyzing their concentrations in breast adipose tissue samples. Sociodemographic data were collected through face-to-face interviews, while data on evolution tumor were retrieved from clinical records. Statistical analyses were performed using Cox regression (overall survival, breast cancer recurrence or metastasis) and binary logistic regression models (joint outcome variable). We also tested for statistical interactions of POPs with age, residence, and prognostic markers. The third vs first tertile of hexachlorobenzene concentrations was associated with a lower risk of all-cause mortality (Hazard Ratio, HR = 0.26; 95 % Confidence Interval, CI = 0.07-0.92) and of the appearance of any of the four events (Odds Ratio = 0.37; 95 % CI = 0.14-1.03). Polychlorinated biphenyl 138 concentrations were significantly and inversely associated with risk of metastasis (HR = 0.65; 95 % CI = 0.44-0.97) and tumor recurrence (HR = 0.69; 95 % CI = 0.49-0.98). Additionally, p,p'-dichlorodiphenyldichloroethylene showed inverse associations with risk of metastasis in women with ER-positive tumors (HR = 0.49; 95 % CI = 0.25-0.93) and in those with a tumor size <2.0 cm (HR = 0.39; 95 % CI = 0.18-0.87). The observed paradoxical inverse associations of POP exposure with breast cancer evolution might be related to either a better prognosis of hormone-dependent tumors, which have an approachable pharmacological target, or an effect of sequestration of circulating POPs by adipose tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Oral cancer causes significant morbidity and mortality. Chemoprevention utilizes medication or natural compounds to reverse oral premalignant lesions and to prevent second primary tumors., Methods: A comprehensive PubMed database and Cochrane Library search from 1980 to 2021 was performed using the keywords "leukoplakia," "oral premalignant lesion," and "chemoprevention.", Results: Chemopreventive agents included retinoids, carotenoids, cyclooxygenase inhibitor, herbal extracts, bleomycin, tyrosine kinase inhibitors, metformin, and immune checkpoint inhibitors. Although some agents demonstrated effect in reducing premalignant lesions and preventing second primary tumors, the results among different studies were highly variable., Conclusions: The results of different trials, albeit inconsistent, provided substantial information for future studies. In the era of personalized medicine, future studies will focus on identifying specific biomarkers and molecular profile to monitor and to prevent malignant transformation. Larger trials are warranted to validate the effect of chemopreventive agents., (© 2023 Wiley Periodicals LLC.)

Head and neck cancer is among the top ten cancers worldwide, with most lesions in the oral cavity. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral malignancies and is a significant public health concern. Patients with OSCC are at increased risk for developing concomitant tumors, especially in the oral cavity, due to widely genetically susceptible mucosa to carcinogenic factors. Based on fulfilling specific criteria, these concomitant tumors can be called second primary tumors (SPTs), which can be further categorized into metachronous and synchronous tumors. This research reviews the literature that investigated the concurrent OSCC with second or multiple primaries to improve understanding of the definition, classification guidelines, and its effect on cancer survival. It also highlights the current investigation methods, the variation of standard treatment approaches due to such a phenomenon, and preventive measures discussed in the literature.

Computed tomography (CT) scan has been an integral part of the diagnostic workup for patients with head and neck squamous cell carcinoma. Our study was designed to find out the incidence of distant metastasis and second primary tumor and to correlate the cost-effectiveness of CT thorax in detecting the same. This study was conducted among 326 cancer patients who visited our center with curative intent in the year 2021, with lesions in various head and neck subsites. Data were collected based on their pathological TNM staging and the presence of distant metastasis as evident on their CT thorax imaging with various variables related to the disease. Incremental cost-effectiveness ratio (ICER) was calculated for detecting a single metastatic deposit and second primary tumor in terms of Indian currency and was correlated to each subsite and stage of disease at presentation. Out of these 326 patients, 281 patients were included in our study after considering the inclusion criteria, and among these 281 patients, 235 of them underwent CT thorax for metastatic workup. No patient was found to have a second primary. Metastases were found in 12 patients. The site of primary lesion and clinical tumor (cT) staging were found to be significantly influencing the incidence of metastasis on CT thorax. ICER was least for larynx, pharynx, and paranasal sinuses and was highest for oral cavity primaries and early-stage disease. As per our observations and results of ICER, CT thorax is indeed a valuable modality but should be used judiciously when it comes to initial diagnostic workup., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2022.)

Background: The major goal of routine follow-up in oropharyngeal squamous cell carcinoma (OPSCC) patients is the asymptomatic detection of new disease in order to improve survival. This study evaluated the effect of routine follow-up on overall survival (OS)., Methods: A retrospective cohort of 307 consecutive OPSCC patients treated with curative intent between 2006 and 2012 was analyzed. The effectiveness of routine follow-up was studied by comparing treatment-intent and OS in patients with asymptomatically versus symptomatically detected new disease., Results: Three- and five-year risks of new disease were 29% (95% CI: 24-34) and 33% (95% CI: 27-39). Of the 81 patients with locoregional recurrence or second primary head and neck cancer, 8 (10%) were detected asymptomatically with no difference in OS with those detected with symptoms., Conclusions: Asymptomatic detection of new disease during routine visits was not associated with improved OS. The focus of follow-up should be on providing psychosocial care and rehabilitation., (© 2022 Wiley Periodicals LLC.)

The aim was to investigate clinical course of disease in patients with malignant laryngeal tumors with emphasis on various forms of disease recurrence (local recurrence, metastasis to regional lymph nodes, occurrence of second primary tumor). A retrospective research including 78 patients with histopathologically confirmed diagnosis of squamous cell laryngeal carcinoma was conducted. Information on cancer stage, histologic grade, type of treatment and disease recurrence was obtained from medical history. Tissue samples of the patients were submitted to immunohistochemical analysis and assessment of Ki-67 proliferation index expression. The occurrence of second primary tumor was found to be related to the significantly higher Ki-67 proliferation index. The number of patients having not undergone oncologic therapy and remained free from disease recurrence was significantly higher than expected. Treatment outcome depends on patient age, histologic grade, radiotherapy applied, and clinical course of disease. It is necessary to define the predictive factors of various forms of disease recurrence more precisely in order to identify better treatment options for patients with malignant tumors of the larynx.

Malignancies of the head and neck (HN) region and esophagus are among the most common cancers worldwide. Due to exposure to common carcinogens and the theory of field cancerization, HN cancer patients have a high risk of developing second primary tumors (SPTs). In our review of 28 studies with 51,454 HN cancer patients, the prevalence of SPTs was 12%. The HN area is the most common site of SPTs, followed by the lungs and esophagus, and 13% of HN cancer patients have been reported to have esophageal high-grade dysplasia or invasive carcinoma. The prognosis of HN cancer patients with concomitant esophageal SPTs is poor, and therefore identifying esophageal SPTs as early as possible is of paramount importance for risk stratification and to guide the treatment strategy. Image-enhanced endoscopy, especially using narrow-band imaging endoscopy and Lugol's chromoendoscopy, has been shown to improve the diagnostic performance in detecting esophageal neoplasms at an early stage. Moreover, the early detection and minimally invasive endoscopic treatment of early esophageal neoplasm has been shown to improve the prognosis. Well-designed prospective studies are warranted to establish appropriate treatment and surveillance programs for HN cancer patients with esophageal SPTs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chung, Liao, Wu, Lo, Hsieh, Lee, Liu, Kuo and Shueng.)

Purpose: Narrow band imaging (NBI) enhances mucosal vasculature and could help in the identification of recurrences. We assessed the effectiveness of NBI with flexible video-endoscope in the early detection of recurrence after treatment of head and neck squamous cell carcinoma, its diagnostic advantage over high-definition white-light (HD WL) endoscopy, also in relation to recurrence site, and the influence of previous radiotherapy (RT) or chemotherapy (CT). Moreover, we investigated the association between index tumor site and the risk of developing recurrence, and the relation between index tumor site and recurrence site., Methods: From January 2018 to November 2020, 160 patients previously treated with surgery and/or RT ± CT were evaluated using NBI with flexible video-endoscope. Sensitivity, specificity, positive/negative predictive value, and accuracy were calculated for NBI and HD WL, and compared using the McNemar test. The Fisher exact test was used to compare the other associations investigated., Results: The difference between NBI and HD WL sensitivity was statistically significant (p < 0.001). The NBI diagnostic advantage was 62.5%, highest in the hypopharynx (p = 0.05), and was not influenced by previous RT or CT (p = 0.49). Index tumor site statistically related with recurrence site (p < 0.001), but not with the risk of developing recurrence (p = 0.81)., Conclusion: NBI with flexible video-endoscope could represent a valid option to detect recurrence early during the follow-up, especially in a difficult-to-visualize site such as the hypopharynx., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Therapy of epitheloid angiomyolipomas (eAML) may be challenging, since unlike classical angiomyolipomas this rare subclass of benign mesenchymal angiomyolipomas may present with lymph node metastases, local recurrent disease, and/or systemic metastatic disease in up to 30% of cases., Objectives: We report here for the first time in Germany a case of eAML after successful treatment of malignant melanoma., Materials and Methods: Clinical and histological findings as well as results of the genetic analysis of the angiomyolipoma are presented., Results: A somatic, truncating mutation of the TSC2 gene was found in the angiomyolipoma., Conclusion: The relationship to histologically similar tumor entities are presented and therapeutic options based on the genetic classification are discussed., (© 2021. The Author(s).)

Background: The aim of this study was to identify risk factors for the development of second primary tumors (SPTs) in the head and neck region, lungs, and esophagus in patients with head and neck cancer., Methods: We collected data from 1581 patients. A cause-specific Cox model for the development of an SPT was fitted, accounting for the competing risks residual/recurrent tumor and mortality., Results: Of all patients, 246 (15.6%) developed SPTs. Analysis showed that tobacco and alcohol use, comorbidity, and the oral cavity subsite were risk factors for SPTs. The C-index, the discriminative accuracy, of the model for SPT was 0.65 (95% confidence interval, 0.61-0.68)., Conclusions: Our results show that there is potential to identify patients who have an increased risk to develop an SPT. This might increase their survival chances and quality of life. More research is needed to provide head and neck clinicians with definitive recommendations., (© 2021 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Surgery is one of the mainstays of head and neck cancer treatment, and aims at radical resection of the tumor with 1 cm tumor-free margins to obtain locoregional control. Surgical margins are evaluated by histopathological examination of the resection specimen. It has been long an enigma that approximately 10-30% of surgically treated head and neck cancer patients develop locoregional recurrences even though the resection margins were microscopically tumor-free. However, the origins of these recurrences have been elucidated by a variety of molecular studies. Recurrences arise either from minimal residual disease, cancer cells in the surgical margins that escape detection by the pathologist when examining the specimen, or from precancerous mucosal changes that may remain unnoticed. Head and neck tumors develop in mucosal precursor changes that are sometimes visible but mostly not, fueling research into imaging modalities such as autofluorescence, to improve visualization. Mostly unnoticed, these precancerous changes may stay behind when the tumor is resected, and subsequent malignant progression will cause a local relapse. This led to a clinical trial of autofluorescence-guided surgery, of which the results were reported in 2020. This review focuses on the most recent literature of the improved diagnosis of the resection margins of surgically treated head and neck cancer patients, the pathobiological origin of recurrent disease, and relevant biomarkers to predict local relapse. Directions for further research will be discussed, including potential options for improved and personalized treatment, based on the most recently published data.

Background: Patients with head and neck squamous cell carcinoma (HNSCC) can develop lung squamous cell carcinoma (LuSCC), which could be the second primary tumor or HNSCC metastasis. Morphologically it is difficult to distinguish metastatic HNSCC from a second primary tumor which presents a significant diagnostic challenge. Differentiation of those two malignancies is important because the recommended treatments for metastatic HNSCC and primary LuSCC differ significantly. We investigated if the quantification of the promotor methylation status in HNSCC and LuSCC differs., Methods: Primary HNSCC (N = 36) and LuSCC (N = 17) were included in this study. Methylation status in the ASC/TMS1/PYCARD (apoptosis-associated speck-like protein containing a caspase recruitment domain; 8 CpG sites) and MyD88 (Myeloid differentiation primary response protein 88; 10 CpG sites) promoters was analyzed. Bisulfite converted DNA, isolated from tumor tissue was quantified using pyrosequencing. Results of pyrosequencing analysis were expressed as a percentage for each tested CpG site. Receiver-operating characteristic (ROC) curve analysis was used for the evaluation of the diagnostic properties of selected biomarkers., Results: CpG sites located in the promoters of ASC/TMS1/PYCARD&#95;CpG8 (- 65 upstream) and MyD88&#95;CpG4 (- 278 upstream) are significantly hypermethylated in the HNSCC when compared with LuSCC (p ≤ 0.0001). By performing ROC curve analysis we showed that corresponding areas under the curve (AUC) were 85-95%, indicating that selected CpG sites are useful for a distinction between primary LuSCC and primary HNSCC., Conclusions: Results of the present study indicate that there is a significant difference in the methylation status of tested genes between primary HNSCC and LuSCC. However, to prove this approach as a useful tool for distinguishing second primary LuSCC from HNSCC metastasis, it would be necessary to include a larger number of samples, and most importantly, metastatic samples.

Introduction: Second primary tumors (SPTs) in head and neck cancer are thought to occur from premalignant lesions that are present at the time of the primary tumor diagnosis. The association of the modality used to treat the primary lesion with SPT occurrence is not clear., Objective: The aim of the study was to assess the incidence of SPTs in patients with head and neck malignancies, according to treatment modality., Methods: We conducted a retrospective cohort study. All patients who were treated at Soroka Medical Center between 2000 and 2013 for a head and neck squamous cell carcinoma were assessed. Data analysis included tumor site of the primary and second primary and treatment modality of the primary tumor. In addition, demographics as well as habits were recorded as well., Results: Of the 184 patients included in the cohort, SPT developed in 31 patients (17%) with a median time to diagnosis of 4.3 years. Smoking was reported in 74% of those with SPT and 78% of those without. The most common site for SPT was the lungs, with 13 cases, 42% of the total SPTs. Among patients who developed an SPT, for 12 of those with an index tumor in the oral cavity or oro-hypopharynx, 8 (67%) developed an SPT in the same location; for 18 of those with an index tumor in the larynx, 11 (61%) developed a SPT in the lungs and bronchi (p = 0.001). On multivariate analysis, the treatment modality used was not found to be associated with the occurrence of SPTs and the radiotherapy showed no protective or harmful effect (HR 0.64 p = 0.24)., Conclusion: Treatment modality used for head and neck cancer does not seem to be associated with the occurrence of SPTs., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To assess the incidence, types, and outcomes of second primary tumors (SPT) in cases of retinoblastoma (RB) from a referral Tertiary eye care center METHODS: Retrospective chart review of 7 cases RESULTS: All 7 (100%) cases had bilateral RB at presentation. The mean age at diagnosis of RB was 16 months (median 7 months; range 5-72 months). Treatment of RB with intravenous chemotherapy was noted in 3 (43%) patients, 1 (14%) patient had received external beam radiotherapy (EBRT) to the orbit, 1 (14%) patient had received a combination of chemotherapy and orbital EBRT, while 4 (57%) patients had undergone primary enucleation of the worse eye and focal treatment of the better eye. The mean age at detection of SPT was 15 years (median 8 years; range 6-46 years). The mean time interval between diagnosis of RB and SPT was 13 years (median 7 years; range 1-41 years). The SPT's included osteosarcoma of long bone (n = 2), eyelid sebaceous gland carcinoma (n = 2), ventricular ependymoma (n = 1), orbital neuroblastoma (n = 1), and acute lymphoblastic leukemia (n = 1). All patients received treatment for the SPT with either surgical excision (n = 2), intravenous chemotherapy (n = 1), or a combination of surgery/chemotherapy/radiotherapy (n = 4). Over a mean follow-up period of 8 years (median 8 years; range 4-11 years), one (14%) patient died, while other 6 (86%) patients are alive and well., Conclusion: Though the incidence of SPT's in cases of RB is rare, life-long follow-up is mandatory in at-risk patients.

Background: Sarcomatoid variant of oral squamous cell carcinoma (OSCC) is aggressive tumors that frequently recur and metastasize. Our aim was to determine the survival outcomes and factors that predict its incidence in recurrent and second primary tumors (SPT)., Methods: We retrospectively analyzed the records of SPT and recurrent OSCC cases with sarcomatoid differentiation. The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method. Logistic regression was used to identify the factors associated with SPT and recurrent sarcomatoid OSCC. Recursive partitioning was performed to classify the sample based on the clinicopathological factors of the index tumor., Results: A total of 82 patients were included in the study with a median survival, calculated from the date of diagnosis of recurrence or SPT, of 6 months (recurrence-2 months, SPT-8 months). The 3-year OS for the recurrence group was 19.9% and for SPT group was 29%. Perineural invasion in the index tumor was significantly associated with sarcomatoid differentiation in the recurrent tumor. At one end of the spectrum of the recursive partitioning were the SPTs that had small index tumor sizes and DOI/thickness less than 14.5 cm (lowest risk), and at the other end were recurrent diseases that had index tumors of advanced T stage (highest risk)., Conclusion: Sarcomatoid variant in the recurrent/SPT OSCC infers a poor prognosis. Recurrent disease that had an index tumor with advanced T stage carries the worst outcomes. Perineural invasion in the index tumor can help predict the presence of sarcomatoid carcinoma in the recurrent or SPT., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: Second primary tumors (SPTs) significantly increase the mortality in patients with head and neck squamous cell carcinomas (HNSCCs). Virtual chromoendoscopy (VCE) could complement or replace lugol chromoendoscopy (LCE) for early esophageal second primary tumor (ESPT) detection. An overview of the existing techniques and their diagnostic performance in early detection of esophageal squamous cell neoplasms is provided., Recent Findings: Nowadays, LCE is the golden standard to detect ESPTs. Recently, multiple new VCE techniques have been developed. Especially narrow-band imaging (NBI) is promising. It shows similar sensitivity to LCE, but a significantly higher specificity. Patients with HNSCC are prone to develop ESPTs, both synchronous and metachronous, with a substantial negative impact on survival rates. Therefore, active screening and follow-up is necessary. LCE is an effective screening method, but has some disadvantages. Countering these drawbacks, NBI shows a high potential in early ESPT detection in high-risk patients. Additional multicenter studies are needed to compare diagnostic performance and cost-effectiveness of NBI and other VCE techniques with LCE.

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The incidence and survival of oral squamous cell carcinoma (OSCC) patients have increased in recent years. Understanding their long-term survival aspects is essential for optimal treatment and follow-up planning. Almost one in five cancers diagnosed occurs nowadays in individuals with a previous diagnosis of cancer., Methods: Patients diagnosed with primary OSCC during 1953-2015 were retrieved from the Finnish Cancer Registry. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population., Results: Among 6602 first primary OSCC patients there were 640 (10%) SPCs. The SIR for SPCs was 1.85 (95% CI: 1.71-1.99, P < .001) corresponding to an EAR of 8.78 (95% CI: 7.29-10.26)., Conclusions: Health care professionals should be aware of the second primary cancer risk after management of primary OSCC and patients need to be counseled about this phenomenon., (© 2020 Wiley Periodicals, Inc.)

Background: In patients with squamous cell carcinoma of the cervix (SCCC), a squamous cell carcinoma (SqCC) in the lung represents either a second primary tumor or metastasis. This distinction between second primary tumors and lung metastases in patients with SCCC significantly influences patient prognosis and therapy. Here, we aimed to differentiate second primary tumors from lung metastases in patients with SCCC by exploring the HPV status in SqCCs involving the lung within a large cohort., Methods: P16 expression was assessed using immunohistochemistry on tissue microarrays including a total of 415 primary lung SqCCs and 21 lung SqCCs with prior SCCC. Following this, we performed HPV DNA typing and the sensitive RNAscope in situ method to screen all the cases for HPV E6/E7 expression, which is a more reliable indicator of transcriptively active HPV in tumor cells., Results: The p16 positive expression rate was 13.7% (57/415) in primary lung SqCCs, but HPV DNA was not detected in any of the 57 primary lung SqCC cases that positively expressed p16. In contrast, HPV DNA was detected in all cases (21/21) with prior SCCC. Consistently, all 21 lung SqCCs with prior SCCC (21/21) showed extensive HPV16 E6/E7 expression. In striking contrast, none of the primary lung SqCCs (0/415) had a detectable RNAscope signal., Conclusions: HPV does not seem to play a role in the development of primary lung SqCCs. HPV detection may be helpful in distinguishing second primary tumors from lung metastases in patients with SCCC., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: As treatment modalities for medulloblastoma have developed and overall survival (OS) has improved, there are relatively limited data on the impact of long-term effects such as risk of second primary tumors (SPT). To address the knowledge gap, we analyzed factors associated with the risk of SPT and OS by treatment modality for medulloblastoma., Methods: We queried the Surveillance, Epidemiology, and End Results (SEER)-18 database for patients diagnosed with medulloblastoma in 1973-2014. Patients were then grouped by age, gender, race, geographic region, histology, adjuvant treatment (no radiation [RT] and no chemotherapy [CT], RT and CT, RT alone, or CT alone), era of diagnosis (1973-1994 or 1995-2014), and survival time. Cumulative incidence, factors associated with SPT and OS were analyzed., Results: Of 2271 patients, 146 developed SPT, of which 42 were benign. The incidence of SPT was 3.1% and 4.9% at 10 and 15 years, respectively. The incidence of SPT was 3.1% with RT + CT versus 3.7% with RT alone at 10 years. The most common site for an SPT was the central nervous system. Female gender (P = 0.01) and longer OS of ≥21 years (P < 0.01) were associated with higher risk of SPT. RT + CT led to better OS than RT only (66.1% and 61.4% vs 55.6% and 49.7% at 10 and 15 years) (P < 0.01)., Conclusions: Medulloblastoma patients have a relatively low risk of SPT at 10 years with treatment. Use of RT + CT led to better OS with no statistical difference in SPT compared with the RT alone., (© 2020 Wiley Periodicals LLC.)

The traditional concept of post-treatment surveillance in head and neck cancer patients relies on examinations directed at early detection of disease recurrence and/or second primary tumors. They are usually provided by ear, nose and throat specialists with complementary input from radiation oncologists and medical oncologists. Emerging evidence underscores the importance of monitoring and effective management of late adverse events. One of the major drawbacks is a lack of prospective controlled data. As a result, local institutional policies differ, and practice recommendations are subject to continuing debate. Due to the economic burden and impact on emotional comfort of patients, intensity and content of follow-up visits are a particularly conflicting topic. According to the current evidence-based medicine, follow-up of head and neck cancer patients does not prolong survival but can improve quality of life. Therefore, an approach giving priority to a multidisciplinary care involving a speech and swallowing expert, dietician, dentist, and psychologist may indeed be more relevant. Moreover, on a case-by-case basis, some patients need more frequent consultations supplemented by imaging modalities. Human papillomavirus positive oropharyngeal cancer tends to develop late failures at distant sites, and asymptomatic oligometastatic disease, especially in the lungs, can be successfully salvaged by local ablation, either surgically or by radiation. The deep structures of the skull base related to the nasopharynx are inaccessible to routine clinical examination, advocating periodic imaging supplemented by nasofibroscopy as indicated. Anamnesis of heavy smoking justifies annual low-dose computed tomography screening of the thorax and intensive smoking cessation counseling. Finally, some cancer survivors feel more comfortable with regular imaging, and their voice should be taken into consideration. Future development of surveillance strategies will depend on several variables including identification of reliable predictive factors to select those who could derive the most benefit from follow-up visits, the availability of long-term follow-up data, the results of the first randomized trials, resource allocation patterns, infrastructure density, and the therapeutic landscape of locally advanced and recurrent and/or metastatic disease, which is rapidly changing with the advent of immune checkpoint inhibitors and better utilization of local approaches., (Copyright © 2020 Szturz, Van Laer, Simon, Van Gestel, Bourhis and Vermorken.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2019 Wiley Periodicals, Inc.)

Objective: To analyze the characteristics of the second primary tumor affecting the survival of patients with lymphoma, and to explore the risk factors of death from the second primary tumor. Methods: The medical records and related death information of 1 173 lymphoma patients who had already died with known causes were collected. The basic causes of death and the characteristics of patients who died of the second primary tumor were analyzed. Cox regression model was used to analyze the risk factors of lymphoma patients who died of the second primary tumor. Results: Among the 1 173 patients who had died, 94 (8.0%) died of the second primary tumor, 935 (79.7%) died of the primary lymphoma and 144 (12.3%) died of other diseases. The second primary tumor accounted for 17.5% (38/217) of all causes of death in patients with the survival period of more than 5 years, and the second primary tumor accounted for 28.3% (17/60) of all causes of death in patients with the survival period of more than 10 years. Among 94 cases who died of second primary tumors, 31 died of lung cancer, 15 died of gastric cancer, 13 died of liver cancer, 9 died of pancreatic cancer, 6 died of colorectal cancer, 6 died of second primary lymphoma and 14 died of other types of tumors. Univariate Cox regression analysis showed that age, first-line treatment effect, and chest or mediastinal radiotherapy were associated with the death from second primary tumors for lymphoma patients (all P <0.05). Multivariate Cox regression analysis showed that the effect of first-line treatment ( P =0.030) and the chest or mediastinal radiotherapy ( P =0.039) were independent factors for the death of lymphoma patients from the second primary tumor. Conclusions: The second primary tumor is an important factor affecting the survival of lymphoma patients, and the risk of death from second primary tumors increases significantly over time. The effect of first-line treatment and radiotherapy in the chest or mediastinum are independent factors for the death of lymphoma patients from the second primary tumor.

Background: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment., Methods: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival., Results: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17)., Conclusions: The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Introduction: Second 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)., Methods: Twenty-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., Results: Mean 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., Conclusion: Active 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., Competing Interests: All authors declare no personal or professional conflicts of interest, and no financial support from the companies that produce and/or distribute the drugs, devices, or materials described in this report. This study project was supported by a grant from Siriraj Research Fund (grant no. [IO] R016032009), Faculty of Medicine Siriraj Hospital, Mahidol University., (© 2019 Anekpuritanang et al.)

Introduction: Routine follow-up after curative treatment of patients with oral squamous cell carcinoma (OSCC) is common practice considering the high risk of second primaries and recurrences (ie second events). Current guidelines advocate a follow-up period of at least 5 years. The recommendations are not evidence-based and benefits are unclear. This is even more so for follow-up after a second event. To facilitate the development of an evidence- and personalized follow-up program for OSCC, we investigated the course of time until the second and subsequent events and studied the risk factors related to these events., Materials and Methods: We retrospectively studied 594 OSCC patients treated with curative intent at the Head and Neck Cancer Unit of the Radboud University Medical Centre from 2000 to 2012. Risk of recurrence was calculated addressing death from intercurrent diseases as competing event., Results: The 1-, 5- and 10-year cumulative risks of a second event were 17% (95% CI:14%;20%), 30% (95% CI:26%;33%), and 37% (95% CI:32%;41%). Almost all locoregional recurrences occurred in the first 2 years after treatment. The incidence of second primary tumors was relatively stable over the years. The time pattern of presentation of third events was similar., Discussion: Our findings support a follow-up time of 2 years after curative treatment for OSCC. Based on the risk of recurrence there is no indication for a different follow-up protocol after first and second events. After 2 years, follow-up should be tailored to the individual needs of patients for supportive care, and monitoring of late side-effects of treatment., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Esophageal 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 Methods: Patients 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., Results: Totally 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)., Conclusions: IEE screening for esophageal SPTs is helpful in risk stratification and prognosis prediction for HNC patients. Routine IEE screening is recommended in HNC patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: There are conflicting recommendations and possibly overuse of imaging for surveillance of second primary tumors for patients with a history of head and neck paraganglioma., Methods: Retrospective cohort study of 234 adults with head and neck paragangliomas (1990-2010) followed for a mean of 7.5 ± 8.4 years., Results: The rate of second paraganglioma was 1.7% after 5 years and 5.1% after 10 years, yielding an incidence of 6.65 per 1000 person-years. Only 1.3% of patients (2.59 per 1000 person-years) ever had a second paraganglioma in the chest, abdomen, or pelvis. Patients with a hereditary paraganglioma (hazard ratio [HR] = 4.84, 95% confidence interval [CI]: 1.52-15.43) or carotid body tumor (HR = 3.55, 95% CI: 1.15-10.99) were at greater risk., Conclusions: The incidence rate of a second primary paragangliomas is low but increases with hereditary disease. These results question the utility of repeated imaging outside of the neck to screen for second paragangliomas., (© 2019 Wiley Periodicals, Inc.)

Background: Early 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., Methods: A systematic review of all available databases was performed to find all Lugol chromoendoscopy screening studies., Results: Fifteen 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%., Conclusion: Our 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., (© 2018 The Authors. Head & Neck published by Wiley Periodicals, Inc.)

Background: We investigated risk and prognostic factors for second primary squamous cell carcinoma (SCC) in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT)., Methods: A total of 49 021 patients with NPC were treated at Sun Yat-Sen Cancer Center between January 1970 and December 2009. The incidence and management of second primary SCCs were analyzed., Results: A total of 142 patients (0.29%) developed second primary SCC, with 78.2% in the upper aerodigestive tract. Older age, smoking, and chemotherapy were associated with an increased rate of second primary SCC. The 3, 5, and 10-year overall survival (OS) rates for second primary SCC were 47.18%, 31.69%, and 11.97%, respectively. Advanced age, family history of cancer, and treatment modality were independent prognostic factors for survival., Conclusion: Second primary tumors rarely develop in patients with NPC treated with RT, but when this occurs, second primary SCC comprises a majority of these. Intensity-modulated RT may shorten the latency to second primary SCC. Surgery as the first-line treatment may improve survival and prognosis., (© 2018 Wiley Periodicals, Inc.)

The oral cavity is the commonest subsite of head and neck squamous cell carcinoma (HNSCC). Because of the rising incidence and increasing survival, more patients will be enrolled in a routine follow-up program. This review gives an overview of the evidence and guideline recommendations concerning follow-up after oral squamous cell carcinoma (OSCC). There is limited evidence concerning the effectiveness of follow-up after OSCC. This lack of evidence is reflected in a variation in guideline recommendations with respect to test interval and duration (i.e. for 3-5 years or lifelong). Most studies on the value of routine follow-up after curative treatment include all HNSCC subsites. The available literature shows, that these subsites have a different timing of recurrence and a different risk of second primary tumors at different locations. This leaves no rationale for applying the same follow-up program to each of the HNSCC subsites. There is agreement in the literature that OSCC follow-up can either be discontinued after two or three years or should be lifelong based on the risk of second primary tumors. Many authors advocate a personalized follow-up regimen that is based on the risk of new disease rather than a one-size-fits-all surveillance program. The literature is conflicting about the survival benefits of asymptomatic detection of new disease for HNSCC. To aid the development of evidence-based follow-up advise after OSCC, future research should focus on risk stratification, the value of symptom-free detection of recurrences and the active role that patients might play in determining their own follow-up regimen., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: To evaluate the incidence of colon cancer as a second primary cancer (CCSPC) and the survival outcomes of women with and without CCSPC after the diagnosis of endometrial cancer (EC)., Methods: The standardized incidence ratio (SIR) of CCSPC and survival outcomes of EC survivors with and without CCSPC were analyzed using data from January 1 1993 to December 31 2011, obtained from the Korea Central Cancer Registry., Results: Of 14,797 EC survivors, 147 (0.99%) developed CCSPC after an average interval of 5.5 years. The SIR of CCSPC among EC survivors was 2.56, higher than that of colon cancer in the general population. The SIR of CCSPC was highest for the ascending (3.77), followed by the transverse (3.45), descending colon (2.06), and rectum (1.99). The risk of a proximal site of CCSPC was high, especially within 5 years after the diagnosis of EC in the ascending (SIR, 4.37) and transverse (4.91) colon, and in young survivors (< 60 years) in the ascending (5.19) and transverse (3.82) colon. The 5- and 10-year overall survival rates were 84.8 and 80.4% among survivors with EC only and 89.2 and 76.3% for survivors with CCSPC, respectively., Conclusions: The risk of CCSPC among EC survivors increases especially in the proximal colon in young survivors. These results could be used for surveillance and counseling of EC survivors.

Radiotherapy for nasopharyngeal carcinoma has been reported to cause second primary oral squamous cell carcinoma (s-OSCC). The prognosis and pathologic characteristic of s-OSCC are largely unknown. Bmi1 was associated with the repair of radiation-induced DNA damage, suggesting its possible involvement in the pathologic process of s-OSCC. Herein, we compared the prognosis between s-OSCC and primary OSCC (p-OSCC) and explored the involvement of Bmi1 in s-OSCC development. In this retrospective study, s-OSCC and p-OSCC patients were matched by propensity scores. Their outcomes were compared by univariate and multivariate analyses. The expression of Bmi1 in s-OSCC and p-OSCC was detected by immunohistochemistry (IHC). Radiation-induced Bmi1 alteration in early-stage was explored in a rat model and HaCaT cells. After matching, 116 pairs of patients with highly balanced characteristics were included. In univariate analysis, the overall survival (OS), disease-specific survival (DSS), and local recurrence-free survival (LRFS) were poorer in s-OSCC than in p-OSCC (P < 0.05), while their regional metastasis-free survival (RMFS) was parallel (P = 0.112). Multivariate analysis further revealed that radiotherapy history was an independent risk factor for OS, DSS, and LRFS (P < 0.05). IHC results showed that the positive rate of Bmi1 was higher in s-OSCC (P = 0.0027). In a rat model of radiotherapy-induced mucositis, Bmi1 upregulation was observed 8 days after irradiation. Consistently, Bmi1 was upregulated in HaCaT cells 1 h after irradiation, and its upregulation was in accord with X-ray exposure duration. In conclusion, the prognosis of s-OSCC is poorer as compared to p-OSCC, which may be attributed to Bmi1 upregulation., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Cancers of the head and neck region are among the leading causes of cancer-related mortalities worldwide. Oral leukoplakia and erythroplakia are identified as precursor lesions to malignancy. Patients cured of an initial primary head and neck cancer are also susceptible to developing second primary tumors due to cancerization of their mucosal field. Multi-step acquisition of genetic mutations leading to tumorigenesis and development of invasive cancer has been previously described. Recently, whole exome sequencing of tumor specimens has helped to identify driver mutations in this disease. For these reasons, chemoprevention or the use of systemic or biologic agents to prevent carcinogenesis is an attractive concept in head and neck cancers. Nonetheless, despite extensive clinical research in this field over the past couple decades, no standard of care option has emerged. This review article reports on targeted interventions that have been attempted in clinical trials to date, and focuses on novel molecular pathways and drugs in development that are worthy of being tested for this indication as part of future endeavors., Competing Interests: The authors declare no conflicts of interest that would impact this manuscript.

Introduction: The development of a second primary malignancy in a patient with a preexisting diagnosis of metastatic cancer may be easily overlooked or misattributed to progression of disease. We report 3 patients with clear-cell renal cell carcinoma (RCC) metastatic to the lungs who were subsequently diagnosed with non-small-cell lung cancer (NSCLC). We examined the frequency of this occurrence within our institution and report on the radiographic findings that may help distinguish between metastatic RCC and primary lung cancers., Methods: Patients who received systemic targeted therapy for metastatic RCC at our institution between January 2006 and October 2013 were identified, and the proportion and incidence rate for developing NSCLC with preexisting metastatic RCC were calculated., Results: Two percent (3/151; 95% confidence interval [CI], 0.68%-5.68%) of patients treated for metastatic RCC with systemic targeted therapies at our institution were subsequently diagnosed with NSCLC, increasing to 3.5% (3/85; 95% CI, 1.21%-9.87%) among patients with known RCC pulmonary metastasis. The incident rate for development of NSCLC in patients with metastatic RCC was 0.87 per 100 person-years (95% CI, 0.22-2.4)., Conclusion: The subsequent diagnosis of a primary lung cancer in metastatic RCC patients occurred in 2% of patients at our institution and is underreported in the literature. Primary NSCLC may be underdiagnosed in patients with metastatic RCC. Both the radiographic appearance and clinical behavior of a lesion may hold clues that can help distinguish between a new primary and progression of metastatic disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Narrow-band imaging (NBI) is an optical technique enhancing mucosal vasculature. The aim of this study is to assess the effectiveness of rigid NBI endoscopy in the early detection of second primaries or local recurrences after treatment for oral (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC), its advantage over standard white-light (WL) endoscopy, and the influence of previous radiotherapy, the learning curve, and lesion site. Between January 2013 and June 2015, 195 patients treated for OSCC or OPSCC with surgery alone (group A) or radiotherapy with or without surgery and/or chemotherapy (group B) underwent additional follow-up assessments using NBI. Sensitivity, specificity, positive/negative predictive values (PPV and NPV), and accuracy for detecting second primaries or local recurrences were calculated for patients with at least two NBI assessments. The effect of previous radiotherapy was determined by test of proportions and that of the learning curve and lesion site with Fisher's exact test. 138/195 patients were included in the analysis. NBI sensitivity, specificity, PPV, NPV, and accuracy for groups A and B were 89.5 vs 100%, 85.2 vs 81.5%, 65.4 vs 69.7%, 96.3 vs 100%, and 86.3 vs 87%, respectively. The diagnostic gain of NBI was 88.2% in group A and 69.6% in group B. The learning curve was the main source of false positives (p = 0.025), whereas radiotherapy and lesion site were uninfluential (p = NS). NBI appears useful for follow-up after treatment for OSCC or OPSCC, its performance being affected only by the learning curve and not by previous treatment or lesion site.

The cytotoxic agent, eribulin represents a new standard of care in the treatment of heavily pretreated metastatic breast cancer patients. Here, we describe our experience with eribulin in a patient with a controlled primary breast cancer, who showed an aggressive recurrence of the primary tumor, including metastatic disease. Treatment management of the second primary tumor included six lines of chemotherapy and three lines of hormonal therapy, including eribulin as sixth line among all chemotherapies received. Eribulin treatment achieved a fast response to all metastatic sites and decelerated the aggressive evolution of the second disease.

As the patients population ages, cancer screening increases, and cancer treatments improve, millions more head and neck carcinoma (HNC) patients will be classified as cancer survivors in the future. Change in epidemiology with human papillomavirus related HNC leads to a number of young treated patients. After treatment for HNC intensive surveillance, including ear, nose and throat (ENT) endoscopy, imaging, and serology, confers a survival benefit that became less evident in unresectable recurrence. We performed a comprehensive revision of literature and analyzed the experience of our centre. We revised publications on this topic and added data derived from the interdisciplinary work of experts within medical oncology, ENT, and radiation oncology scientific societies. We retrospectively collected local and distant recurrence of chemoradiation treated patients at Santa Croce and Carle University Hospital. A HNC follow-up program is not already codified and worldwide accepted. There is a need of scheduled follow-up. We suggest adopting a standardized follow-up guideline, although a multidisciplinary approach is frequently requested to tailor surveillance program and treatment on each patient., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Although second primary tumors are common in patients with oral squamous cell carcinoma (OSCC), their predisposing factors and treatment guideline remain uncertain., Methods: Three hundred ninety-four patients with OSCC who received radical surgery from January 2002 to December 2009 were retrospectively reviewed., Results: Forty-five patients developed oral second primary tumors. Areca quid chewing, tongue tumors, and nodal metastasis were risk factors for second primary tumors. Multivariate analyses revealed that no second primary tumor (hazard ratio [HR] = 5.046; 95% confidence interval [CI] = 3.704-12.246; p = .003), contralateral neck dissection for ipsilateral second primary tumors (HR = 6.254; 95% CI = 3.027-13.365; p = .007), and postoperative radiotherapy (RT; HR = 3.987; 95% CI = 1.099-10.381; p = .040) were independent favorable prognostic factors., Conclusion: Areca quid chewing, tongue tumors, and nodal metastasis predisposed patients with OSCC to second primary tumor development. Elective dissection of the contralateral neck in patients with second primary tumors ipsilateral to index tumors and postoperative RT for eligible patients should always be considered in the management of oral second primary tumors. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1466, 2016., (© 2016 Wiley Periodicals, Inc.)

The incidence of Second Primary Tumors in the upper aerodigestive tract varies from 5 to 30 %. Most of them are located either in the same anatomical region or in the lungs, and are related to a poor overall survival. Our objective is to assess the incidence of Second Primary Tumors, factors related to its outcome, frequent associations, and impact on overall survival. 27 patients with Second Primary Tumors were reviewed out of 307 with head and neck cancer, between 2002 and 2011. Patients had a minimum follow-up period of 3 years, or until their death after the last treatment. Sex: 85.2 % were male; male:female ratio of 23:4. The mean age of appearance for the primary tumor was 66.8 years. Only 1 patient had a synchronous Second Primary Tumor, while 26 had metachronous Second Primary Tumors. Second neoplasms were grouped into synchronous and metachronous for statistical analysis. The following parameters were considered: age at diagnosis of the first tumor, gender, smoking and persistence of the habit, primary tumor's location in the larynx, association between two squamous cell carcinomas (index and second primary tumor), and radiotherapy for the primary tumor. The incidence of Second Primary Tumors was 8.79 %. Overall survival of metachronous tumors was 95 months (7.9 years). The primary tumor's location that prevailed when developing a Second Primary Tumor was the larynx. Regarding the histology, the most common association was head and neck squamous cell carcinoma with head and neck squamous cell carcinoma (9 patients). The Second Primary Tumor was the cause of death in 51.9 % of the patients and its most frequent location was the lungs. 19 patients underwent radiotherapy. Second Primary Tumors are common in the head and neck. The authors would like to enforce the importance of an extended follow-up, since second neoplasms worsen considerably the patient's prognosis. Patients who keep on smoking after treatment decrease even more their overall survival.

The pediatric ocular tumor retinoblastoma readily metastasizes, but these lesions can masquerade as histologically similar pediatric small round blue cell tumors. Since 98% of retinoblastomas have RB1 mutations and a characteristic genomic copy number "signature", genetic analysis is an appealing adjunct to histopathology to distinguish retinoblastoma metastasis from second primary cancer in retinoblastoma patients. Here, we describe such an approach in two retinoblastoma cases. In patient one, allele-specific (AS)-PCR for a somatic nonsense mutation confirmed that a temple mass was metastatic retinoblastoma. In a second patient, a rib mass shared somatic copy number gains and losses with the primary tumor. For definitive diagnosis, however, an RB1 mutation was needed, but heterozygous promoter→exon 11 deletion was the only RB1 mutation detected in the primary tumor. We used a novel application of inverse PCR to identify the deletion breakpoint. Subsequently, AS-PCR designed for the breakpoint confirmed that the rib mass was metastatic retinoblastoma. These cases demonstrate that personalized molecular testing can confirm retinoblastoma metastases and rule out a second primary cancer, thereby helping to direct the clinical management., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Image-enhanced endoscopy is helpful for screening of a second primary neoplasm in patients with esophageal and head and neck cancer. The purpose of this meta-analysis was to determine the diagnostic efficacy of white-light imaging (WLI), narrow band imaging (NBI), and Lugol chromoendoscopy for second primary neoplasm detection. A review of the PubMed/Cochrane databases up to May 2014 was performed. Meta-analysis was done by Meta-DiSc software and the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 4918 patients from 16 prospective and randomized trials were enrolled. For WLI, NBI, and Lugol chromoendoscopy, the pooled sensitivities were 53% (95% confidence interval [CI] = 48% to 59%), 87% (95% CI = 83% to 90%), and 88% (95% CI = 85% to 91%), respectively; the pooled specificities were 99% (95% CI = 98% to 99%), 95% (95% CI = 94% to 96%), and 63% (95% CI = 61% to 66%), respectively; and the areas under the receiver-operating characteristic (ROC) curve were 66%, 97%, and 82%, respectively. NBI endoscopy has the most highly accurate diagnostic performance for detection of second primary neoplasms in high-risk patients. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2343-E2349, 2016., (© 2015 Wiley Periodicals, Inc.)