Detection Of Second Primary Tumors Research Articles

Second primary tumors in retinoblastoma survivors: a study of 7 Asian Indian patients.

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 16months (median 7months; range 5-72months). 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 15years (median 8years; range 6-46years). The mean time interval between diagnosis of RB and SPT was 13years (median 7years; range 1-41years). 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 8years (median 8years; range 4-11years), one (14%) patient died, while other 6 (86%) patients are alive and well. Though the incidence of SPT's in cases of RB is rare, life-long follow-up is mandatory in at-risk patients.

Developing a Novel Machine Learning-Based Classification Scheme for Predicting SPCs in Colorectal Cancer Survivors

Colorectal cancer is ranked third and fourth in terms of mortality and cancer incidence in the world. While advances in treatment strategies have provided cancer patients with longer survival, potentially harmful second primary cancers can occur. Therefore, second primary colorectal cancer analysis is an important issue with regard to clinical management. In this study, a novel predictive scheme was developed for predicting the risk factors associated with second colorectal cancer in patients with colorectal cancer by integrating five machine learning classification techniques, including support vector machine, random forest, multivariate adaptive regression splines, extreme learning machine, and extreme gradient boosting. A total of 4287 patients in the datasets provided by three hospital tumor registries were used. Our empirical results revealed that this proposed predictive scheme provided promising classification results and the identification of important risk factors for predicting second colorectal cancer based on accuracy, sensitivity, specificity, and area under the curve metrics. Collectively, our clinical findings suggested that the most important risk factors were the combined stage, age at diagnosis, BMI, surgical margins of the primary site, tumor size, sex, regional lymph nodes positive, grade/differentiation, primary site, and drinking behavior. Accordingly, these risk factors should be monitored for the early detection of second primary tumors in order to improve treatment and intervention strategies.

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

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

Clinical relevance of circulating microRNAs as lung cancer biomarkers

INVITED SPEAKER ABSTRACTS Clinical relevance of circulating microRNAs as lung cancer biomarkers Mattia Boeri, Gabriella Sozzi, Ugo Pastorino Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy Improvements in clinical management of lung cancer have been modest over the last 20 years and with almost 1.6 million deaths worldwide (19% of the total) it still has the highest mortality rate among cancers. So far no valid biomarker has proven to be useful in lung cancer clinical practice and in reducing mortality. Technical limitations, as well as genetic and biological tumor heterogeneity have likely limited the successful identification of tumorspecific markers. An interesting landmark to identify novel and more reliable biomarkers is searching for candidates by looking not only at the tumor itself but also at the interplay between the tumor and the host with the aim to identify changes related to the biological reactivity of the host to a developing cancer. MicroRNAs (miRNAs) are 19 to 25 nucleotide-long non-coding RNAs regulating gene expression by binding complementary sequences of target mRNAs. MicroRNAs have a role in cell-to cell communication and are actively released in the extracellular space included in vesicles or bounded to proteins protecting them from RNase activity. In this respect, circulating microRNAs represent ideal candidates since biomarkers could reflect both the early changes in the pulmonary environment or the cross-talk between the tumor and its surrounding microenvironment. MicroRNAs-based liquid biopsies are emerging as promising tools for individual risk stratification, for the diagnosis and prognosis of lung cancer and more recently as predictive biomarkers of response to therapy. In our Institution, a specific circulating microRNA signatures classifier (MSC) was generated and validated in plasma samples collected from volunteers enrolled in Low Dose Computed Tomography (LDCT) lung cancer screening trials, in order to set-up a minimally invasive test able to detect lung cancer in its early stages. LDCT is considered the gold standard for the early detection of lung cancer. Results of a USA randomized screening trial reported a significant increase in the number of lung cancer diagnoses, especially at lower stages, and a Journal of Thoracic Oncology Vol. 11 No. 2S: S2-S15 reduction of mortality up to 20%. On the other hand, two major issues emerged from screening studies: the high number of false positive cases identified by LDCT (over 95%) and the overdiagnosis issue (estimated over 18% in the NLST trial), leading to further examinations or unnecessary surgical procedures with remarkable increasing of costs and morbidities. The MSC stratifies patients in 3 levels of risk: high, intermediate and low. In large retrospective studies using plasma samples collected from more than 1000 volunteers enrolled in the INT/IEO and in the MILD screening trials, the MSC resulted in 87% sensitivity, 81% specificity and 99% negative predictive value. Moreover, the combined use of LDCT and the MSC test showed a 5-fold reduction in the number of false positive cases obtained with LDCT alone. Considering the 111 (3.3%) lung cancer cases detected during the first 5 years of these two screening trials, 84 had a plasma sample available to perform the MSC test. In this cohort the MSC was able to predict the disease occurrence two years before LDCT detection and the 5-year survival was respectively 88.9% for low risk MSC, 79.5% for intermediate risk MSC and 40.1% for high risk MSC (p1⁄40.001). Another possible use of liquid biopsy could be the monitoring of the disease status after treatment or surgical resection. The MSC test was thus employed to analyze 100 longitudinally-collected plasma samples obtained from 31 alive patients (28 disease-free and 3 relapsing) after surgical resection of primary lung tumors. Considering the 25 disease-free patients positive to the MSC test at the time of diagnosis, a reduction of MSC risk profile was observed in 19 (76%) post-surgery plasma samples. Whereas in the 3 relapsing patients an increase of the MSC risk level was observed at the time of detection of second primary tumor or metastatic progression. So far the MSC test showed very promising results in screening settings, being able to improve individual risk assessment and the performance of LDCT. Further analysis will provide information about the sensitivity of the MSC in clinically detected lung cancer. The MSC risk levels are also being evaluated according to other risk factors such as smoking habits (measured as Pack Year), the inflammation levels (measured as C-reactive protein) or the forced expiratory volume (FEV-1). Finally, by targeted NGS we are profiling the mutational load of screening detected tumors in order to analyze association with the MSC risk profile.

Multiple Primary Tumors in Differentiated Thyroid Carcinoma and Relationship to Thyroid Cancer Outcome

Patients with differentiated thyroid carcinoma (DTC) have long-life expectancy and are at risk for developing a second primary cancer. Aim of this study was to assess the occurrence of DTC in conjunction with other primary neoplasms. It was also aimed to explore the possibility of synchronous or metachronous other malignancies having an impact on clinical course of thyroid carcinoma. Clinical records of 1680 DTC patients treated and followed in our institution over last twenty years were reviewed. Forty-five second primary tumors were found in 42 patients. These patients were classified into 3 groups as antecedent (group I), synchronous (group II) or subsequent (group III) according to the timing of occurrence of non-thyroidal malignancy. The initial characteristics of thyroid neoplasm were compared between patients with DTC plus another tumor and DTC only. Kaplan-Meier Survival Analysis was used to estimate the survival probability for patients with DTC alone and DTC plus another primary tumor. There were 15 synchronous and 30 metachronous tumors in 42 patients. Three of them had triple tumors. The most common second primary was lympho-haematological and upper aero digestive system tumors in group I and II respectively, whereas a variety of tumors were noted in group III. Despite the more common occurrence of unfavourable prognostic factors in patients with multiple cancers than thyroid cancer alone, complete response to radioiodine therapy and recurrence free survival rate was similar in both groups (p>0.05). The results of the current series imply that the occurrence of multiple primary tumors is not uncommon in patients with DTC. Close medical surveillance and the use of advanced screening modalities might lead to the detection of second primary tumors in DTC. However, the presence of second primary seems not to affect the clinical course of DTC.

Follow-up after treatment for breast cancer in young women

The majority (80%) of breast cancers are diagnosed in women over the age of 50; only 5% will be in their 20s and 30s. These women have specific needs that include genetic counselling, psychological support, advice with regard to fertility and pregnancy issues and information on coping with treatment-related morbidity. The primary purpose of follow-up is often regarded as the early detection of recurrence as well as the detection of second primary tumours. Rather than concentrating solely on detecting cancer recurrence, clinicians need to be more susceptive to symptoms related to treatment morbidity and to the information needs of their patients. This paper outlines the specific issues listed above that need to be addressed in follow-up clinics and highlights interventions that may help improve the value of follow-up appointments and quality of life for young women with breast cancer.

Survival in second primary malignancies of patients with head and neck cancer.

Second primary tumours occur frequently in patients with a history of head and neck malignancies. Delays in making an early and correct diagnosis can seriously affect the therapy management and survival. This was a retrospective study of 120 patients with a history of head and neck cancer, presenting with a second primary tumour. Current follow-up strategies and the use of routine sonographic imaging of the head and neck regions were evaluated, and the impact that tumour chronology, the tumour site and the various treatment modalities have on the survival were assessed. Forty-two per cent of patients developed a metachronous second malignancy more than five years after diagnosis of the index tumour. The accuracy of colour-duplex sonography in detection of second primaries in the head and neck was 82.3 per cent. First and second primary tumours located in the larynx were observed to have the highest five-year survival rate. Patients who developed metachronous tumours had a five-year survival rate of 68.9 per cent for the index tumours, and a 26 per cent five-year survival rate with the occurrence of a second neoplasm. With synchronous tumours a mean survival time of 18 months and a five-year survival rate of 11.9 per cent was found (p < 0.0001). Where clinically appropriate an aggressive treatment strategy was employed and yielded the most favourable results with a five-year survival rate of 66.8 per cent and 35.9 per cent for index tumours and second primary malignancies, respectively. Since more than 40 per cent of the metachronous second primaries in patients with a history of head and neck malignancy occur beyond the five-year follow-up period, an extended protocol with individually adjusted close monitoring of high-risk patients seems appropriate. Colour-duplex sonography is a valuable screening investigation for the early detection of second primary tumours. The treatment of a second primary is often less successful than for the same malignancy occurring primarily. The prognosis of synchronous tumours is significantly lower when compared to malignancies of a metachronous nature, despite some encouraging individual results. Only the early implementation of aggressive treatment methods for second primaries is successful in terms of survival.

Carcinoma of the lung and multiple primary malignant tumors

To evaluate the incidence of multiple primary malignancies combined with lung and other organs and their relationship. All patients who consecutively treated for lung cancer from December 1964 to December 1992, were retrospectively analyzed regarding the recurrence of a synchronous primary tumor elsewhere in the body. Of total 1019 patients reviewed, 21 (2.1%) had associated carcinoma of other organs. In these 21 patients, the incidence of associated aerodigestive tract cancer was 71.4% (15/21) and that of other organs was 28.6% (6/21). Five patients had simultaneous cancer with the lung cancer and 16 had metachronous cancer. Multiple primary tumors in patients with carcinoma of the lungs is not a rare phenomenon. Surveillance programs for detection of second primary tumors should focus on these patients.

Postoperative Adjuvant Therapy for Patients With Resected Non-Small Cell Lung Cancer: Still Controversial After all These Years

Patients with clinical stage I and II non-small cell lung cancer (NSCLC) generally are considered candidates for surgical resection, with cure rates as high as 80% reported for some subsets. Locoregional and systemic adjuvant therapies have been evaluated in patients with lymph node involvement or pathologic T3 status, although considerable controversy regarding an appropriate standard of care continues to exist. Several trials have evaluated postoperative radiation therapy, the majority of which suggest that overall survival may be only minimally improved with this adjuvant therapy, but local failure is probably reduced. Trials evaluating the role of adjuvant chemotherapy have been few, often enrolling small numbers of patients. Several recent reviews summarizing the results of these trials suggest that, although some adjuvant chemotherapy regimens may have biological activity, results have not been consistent, and further study is warranted for regimens that include newer chemotherapy agents. CNS relapse is one of the most common sites of metastasis in NSCLC, and prophylactic cranial irradiation (PCI) has been evaluated in a number of trials to reduce the risk of local failure at this site. Data from these trials strongly suggest that a prospective trial of PCI in patients with NSCLC at high risk for isolated CNS relapse is warranted. Future clinical trials evaluating new radiographic, immunologic, and molecular technologies for early detection of second primary tumors also should be considered, particularly in patients with resected T1N0M0 lesions.

18F-fluorodeoxyglucose dual-head positron emission tomography as a procedure for detecting simultaneous primary tumors in cases of head and neck cancer

Second primary tumors are a leading cause of death among patients with head and neck cancer; therefore, early detection of these tumors is necessary. In the current study, the authors aimed to evaluate the diagnostic capacity of (18)F-fluorodeoxyglucose dual-head positron emission tomography (FDG-PET) for detecting second primary tumors in patients presenting with primary head and neck cancer. The authors prospectively studied a case series of 68 consecutive patients with a primary tumor in the oral cavity or oropharynx. Within a period of 3 weeks, clinical examination, chest X-ray, computed tomography, and ultrasonography of the head and neck were performed on all patients. Irrespective of the results, patients underwent FDG-PET of the head, neck, and chest. Due to its low yield in the detection of second primary tumors, panendoscopy was not used in this study. All patients were followed up for at least 6 months to assess the number of simultaneous and synchronous tumors missed by FDG-PET. In 12 of 68 patients (18%; 95% confidence interval [CI]: 8-28%), a second simultaneous primary malignant tumor was found by FDG-PET. Five of these tumors (7%; 95% CI: 1-13%) were also detected by clinical or radiologic examination (P = 0.016). With one exception, all tumors were found in the epithelium of the upper digestive and respiratory tract. However, even when the patient with a second primary tumor in the thyroid was excluded from evaluation, FDG-PET significantly improved the detection rate of second primaries (P = 0.031). In none of the 68 patients studied were additional simultaneous or synchronous primary tumors found during follow-up. The use of FDG-PET significantly increases the rate of detection of simultaneous second primary tumors. The results of our study suggest that most of the second primary tumors are detected in an early stage.

18F‐fluorodeoxyglucose dual‐head positron emission tomography as a procedure for detecting simultaneous primary tumors in cases of head and neck cancer

BACKGROUND Second primary tumors are a leading cause of death among patients with head and neck cancer; therefore, early detection of these tumors is necessary. In the current study, the authors aimed to evaluate the diagnostic capacity of 18F-fluorodeoxyglucose dual-head positron emission tomography (FDG-PET) for detecting second primary tumors in patients presenting with primary head and neck cancer. METHODS The authors prospectively studied a case series of 68 consecutive patients with a primary tumor in the oral cavity or oropharynx. Within a period of 3 weeks, clinical examination, chest X-ray, computed tomography, and ultrasonography of the head and neck were performed on all patients. Irrespective of the results, patients underwent FDG-PET of the head, neck, and chest. Due to its low yield in the detection of second primary tumors, panendoscopy was not used in this study. All patients were followed up for at least 6 months to assess the number of simultaneous and synchronous tumors missed by FDG-PET. RESULTS In 12 of 68 patients (18%; 95% confidence interval [CI]: 8–28%), a second simultaneous primary malignant tumor was found by FDG-PET. Five of these tumors (7%; 95% CI: 1–13%) were also detected by clinical or radiologic examination (P = 0.016). With one exception, all tumors were found in the epithelium of the upper digestive and respiratory tract. However, even when the patient with a second primary tumor in the thyroid was excluded from evaluation, FDG-PET significantly improved the detection rate of second primaries (P = 0.031). In none of the 68 patients studied were additional simultaneous or synchronous primary tumors found during follow-up. CONCLUSIONS The use of FDG-PET significantly increases the rate of detection of simultaneous second primary tumors. The results of our study suggest that most of the second primary tumors are detected in an early stage. Cancer 1999;86:2370–7. © 1999 American Cancer Society.