Application of 18F-FDG PET/CT imaging radiomics in the differential diagnosis of single-nodule pulmonary metastases and second primary lung cancer in patients with colorectal cancer.

OBJECTIVE: It is crucially essential to differentially diagnose single-nodule pulmonary metastases (SNPMs) and second primary lung cancer (SPLC) in patients with colorectal cancer (CRC), which has important clinical implications for treatment strategies. In this study, we aimed to establish a feasible differential diagnosis model by combining 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) radiomics, computed tomography (CT) radiomics, and clinical features. MATERIALS AND METHODS: CRC patients with SNPM or SPLC who underwent 18F-FDG PET/CT from January 2013 to July 2022 were enrolled in this retrospective study. The radiomic features were extracted by manually outlining the lesions on PET/CT images, and the radiomic modeling was realized by various screening methods and classifiers. In addition, clinical features were analyzed by univariate analysis and logistic regression (LR) analysis to be included in the combined model. Finally, the diagnostic performances of these models were illustrated by the receiver operating characteristic (ROC) curves and the area under the curve (AUC). RESULTS: We studied data from 61 patients, including 36 SNPMs and 25 SPLCs, with an average age of 65.56 ± 10.355 years. Spicule sign and ground-glass opacity (GGO) were significant independent predictors of clinical features (P = 0.012 and P < 0.001, respectively) to build the clinical model. We achieved a PET radiomic model (AUC = 0.789), a CT radiomic model (AUC = 0.818), and a PET/CT radiomic model (AUC = 0.900). The PET/CT radiomic models were combined with the clinical model, and a well-performing model was established by LR analysis (AUC = 0.940). CONCLUSIONS: For CRC patients, the radiomic models we developed had good performance for the differential diagnosis of SNPM and SPLC. The combination of radiomic and clinical features had better diagnostic value than a single model.

Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy.

OBJECTIVES: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. METHODS: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. RESULTS: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). CONCLUSIONS: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

Personal history of cancer as a risk factor for second primary lung cancer: Implications for lung cancer screening.

BACKGROUND: Personal history of cancer is an independent risk factor for lung cancer but is omitted from existing lung cancer screening eligibility criteria. In this study, we assess the lung cancer risk among cancer survivors and discuss potential implications for screening. METHODS: This was a retrospective, secondary analysis of data from the Surveillance, Epidemiology and End Results (SEER) registry and the MD Anderson Cancer Center (MDACC). We estimated the standardized incidence ratios (SIRs) for lung cancer by site of first primary cancer using data from SEER. We assessed the lung cancer risk among head and neck cancer survivors from MDACC using cumulative incidence and compared the risk ratios (RR) by individuals' screening eligibility status. RESULTS: Other than first primary lung cancer (SIR: 5.10, 95% CI: 5.01-5.18), cancer survivors in SEER with personal history of head and neck cancer (SIR: 3.71, 95% CI: 3.63-3.80) had the highest risk of developing second primary lung cancer, followed by bladder (SIR: 1.86, 95% CI: 1.81-1.90) and esophageal cancers (SIR: 1.78, 95% CI: 1.61-1.96). Head and neck cancer survivors had higher risk to develop lung cancer compared to the National Lung Screening Trial's subjects, (781 vs. 572 per 100,000 person-years, respectively). Head and neck cancer survivors ineligible for lung cancer screening seen at MDACC had significantly higher lung cancer risk than head and neck cancer survivors from SEER (RR: 1.9, p < 0.001). CONCLUSION: Personal history of cancer, primarily head and neck cancer, is an independent risk factor for lung cancer and may be considered as an eligibility criterion in future lung cancer screening recommendations.

Fine-needle aspiration diagnosis of secondary malignant tumors of the thyroid gland: A single-institution experience of 17 cases.

BACKGROUND: Fine-needle aspiration (FNA) is the most commonly used preoperative pathological diagnostic tool for thyroid tumors. Secondary malignant tumors of the thyroid gland account for less than 3% of all thyroid malignancies. The aim of this study was to investigate the types and cytopathological features of secondary thyroid tumors, evaluate diagnostic pitfalls in FNA. METHODS: Cases of secondary thyroid tumors diagnosed in the Department of Pathology of Shaanxi Provincial People's Hospital were collected, and their clinical data, cytologic features, immunohistochemical results, and histopathological diagnoses were summarized. RESULTS: The study included 17 cases (8 males and 9 females) with a mean age of 60.4 ± 9.4 years (range, 45-83 years). Six cases had a known history of primary malignancy prior to FNA aspiration diagnosis. The most common organs of origin were the lungs (5 cases, 3 adenocarcinoma, and 2 small-cell carcinoma) and esophagus (5 cases, 3 squamous-cell carcinoma, 1 adenocarcinoma, and 1 small-cell carcinoma). The next most common was squamous-cell carcinoma of the larynx (3 cases), and gastric tumor (2 cases), including 1 lymphoma and 1 adenocarcinoma. Cell blocks and immunohistochemistry were performed in 12 of these cases. Comparison of the impact of positive history and IHC availability on the accuracy of pathologic diagnosis showed that both were statistically significant. CONCLUSION: FNA is an effective means of diagnosing secondary malignancies of the thyroid, in which knowledge of the patient's history of malignancy is essential, and the use of cell blocks and immunohistochemistry helps to clarify the pathological diagnosis.

Second Malignant Neoplasms Following Treatment for Hepatoblastoma: An International Report and Review of the Literature.

Treatment intensification has improved survival in patients with hepatoblastoma (HB); however, these treatments are associated with an increased risk of late effects, including second malignant neoplasms (SMNs). Data is limited regarding SMNs following HB treatment. Cases of SMNs following treatment for HB reported in the literature and from personal communication were analyzed to further assess this late effect. Thirty-eight patients were identified. The median age at diagnosis of HB was 16 months (range: 3 to 168 mo). All patients had received a platinum agent, and almost all had anthracycline exposure. The SMNs reported were hematopoietic malignancies (n=19), solid tumors (n=12), and post-transplant lymphoproliferative disorder (n=7). Of the 36 patients with outcome data, 19 survived. SMNs following HB treatment were primarily seen in patients with chemotherapy exposure, a history of liver transplantation, hereditary tumor predisposition syndromes, and/or a history of radiation treatment. Hematopoietic malignancies were the most common SMN reported in this cohort and were diagnosed earlier than other SMNs. Prospective collection of data through a companion late effects study or international registry could be used to further evaluate the rates and risks of SMNs as well as tumor predisposition syndromes in patients treated for HB.

The diagnostic yield of colonoscopic surveillance following resection of early age onset colorectal cancer.

BACKGROUND: The primary benefit of post-colorectal cancer (CRC) colonoscopic surveillance is to detect and remove premalignant lesions to prevent metachronous CRC. Current guidelines for long-term colonoscopic surveillance post early age onset CRC (EOCRC) resection are based on limited evidence. The aims of this study were to assess the diagnostic yield of colonoscopic surveillance post-EOCRC resection and identify molecular and clinicopathological risk factors associated with advanced neoplasia. METHODOLOGY: A retrospective cohort study of prospectively collected data was conducted at St Mark's hospital, London, United Kingdom, for patients diagnosed with EOCRC who underwent at least one episode of post-CRC colonoscopic surveillance between 1978 and 2022. We collected clinicopathological data including tumour molecular status and neoplasia detection rates. RESULTS: In total, 908 colonoscopic surveillance procedures were performed in 195 patients over 2581.3 person-years of follow-up. The diagnostic yields of metachronous CRC, advanced adenomas and non-advanced adenomas were 1.76%, 3.41% and 22.69% respectively. Sixteen patients (8.21%) developed metachronous CRC, and the majority (87.5%) were detected more than 3 years post index EOCRC diagnosis. Detection of advanced neoplasia was significantly higher in EOCRC patients with Lynch syndrome (26.15%) compared with those in whom Lynch syndrome was excluded (13.13%) (OR, 2.343; 95% CI, 1.014-5.256; p = 0.0349). CONCLUSIONS: During colonoscopic surveillance post-EOCRC resection, the long-term risk of developing metachronous advanced neoplasia remains high in the context of Lynch syndrome, but this trend is not as clearly evident when Lynch syndrome has been excluded.

Routine image-enhanced endoscopic surveillance for metachronous esophageal squamous cell neoplasms in head and neck cancer patients.

BACKGROUND: Esophageal squamous cell neoplasms (ESCNs) are common second primary tumors in patients with head and neck cancer. Image-enhanced endoscopy (IEE) with Lugol chromoendoscopy or magnifying narrow-band imaging both increase the detection of early ESCNs. No evidence-based ESCN surveillance program for head and neck cancer patients without a history of synchronous ESCNs exists. We aimed to evaluate the performance of an IEE surveillance program with magnifying narrow-band imaging endoscopy and Lugol chromoendoscopy. METHODS: From April 2016, we routinely used IEE with magnifying narrow-band imaging and Lugol chromoendoscopy to evaluate patients with head and neck cancer history. All patients who were negative for ESCNs at the first surveillance endoscopy and received at least 2 IEEs through December 2019 were included. Demographic profiles, clinical data, cancer characteristics, IEE results and pathology reports were analyzed. RESULTS: A total of 178 patients were included. Only 4 patients (2.2%) developed metachronous ESCNs during follow-up, all of whom received curative resection treatment. The interval for the development of metachronous ESCNs was 477 to 717 days. In multivariate Firth logistic regression and Kaplan‒Meier survival curve analysis, Lugol's voiding lesion type C had an increased risk of esophageal cancer development (adjusted odds ratio = 15.71; 95% confidence interval, 1.33-185.87, p = 0.029). Eight patients died during the study period, and none of them had metachronous ESCNs. CONCLUSIONS: IEE with magnifying narrow-band imaging and Lugol chromoendoscopy is an effective surveillance program in head and neck cancer patients without a history of ESCNs. Annual surveillance can timely detect early ESCNs with low ESCN-related mortality.

When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report.

BACKGROUND: Retinoblastoma (rb) is the most frequent intraocular tumor, accounting for 3% of all childhood cancers. Heritable rb survivors are germline carriers for an RB1 mutation and have a lifelong risk to develop non-ocular second primary tumors (SPTs) involving multiple other organs like the bones, soft tissues, or skin. These SPTs usually become manifest several years succeeding the diagnosis of rb. In our instance, however, a non-ocular SPT presented prior to the diagnosis of heritable rb. CASE PRESENTATION: We report a rare case of a monozygotic twin who presented with primary rhabdomyosarcoma (RMS) preceding the manifestation of heritable rb. The rb was diagnosed when the child developed strabismus while already on therapy for the RMS. The child underwent therapy for both as per defined treatment protocols. The rb regressed well on treatment, but the RMS relapsed and the child developed multiple refractory metastatic foci and succumbed to his disease. CONCLUSIONS: Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.

Gastrointestinal: Weight gain increases the risk of metachronous advanced colorectal neoplasm observed in post-polypectomy surveillance colonoscopy.

BACKGROUND AND AIM: Although obesity is a known risk factor for colorectal neoplasms, the correlation between weight change and colorectal neoplasm is unclear. Thus, we aim to evaluate the association between weight change and advanced colorectal neoplasm (ACRN) recurrence during post-polypectomy surveillance colonoscopy. METHODS: This retrospective cohort study included 7473 participants diagnosed with colorectal neoplasms between 2003 and 2010 who subsequently underwent surveillance colonoscopies until 2020. We analyzed the association between the risk of metachronous ACRN and weight change, defining stable weight as a weight change of <3% and weight gain as a weight increase of ≥3% from baseline during the follow-up period. RESULTS: During a median 8.5 years of follow-up, 619 participants (8.3%) developed ACRN. Weight gain was reported as an independent risk factor for metachronous ACRN in a time-dependent Cox analysis. A weight gain of 3-6% and ≥6% had adjusted hazard ratios (AHRs) of 1.48 (95% confidence interval [CI]: 1.19-1.84) and 2.14 (95% CI: 1.71-2.69), respectively. Participants aged 30-49 and 50-75 years with weight gain of ≥6% showed AHRs of 2.88 (95% CI: 1.96-4.21) and 1.90 (95% CI: 1.43-2.51), respectively. In men and women, weight gain of ≥3% was significantly correlated with metachronous ACRN. CONCLUSIONS: Weight gain is associated with an increased risk of metachronous ACRN. Furthermore, weight gain is associated with the recurrence of ACRN in both men and women regardless of age.

Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors.

PURPOSE: This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT). MATERIALS AND METHODS: Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk. RESULTS: A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively. CONCLUSION: The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem. AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors. METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6 months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92 years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60 years and older were negatively associated with CBC. CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.

Best practice & research clinical haematology: Screening for breast cancer in hodgkin lymphoma survivors.

Childhood and young adult survivors of Hodgkin lymphoma are at an elevated risk of developing breast cancer. Breast cancer risk is felt to originate from chest wall radiation exposure prior to the third decade of life, with incidence beginning to rise approximately eight to ten years following Hodgkin lymphoma treatment. Although incidence varies according to age at radiation exposure, dosage, and treatment fields, cohort studies have documented a cumulative incidence of breast cancer of 10-20% by 40 years of age. Women with a history of chest radiation for Hodgkin lymphoma are counselled to begin screening with bilateral breast MRI at 25 years of age, or eight years after radiation, whichever occurs later. Outside of high-risk surveillance, the optimal management approach for women with prior radiation exposure continues to evolve. When diagnosed with breast malignancy, evidence supports consideration of unilateral therapeutic and contralateral prophylactic mastectomy, although breast conserving surgery may be considered following multidisciplinary assessment. This review will address the epidemiology, characteristics, screening and management guidelines, and breast-cancer prevention efforts for Hodgkin lymphoma survivors treated with radiation therapy in adolescence and young adulthood.

Incidence and mortality of second primary malignancies after lymphoma: a population-based analysis.

BACKGROUND: Second primary malignancies (SPMs) account for an increasing proportion of human malignancies. We estimated the incidence, risk factors and outcomes in lymphoma survivors with SPMs. METHODS: Patients diagnosed with SPMs after primary lymphoma from 2010 to 2021 were included in this study. The incidence, mortality and clinical characteristics of SPMs in our center and Surveillance, Epidemiology, and End Results database were delineated and analyzed. Standardized incidence ratio quantified second cancer risk. RESULTS: A total of 2912 patients of lymphoma were included, 63 cases of SPM met the inclusion criteria, with the prevalence of SPMs after lymphoma was 2.16%. The male-to-female ratio of 2.32:1. The majority of these patients were older (≥60 years old, 61.90%) and previously treated with chemotherapy (68.25%). The common types among SPMs were digestive system tumors (42.86%), respiratory system tumors (20.63%) and urinary system tumors (12.70%). Additionally, cancer risks were significantly elevated after specific lymphoma though calculating the expected incidence. In terms of mortality, the diagnosis of SPMs was significantly associated with an increased risk of death over time. Moreover, although the outcome was favorable in some SPM subtypes (thyroid and breast cancer), other SPMs such as stomach and lung tumors had a dismal prognosis. CONCLUSION: With the improvement of medical standards, the survival of lymphoma patients has been prolonged. However, the incidence of SPM is increasing, particularly among men and older lymphoma survivors. Therefore, more attention should be invested in the SPM to further improve the prognosis of these patients.

Patterns of SPM incidence varied between China and Northern America.The incidence of SPM was higher among men and older lymphoma survivors.Patients with SPM are divided into low-risk and high-risk according to survival analysis.

Risk of Multiple Primary Cancers in Patients With Merkel Cell Carcinoma: A SEER-Based Analysis.

Importance: The risk of subsequent primary cancers after a diagnosis of cutaneous Merkel cell carcinoma (MCC) is not well established. Objective: To evaluate the risk of subsequent primary cancers after the diagnosis of a first primary cutaneous MCC. Design, Setting, and Participants: This cohort study analyzed data from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program from January 1, 2000, to December 31, 2019. In all, 6146 patients diagnosed with a first primary cutaneous MCC were identified. Main Outcomes and Measures: The primary outcome was the relative and absolute risks of subsequent primary cancers after the diagnosis of a first primary MCC, which were calculated using the standardized incidence ratio (SIR; ratio of observed to expected cases of subsequent cancer) and the excess risk (difference between observed and expected cases of subsequent cancer divided by the person-years at risk), respectively. Data were analyzed between January 1, 2000, and December 31, 2019. Results: Of 6146 patients with a first primary MCC diagnosed at a median (IQR) age of 76 (66-83) years, 3713 (60.4%) were men, and the predominant race and ethnicity was non-Hispanic White (5491 individuals [89.3%]). Of these patients, 725 (11.8%) developed subsequent primary cancers, with an SIR of 1.28 (95% CI, 1.19-1.38) and excess risk of 57.25 per 10 000 person-years. For solid tumors after MCC, risk was elevated for cutaneous melanoma (SIR, 2.36 [95% CI, 1.85-2.97]; excess risk, 15.27 per 10 000 person-years) and papillary thyroid carcinoma (SIR, 5.26 [95% CI, 3.25-8.04]; excess risk, 6.16 per 10 000 person-years). For hematologic cancers after MCC, risk was increased for non-Hodgkin lymphoma (SIR, 2.62 [95% CI, 2.04-3.32]; excess risk, 15.48 per 10 000 person-years). Conclusions and Relevance: This cohort study found that patients with MCC had an increased risk of subsequently developing solid and hematologic cancers. This increased risk may be associated with increased surveillance, treatment-related factors, or shared etiologies of the other cancers with MCC. Further studies exploring possible common etiological factors shared between MCC and other primary cancers are warranted.

Characteristics and classification of first primary cancer patients with second primary cancer: a population-based cohort study.

Cancer survivors have an increased risk of developing subsequent primary tumors. However, the characteristics of first primary cancers (FPCs) with various types of second primary cancers (SPCs) are poorly understood, which hinders screening strategies. We analyzed data from 1,893,258 patients from the Surveillance, Epidemiology, and End Results (SEER) database to characterize and classify of FPC patients with subsequent SPCs at the pan-cancer level. In total, 3% of patients had SPC, with varied incidence rates observed depending on the types of FPC. Their onset patterns of SPC and diversity of SPC varied. Based on the diversity of the high-incidence sites of SPC, we classified FPCs into two categories: FPCs that require whole-body screening and those that need screening of particular body parts. Moreover, according to the different timing of high incidence of SPCs, our system classifies FPCs into two subtypes: FPCs that require long-term monitoring for the occurrence of SPCs and those that require screening at specific time points for SPCs. Furthermore, we identified 11 anatomical sites where over half of FPC types are prone to SPC occurrence at these locations. The risk factors for SPC occurrence in different FPC types and prognostic factors were also elucidated. Overall, we characterize and classify of FPC patients with subsequent SPCs at the pan-cancer level, which can guide the development of distinct screening strategies for each FPC type.

[Clinical characteristics and efficacy of oropharyngeal carcinoma with secondary primary tumor].

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.

Head and neck cancer with synchronous nodules of the lung as a diagnostic and therapeutic challenge - A systematic review.

Head and neck squamous cell carcinoma (HNSCC) often presents with synchronous nodules of the lung (sNL), which may be benign nodules, second primary malignancies or metastases of HNSCC. We sought to gain an insight into the incidence of sNL and synchronous second primary of the lung (sSPML) in HNSCC patients and current opinions on useful diagnostic and therapeutic approaches. We conducted a systematic search of the PubMed database for articles that reported the simultaneous detection of HNSCC and sNL/sPML, within the timeframe of diagnosis and staging. Only studies involving humans were included, without restrictions for sex, age, ethnicity, or smoking history. All articles were categorised according to the Oxford Centre of Evidence-Based Medicine levels and their data collected. Data from 24 studies were analysed. Amongst HNSCC, the mean overall incidence rate of sNL and sSPML was 11.4% (range: 1.3-27%) and 2.95% (range: 0.4-7.4%), respectively. The possibility of a sNL to be a sSPML cannot be ignored (mean: 35.2%). Studies investigating smoking habits showed that the majority (98-100%) of HNSCC patients with sSPML were previous or active smokers. Detection of human papillomavirus through DNA analysis, p16 immunohistochemistry, and identification of clonal evolution were useful in differentiating metastasis from sSPML. 18FDG-PET scan was the most reliable method to diagnose sSPML (sensitivity: 95%; specificity: 96%; positive predictive value: 80%). With early sSPML detection and curative treatment, the 5-year overall survival rate is 34-47%. However, the proposed advantage of early detection warrants further evidence-based justification.