Primary Disease Stage Research Articles

Testing the external validity of the POUT III trial (adjuvant platnium-based chemotherapy in upper tract urothelial carcinoma) in a North American cohort

ObjectiveThe European POUT III randomized controlled trial provided level-one evidence that adjuvant platinum-based chemotherapy is the standard of care following nephroureterectomy (RNU) for locally invasive or node-positive upper tract urothelial carcinoma. We aim to assess this European randomized controlled trial's generalizability (external validity) to a North American cohort, using a nationwide database. Materials and MethodsTo compare trial patients with those seen in real-world practice, we simulated the trial inclusion criteria using data from the National Cancer Database (NCDB). We identified patients with histologically confirmed transitional cell carcinoma who underwent RNU. The available demographic characteristics of the NCDB cohort were compared with the POUT III trial cohort using Chi-squared test. ResultsThe NCDB cohort (n = 3,380) had a significantly higher proportion of older patients (age ≥ 80: 23.5% vs. 5%), and more males (68% vs. 56.2%) than the POUT cohort (Table 1, both p < 0.001). Additionally, the rate of advanced nodal disease was higher in the NCDB (N1 9.6%, N2 9.3%) than in the POUT (N1 6%, N2 3%) cohort (p < 0.001). A more extensive lymph node dissection was performed in NCDB vs. POUT patients (node≥10 10.9% vs. 3%, p < 0.001). Sensitivity analysis removing all subjects with a Charlson Comorbidity Index > 0 did not change the significance of any results. ConclusionsWhile the primary disease stage was similar, the rate of advanced nodal disease was significantly higher in NCDB, which might be explained partially by the more extensive lymph node dissection performed in the latter. These differences warrant caution when applying the POUT III findings to North American patients.

Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. However, no specific molecular therapeutic targets or biomarkers have been figured out for use in precision medicine, and the exact mechanism by which antitumorigenic effects occur is still unclear. Therefore, it is necessary to conduct further studies on the development and mechanisms associated with CCA. We examined the clinical data and pathological features of patients with cholangiocarcinomas. We investigated the associations between DNA Topoisomerase II Alpha (TOP2A) expression and patient outcomes, such as metastasis-free survival (MFS) and disease-specific survival (DSS), as well as clinical characteristics and pathological results. TOP2A expression was shown to be upregulated in CCA tissue sections by immunohistochemistry staining and data mining. Moreover, we observed that the TOP2A expression correlated with clinical features, such as the primary tumor stage, histological variants, and patients with hepatitis. Furthermore, high expression of TOP2A was associated with worse survival outcomes in terms of the overall survival (p < 0.0001), disease-specific survival (p < 0.0001), and metastasis-free survival (p < 0.0001) compared with patients in the low TOP2A expression group. This indicates that a high level of TOP2A expression is related to an unfavorable prognosis. Our results show that TOP2A is highly expressed in CCA tissues, and its upregulation is correlated with the primary disease stage and poor prognosis significantly. Consequently, TOP2A is a prognostic biomarker and a novel therapeutic target for the treatment of CCA.

The Clinical Utility and Cost of Routine Staging Exam under Anesthesia for Oral Cavity Squamous Cell Carcinoma

Introduction: The standard complete evaluation of patients with head and neck squamous cell carcinoma (HNSCC) has included a staging exam under anesthesia (EUA) since the 1970s. The EUA for all sites of HNSCC has historically consisted of panendoscopy for the purpose of diagnostic biopsy, accurate staging of primary disease, and identification of second primary tumors. However, due to the accessibility of the oral cavity, the sole purpose of EUA for tumors of this site is to identify second primary tumors. Since the EUA became the gold standard for evaluation of HNSCC, there have been significant advancements in less invasive technologies such as CT, PET-CT, MRI, and fiberoptic examination. In this study, we sought to determine the value to patient care and cost-effectiveness of EUA in patients with oral cavity squamous cell carcinoma (OCSCC). Methods: A retrospective chart review identified 77 patients who underwent EUA for OCSCC. Results: The most common subsites were the oral tongue and floor of mouth (59.7% and 24.7% respectively). All underwent direct laryngoscopy, 94.8% underwent esophagoscopy, and 20.8% underwent flexible transnasal examination in clinic prior to EUA. For 90.9% of patients, the EUA did not change initial T-staging based on clinical examination and imaging. The remaining 9.1% of patients were upstaged after EUA, however this change did not impact the treatment plan. Second primary tumors were identified in 3.9% of patients, all were found in either the oral cavity or oropharynx, and were also identified with clinical examination or imaging. Analysis of patient charges determined an average cost of $8,022.93 per patient under the current paradigm involving EUA, however with a new algorithm eliminating mandatory EUA average cost decreases to $1,448.44. Conclusion: Formal EUA has historically been the gold standard for all HNSCC tumors. However, when performed for cases of oral cavity carcinoma, it is safe and cost effective to limit its use to select clinical scenarios.

C-POST Protocol Update: A Phase 3, Randomized, Double-Blind Study of Adjuvant Cemiplimab vs. Placebo Post Surgery and Radiation Therapy in Patients with High-Risk Cutaneous Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with an incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is >95%, some patients have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Postoperative radiation therapy (RT) is recommended for these patients, but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for patients with high-risk CSCC. Here, we provide a summary of the most recent study protocol amendment. <h3>Materials/Methods</h3> C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for patients with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50 Gy, within 10 weeks before randomization) (NCT03969004). Patients with at least one of the following high-risk features are eligible: (1) nodal disease with (a) extracapsular extension and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of extracapsular extension; (2) in-transit metastases; (3) T4 lesion; (4) perineural invasion; and (5) recurrent CSCC with at least one other risk factor. Patients with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), patients are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), patients in the placebo arm who experience disease recurrence and patients in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. The trial is expected to enroll 412 patients from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival; secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic. <h3>Results</h3> Not applicable (trial in progress) <h3>Conclusion</h3> Not applicable (trial in progress)

Significance of metabolic tumor volume and total lesion uptake measured using Ga-68 labelled prostate-specific membrane antigen PET/CT in primary staging of prostate cancer.

To evaluate the accuracy of Ga-68 prostate-specific membrane antigen positron-emission-tomography and computed-tomography(PSMA-PET/CT) in primary nodal staging of prostate cancer (PCa), and the predictive value of volumetric parameters derived from Ga-68- PSMA-PET/CT data in lymph node(LN) metastasis and correlation with histopathological and surgical outcomes. Seventy-seven patients with newly diagnosed, biopsy-proven PCa who underwent Ga-68-PSMA-PET/CT for primary staging of disease and underwent radical prostatectomy with extendend pelvic LN dissection were evaluated retrospectively. 2 experienced nuclear medicine specialists have retrospectively reviewed PET/CT images blinded to all histopathological and clinical data. Sensitivity, specificity, positive predictive value(PPV), and negative predictive value(NPV) for the detection of LN metastases were analyzed per-patient. Volumetric and semiquantitative PET parameters of the primary prostate lesions including SUVmax,metabolic tumor volume(MTV), and total lesion uptake(TLU) were measured and recorded. Primary tumor SUVmax, MTV and TLU were found significantly higher in patients who were in higher ISUP Grade groups 3,4,5 after surgical treatment (P = 0.021,P = 0.049,P = 0.032, respectively). The sensitivity, specificity, PPV and NPV on LN metastasis detection of Ga-68-PSMA-PET/CT was found 60%, 91%, 82% and 78% respectively. Although the distribution of the measured primary tumor MTV and TLU values were higher in histopathologically proven LN metastasis positive patients compared to negative patients, only TLU was statistically significant(P = 0.023). Increase in primary tumor TLU values were correlated with higher pT stages and surgical margin positivity(P = 0.034). Ga-68-PSMA-PET/CT is of clinically valuable for primary staging. Measuring and adding these 2 parameters in routine clinical evaluation may increase the prediction power of high-grade disease confirmed by surgery.

C-POST protocol update: A phase 3, randomized, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation therapy (RT) in patients (pts) with high-risk cutaneous squamous cell carcinoma (CSCC).

TPS9592 Background: CSCC is the second most common skin cancer with an estimated incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is &gt; 95%, some pts have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension (ECE), and prior treatment. Postoperative RT is recommended for these pts but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for pts with high-risk CSCC. Here, we provide summary of the most recent study protocol amendment. Methods: C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50Gy, within 10 weeks before randomization) (NCT03969004). Pts with at least one of the following high-risk features are eligible: (1) nodal disease with (a) ECE and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of ECE; (2) in-transit metastases; (3) T4 lesion; (4) perineural invasion; and (5) recurrent CSCC with at least one other risk factor. Pts with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), pts are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence and pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab for up to 96 weeks. The trial is expected to enrol 412 pts from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival; secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic. Clinical trial information: NCT03969004.

The Clinical Features of Incidentally Diagnosed Urothelial Bladder Cancer: A Retrospective Data Analysis

Introduction: The aim of this study was to evaluate the prevalence and clinical features of incidental bladder cancer (BC) diagnosis, with special emphasis on possible associations between incidental diagnosis and primary disease stage or grade. Methods: We retrospectively included 501 consecutive patients who underwent transurethral resection of bladder tumor and were diagnosed with primary urothelial carcinoma of the bladder between January 2013 and February 2021 in a university hospital. The type of diagnosis (incidental or nonincidental), patient baseline characteristics and primary stage and grade were studied for interdependencies. Results: 28.5% of all patients and 19.8% of high grade (HG) BC patients had been diagnosed incidentally, most commonly with ultrasound. Incidental diagnosis was associated with lower primary stage and grade of the disease. Most importantly, on multivariable analysis, which included baseline patient characteristics and type of diagnosis, in the subgroup of HG BC patients, muscle-invasive BC (MIBC) or metastatic disease was three times less likely to be diagnosed incidentally than non-MIBC (odds ratio: 0.31, 95% confidence interval: 0.14–0.71, p = 0.006). Conclusions: The study is first to demonstrate that incidental diagnosis of HG BC may be surprisingly prevalent and associated with lower rates of muscle invasion or metastatic disease.

Epidemiology of oligometastatic non-small cell lung cancer: results from a systematic review and pooled analysis.

BackgroundTo describe the incidence and the clinical characteristics of oligometastatic non-small cell lung cancer (NSCLC) patients. Oligometastatic NSCLC is gaining recognition as a clinical condition with a different prognosis compared to multi metastatic disease. Usually, four different scenarios of oligometastatic disease can be described but not epidemiological data are available. To date, it is difficult to delineate an exhaustive epidemiological scenario because no uniform or shared definition of oligometastatic status exists, even though a recent consensus defined synchronous oligometastatic disease as having a maximum of 5 metastases in 3 different organs.MethodsA systematic review and a pooled analysis of literature were performed. Article selection was based on the following characteristics: focus on lung cancers; dealing with oligometastatic settings and providing a definition of oligometastatic disease; number of metastatic lesions with or without the number of organs involved; providing some incidence or clinical characteristics of oligometastatic NSCLC patients. Series focusing on a specific single metastatic organ were excluded. The research was launched in MEDLINE (OvidSP) in March 2020. Full articles were individually and collectively read by the authors according to the previous criteria. Each author inspected the reference list included in the eligible articles. If the selection criteria were recognized, the article was reviewed by all authors and then included. Data on patient clinical features were pooled together from 31 articles selected.ResultsA total number of 31 articles have been selected for the analysis. The following variables were extracted from the publications: (I) number of metastases, (II) number of organs involved, (III) number of patients, (IV) number and percentage of males and females, (V) number and percentage of squamous and non-squamous histology, (VI) T and N status and/or stage of primary disease for oligometastatic setting. The data collected have been analyzed according to the oligometastatic setting.ConclusionsOligometastatic status is globally identified as a different clinical condition from multi metastatic NSCLC, although the clinical characteristics were consistent in the general metastatic population, even with a lower-than-expected TN status. The brain and bones were the most frequent organs involved. Lacking consensus definition, these results must be interpreted cautiously and a prospective evaluation is urgently needed.

Ovarian metastases from breast cancer: A report of 24 cases

ObjectiveThe purpose of this study was to investigate the epidemiological, demographical characteristics and survival outcomes of the patients with ovarian metastases from breast cancer. Study designMedical records of 24 patients with pathologically confirmed metastases in ovaries treated at two tertiary hospitals between 2000 and 2019 were reviewed retrospectively. Patients’ as well as tumor characteristics, and treatment data were collected. Ovarian metastases of breast cancer were documented using a system of analogous to the FIGO classification for ovarian cancer. Survival after primary breast cancer diagnosis and after diagnosis of metastases in ovaries were calculated. Outcomes were compared between the three different procedures bilateral salpingo-oophorectomy, total hysterectomy with bilateral salpingo-oophorectomy, and total hysterectomy with bilateral salpingo-oophorectomy with omentectomy. ResultsThe majority of patients had estrogen receptor positive (87 %) and progesterone receptor positive (91 %), 80 % patients were HER2/neu negative. The majority of patients had primary tumor stage by TNM classification T1 (33 %) and T2 (50 %); node- negative (25 %) and node-positive (75 %); 71 % of patients had no distal metastases in primary breast cancer diagnosis (M0) while 29 % of patients had distant metastases. The median age of primary breast cancer diagnosis was 46.5 ± 10.4 years (range 25–69). The mean time to occurrence of secondary ovarian malignancies after primary breast cancer diagnosis was 62.9 ± 62.8 months (range 0–219). The majority of women underwent adnexectomy (37.5 %) or total hysterectomy with adnexectomy (37.5 %). The mean survival after breast cancer treatment was 72 months, and the mean survival after discovery of ovarian metastases was 25 months. ConclusionsOur results showed that more radical surgical treatment of metastases to ovaries has no increase of survival among patients. However, it should be noted that this may be affected by different stage of primary disease. Thus, larger and more standardized studies need to be done in order to confirm prognostic features and the choice of surgical volume.

A phase III, randomized, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation therapy (RT) in patients (pts) with high-risk cutaneous squamous cell carcinoma (CSCC).

TPS10084 Background: CSCC is the second most common skin cancer. While the surgical cure rate for CSCC is &gt; 95%, a proportion of pts are considered to have high risk for recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Post-operative RT is recommended for pts with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur. This study evaluates the efficacy of cemiplimab, a human anti‒PD-1 monoclonal antibody, as an adjuvant therapy for pts with CSCC with high-risk features, after surgery and RT. Methods: This randomized, placebo-controlled, double-blind, multicenter, Phase 3 study will evaluate cemiplimab as an adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who have completed surgery and post-operative RT (NCT03969004). Immunocompromised pts were excluded. The trial will enrol 412 pts from about 100 sites in North America, Europe, and Asia-Pacific regions. Pts with at least one of the following high-risk features are eligible: a) nodal disease with extracapsular extension b) in-transit metastases c) T4 lesion d) perineural invasion, and e) recurrent CSCC with at least one other risk factor. In Part 1 (blinded), pts will be randomized 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks (Q3W) for up to 48 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence or pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 will be eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. Key objectives are to compare disease-free survival (primary) as well as overall survival, freedom from locoregional relapse, and distant relapse (secondary) of adjuvant cemiplimab vs placebo in pts with high-risk CSCC. This study is currently open for enrollment. Clinical trial information: NCT03969004.

1372TiP - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)

BackgroundCSCC is the second most common skin cancer. While the surgical cure rate for CSCC is>95%, a proportion of pts are considered to have high-risk for recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Post-operative RT is recommended for pts with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur. This study evaluates the efficacy of cemiplimab, a human anti–PD-1 monoclonal antibody, as an adjuvant therapy for pts with CSCC with high-risk features, after surgery and RT. Trial designThis randomised, placebo-controlled, double-blind, multicentre, Phase III study will evaluate cemiplimab as an adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who have completed surgery and post-operative RT. Immunocompromised pts were excluded. The trial will enrol 412 pts from about 100 sites in North America, Europe, and Asia-Pacific regions. Pts with at least one of the following high-risk features are eligible: a) nodal disease with extracapsular extension b) in-transit metastases c) T4 lesion d) perineural invasion and e) recurrent CSCC with at least one other risk factor. In Part 1 (blinded), pts will be randomised 1:1 to receive 350mg cemiplimab or placebo intravenously every 3 weeks (Q3W) for up to 48 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence or pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 will be eligible to receive open-label 350mg Q3W cemiplimab for up to 96 weeks. Key objectives are to compare disease-free survival (primary) as well as overall survival, freedom from locoregional relapse, and distant relapse (secondary) of adjuvant cemiplimab vs placebo in pts with high-risk CSCC. Editorial acknowledgementMedical writing support and typesetting was provided by Bu Reinen of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Legal entity responsible for the studyRegeneron Pharmaceuticals, Inc., and Sanofi. FundingRegeneron Pharmaceuticals, Inc., and Sanofi. DisclosureD. Rischin: Research grant / Funding (institution), Non-remunerated activity/ies: Regeneron Pharmaceuticals, Inc.; Research grant / Funding (institution), Non-remunerated activity/ies: GSK; Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Merck; Research grant / Funding (institution), Non-remunerated activity/ies: Bristol-Myers Squibb; Research grant / Funding (institution): Roche. M.G. Fury: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. I. Lowy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. E. Stankevich: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. S. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. H. Han: Full / Part-time employment: Regeneron Pharmaceuticals, Inc. S.V. Porceddu: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy: UpToDate; Advisory / Consultancy: Oral Oncology.

Anti-PSMA 124I-scFvD2B as a new immuno-PET tool for prostate cancer: preclinical proof of principle

BackgroundProstate cancer (PCa) is the second leading cause of cancer-related death in the Western population. The use in oncology of positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease and detection of metastatic lesions. Prostate-specific membrane antigen (PSMA) expression, directly related to androgen-independence, metastasis and progression, renders this tumour associate antigen a good target for the development of new radiopharmaceuticals for PET. Aim of this study was to demonstrate in a preclinical in vivo model (PSMA-positive versus PSMA-negative tumours) the targeting specificity and sensitivity of the anti-PSMA single-chain variable fragment (scFv) labelled with 124I.MethodsThe 124I-labeling conditions of the antibody fragment scFvD2B were optimized and assessed for purity and immunoreactivity. The specificity of 124I-scFvD2B was tested in mice bearing PSMA-positive and PSMA-negative tumours to assess both ex-vivo biodistribution and immune-PET.ResultsThe uptake fraction of 124I-scFvD2B was very high on PSMA positive cells (range 75–91%) and highly specific and immuno-PET at the optimal time point, defined between 15 h and 24 h, provides a specific localization of lesions bearing the target antigen of interest (PSMA positive vs PSMA negative tumors %ID/g: p = 0.0198 and p = 0.0176 respectively) yielding a median target/background ratio around 30–40.ConclusionsPreclinical in vivo results of our immuno-PET reagent are highly promising. The target to background ratio is improved notably using PET compared to SPECT previously performed.These data suggest that, upon clinical confirmation of sensitivity and specificity, our anti-PSMA 124I-scFvD2B may be superior to other diagnostic modalities for PCa. The possibility to combine in patients our 124I-scFvD2B in multi-modal systems, such as PET/CT, PET/MR and PET/SPECT/CT, will provide quantitative 3D tomographic images improving the knowledge of cancer biology and treatment.

Favorable radiation field decrease in gastric marginal zone lymphoma : Experience of the German Study Group on Gastrointestinal Lymphoma (DSGL).

Long-term impact of stage-adapted field reduction in alarge cohort of gastric marginal zone lymphoma (gMZL) patients treated conservatively with curative radiation therapy (RT). Prospective analysis of paper records of 290 patients with stage IE-IIE gMZL, treated in 78radiotherapeutic institutions in Germany from 1992-2013. Stage-adapted radiation fields decreased from extended field (EF) to involved field (IF) over the course of three consecutive prospective trials of the German Study Group on Gastrointestinal Lymphoma (DSGL). Treatment results were compared between the three cohorts. Overall collective with median age of 60years, slight male predominance (m:f = 1.1:1) and ratio of disease stageI:stage II = 2.1:1. Median follow-up 6.4years in total: 13.0 years in the first gastrointestinal study (GIT 1992), 8.2years in the second (GIT 1996) and 4.7years in the third study (DSGL 01/2003). Stage-adapted radiation field decrease together with further technological development led to reduced relative frequencies of acute/chronic adverse effects and until now was accompanied by lower disease recurrence. The third study design with smallest field size (IF in stageI, locoregional EF in stageII) achieved the best survival outcome at the 5‑year follow-up (overall survival 92.7%, event-free survival 89.5% and lymphoma-specific survival 100.0%). Disease relapse observed in 10patients. Cumulative incidence of disease-specific death was 1.7% of the followed patients. Primary disease stage associated with lymphoma-specific survival. Stage-adapted reduction towards IF in gMZL resulted in favorable adverse effects, local control and survival rates. These results support further decreases in modern RT of gMZL.

Abstract B28: Clinicopathological features associated with late recurrence of gastric cancer

Abstract Background: Because most cases of cancer recurrence occur within 5 years, routine surveillance is also recommended for first five years. However, few patients experience late recurrence of disease, and the mechanism of late recurrence is not clearly revealed. The purpose of this study is to evaluate the clinicopathological features predicting the risk of late recurrence in gastric cancer patients. Methods: From January 2006 to December 2013, we retrospectively reviewed 813 patients who were diagnosed and treated with gastric cancer in Yonsei cancer center. Result: Among 226 patients who experienced recurrence of gastric cancer, 212 patients were diagnosed with recurrence within first five years from the curative resection of primary cancer, and 14 patients were diagnosed with recurrence of disease beyond 5 years. In comparison with early recurrence (≤ 5 years), the patients with late recurrence (&amp;gt; 5 years) had primary disease of stage I/II (vs. stage III; HR, 4.5; 95% CI, 1.5-14.1; P=0.009), well or moderately differentiated histology (vs. poorly differentiated or signet ring cell; HR, 4.2; 95% CI, 1.4-13.1; P=0.013), and did not receive adjuvant chemotherapy (HR, 0.3; 95% CI, 0.1-0.9; P=0.028). All the 21 patients with HER2 positive gastric cancer experienced early recurrence. Conclusion: Late recurrence of gastric cancer is possibly not influenced by advanced stage of primary disease. More attempts to find high risk groups for late recurrence of gastric cancer are needed. Citation Format: Ji Soo Park, Chu Ree Won, Taeil Son, Hyoung-Il Kim, Woo Jin Hyung, Sung Hoon Noh, Tae Il Kim. Clinicopathological features associated with late recurrence of gastric cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B28.

False Positive Positron Emission Tomography / Computed Tomography Scans in Treated Head and Neck Cancers.

ObjectivePositron emission tomography/computed tomography (PET/CT) imaging for head and neck cancers (HNC) is commonly utilized for post-treatment assessment. Though PET/CT in this setting has been reported to have high negative predictive values (> 90%), positive predictive values have been reported at approximately 50%, leading to high rates of false positivity (FP) and troubling management decisions for both patient and practitioner. The objective of this study was to identify patient, disease, treatment and imaging factors that might be associated with a higher likelihood of FP on initial post-treatment PET/CT imaging for patients treated for HNC. Materials and methodsA retrospective chart review was performed on 84 patients treated for HNC who received radiation therapy (RT) as part of their overall management from October 2005 to August 2013. Of the patients screened, 19 were found to have mucosally based squamous cell carcinoma (SCC) with positive initial post-treatment PET/CT studies (23%). Fisher’s exact test was used to analyze the association between categorical variables and FP, including patient's gender, disease laterality, primary tumor site and stage, nodal and overall stage, high dose RT fraction size, number of RT fractions completed, total RT dose, biologically effective dose and timing of PET/CT acquisition. Wilcoxon rank-sum test was used to analyze the association between continuous variables and FP, including patient age, total elapsed days of RT, an amount of infused fluorodeoxyglucose 18F-FDG, pre-PET/CT serum glucose levels, and maximum standardized uptake value SUVmax. Statistically significant findings were those that were deemed p <0.05.ResultsAmong patients with positive initial post-treatment PET/CT scans for treated HNC, there was a lower proportion of higher primary disease stage associated with FP versus true positivity (T-stage 3-4: 20 vs 78%, respectively, p=0.023). We also discovered that 50% of patients that underwent confirmation for FP findings suffered serious complications as a direct consequence of invasive exploratory procedures.ConclusionsAlthough PET/CT is known for its exceptional negative predictive value (> 90%) in the post-treatment setting for HNC, high rates of FP remains a clinical challenge. Our study suggests that tumor stage (T-stage) may impact FP rates in positive initial post-treatment PET/CT scans. We recommend careful multidisciplinary discussion regarding positive PET/CT studies in the post-treatment setting for HNC, particularly if invasive intervention is considered.

Follow-up of survived children supported by extracorporeal membrane oxygenation

Objective: To summarize the follow-up of children treated with venoarterial extracorporeal membrane oxygenation (ECMO) by incision of internal carotid artery-vein. Method: This was a retrospective study, 10 children in whom the conventional therapy failed, but survived after treatment with ECMO technique through right internal jugular artery-venous incision and ligation after ECMO in pediatric intensive care unit (PICU) of Fudan University were followed up from December 2011 to December 2015. Primary disease situation, neurological development, growth and development, quality of life and personality development were included. All children were followed up once every six months after discharge, and once a year after 2 years. The longest follow-up period was 2 years. Result: Of the 10 children 6 were boys and 4 girls, and ranged in age of onset from 1 day to 12 years . Five children had neurological problems, including abnormal brain CT (n=3), abnormal electroence phalogram (EEG) (n=3), and mental retardation (n=2). Three of those children had a history of hypoxia, 2 of whom accepted cardiopulmonary resuscitation. Eight children had normal brainstem evoked potential (BEAP) examinations. Primary diseases were all well controlled except for 6 children who had different degrees of sequelae, including mild arrhythmia (n=1), heart structure abnormality (n=2) and abnormal pulmonary function (n=3). The sequelae caused by the primary diseases were just embodied in examination. Their head circumference measurement and physical examination showed no obvious abnormalities, and blood biochemical tests, hemoglobin and blood gas analysis were also normal. One child's height was less than P3. The one who accepted cardiopulmonary resuscitation (CPR) at early stage of primary disease had trouble in daily life, presenting uncoordinated and unstable walking. One child was slightly bad tempered and asocial, and the rest were normal. Conclusion: The rest could take care of themselves. The ECMO sequelae of those survived children were mostly caused by primary diseases. ECMO treatment is safe and has less adverse consequences.

Comparison of long-term oncologic outcomes between radiofrequency ablation and surgical resection for metachronous isolated hepatic metastases from colorectal cancer

Purpose We compared oncologic outcomes between surgery and radiofrequency ablation (RFA) in patients with metachronous isolated hepatic metastases from colorectal cancer. Methods We retrospectively analyzed 123 patients treated with hepatic resection and 82 patients treated with RFA for metachronous hepatic metastases between April 2000 and October 2011. Re-recurrence pattern and 3-year re-recurrence free survival (RFS) rate compared between groups. Factors associated with RFS were evaluated. Results The patients in the two groups were similar in age, gender, location of primary tumor, disease-free interval to hepatic metastasis, pathological stage of primary disease, number of metastatic lesions. The mean diameter of the biggest hepatic metastatic lesion was significantly larger in the resection group than in the RFA group. The RFS rate after hepatic metastasis treatment was significantly higher in the resection group than in the RFA group (48.6% vs. 33.7%, respectively; P=0.015). Marginal recurrence at the RFA site was observed in 14 of the 82 patients (17.1%). The size and number of metastatic lesions, stage of primary disease, disease-free interval to hepatic metastasis, and modality of treatment were confirmed as re-recurrence-associated factors after hepatic metastasis treatment. Among patients with solitary metastases of ≤3 cm, the RFS rate was not different between the resection and RFA groups (52.4% vs. 53.4%, respectively; P=0.491). Conclusion Surgical resection for metachronous hepatic metastases achieved higher RFS and lower local recurrence rates. However, the RFS rate in patients with a solitary hepatic metastasis of ≤3 cm was similar between the resection and RFA groups. Keywords: Metastasis, Liver, Colorectal neoplasm, Radiofrequency ablation, Hepatectomy

Laser Doppler Flow Meter: A New Approach for Calculation of Human Blood Flow Rate

In this paper, we are going to introduce the new technique for measurement of blood flow rate in humans based on LDF (Laser Doppler Flowmetry) technique. We had developed overall embedded system which takes input from laser Doppler blood flow sensor & gives output on personal computer via wireless communication. The structure of the sensor consists of two compartments with a light dependant resistor (LDR) and a laser diode in each. The size & weight of sensor & overall system is very less. The overall system is powered through a dedicated battery & hence power saving arrangement is also provided. Proper blood flow in human body is essential because an adequate amount of blood supply is necessary for the proper functioning of all body organs as blood carries all the nutrients and oxygen that our body needs to stay healthy. Improper blood flow rate is main symptoms of various diseases. The measurement of the blood flow can therefore provide essential information for the judgment of diseases. Since changes in blood flow occurs with the very primary stage of disease, with a fast, reliable blood flow measurement technique, the physicians have a new option for early disease diagnosis. So using this system, we can successfully & easily able to measure human blood flow rate. Major advantage of this technique is this method is noninvasive which means not involving the introduction of instruments into the body[1][2]

OC-092 Impact of colorectal cancer primary node status on survival following colorectal liver metastases resection

<h3>Introduction</h3> Overall survival for primary colorectal cancer (CRC) is known to be correlated with primary stage (Duke’s classification), though the effect of primary disease stage once metastatic spread has occurred needs defining. Primary tumour lymph node status has been previously postulated to negatively impact survival following colorectal liver metastases (CLRM) resection.¹ The objective of the study was to determine the relation between primary CRC node status and survival (disease free survival [DFS] and overall survival [OS]) for patients undergoing hepatic resections for CRLM. <h3>Method</h3> Data was collected from a prospectively maintained database of patients undergoing hepatectomy for CRLM between 1 January 2005 and 31 December 2012. Patient demographics, primary CRC staging, operative details, pathology, recurrence and survival data were collected. Primary staging was assessed using the TNM and Dukes grading system, with Dukes A and B classed as node negative, and Dukes C classified as node positive. OS and DFS were analysed using Kaplan-Meier survival curves and log-rank tests. <h3>Results</h3> The study included 866 patients, with a mean age of 66 years [23–91]. Of the sample population, 65.8% were male. Of these, 743 patients had primary tumour staging data available. Patients with node negative primary tumours (Dukes A and B) had a significantly longer OS than patients with node positive disease [Dukes C] (median OS 68 <i>vs</i>43 months, χ²p = 0.002). Patients with node negative primaries also had a significantly longer DFS than patients with node positive disease (median DFS 20 <i>vs</i>16 months, χ²p = 0.002). <h3>Conclusion</h3> Patients with CRLM who have a Dukes C primary colorectal tumour have a shorter OS and are likely to re-occur earlier post liver resection than those with node negative primary cancer (Dukes A and B). There may be merit in stratifying follow up post CRLM resection, in view of likelihood of recurrent disease. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Tomlinson J, Jarnagin W, DeMatteo R, <i>et al</i>. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–4580

Time-course pattern of blood 25-hydroxycholecalciferol is asignificant predictor of survival outcome in metastatic colorectal cancer: aclinical practice-based study.

Vitamin Ddeficiency has been implicated in the epidemiology of common malignancies including colorectal cancer. We studied consecutive blood levels of 25-hydroxycholecalciferol (25-OHD) in relation to other clinical and laboratory variables in metastatic colorectal cancer patients to ascertain whether their variations may be prognostic or predictive parameters of survival outcomes. Eighty four patients treated with first-line oxaliplatin-based chemotherapy with or without bevacizumab were included. The patients were enrolled on the intent-to-treat basis considering their performance status, comorbidities and laboratory parameters to be medically apt for intensive chemotherapy. Overall survival and progression-free survival were selected as the primary outcomes. Progression free survival and overall survival medians were 15.4 months and 41.2months, respectively. The cut-off levels of 40 nmol/l for 25-OHD and 11 µg/l for first CEA were identified to be clinical decision levels stratifying patients to the respective prognostic groups. We found that the most consistent outcome predictors were i) any patient surgery, ii) CEA and, independently, iii) time-related blood levels of 25-OHD. We confirmed fundamental and consistent vitamin Ddeficiency in metastatic colorectal cancer. We demonstrated that all patients with at least one blood level above 40 nmol/l versus all below this cut-off showed profound differences in their disease outcomes. The primary disease stage or time to metastatic stage did not influence the predictive power of blood 25-OHD levels, implying that the time-course pattern of 25-OHD but not the first single measurement may be an independent prognostic factor.