Synchronous Malignancies Research Articles

Synchronous Breast Carcinoma and Other Solid Malignancies: MDCT Evaluation

Background and Objectives: The incidence of synchronous primary malignant tumors is increasing due to the ageing of the population and advances in medical technology. In this retrospective study; we review the multidetector computed tomography (MDCT) findings of synchronous breast carcinoma and other solid malignancies. Methods and Materials: This retrospective study included 65 patients confirmed with diagnosis of synchronous breast carcinoma and other solid malignancies. The patients aged ranged from 35 – 78 years. CT scanning was performed using 128 MDCT in all patients. All one hundred-thirty malignancies were underwent pathological evaluation. Results: Out of 4120 patients with breast carcinoma; 65 patients were diagnosed with other synchronous primary solid malignancy. All one hundred-thirty malignancies were confirmed pathologically. Breast carcinoma detected in all 65 patients; of them metastatic breast carcinoma detected in 8 patients. Hepatocellular carcinoma detected in 18 patients. Non-Hodgkin lymphoma (NHL) detected in 12 patients. Endometrial carcinoma detected in 8 patients. Uterine sarcoma detected in 3 patients. Malignant mixed Mullerian tumor detected in one patient. Ovarian carcinoma detected in 5 patients. Renal cell carcinoma detected in 4 patients. Thyroid carcinoma detected in 4 patients. Gastric carcinoma detected in 2 patients. Colonic carcinoma detected in 2 patients. Ano-rectal carcinoma detected in one patient. Hilar cholangiocarcinoma detected in 2 patients. Malignant melanoma detected in 2 patients. Bronchogenic carcinoma detected in one patient. Conclusions: Patients with breast carcinoma have a risk of other synchronous primary malignancy. So, careful preoperative examination is recommended to improve the patients’ prognosis. MDCT scanning is accurately imaging modality for evaluation of synchronous breast carcinoma and other solid malignancies. The aim of treatment in cancer patients should always be curative even in the presence of multiple malignancies. Funding Statement: There was no financial support for this research and publication. Declaration of Interests: The author declares that there is no conflict of interest. Ethics Approval Statement: The study was approved by the institutional research ethics review committee (Mansoura University/Faculty of Medicine/ Egypt). IRB reference number is “R.20.02.753

Risk Factors of Metastatic Lymph Nodes in Papillary Thyroid Microcarcinoma

IntroductionPapillary thyroid microcarcinoma (PTMC) usually has an indolent course, but some have worse prognostic factors, such as the presence of central (6.9%–51.5%) and lateral (3%–49.6%) lymph node metastases. The aim of this study is to analyze the factors associated with PTMC with metastatic lymph nodes and its long-term prognosis. MethodsRetrospective study whose study population consists of patients with PTMC (size ≤1cm). Patients with previous thyroid surgery, other synchronous malignancies and ectopic location of the PTMC were excluded. Two groups were compared: PTMC without metastatic lymph nodes (group 1) and PTMC with metastatic lymph nodes (group 2). A multivariate analysis using a logistic regression model and a Kaplan–Meier survival analysis with log-rank test were performed. ResultsOut of the 161 selected patients, 9.3% (n=15) had metastatic lymph nodes. Multifocality (OR 5.284, 95%CI 1.056–26.443; P=.043) and extrathyroidal extension (OR 7.687, 95%CI 1.405–42.050; P=.019) were associated with the presence of metastatic lymph nodes. In PTMC with metastatic lymph nodes, more aggressive treatments were performed: lymphadenectomy (4.8% vs. 100%; P<.001) and radioactive iodine (24.7% vs. 100%; P<.001). During a mean follow-up of 119.8±65 months, one recurrence was detected in group 2 (0% vs. 6.7%; P=.093). No patients died due to the disease. ConclusionsMultifocality and extrathyroidal extension of PTMC were associated with the presence of metastatic lymph nodes. Metastatic PTMC, with more aggressive treatments, presents an excellent long-term prognosis.

Microcarcinoma papilar de tiroides con extensión extratiroidea mínima. ¿Tiene un curso tan indolente para precisar un tratamiento menos intensivo?

BackgroundAlthough the incidence of papillary thyroid microcarcinoma (PTMC) has increased in recent decades, the role played by minimal extrathyroidal extension (mETE) in the prognosis of PTMC is still unclear. The aim of this study is to analyze the factors associated with PTMC with mETE and its long-term prognosis. Material and methodsWe conducted a retrospective study on patients with a histological diagnosis of PTMC. We excluded patients who had previously undergone thyroid surgery, those who had other synchronous malignancies, those with an ectopic location of the PTMC, and those lost to follow-up within 2years. We compared group 1 (PTMC without extrathyroidal extension) to group 2 (PTMC with mETE) and performed a multivariate analysis. ResultsWe observed PTMC with mETE in 11.2% (n=18) of patients. On the multivariate analysis, mETE was associated with age ≥45 years (OR: 4.383; 95% CI: 1.051-18.283, p = .043), tumor size ≥8mm (OR: 5.913; 95% CL: 1.795-19.481; p = .003), bilaterality (OR: 4.430; 95% CI: 1.294-15.173; p = .018) and metastatic lymph nodes (OR: 12.588; 95% CI: 2.919-54.280; p = .001). During a mean follow-up of 119.8±65 months, one recurrence was detected in group 2 (0% vs. 5.6%; p = .112). No patients died of the disease. Disease-free survival was lower in group 2 (124.9±5.6 vs. 97.4±10.3 months; p = .034). ConclusionsThe mETE of PTMC is a factor of worse prognosis associated with the presence of metastatic lymph nodes and a lower rate of disease-free survival.

Factores de riesgo de metástasis ganglionares en el microcarcinoma papilar de tiroides

IntroductionPapillary thyroid microcarcinoma (PTMC) usually has an indolent course, but some have worse prognostic factors, such as the presence of central (6.9%-51.5%) and lateral (3%-49.6%) lymph node metastases. The aim of this study is to analyze the factors associated with PTMC with metastatic lymph nodes and its long-term prognosis. MethodsRetrospective study whose study population consists of patients with PTMC (size ≤1cm). Patients with previous thyroid surgery, other synchronous malignancies and ectopic location of the PTMC were excluded. Two groups were compared: PTMC without metastatic lymph nodes (group 1) and PTMC with metastatic lymph nodes (group 2). A multivariate analysis using a logistic regression model and a Kaplan-Meier survival analysis with log-rank test were performed. ResultsOut of the 161 selected patients, 9.3% (n=15) had metastatic lymph nodes. Multifocality (OR 5.284, 95%CI 1.056-26.443; P=.043) and extrathyroidal extension (OR 7.687, 95%CI 1.405-42.050; P=.019) were associated with the presence of metastatic lymph nodes. In PTMC with metastatic lymph nodes, more aggressive treatments were performed: lymphadenectomy (4.8% vs. 100%; P<.001) and radioactive iodine (24.7% vs. 100%; P<.001). During a mean follow-up of 119.8±65 months, one recurrence was detected in group 2 (0% vs. 6.7%; P=.093). No patients died due to the disease. ConclusionsMultifocality and extrathyroidal extension of PTMC were associated with the presence of metastatic lymph nodes. Metastatic PTMC, with more aggressive treatments, presents an excellent long-term prognosis.

Synchronous Esophageal and Renal Malignancies with Unexpected Site of Metastasis: A Case Report

Introduction: Esophageal cancer is the fifth most common cancer in Asia. Synchronous malignancies with an esophageal malignancies is not uncommon however synchronous esophageal malignancy and renal cell carcinoma is rare. Case Report: A 70 years old non smoker man with comorbid of hypertension and diabetes mellitus presented with multiple episode of hemoptysis and pleuritic chest pain within one day duration. He also complaint of worsening dysphagia to solid food for 1 month duration with constitutional symptoms. Otherwise he does not have any other symptoms. Clinically he was pale and cachexic, otherwise all systemic examination was unremarkable. His blood investigation reveal low hemoglobin level of 9.9g/L with normal coagulation and renal profile. He underwent Oesophagoduodenoscopy which showed a tumor narrowing the lumen of the lower esophagus. Biopsy of the tumor revealed esophageal adenocarcinoma. CT thorax, abdomen and pelvis showed smooth circumferential wall thickening of the distal part of the esophagus near the gastroesophageal junction. Incidentally, there were heterogenous enhancing lobulated mass seen at the lower pole of left kidney with no obstructive uropathy features. Otherwise, others solid organ were normal. A left renal mass biopsy performed revealed renal cell carcinoma. An oncologist opinion was gathered for initiation of palliative chemotherapy however he developed symptomatic malignant pleural effusion which need a drainage. HRCT Thorax revealed multiple bilateral intrapulmonary nodule. He also complaint of a new right upper eyelid mass that increasing in size with contact bleeding however does not affect his visual. An assessment from an ophthalmologist and CT orbital performed consistent with features of a metastasis. Conclusion: Synchronous malignancies with an esophageal malignancies is not uncommon. Most common site reported is head and neck followed by lung malignancies. However synchronous esophageal malignancies and renal cell carcinoma is rare. Esophageal malignancies often have distant metastasis to the liver, lung and bone however rare to the eyelid.

Pancreatic resection in patients with synchronous extra-pancreatic malignancy: outcomes and complications.

Patients may present with a resectable pancreatic tumour in the context of a concurrent primary extra-pancreatic malignancy. These patients pose a dilemma regarding their suitability for surgery. We evaluated our experience with such patients who underwent pancreatic resection with curative intent and detailed their outcomes and rationale for surgical decision-making. A retrospective review of patients with pancreatic concurrent extra-pancreatic primary malignancy who underwent pancreatic resection at our institution over a 12-year period (2005-2016) was performed. Clinical, histopathological and perioperative outcomes were reviewed. Ten patients with a median age of 74 years (40-85 years) were identified. Secondary primary tumours included thyroid (n = 2), gastrointestinal (n = 4), small bowel neuroendocrine (n = 1), renal (n = 1) and haematological malignancies (n = 2). Pancreatic tumours included pancreatic ductal adenocarcinomas (n = 6), solid pseudopapillary neoplasms (n = 2) and ampullary carcinomas (n = 2). After a median follow up of 41.3 months (31.3-164 months), 8 of 10 patients were still alive. Two patients died due to metastatic disease from the secondary malignancy (small bowel neuroendocrine tumour and sigmoid colon adenocarcinoma). The post-operative complication rate was 30% with no perioperative 90-day mortality. Selected patients with a pancreatic and concurrent primary extra-pancreatic malignancy may undergo curative pancreatic resection with favourable outcomes.

Distant metastases and synchronous malignancies on FDG-PET/CT in patients with head and neck cancer: a retrospective study.

BackgroundFluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been proven to be a good method to detect distant spread of head and neck cancer (HNC). However, most prior studies are based on Asian populations and may not be directly transferable to western populations.PurposeTo investigate the frequency and distribution of distant metastases and synchronous malignancies detected by PET/CT in HNC in a northern Swedish population.Material and MethodsAll primary whole-body FDG-PET/CT examinations performed on the suspicion of HNC (n = 524 patients) between 1 January 2013 and 31 December 2016 at Umeå University Hospital in Sweden were retrospectively reviewed . After the exclusion of 189 examinations without evidence of primary HNC, 335 examinations were analyzed.ResultsDistant metastases were detected in 10 (3%) patients, all with advanced primary tumors corresponding to TNM stage 3–4, most frequently in salivary gland adenocarcinoma, where 50% of patients had distant spread. Four patients had metastases below the diaphragm, representing 20% of the salivary gland malignancies. In the remaining six patients, metastases were supraphrenic, of which all but one were identified by CT alone. Synchronous malignancies were discovered in 14 (4.2%) patients, of which five were below the diaphragm.ConclusionThe overall frequency of distant spread and synchronous malignancy in primary HNC was generally low. However, the risk for distant metastases below the diaphragm was relatively higher in salivary gland adenocarcinoma, supporting whole-body FDG-PET/CT in the primary diagnostic work-up in these patients.

The impact of synchronous malignancies on survival in patients with early stage curable non-small-cell lung cancer

BACKGROUNDTo determine if synchronous extrapulmonary malignancies in early stage lung cancer impact survival and cost of care in the current era of improved therapies and diagnostics. METHODSPatients with stage I and II lung cancer were identified from the Ontario Cancer Registry and prognostic factors were obtained from provincial health administrative databases. Synchronous extrapulmonary malignancies were defined as those detected within 6 months from diagnosis of the lung primary. Survival was calculated using the Kaplan-Meier method and examined based on a 6-month landmark time point. The log-rank test and Cox proportional hazards regression was used to examine the effect of synchronous primaries on survival, univariately and after adjusting for prognostic factors. Cost of care was calculated by summing fees for all provincially funded services over 3 years. RESULTSIn a cohort of 6890 patients, those with synchronous malignancy had a HR of 1.32 (p = 0.026) for death in stage I patients, adjusted for other factors, while no association was found for stage II patients (HR=1.00, p = 0.99). 18F-FDG-PET/CT up to 6 months prior to lung cancer diagnosis had a HR of 0.84 (p = 0.003) for death adjusted for other factors. 3-year costs of care for these patients were $79,540 versus $54,520 in those without a synchronous malignancy (p<0.001). CONCLUSIONExtrapulmonary malignancies in stage I lung cancer patients may negatively impact survival with no such association for stage II patients. 18F-FDG-PET/CT performed before lung cancer diagnosis is associated with better survival. Cost of care is higher in patients with synchronous malignancies.

A case of synchronous dual malignancy with the index malignancy in the lower alveolus and a second primary malignancy in the left breast

Multiple primary malignancies are nowadays commonly detected due to better radiological techniques, greater awareness and an increase in number of elderly cancer survivors. We are reporting a rare case of patient having dual synchronous malignancy of carcinoma left lower alveolus and ductal carcinoma in left breast who presented to the department of surgical oncology and integrated breast care center. The patient is on regular follow-up, and currently, there was no evidence of recurrent or residual disease. No such case has ever been reported, and despite a thorough check on all, we are unable to find any previously reported case. Hence, to the best of our knowledge, this case is the first of its kind to have simultaneous presentation of synchronous dual malignancies involving left lower alveolar and left breast cancers.

Outcomes of incidental pulmonary nodules in head-and-neck squamous cell cancer patients treated with curative intent

Introduction: Incidental pulmonary nodule(s) (IPNs) are a common finding during staging imaging for the head-and-neck squamous cell cancers (HNSCC) treated with curative intent. Currently, the incidence of metastasis or synchronous malignancies and outcomes for IPN in this population is unknown. Methods: All cases (n = 2489) reviewed at a tertiary Australian Institution's head and neck (H and N) multidisciplinary meeting, from January 2010 to December 2014, were included. Of these patients, 310 (12.5%) had an HNSCC with an IPN that had been detected during staging imaging. These patients were also to undergo treatment by curative intent. Clinicopathological characteristics, the incidence of malignancy, progression-free survival, and overall survival (OS) were collected retrospectively over 5 years. Results: The median age of patients with an IPN was 66 (range 25–95) years. Tissue diagnosis of IPN was attempted in 46 (14.8%) patients due to radiological suspicion of malignancy. Malignancy was confirmed in 33 (11.0%) patients. From these, 33 patients, 11 (30.3%) had histological diagnoses of nonsquamous cell lung cancers and hence are not due to metastatic spread from a primary HNSCC. Age, gender, previous malignancies, smoking status, p16 status, stage, or primary site did not predict for malignancy. The incidence of pulmonary metastasis in patients who did not undergo tissue biopsy due to low clinical and radiological suspicion of malignancy (n = 244) occurred in 10 patients (4.1%). At the time of analysis, 91 (29.4%) patients had died, and tumor recurrence had occurred in 82 (26.5%) patients. The mean OS was 48 months (95% confidence interval: 44–51). OS was significantly associated with greater age (hazards ratio [HR] 1.04, P < 0.001); immunosuppression (HR 2.15, P = 0.013); and biopsy being attempted (HR 1.78, P = 0.013). There was no biopsy related mortality. Discussion: Detection of an IPN in patients undergoing workup for H and N cancer is common. The risk of malignancy in these IPNs however, is low. We did not identify any clinicopathological parameters to predict malignancy in this setting. Advanced age, current smoking status, and history of immunosuppression predict for poor outcomes. Further work is being undertaken to analyze radiological features that may predict malignancy in an IPN found during the radiological staging of HNSCC.

The relationship between primary breast and primary lung cancer: A case series

Introduction: Prior to the initiation of curative treatment, patients with a confirmed breast malignancy undergo staging to assess for the presence of any metastasis. There are instances where instead of metastatic lesions, the patient is diagnosed with a primary lung malignancy. This is identified when the patient is given chemotherapy directed at the breast primary, but the lung lesion does not improve on imaging. Lung biopsy then confirms this diagnosis. Case Series: This case series highlights three such patients who were treated at Mater Dei Hospital, Malta. All three were first diagnosed with the breast malignancy and were later found to have a second primary in the lung. Management of these patients was always through a multidisciplinary team approach, involving the breast surgeons, cardiothoracic surgeons, the oncologist, respiratory physicians, breast and lung specialized radiologists, and the breast care nurses. Relevant literature is also discussed with a focus on synchronous breast and lung malignancies. Conclusion: The main conclusion from this case series is that it would be beneficial if all patients with breast cancer are regularly screened for a lung malignancy/metastasis by at least a chest X-ray. It is important to keep in mind the link between the two organs and the potential presence of a separate lung primary.

Synchronous tumours detected during cancer patient staging: prevalence and patterns of occurrence in multidetector computed tomography.

PurposeThe incidental detection of one or more additional primary tumours during computed tomography (CT) staging of a patient with known malignancy is rare but possible. This occurrence should be considered by the radiologist when a new lesion is detected, especially if the lesion location is atypical for metastases. The purpose of this report was to document the usefulness of total body CT scan to detect synchronous primary malignancies in cancer patients undergoing a staging workup.Material and methodsThis was done by reviewing the staging CT studies of the adult patients with a newly diagnosed cancer evaluated during a five-year period in a single cancer institute in order to identify any possible correlation, establishing which tumours are more frequently combined with a second tumour and which second tumours are more commonly present.ResultsAmong the patients with a second tumour, the most frequent first primary tumours were melanoma (eight patients, 17.8%), lymphoma (seven patients, 15.6%), and prostate carcinoma (seven patients, 15.6%). The most frequent incidentally detected second tumours were hepatocellular carcinoma (nine patients, 20% of 45 incidental tumours), renal carcinoma (eight patients, 17.8%), lung carcinoma (seven patients, 15.6%), and bladder carcinoma (four patients, 8.9%). One patient had three primary tumours synchronously.ConclusionsWe believe that the radiologist’s knowledge of the prevalence and pattern of occurrence of these multiple primary malignancies represents added diagnostic value.

The clinicopathologic features of multiple primary malignancies in hematology: A cross sectional descriptive study

In Turkish literature there are very few studies regarding multiple primary malignancies (MPM). The aim of this study was to analyze the synchronous and the metachronous malignancies that occurred with a hematologic malignancy. All the patients with a hematologic malignancy were enrolled in this cross-sectional, definitive retrospective study. Data were obtained from the medial records. Patients’ characteristics including demographic features, treatment protocols and overall survival (OS) were recorded. Among 663 patients with a hematologic malignancy, there were 26 patients with MPMs (3.9%). Synchronous malignancies constitute 0.9% and metachronous malignancies were present in 3%. In men diffuse large B-cell lymphoma (DLBCL) and non-small cell lung carcinoma (NSCLC) and in women breast and acute myeloid leukemia were the most common primary and secondary MPMs respectively. The mean cumulative OS of all patients with MPMs was 246.3±33.4 months and the 5 years-OS was 91.3%. In synchronous MPMs the most frequent concomitant tumors were DLBCL and NSCLC. In metachronous tumors the median time interval between first and second malignancies was 69.5 months (range: 31-312). In four patients there were three MPMs. After radiotherapy three patients developed breast, thyroid and skin cancers and in one patient who received radioiodine for the treatment of thyroid carcinoma, DLBCL had developed. The chemotherapeutic agents applied for the primary malignancies consisted of alkylating agents, antimetabolites, anthracyclines, topoisomerase II inhibitors, monoclonal antibodies and mitotic inhibitors. In 75% of the patients with DLBCL who had received R-CHOP chemotherapy regimen, NSCLC had developed during the follow-up period. In conclusion secondary malignancies with hematologic malignancies are not rare and the clinicians should keep the possibility of secondary malignancies in mind and be suspicious during diagnostic evaluations. Warning with regard to the risk of development of secondary malignancies due to the primary treatment should be given to any patient with a hematologic malignancy.

Evaluation of Diagnostic Accuracy and Impact of Preoperative Positron Emission Tomography/Computed Tomography in the Management of Early Operable Breast Cancers.

Aim:Our aim of this study was to evaluate the diagnostic accuracy of staging positron emission tomography/computed tomography (PET/CT) in early breast cancers (EBCs) and to assess its impact on disease management.Patients and Methods:We retrospectively reviewed preoperative PET/CT scans of patients from January 2015 to December 2018 with Stage I/II, clinically T1–T2 N0–N1 breast cancers. The diagnostic performance of PET/CT for nodal (N) and distant metastases (M), its correlation with patient/tumor-specific factors, and its impact on disease management were analyzed using histopathology/clinical follow-up as standards of reference.Results:Of 158 patients evaluated, 14% of patients were Stage I (T1N0), 60% were Stage IIA (T1N1, T2N0), and 26% were Stage IIB (T2N1). Sensitivity, specificity, and the diagnostic accuracy of PET/CT for axillary staging were 76%, 97%, and 84% and for distant metastasis evaluation were 100%, 98%, and 99%, respectively. The diagnostic accuracy of PET/CT for axillary staging was lower for low-grade, T1 tumors, postmenopausal group, and luminal A pathological subtype (77%, 84%, 81%, and 73%, respectively) compared to high-grade, T2 tumors, premenopausal group, and nonluminal A subtype (88%, 88%, 94%, and 87%, respectively). Distant metastases were detected on PET/CT in overall 16% (n = 25) of the patients (9% in Stage IIA and 27% in Stage IIB). PET/CT also incidentally identified clinically occult internal mammary nodes in 5% (n = 8) and organ-confined synchronous second malignancies in 5% (n = 8) of the patients.Conclusion:Preoperative PET/CT should be considered in all EBCs> 2 cm as it upstages the disease and alters management in about 24% of these patients. Given its high specificity for axillary staging PET/CT, patients with PET-positive axilla can be subjected to axillary dissection and those with PET-negative axilla to sentinel lymph node biopsy. The yield and diagnostic accuracy of PET/CT is less for low-grade tumors <2 cm and with luminal A subtype.

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English

Rare case presentation: DLBCL and plasma cell myeloma coexisting together

The synchronous presence of dual hematological malignancy is an uncommon finding. In the present case, an 82-year-old male, presented with lymph nodal mass which was diagnosed as diffuse large B cell lymphoma (DLBCL) on histopathology and plasma cell myeloma (PCM), was diagnosed with identification of clonal plasma cells in the bone marrow. Interestingly, both clonal plasma cells and lymphoma cells showed lambda light chain restriction. The patient also developed spontaneous tumor lysis syndrome which can be seen in aggressive hematopoietic malignancies. The present case is a rare presentation of synchronous dual hematological malignancies and poses diagnostic and therapeutic challenge.

Is panendoscopy a necessary staging procedure in patients with lacking risk factors and oral squamous cell carcinoma?

ObjectivesRoutine panendoscopy is used to detect synchronous malignancies of the upper aerodigestive tract in staging of oral squamous cell carcinoma. The goal of this study was to investigate the occurrence of synchronous malignancies at time of diagnosis using panendoscopy. To challenge the role of panendoscopy as inherent part of routine staging procedures, we were especially interested in low risk patients. Materials and methodsRetrospectively, a cohort of 484 patients with pathologically confirmed diagnosis of primary oral and oropharyngeal squamous cell carcinoma was investigated. Electronically recorded findings of in-house conducted panendoscopy were retrieved and evaluated for the occurrence of pathological changes of the mucosa. In case of synchronous malignancies, findings were correlated to preoperative radiographic imaging. Patients were classified as high or low risk. Patients with lacking risk factors (no smoking, no drinking in history) were defined as low risk patients. ResultsOverall, we detected three synchronous malignancies of the upper aerodigestive tract (3/484; 0.6%). Two non-small cell lung cancers were detected in patients with a smoking history of 60 pack years. One esophageal carcinoma in situ was detected in a patient with reported alcohol consumption. No synchronous malignancy was detected in patients without risk factors and no malignancy was previously detected by diagnostic imaging. ConclusionPre-treatment panendoscopy can reveal synchronous malignancies of the upper aerodigestive tract in patients with primary oral squamous cell carcinoma. Risk stratification of patients can avoid unnecessarily conducted panendoscopy in patients without risk factors. This may lead to a higher cost-efficacy in public health system, less treatment-related complications and earlier treatment initiation.

Trends in peritoneal surface malignancies: evidence from a Czech nationwide population-based study

BackgroundThe aim of this study is to identify the incidence trends of primary and secondary peritoneal surface malignancies in a representative Czech population.MethodsData were obtained from patients registered in the Czech National Cancer Registry between 1979 and 2016. The incidence rates were analyzed between 2012 and 2016. To observe the incidence trends, we analyzed the data from two time periods, 1979–2005 and 2006–2016. The analyzed data included age, sex, and the histological types and primary origins of the malignancies. The Cochrane-Armitage test for linear trends was used for verification of the null hypothesis. The significance level established for hypothesis testing was p = 0.05.ResultsBetween 2012 and 2016, 230 patients with primary peritoneal tumors were identified and divided into the following groups according to their “International Statistical Classification of Diseases and Related Health Problems, 10th revision” codes: malignant neoplasm of specified parts of the peritoneum (C48.1); malignant neoplasm of the peritoneum, unspecified (C48.2); and malignant neoplasm of overlapping sites of the retroperitoneum and peritoneum (C48.8). Moreover, 549 primary tumors of the appendix (C18.1, encompassing all appendiceal malignancies) and 3137 secondary synchronous peritoneal carcinomatoses of other primary origins were documented. The age-adjusted incidence of primary peritoneal tumors in 2012–2016 was 4.36/year/1,000,000 inhabitants. The age-adjusted incidence of synchronous secondary peritoneal malignancies in 2014–2016 was 99.0/year/1,000,000 inhabitants. The diagnoses of primary peritoneal malignancies followed a stable trend between 1979 and 2016. However, the incidences of primary tumors of the appendix increased by 76.7%.ConclusionsThe data produced in our study ought to clarify the status of peritoneal surface malignancies in the Czech Republic, which can lead to improved planning and development of therapeutic interventions as well as physician training.

Perianal Paget's Disease: The 17-Year-Experience of a Single Institution in Taiwan.

Aim To determine the incidence, prognosis, and immunophenotypes (CK7, CK20, CDX2, and GCDFP-15) of primary or secondary perianal Paget's diseases (PPDs). Methods Twenty-three PPD patients were recruited, including 10 primary and 13 secondary PPDs. Immunophenotypes of PPD were analyzed. Results In 23 PPD patients, 14 (60.9%) were male and the median age was 75 years. Three (13.0%, 2 primary and 1 secondary PPDs) had recurrence and two (8.7%, both primary PPDs) had invasive PPDs. The colorectal cancers (CRCs) in secondary PPD cases were located in anorectal area for 9 patients while 4 were located in the rectum; 5, 2, 4, and 2 were in stages I, II, III, and in uncertain stage, respectively. The distant metastasis rates of CRC in the secondary PPD patients during follow-up were 40% (2/5), 0% (0/2), and 50% (2/4) for stages I, II, and III, respectively. Other synchronous or metachronous malignancies included cholangiocarcinoma, urothelial carcinoma, anorectal small-cell carcinoma, and unknown hepatic malignancy. One primary PPD patient died from the metastases of invasive Paget's disease while 3 secondary PPD patients died from the metastases of CRCs during follow-up. Immunohistochemical staining showed CK7 (7/10 and 6/13), CK20 (6/10 and 10/13), CDX2 (6/10 and 12/13), and GCDFP-15 (3/10 and 0/13) positivities in primary and secondary PPD patients, respectively. The immunophenotypes were not statistical significantly related to synchronous CRC (P = 0.402, 0.650, 0.127, and 0.068 for CK7, CK20, CDX2, and GCDFP-15, respectively). Conclusions The incidence of concurrent CRC in PPD patients is not low. An adequate survey for CRC should be considered for PPD patients at initial diagnosis. In this series of study, stage I CRC with PPD would have a higher metastatic rate, thus indicating aggressive treatment and follow-up. The CK7, CK20, CDX2, and GCDFP-15 immunostaining results for the PPD patients were not predictive of primary or secondary type.

P2.04-19 Neoadjuvant Chemotherapy Is Associated with Immunogenic Cell Death and Increased T Cell Infiltration in Early-Stage NSCLC

Recent success using immune checkpoint blockade (ICB) in the metastatic setting has raised the need to understand the immune microenvironment (IME) in early-stage disease. Moreover, pre-clinical evidence suggests that cytotoxic agents can modulate this IME. A recent study conducted by our group showed that non-small cell lung cancer (NSCLC) patients who received neoadjuvant chemotherapy followed by surgery (NCT), as compared to patients who received upfront surgery (US), had higher densities of CD3+ lymphocytes and CD68+ tumor-associated macrophages (TAMs). CD3+CD4+ lymphocytes and TAMs also correlated with better clinical outcomes. In this study, we explored the relationships between NCT and the IME by harvesting tumor samples of multiple surgical NSCLC cohorts. The PROSPECT microarray database was queried in NCT (n=45) and US (n=200) patients to investigate differentially expressed genes related to immunogenic cell death (ICD), susceptibility to CD8+ T cell and NK cell cytotoxicity, priming of antigen presenting cells, immunosuppressive enzymes and intra-tumoral cytokines. Available data from the ImmunogenomiC prOfiling of NSCLC (ICON) and other surgical NSCLC cohorts was evaluated to determine: 1) differential immune profiling using FACS (NCT=17; US=39) and multiplex IHC imaging (NCT=10; US=72); 2) plasma circulating cytokines (NCT=18; US=73); 3) tumor mutational burden (TMB) (NCT=40; US=61). Participants who received NCT or US were excluded according to these criteria: 1) concurrent treatment in addition to NCT; 2) sarcomatoid and small cell histologies; 3) clinical or pathological TNM Stage 4 disease; 4) synchronous malignancies other than lung. PROSPECT NCT patients expressed increased damage-associated molecular pattern (DAMP) genes (HSPA2, HSPA4, HSPE1, and S100A2; p<0.05) and T cell-related chemotaxis and antigen presentation genes (CXCR7, CD1A; p<0.05). Concordantly, the ICON cohort FACS results showed that NCT patients display increases in: 1) infiltration of CD8+ T cells (p=0.004); 2) proliferating Ki67+CD8+ T cells (p=0.02); 3) tissue resident memory CD8+CD103+ (p=0.02) and CD4+CD103+ non-Treg cells (p=0.01). Trends from the ICON multiplex IHC also highlighted increases in CD8+ T cells (p=0.09), CD20+ cells (p=0.08), as well as PD-L1+ malignant cells (p=0.08) and PD-L1+ TAMs (p=0.08) in NCT patients, the latter finding being supported by increased circulating MCP-1 (p=0.03). TMB was similar between NCT and US groups (p=0.912). Our data provides the first evidence of ICD (i.e., increased DAMP gene expression) following NCT in human early-stage NSCLC. Furthermore, our data highlights the association of NCT with a favorable IME (i.e., increased T cell infiltration), supporting the rationale of NCT and ICB combinations in localized NSCLC.