Development Of Second Primary Tumors Research Articles

Abstract PO3-08-03: Comparing prognosis for BRCA1, BRCA2 and non-BRCA breast cancer

Abstract BACKGROUND Breast Cancer (BC) is the most diagnosed malignancy and the leading cause of cancer death in women worldwide. Approximately 10% of BC cases are hereditary, and up to 25% have been linked to germline variants of specific genes. Germline pathogenic variants (PV) in BRCA1 and BRCA2 genes, which account for 20% of familial BC cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome. BRCA1 e BRCA2 are tumor suppressor genes, which interact with recombination/DNA repair proteins in pathways that participate in preserving intact chromosome structure, particularly on the DNA double chain. So far, more than 7000 PV were identified on these genes, including the Portuguese founder mutation (BRCA2 c.156_157insAlu), which accounts for a great proportion of BC cases in our country. BRCA1 and BRCA2 associated BC have distinct clinicopathological characteristics. Long-term follow-up data related to prognosis and survival of either BRCA1 or BRCA2 BC patients is conflicting. Two large meta-analysis report worse overall survival for both, when compared to sporadic BC, whereas two other large meta-analysis concluded on worse overall survival only for BRCA1 patients, with similar overall survival for BRCA2 patients. One meta-analysis reports similar survival for both groups. We report the analysis of our cohort of BRCA1/2 BC patients included in our multidisciplinary program. Our goal is to compare clinicopathological characteristics and prognosis between BRCA1 and BRCA2 BC and with a control group without germline PV (non-BRCA). METHODS Prospective follow-up was proposed to patients with a diagnosed BRCA1/2 PV. This study included BRCA1/2 patients with BC as first cancer diagnosis, observed between January 2000-May 2023. A control group, with similar phenotype and histological characteristics, without germline PV was used. Statistical analysis was performed to compare characteristics and prognosis between BRCA1 and BRCA2 and non-BRCA BC. ANOVA test was used to compare the age at diagnosis; chi-square was used to compare categorical variables, such as histological subtype and clinical staging at diagnosis; log rank was used to compare the primary and secondary endpoints – overall survival (OS) and invasive disease-free survival (iDFS), respectively. RESULTS From 1077 individuals who tested positive for BRCA1/2 PV, 345 patients had BC, mostly with a BRCA2 PV (66.4%). A control group of 339 individuals was assembled. BRCA2 BC was mostly luminal, as non-BRCA patients, compared with BRCA1 (73.8% vs. 65.8% vs. 25.9%, p< 0.001) and BRCA1 was mostly triple negative, compared with non-BRCA and BRCA2 (65.5% vs. 16.5% vs. 13.3%, p< 0.001). For a mean follow-up time of 10.6 years (±5.6), recurrence was similar, with central nervous system (CNS) metastases being more frequent for BRCA1 (66.7% vs. 23.7% in non-BRCA, and vs. 9.1% in BRCA2, p< 0.001), and bone metastases were predominant for BRCA2 BC (57.5% vs 33.3% in non-BRCA, and vs. 9.1% in BRCA1, p=0.003). Non-BRCA BC showed longer time to recurrence (99.3 months vs. 76.5 months in BRCA2 BC, and vs. 61.2 months in BRCA1 BC, p=0.010), although longer OS was observed in BRCA2 BC (136.2 months vs. 121.7 months in BRCA1 BC, and vs. 113.2 months in non-BRCA, p< 0.001). Development of second primary tumors was more frequent in BRCA2 patients, compared with BRCA1 (20.9% vs 9.2%, p=0.002). DISCUSSION In the Portuguese population, BRCA2 BC is more frequent than BRCA1 BC. Relapses occurred later for BRCA2 BC, affecting mostly the bone, whereas BRCA1 BC relapsed in CNS. As it is stated in the literature, BRCA1 BC is consistent with triple negative, as BRCA2 BC is more associated with luminal subtype. Differences in iDFS favored non-BRCA patients, whereas OS was significantly improved in BRCA2 BC patients. This is the biggest cohort presented in the Portuguese population and one of the biggest presenting BRCA2 BC patients. Table 1 Characteristics of patients according to BRCA1/2 mutation status (n = 684) Citation Format: Pedro Antunes Meireles, Catarina Bexiga, Sofia Fragoso, Sidónia Santos, Teresa Duarte, Fátima Vaz. Comparing prognosis for BRCA1, BRCA2 and non-BRCA breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-03.

Survival analysis of Sudanese oral squamous cell carcinoma patients with field of cancerization

BackgroundThe late presentation and diagnosis of OSCC account for the large number of patients with the advanced form of the disease. In Sudan, cases with delayed presentation, particularly those with risk factors such as Toombak dipping and alcohol consumption, frequently present with extensive lesions and a wide area of Field cancerization which characterized by the presence of genetic and epigenetic changes in histologically normal-appearing tissues, and have increased risk for recurrent and second primary tumors. This necessitates more aggressive treatment and is usually associated with poorer outcomes. The present study aims to investigate the survival of oral squamous cell carcinoma patients with a wide field of cancerization.MethodsThis prospective longitudinal study includes ninety-three oral cancer patients with extensive fields of cancerization who underwent surgical treatment at Khartoum Teaching Dental Hospital (KTDH) conducted from 2019 to 2023. These patients were regularly assessed for clinical changes such as recurrence, the development of second primary tumours, and overall survival over a period of one year.ResultsOut of the 93 patients, 57 (61.3%) were males, and 36 (38.7%) were females. The majority of the patients (82%) had stage IV tumours, and 62.3% had nodal metastasis. Twenty-eight (30%) patients developed recurrences, and 14 (15%) developed second primary tumours. The overall one-year survival rate was 89%, and all deceased patients passed away within 12 months. The survival rate for patients with different types of recurrences varied, with patients who had regional, local, and locoregional recurrences having survival rates of 87%, 74%, and 72%, respectively. Patients who did not experience a recurrence had a one-year survival rate of 92%. Patients who developed second primary tumours had an 86% survival rate. The survival rates for OSCC patients at stages III, IVa, and IVb were 90%, 90%, and 71%, respectively.ConclusionIn this study, 62% of patients had nodal metastasis, 30% developed recurrence, and 15% developed second primary tumours. The overall one-year survival rate was 89%, although the development of recurrences and second primary tumours had a negative impact on the survival rate.

From Diagnosis to Remission Navigating Innovative Tumor Markers and Uncovering Hidden Risk in Breast Cancer Care, a Review Article.

Breast cancer is a leading cause of cancer-related deaths worldwide, and its management requires a multi-disciplinary approach. This review article aims to provide an overview of the use of tumor markers in breast cancer diagnosis, prognosis, and treatment monitoring, as well as the assessment of risk for recurrence and the development of second primary tumors. The article also discusses the challenges associated with the interpretation of tumor marker results and the integration of risk assessment tools into clinical practice. Overall, the review provides a comprehensive overview of the current state of knowledge on tumor markers and risk assessment in breast cancer care, and offers insights into how these tools can be used to optimize patient outcomes. Method: This review article was conducted by searching electronic databases such as PubMed, Medline, and Scopus, using a combination of keywords related to breast cancer, tumor markers, risk assessment, and clinical management. The search was limited to articles published in English language, and the final selection was based on the relevance and quality of the studies. Tumor markers such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 are important in breast cancer diagnosis, prognosis, and treatment. They can be used to guide treatment decisions, monitor response to therapy, and detect recurrence. Risk assessment tools such as Adjuvant! Online and PREDICT can also provide valuable information for clinicians and patients in making informed decisions regarding treatment and follow-up. However, the interpretation of tumor marker results and the integration of risk assessment tools into clinical practice requires careful consideration and collaboration between the multidisciplinary team. Conclusion: The review highlights the potential benefits and limitations of tumor markers in breast cancer care, including their ability to predict risk, monitor treatment response, and facilitate early detection of disease recurrence. However, the use of these markers must be balanced against their potential for false-positive and false-negative results, as well as the need for careful interpretation and clinical context.

Associations of accumulated persistent organic pollutants in breast adipose tissue with the evolution of breast cancer after surgery

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.

Radiotherapy upregulated immune checkpoints contribute to the development of second primary OSCC.

Radiation injury is common after radiotherapy for head and neck cancer. Radiotherapy can reshape the immune microenvironment and cause immunosuppression, including dysregulation of immune checkpoints (ICs). However, the relationship between oral ICs expression after radiation and the development of second primary tumors is unclear. Clinical specimens of second primary oral squamous cell carcinoma after radiotherapy (s-OSCC) and primary OSCC (p-OSCC) were collected. The expression and prognostic value of PD-1, VISTA, and TIM-3 were analyzed using immunohistochemistry. To further clarify the relationship between radiation and ICs alteration, a rat model was constructed to explore the spatiotemporal changes of ICs in the oral mucosa after radiation. In carcinoma tissue, the expression of TIM-3 was higher in s-OSCC than in p-OSCC, while the expression of PD-1 and VISTA was similar between the groups. In para-carcinoma tissue, the expression of PD-1, VISTA, and TIM-3 was higher in s-OSCC. High ICs expression was associated with poor survival. In the rat model, ICs were locally upregulated in the irradiated tongue. Moreover, there was a bystander effect, in which the ICs were also upregulated in the unirradiated site. Radiation may upregulate ICs expression in oral mucosa and contribute to the development of s-OSCC.

Case report on Reversal of Field Cancerization using Nutraceuticals mapped to the aberrant pathways deciphered via NGS analysis of the neoplastic oral mucosa

Head and neck cancer, particularly oral cancer, presents a significant health concern in Southeast Asia with a high incidence rate, advanced stage of presentation and poor treatment outcomes. The high failure rate is due to recurrence of primary tumor and emergence of second primary tumors (SPTs) due to field cancerization. This case report focuses on a 79-year-old male with a long history of tobacco exposure, resulting in extensive field cancerization within the oral mucosa. This led to sequential development of six primaries both malignant and pre-malignant over the period of 8 years for which the patient underwent multiple surgical resections over these years. The last surgical resection specimen was subjected to Next Generation Sequencing (NGS), genetic and epigenetic alterations were identified causing dysregulation of Janus kinase/signal transducers and activators of transcription signaling pathway (JAK-STAT), Toll-like receptor signalling (TLR) and Extracellular signal regulated kinase (ERK) signalling pathways. The patient post-surgical resection is labelled as disease free; the treatment guidelines do not recommend further prescription of anticancer drugs to prevent another primary and reverse field cancerization. Also, there is lack of approved drugs targeting these pathways, a novel approach was taken using natural supplements (nutraceuticals) to modulate these dysregulated pathways. Curcumin, Epigallocatechin Gallate (EGCG) and Genistein were prescribed to downregulate TLR expression, Boswellia extracts were used to antagonize ERK activation, and Methylsulfonylmethane (MSM), Honokiol, and Berberine were employed to inhibit the JAK-STAT pathway. The patient exhibited good compliance and experienced no adverse effects. Over a span of 24 months, the patient displayed a disease-free status, and the characteristic field cancerization changes within the oral mucosa began to reverse. This unique therapeutic strategy underscores the potential of natural supplements in targeting genetic aberrations and reverting neoplastic processes, ultimately preventing the development of second primary tumors. The study highlights the significance of NGS in unravelling genomic abnormalities underlying neoplasia and supports the exploration of nutraceuticals as a viable option for correcting these aberrations. The successful application of this approach in a real-world case provides a compelling basis for further research and clinical investigation into personalized and integrative approaches for managing oral cancer and potentially other malignancies.

Follow, consider, and catch: second primary tumors in acromegaly patients.

The risk of second primary tumors is increased in general cancer population, however, there is no data on acromegalic cancer patients in this regard. The aim of this study is to determine the prevalence of patients with two primary tumors among acromegalic cancer patients and to evaluate if patients with two primaries have distinct clinical characteristics or risk factors compared to those with one. This is a single-center retrospective cohort study. The study included 63 patients with at least one malignant tumor out of a total number of 394 acromegaly patients. Patients with multiple primary neoplasms were evaluated in detail. This study revealed a 16% cancer prevalence in acromegaly patients, with 14% (9/63) having two primary neoplasms. Papillary thyroid carcinoma was the most prevalent tumor in the entire cancer cohort (41%, 26/63), and in the group of patients with two primaries (44%, 4/9). Patients with two primary tumors were older than those with one when diagnosed with acromegaly (48.3 ± 16.6 vs. 43.3 ± 10.7 years), which might be attributed to a longer diagnostic delay (median of 4.5 vs. 2 years). The period between the onset of acromegaly symptoms and diagnosis was not associated with earlier cancer diagnosis. No relationship between circulating GH or IGF-I levels and the number of neoplasms was found. The development of second primary tumors in acromegalic patients with cancer diagnosis is not rare. Acromegalic cancer patients should be closely monitored for new symptoms or signs that could be associated with second primary tumors.

Prevalence of Transcriptionally Active HPV Infection in Tumor-Free Oropharyngeal Tissue of OPSCC-Patients.

ObjectivesThe natural history of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is still largely unknown. Since reports of second primary tumors (SPTs) in patients with HPV-related OPSCCs are increasing, a multifocal HPV infection, hinting a «virus-induced field effect», has been hypothesized. This study aimed to investigate the HPV-prevalence in normal appearing oropharyngeal tissue in patients with OPSCCs.Materials and Methods49 OPSCC patients undergoing panendoscopy were prospectively enrolled. Tumor specimens and biopsies of normal appearing oropharyngeal tissue adjacent to and distant from the index OPSCC underwent histopathological examination, p16INK4A immunohistochemical staining, HPV DNA and mRNA-detection. Patient characteristics and follow-up data on SPTs were obtained.Results26 of 49 (53%) OPSCC were positive for HPV DNA and p16INK4A. HPV mRNA was detected in 23 of 26 (88%) of these tumor samples. HPV DNA was detected in 36% adjacent mucosa and in 17% distant mucosa samples and only in patients with an HPV-related index OPSCC. HPV mRNA could not be detected in tumor-free distant and adjacent mucosa samples. No evidence of association between HPV detection in normal appearing mucosa and development of second primary tumors was found.ConclusionsHPV was detectable but not transcriptionally active in adjacent/distant tumor-free oropharyngeal tissue. This suggests that a multifocal HPV infection, hinting a «virus-induced fielcd cancerization», may not be pertaining to HPV-related OPSCC.

Head and Neck Cancers Are Not Alike When Tarred with the Same Brush: An Epigenetic Perspective from the Cancerization Field to Prognosis.

Simple SummarySquamous cell carcinomas affect different head and neck subsites and, although these tumors arise from the same epithelial lining and share risk factors, they differ in terms of clinical behavior and molecular carcinogenesis mechanisms. Differences between HPV-negative and HPV-positive tumors are those most frequently explored, but further data suggest that the molecular heterogeneity observed among head and neck subsites may go beyond HPV infection. In this review, we explore how alterations of DNA methylation and microRNA expression contribute to head and neck squamous cell carcinoma (HNSCC) development and progression. The association of these epigenetic alterations with risk factor exposure, early carcinogenesis steps, transformation risk, and prognosis are described. Finally, we discuss the potential application of the use of epigenetic biomarkers in HNSCC.Head and neck squamous cell carcinomas (HNSCC) are among the ten most frequent types of cancer worldwide and, despite all efforts, are still diagnosed at late stages and show poor overall survival. Furthermore, HNSCC patients often experience relapses and the development of second primary tumors, as a consequence of the field cancerization process. Therefore, a better comprehension of the molecular mechanisms involved in HNSCC development and progression may enable diagnosis anticipation and provide valuable tools for prediction of prognosis and response to therapy. However, the different biological behavior of these tumors depending on the affected anatomical site and risk factor exposure, as well as the high genetic heterogeneity observed in HNSCC are major obstacles in this pursue. In this context, epigenetic alterations have been shown to be common in HNSCC, to discriminate the tumor anatomical subsites, to be responsive to risk factor exposure, and show promising results in biomarker development. Based on this, this review brings together the current knowledge on alterations of DNA methylation and microRNA expression in HNSCC natural history, focusing on how they contribute to each step of the process and on their applicability as biomarkers of exposure, HNSCC development, progression, and response to therapy.

Delayed Response After Confirmed Progression (DR) and Other Unique Immunotherapy-Related Treatment Concepts in Cutaneous Squamous Cell Carcinoma.

Non-melanoma skin cancers are one of the most common cancers diagnosed worldwide, with the highest incidence in Australia and New Zealand. Systemic treatment of locally advanced and metastatic cutaneous squamous cell carcinomas has been revolutionized by immune checkpoint inhibition with PD-1 blockade. We highlight treatment issues distinct to the management of the disease including expansion of the traditional concept of pseudoprogression and describe delayed responses after immune-specific response criteria confirmed progressive disease with and without clinical deterioration. We term this phenomenon “delayed response after confirmed progression (DR)”. We also discuss the common development of second primary tumors, heterogeneous disease responses, and expanding clinical boundaries for immunotherapy use.

A cause-specific Cox model for second primary tumors in patients with head and neck cancer: A RONCDOC study.

BackgroundThe 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.MethodsWe 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.ResultsOf 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).ConclusionsOur 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.

Development of second primary tumors and outcomes in medulloblastoma by treatment modality: A Surveillance, Epidemiology, and End Results analysis.

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. 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. 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). 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.

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

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

P40 - Chronic Granulation Tissue Predicts Development of Second Primary Tumors in the Oral Cavity

P40 - Chronic Granulation Tissue Predicts Development of Second Primary Tumors in the Oral Cavity

Incidence of second tumours in high risk prostate cancer patients according to the primary treatment applied

Introduction and objectivesThe onset of second primary tumours should be considered in high-risk prostate cancer patients in the natural course of the disease. Our aim was to evaluate the influence of primary treatment with curative intent for these patients on the development of second primary tumours. Material and methodsA retrospective study of 286 patients diagnosed between 1996 and 2008, treated by radical prostatectomy (n=145) or radiotherapy and androgen blockade (n=141). The homogeneity of both series was analyzed using the Chi-squared test for the qualitative variables, and the Student's t-test for the quantitative variables. A multivariate Cox regression analysis was performed to assess whether the type of primary treatment influenced the development of second tumours. ResultsThe median age was 66 years, and the median follow-up was 117.5 months. At the end of follow-up, 60 patients (21%) had developed a second primary tumour. In the prostatectomy group it was located in the pelvis in 13 (9%) cases, and those treated with radiotherapy and hormonotherapy in 8 (5.7%) cases (p=0.29). The most common organ sites were: colo-rectal in 17 (28.3%) patients, the lung in 11 (18.3%), and the bladder in 6 (10%) patients. In the multivariable analysis, the risk of a second tumour doubled for those treated with radiotherapy and hormonotherapy (HR=2.41, 95% CI: 1.31–4.34, p=0.005) compared to the patients treated by prostatectomy. Age and rescue radiotherapy did not behave as independent predictive factors. ConclusionsThe onset of a second primary tumour was related with the primary treatment given; thus the risk for those treated with radiotherapy and androgen deprivation therapy more than doubled.

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

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

Incidencia de segundos tumores en pacientes con cáncer de próstata de alto riesgo según el tratamiento primario aplicado

Introduction and objectivesThe onset of second primary tumours should be considered in high-risk prostate cancer patients in the natural course of the disease. Our aim was to evaluate the influence of primary treatment with curative intent for these patients on the development of second primary tumours. Material and methodsA retrospective study of 286 patients diagnosed between 1996 and 2008, treated by radical prostatectomy (n=145) or radiotherapy and androgen blockade (n=141). The homogeneity of both series was analysed using the Chi-squared test for the qualitative variables, and the Student's t-test for the quantitative variables. A multivariate Cox regression analysis was performed to assess whether the type of primary treatment influenced the development of second tumours. ResultsThe median age was 66 years, and the median follow-up was 117.5 months. At the end of follow-up, 60 patients (21%) had developed a second primary tumour. In the prostatectomy group it was located in the pelvis in 13 (9%) cases, and those treated with radiotherapy and hormonotherapy in 8 (5.7%) cases (P=.29). The most common organ sites were: colo-rectal in 17 (28.3%) patients, the lung in 11 (18.3%), and the bladder in 6 (10%) patients. In the multivariable analysis, the risk of a second tumour doubled for those treated with radiotherapy and hormonotherapy (HR=2.41, 95%CI: 1.31-4.34, P=.005) compared to the patients treated by prostatectomy. Age and rescue radiotherapy did not behave as independent predictive factors. ConclusionsThe onset of a second primary tumour was related with the primary treatment given; thus the risk for those treated with radiotherapy and androgen deprivation therapy more than doubled.

Abstract 3070: Cancer stem cells in field cancerization of oral squamous cell carcinoma

Abstract Introduction: Field cancerization, the occurrence of transformed cells in the area adjacent to the tumor, has been attributed to the probable reasons of local recurrence of oral squamous cell carcinoma. Cancer stem cells (CSCs) have properties of tumor initiation, migration, and metastasis. The objective of the study was to evaluate their role in field cancerization. Experimental Procedure: A panel of CSCs and its related markers was established from literature and validated in i) samples from surgical margins, ii) samples from 1 cm and 2 cm distance from margin around the tumor and in additional sides. First-phase validation was done in retrospective surgical margins of tumor (N=23) by qPCR and immunohistochemistry. The best marker subset from qPCR to predict recurrence was identified by ROC curve and logistic regression analysis and validated by immunohistochemistry. The final validation is being carried out in prospective samples from tumor-adjacent normal area as mentioned above. The marker profiles were correlated with the histology of the samples and the clinical outcome of the patients on follow-up. Summary of Data: Out of 18 markers selected from literature CD44, CD147, SOX2, Snail, ATR, CyclinD1, MMP9 were selected from gene expression of first-phase validation. Among these SOX2, ATR, Cyclin D1, CD44 and CD147 were selected from IHC of first phase for second-phase validation in prospective samples (n=10) collected from 27 patients, which were clinically normal with varied grades of dysplasia; these samples were evaluated by the selected markers from the first set of validation. The correlation of markers expression with disease outcome of patients and with other clinical parameters is currently ongoing. Conclusion: Our results suggest that CSCs have role in field cancerization and might be predictive of tumor recurrence/reinitiation and/or development of second primary tumor. Citation Format: Simple Mohanta, Ravindra DR, Vikram Kekatpure, Naveen Hedne, Vijay Pillai, Shubhra Chauhan, Naveen BS, Athira Ramakrishnan, Bichu Jacob, Vishak Surendra, Leeky Mohanty, Anjana Muralidharan, Amritha Suresh, Moni Abraham Kuriakose. Cancer stem cells in field cancerization of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3070.

Oral Cancer.

The management of oral cancer is a multidisciplinary endeavour, as each patient presents the treating clinicians with a unique set of challenges the management of which impacts on both survival and quality of life. This article focuses on the management of oral cancer. We highlight the epidemiology and risk factors for oral cancer in Australia, the various clinical presentations that occur and the staging of oral cancer. In the vast majority of cases surgery remains the mainstay of treatment. Radiation and medical oncology is usually used in an adjuvant context. Dental professionals play a critical role in many stages of management from the initial detection, to optimising pre treatment dental health and managing the short and long term sequelae of treatment. Monitouring for recurrence and the development of second primary tumours is a key role.

SYNCHRONOUS MULTIPLE ORAL SQUAMOUS CELL CARCINOMA IN A FEMALE PATIENT: A CASE REPORT AND REVIEW

Oral squamous cell carcinoma (OSCC) is a common oncological problem in India. However, the frequency of developing synchronous carcinomas, i.e., development of second primary tumor (SPT) either simultaneously or within 6 months of the index tumor, in the orofacial region are rare and ranges from 8% to 21%. These lesions are more aggressive, treatment-resistant, and metastasize early. The onset of SPT decreases the 5-year survival by 18–30% as compared to those with a single tumor. Astonishingly, it was found that synchronous OSCCs showed 100% male predominance, with no female predilection. This case of synchronous OSCC in a 58-year-old female had an index tumor involving right side of the mandible and a SPT in the left buccal mucosa. Both the lesions were histopathologically diagnosed well-differentiated squamous cell carcinoma. Hence, the importance of reporting this case lies on the rarity, aggressiveness, and poor prognosis of the lesion and the patient being a female.