Interleukin-6 as a Predictive Factor of Pathological Response to FLOT Regimen Systemic Treatment in Locally Advanced Gastroesophageal Junction or Gastric Cancer Patients.

BACKGROUND: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. METHODS: We conducted this prospective study in the MSCNRIO in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers gave informed consent. Complete blood count, carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA125), carcinoma antigen 19.9 (CA19.9), and fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). RESULTS: Of all the measured parameters, only the IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in the complete pathological response (pCR) vs. the non-pCR group (3.71 pg/mL vs. 7.63 pg/mL, p = 0.004). In all patients with an IL-6 level below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to the Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs. ypN0 (7.69 pg/mL vs. 2.89 pg/mL, p = 0.022). CONCLUSIONS: The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC.

Diagnosis and treatment of peritoneal carcinomatosis - a comprehensive overview.

Peritoneal carcinomatosis, which is the most common malignant process of the peritoneal cavity, originates mostly from colorectal, gastric, and gynaecological malignancies. The differential diagnosis is broad and covers primary peritoneal malignancies, as well as many benign disorders such as endometriosis, and inflammatory and infectious diseases. Peritoneal implants tend to locate in the areas of the physiological stasis of the peritoneal fluid: pelvic peritoneal reflections, right and left paracolic gutters, superior part of the sigmoid mesocolon, ileocolic area, and the right subdiaphragmatic space. The 3 most common imaging findings are ascites, nodular implants, and infiltration of the peritoneal fatty tissue. Several imaging modalities may be applied in patients with peritoneal carcinomatosis. Ultrasound has low sensitivity and specificity, and therefore plays only a marginal role. Computed tomography is the method of choice, due to its availability, cost-effectiveness, and relatively high sensitivity. The sensitivity of magnetic resonance imaging depends on the size of peritoneal implants - in cases of implants larger than 10 mm is comparable to CT. Some studies suggest that PET/CT may be the most sensitive method, yet its usefulness in everyday practice is controversial. The Peritoneal Carcinomatosis Index (PCI) is a scale used to assess the tumour burden in the peritoneum and may serve as a communication tool between clinicians and radiologists. The imaging findings may influence the surgeon's decision on performing cytoreductive surgery, which may be followed by intraperitoneal chemotherapy (HIPEC or EPIC procedures). The introduction of these therapeutic methods has significantly improved the life expectancy of patients with peritoneal carcinomatosis.

Safety and efficacy of the FLOT regimen in the Polish population - an analysis of the prospective trial.

As gastric cancer is associated with poor prognosis, the preferred management of locally advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in European patients is perioperative chemotherapy using the FLOT regimen. Previously published data demonstrate that such treatment is associated with improved disease-free survival (DFS) as well as overall survival (OS) compared to ECF/ECX regimen. In order to collect biomaterial for the identification of serum biomarkers of an early response to neoadjuvant chemotherapy, we performed a prospective study and here, we report the safety and clinical efficacy of this prospective cohort. It was an academic, nonrandomized, prospective study, conducted at Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Between January 2018 and November 2019, we analyzed a total of 61 patients aged 30-77 (median 63 years, 52.5% males and 47.5% females) with histologically confirmed GC or GEJ cancer. The patients were qualified by a multidisciplinary team for perioperative treatment (FLOT regimen). All cases of reported adverse events were recorded and analyzed. All patients received G-CSF prophylactically. After gastrectomy, an assessment of pathological regression was performed according to the Becker classification. A total of 93.4% (57) patients completed four cycles of preoperative chemotherapy and 78.7% (48) received postoperative chemotherapy. All of them experienced grade 1/2 toxicities. The common AE G1/G2 in preoperative versus postoperative chemotherapy were: fatigue (75% vs. 60%), anemia (64% vs. 62%), nausea (60% vs. 60%), peripheral neuropathy (60% vs. 60%), and oral mucositis (59% vs. 50%), respectively. Only 24.6% (15) had G3/4 adverse events during preoperative chemotherapy and only 20.8% (10) during postoperative chemotherapy. The estimated DFS at 3 years was 53% (95% CI 40.5-66.1%) and the estimated OS at 3 years was 60.2% (95% CI 45.1-72.3%). FLOT regimen significantly improved GC and GEJ cancer patients' prognosis with acceptable side-effect profiles.

Perfusion-Diffusion Ratio: A New IVIM Approach in Differentiating Solid Benign and Malignant Primary Lesions of the Liver.

INTRODUCTION: In order to improve the efficacy of intravoxel incoherent motion (IVIM) parameters in characterising specific tissues, a new concept is introduced: the perfusion-diffusion ratio (PDR), which expresses the relationship between the signal S(b) decline rate as a result of IVIM and the rate of signal S(b) decline due to diffusion. The aim of this study was to investigate this novel approach in the differentiation of solid primary liver lesions. Material and Methods. Eighty-three patients referred for liver MRI between August 2017 and January 2020 with a suspected liver tumour were prospectively examined with the standard liver MRI protocol extended by DWI-IVIM sequence. Patients with no liver lesions, haemangiomas, or metastases were excluded. The final study population consisted of 34 patients with primary solid liver masses, 9 with FNH, 4 with regenerative nodules, 10 with HCC, and 11 with CCC. The PDR coefficient was introduced, defined as the ratio of the rate of signal S(b) decrease due to the IVIM effect to the rate of signal S(b) decrease due to the diffusion process, for b = 0. RESULTS: No significant differences were found between benign and malignant lesions in the case of IVIM parameters (f, D, or D ∗) and ADC. Significant differences were observed only for PDR, with lower values for malignant lesions (p = 0.03). The ROC analysis yielded an AUC value for PDR equal to 0.74, with a cut-off value of 5.06, sensitivity of 81%, specificity of 77%, and accuracy of 79%. CONCLUSION: PDR proved to be more effective than IVIM parameters and ADC in the differentiation of solid benign and malignant primary liver lesions.

Radiological and Clinical Efficacy of Intra-Arterial 90Y-DOTATATE in Patients with Unresectable, Progressive, Liver Dominant Neuroendocrine Neoplasms.

This study was performed to determine if intra-arterial (i.a.) administration of 90Y DOTATATE can provide an effective and safe alternative to the accepted standard for i.v. of peptide receptor radionuclide therapy (PRRT) in liver-dominant metastases of gastrointestinal pancreatic neuroendocrine neoplasm (GEP-NEN). A single site, prospective, preliminary case series study included 39 patients with histologically proven liver-dominant NEN. PRRT in the form of 1.15GBq 90Y DOTATATE was given selectively into the liver via radiological catheterization of the hepatic artery, up to four times. The endpoint was radiological response (RECIST). Secondary endpoints assessed clinical well-being post-treatment, progression-free survival (PFS), overall survival (OS), and toxicity. Partial response (PR) was noted in 13% of subjects six weeks post-therapy, increasing to 24% at six months and dropping to 13% at 36 months. Disease progression (DP) was not seen at six weeks, was 5% at six months, and 47% at 36 months. Clinical response based on PS seen in 74% of patients at six weeks, 69% at six months, and 39% at 36 months had PFS and OS, respectively, of 22.7 months and 38.2 months. There was no difference in OS/PFS between those with RECIST PR and SD. One patient had significant toxicity (3%). Use of i.a. PRRT appears to be safe and effective in treating patients with liver-dominant NEN. In addition, the best OS (51 vs. 22 months) was seen when i.a. was used as an upfront treatment of bulky GEP-NEN liver metastases and not after i.v. 90Y DOTATATE. The use of i.a. 90Y DOTATATE PRRT appears to be safe and effective in treating patients with liver-dominant NEN.

Outcomes of Patients with Pulmonary Large Cell Neuroendocrine Carcinoma in I-IV Stage.

Background and Objectives: Large cell neuroendocrine cancer is characterised by poor prognosis. The standard of treatment is still not established. The aim of this study was to assess the predictive factors of overall survival (OS) and progression-free survival (PFS) of pulmonary large cell neuroendocrine carcinoma (LCNEC) and combined LCNEC. Materials and Methods: All patients had confirmed pathology stage I-IV disease recorded between period 2002-2018. Survival curves were estimated by Kaplan-Meier method. Uni- and multivariable analysis was conducted using Cox-regression analysis. Results: A total of 132 patients with LCNEC and combined LCNEC were included. Half of them had clinical stage IIIB/C-IV. Patients were treated with radical (n = 67, including surgery alone; resection with neo-adjuvant or adjuvant chemotherapy, radiochemotherapy, or adjuvant radiotherapy; patients treated with radiochemotherapy alone), palliative (n = 41) or symptomatic (n = 24) intention. Seventeen patients were treated with resection margin R1 or R2. Non-small cell carcinoma (NSCLC) chemotherapy (platinum-vinorelbine; PN schedule) and small-cell lung carcinoma (SCLC) chemotherapy approaches (platinum/carboplatinum-etoposide; PE/KE schedule) were administered in 20 and in 55 patients, respectively. The median (95% Confidence Interval (CI)) OS and PFS were 17 months (9.0-36.2 months) and 7 months (3.0-15.0 months), respectively. Patients treated with negative resection margin, with lower clinical stage, without lymph node metastasis, and with size of primary tumour ≤4 cm showed significantly better OS and PFS. The main risk factors with an adverse effect on survival were advanced CS and positive resection margin. Conclusions: Patients with LCNEC characterized poor prognosis. Independent prognostic factors influencing PFS were initial clinical stage and resection margin R0 vs. R1-2.

Outcomes of Patients with Clinical Stage I-IIIA Large-Cell Neuroendocrine Lung Cancer Treated with Resection.

Large-cell neuroendocrine carcinoma (LCNEC) is a rare malignancy with poor prognosis. The rationale of the study was to determine the survival of LCNEC patients in I-IIIA clinical stages who underwent resection. A total of 53 LCNEC (89%) and combined LCNEC (11%) patients in stages I-IIIA who underwent surgery with radical intent between 2002-2018 were included in the current study. Overall survival (OS) and time to recurrence (TTR) were estimated. Uni- and multivariable analyses were conducted using Cox-regression model. Patients were treated with surgery alone (51%), surgery with radiochemotherapy (4%), with radiotherapy (2%), with adjuvant chemotherapy (41%), or with neoadjuvant chemotherapy (2%). The median (95% Confidence Interval (CI)) OS and TTR was 52 months (20.1-102.1 months) and 20 months (7.0-75.6 months), respectively. Patients treated in clinical stage I showed better OS than patients in stages II-IIIA (p = 0.008). Patients with R0 resection margin (negative margin, no tumor at the margin) and without lymph node metastasis had significantly better TTR. In the multivariate analysis, age was an independent factor influencing OS. Recurrence within 1 year was noted in more than half cases of LCNEC. R0 resection margin and N0 status (no lymph node metastasis) were factors improving TTR. Age >64 years was observed as a main independent factor influencing OS.

A Clinical Efficacy of PRRT in Patients with Advanced, Nonresectable, Paraganglioma-Pheochromocytoma, Related to SDHx Gene Mutation.

Paragangliomas and pheochromytomas (PPGLs) exhibit variable malignancy, advanced/hormonally active/progressive need therapy. PRRT (Peptide Receptor Radionuclide Therapy) could be an option for these patients. To evaluate the effectiveness of PRRT (90Y DOTATATE), based on overall survival (OS) and progression-free survival (PFS), in patients with PPGLs, related to SDHx gene mutation, we conducted a prospective open-label, single-center, phase II study. Thirteen patients were observed, eight PGL1 and five PGL4, all with advanced, non-resectable tumors, and eight had metastases. All were treated with 90Y DOTATATE. Efficacy was based on OS and PFS, and radiological response was based on RECIST. Hormonal activity was evaluated using serum-fractionated free catecholamines. Eight subjects had a clinical response, three were stable, and two exhibited disease progression. Among four patients with hormonally-active PPGLs, three showed a reduction and one showed normalization. OS for all was 68.0 months; PFS was 35.0 months. OS in PGL4 = 25.0 vs. N.R. (not reached) in PGL1. PFS in PGL4 = 12.0 vs. N.R. in PGL1. A difference was seen in the OS and PFS in patients who did not respond clinically, compared to those who did, OS = 22.0 vs. N.R. PFS = 7.0 vs. N.R. A difference in the OS and PFS was noted in patients with liver and bone involvement compared to those without. PRRT is an effective therapy in selected population of patients with SDHx, in those with locally-advanced, non-resectable tumors. Furthermore, it is effective regardless of the secretory status.

Magnetic Resonance Imaging of Uncommon Hepatic Mesenchymal Tumours: Haemangioendothelioma and Angiosarcoma.

BACKGROUND: Primary Hepatic Epithelioid Haemangioendothelioma (HEHE) and Primary Hepatic Angiosarcoma (PHA) are rare mesenchymal tumours with different malignant potential. Whereas HEHE demonstrates low to intermediate malignant potential, PHA is an aggressive malignancy with poor prognosis. The knowledge of typical imaging features of these lesions may facilitate correct diagnosis; however, the ultimate diagnosis of HEHE and PHA is based on histopathologic examination. DISCUSSION: The most typical findings helpful in diagnosing HEHE are: Presence of multiple, confluent nodules located at the liver periphery (in young to middle-aged woman), retraction of the liver capsule, marked hyperintensity on T2-weighted images, "target-sign" appearance, progressive centripetal contrast enhancement, and relatively high Apparent Diffusion Coefficient (ADC) values. More than ≥50% of nodules are hyper- or isointense on Hepatobiliary Phase (HBP) images. CONCLUSION: The imaging features suggestive of PHA are: Occurrence of metastases (lungs, spleen) at the time of diagnosis, presence of a large dominant mass with smaller satellites, heterogeneity and areas of haemorrhage in a dominant mass, progressive contrast enhancement, slightly elevated ADC values as compared to other malignant liver tumours.

Reproducibility of intravoxel incoherent motion of liver on a 3.0T scanner: free-breathing and respiratory-triggered sequences acquired with different numbers of excitations.

PURPOSE: To optimise the intravoxel incoherent motion (IVIM) imaging of the liver on a 3.0T scanner by assessing parameter reproducibility on free-breathing (FB) and respiratory-triggered (RT) sequences acquired with different numbers of signal averages (NSA). MATERIAL AND METHODS: In this prospective study 20 subjects (M/F: 10/10; age: 25-62 years, mean: 39 years) underwent IVIM magnetic resonance imaging (MRI) on a 3.0T scanner using an 18-channel phase-arrayed coil and four different echo-planar sequences, each with 10 b values: 0, 10, 30, 50, 75, 100, 150, 200, 500, and 900 s/mm2. Images were acquired with FB and RT with NSA = 1-4 (FBNSA1-4, RTNSA1-4) and with NSA = 3-6 (FBNSA3-6, RTNSA3-6). Subsequently, for the assessment of reproducibility of IVIM-derived parameters (f, D, D*), each subject was scanned again with an identical protocol during the same session. IVIM parameters were calculated. The distribution of IVIM-parameters for each DWI sequence were given as the median value with first and third quartile. Inter-scan reproducibility for each IVIM parameter was evaluated using coefficient of variance and Bland-Altman difference. Differences between FB sequence and RT sequence were tested using non-parametric Wilcoxon signed-rank test. RESULTS: Mean coefficient of variance (%) for f, D, and D* ranged from 60 to 64, from 58 to 84, and from 82 to 99 for FBNSA1-4 sequence; from 50 to 69, from 41 to 97, and from 80 to 82 for RTNSA1-4 sequence; from 22 to 27, 15, and from 70 to 80 for FBNSA3-6 sequence; and from 21 to 32, from 12 to, and from 50 to 80 for RTNSA3-6 sequence, respectively. CONCLUSIONS: Increasing the number of signal averages for IVIM acquisitions allows us to improve the reproducibility of IVIM-derived parameters. The sequence acquired during free-breathing with NSA = 3-6 was optimal in terms of reproducibility and acquisition time.

Neuroendocrine neoplasms of the small intestine and appendix - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of patients suffering from small intestinal NENs with distant metastases. The main cause of death in patients with carcinoid syndrome is carcinoid heart disease. The most useful laboratory test is the determination of chromogranin A, while concentration of 5-hydroxyindoleacetic acid is helpful in the diagnostics of carcinoid syndrome. For visualisation, ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, double-balloon enteroscopy, and somatostatin receptor scintigraphy may be used. A detailed his-tological report is crucial for the proper diagnostics and therapy of NENs of the small intestine and appendix. The treatment of choice is surgical management, either radical or palliative. The pharmacological treatment of the hormonally active and non-active small intestinal NENs as well as NENs of the appendix is based on long-acting somatostatin analogues. In patients with generalised NENs of the small intestine in progress during the SSA treatment, with good expression of somatostatin receptors, the first-line treatment should be radio-isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered.

The first case of human autochtonous subconjunctival dirofilariosis in Poland and MALT lymphoma as possible consequence of this parasitosis.

The first case of human dirofilarosis in Poland was recorded in 2007. Until that time our country was free of Dirofilaria repens. Recent studies show that 21,4- 60% of dogs in Warsaw region harbour microfilariae, therefore it is becoming a growing problem in Central Europe. In April 2013 a subconjunctival D. repens was removed from the eye of 61-year-old woman. It was the twenty first case of this disease in Poland, the third case of eye dirofilaria and the fourth autochtonous case. The patient had never been abroad, so it was the first case of autochtonous human ocular dirofilariosis in Poland. Nine months after the D. repens had been removed, a MALT lymphoma was discovered. In the article we discuss whether a MALT lymphoma of the lacrimal gland of the eye, previously affected by the parasite, may be the consequence of the invasion.

Delineation variation of lymph node stations for treatment planning in lung cancer radiotherapy.

PURPOSE: To assess the variability among clinicians in the delineation of mediastinal and hilar lymph node stations (LNS) according to the published recommendations in the treatment planning of elective nodal irradiation for lung cancer. METHODS: Nine observers delineated on axial CT scans of five cases the LNS according to the guidelines of the published Atlas. Next, the Volumes of Consensus (VC)--fitting strictly the guidelines--for each LNS and case were collectively defined. Volume of Intersection (VI) as the overlap of the Delineated Volume (DV) for each LNS, case and observer with respective VC was computed. The Concordance Index (CI) for respective LNS and observers was defined as "VI/VC x 100%". The Discordance Index (DI) for respective LNS and observers was defined as "(1-VI/VD) x 100%". RESULTS: Mean values of CI and DI for all observers were 69% and 36%, respectively. For five radiation oncologists who used to work as a team the ways of delineation were similar. The poorest reproducibility was shown for LNS 5, 7, 10R, and 10L. CONCLUSIONS: Although detailed guidelines are used there is still substantial room for improvement. More training in the use of the Atlas is recommended.

[New radiotherapy techniques in the treatment of patients with craniopharyngioma: a report of two cases]. / Zastosowanie nowoczesnych technik radioterapii w leczeniu chorych na czaszkogardlaka na przykladzie 2 przypadków.

The authors report two cases of adult patients with craniopharyngioma recurrence after surgery. In both these patients radiotherapy resulted in a complete regression of the neoplasms, confirmed both by clinical examination and MR imaging. In both cases modern radiotherapy techniques were used so as to spare healthy tissues surrounding the tumor. Case 1. A 56-year-old man was admitted with an extensive (3.5 x 4.0 x 4.0 cm) recurrent craniopharyngioma 3 years after the initial surgery and 3 months after a surgery for relapse. Conformal 3-D planned fractionated radiotherapy to the total dose of 54 Gy in 30 fractions was delivered encompassing the tumor with 5 mm margins. Four months after radiotherapy MR imaging demonstrated a complete regression of the neoplasm and the patient recovered totally from his endocrine deficiency and neurological symptoms. Case 2. A 29-year-old man was irradiated 10 months after the initial surgery when a relapse of craniopharyngioma was found in MR imaging. The largest diameter of this recurrent tumor was 18 mm. The patient was subjected to fractionated stereotactic radiotherapy to the total dose of 54 Gy in 27 fractions. Two months after the treatment his complete recovery was confirmed by MRI. Benefits resulting from the use of more recent radiotherapy techniques in the management of craniopharyngioma are discussed.