Survival According to Primary Tumor Location, Stage, and Treatment Patterns in Locoregional Gastroenteropancreatic High-grade Neuroendocrine Carcinomas

Background: Although the gastrointestinal tract (including the pancreas, gastroenteropancreatic (GEP) is the most common site for extrapulmonary neuroendocrine carcinoma (NEC), the current treatment patterns of locoregional GEP NEC and in particular, the role of surgical resection is unclear. Methods: Data from the National Cancer Database between 2004 and 2016 were used for this study. Results: Of 2314 GEP NEC cases (stages I–III), 52.5% were stage III. Colon was the most common site (30%); 30.9% of all cases were small cell morphology. Age, morphology, stage, and primary site were associated with significant differences in treatment patterns. Management of NEC mimicked that of adenocarcinomas arising at the respective sites: colon NEC most likely to be treated with surgery and chemotherapy; anal and esophageal NEC was primarily likely to receive chemotherapy and radiation, and rectal NEC mostly likely to receive trimodality therapy. However, 25%-40% of patients did not undergo surgical resection even at sites typically managed with curative resection, and there was a trend toward lesser resection over time. The prognostic impact of surgical resection was significant across all stages and correlated with variations in survival across primary sites. Even in patients undergoing chemoradiation, surgery was the only prognostic variable that significantly affected survival in stages I–II patients (HR 0.63) and showed a strong trend in stage III (HR 0.77) patients. Conclusions: Treatment patterns in GEP NEC vary considerably according to stage and primary tumor site. Surgery significantly improved survival in stages I–II patients and showed a strong trend in stage III patients regardless of primary tumor location and other perioperative therapies.publishedVersio

Drug costs and benefits of medical treatments in high-unmet need solid tumours in the Nordic countries

Abstract Regional and hospital decision-makers increasingly require analyses assessing the cost-benefit profile of new cancer drugs. This analysis evaluates the cost-benefit profile of nano albumin-bound paclitaxel (nab-paclitaxel) in pancreatic cancer, versus other drugs indicated in high-unmet need solid tumour indications in Nordic countries (Sweden, Denmark, Finland, Norway and Sweden). For a selected number of cancer dugs, approved for metastatic cancer or non-curable treatment intention patients by the European Medicine Agency (EMA) after 2000, and indicated in high-unmet need solid tumours (defined as OS in first line for trial comparator ≤12 months), a regression analysis was conducted. Overall treatment costs of cancer drugs, divided by OS and PFS months, were related to the clinical improvement offered versus trial comparator. Eleven of 42 drugs (26.2%) with at least one indication in solid tumours met inclusion criteria. On average, a good (R2=0.5359) fit between costs per OS month and OS relative benefit versus trial comparator was observed. Nab-paclitaxel offered an OS improvement of +27% versus trial comparator (average improvement: +31%), at a cost per OS month of €1,684 (average cost: €2,247). Correlation between costs per PFS month and relative PFS benefit versus trial comparator was still observed, but the goodness of fit was lower (R2=0.1853) than for the OS analysis. Treatment costs of new cancer therapies should reflect their clinical value, consistently among different indications with comparable characteristics. Nab-paclitaxel, recently approved in pancreatic cancer, showed a similar cost per OS or PFS month ratio compared to other drugs for high-unmet need solid tumours.Peer reviewe

Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone

BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n=781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04–0.85, P=0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10–0.86, P=0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10–4.49, P=0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P<0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC

Profiling of VEGFs and VEGFRs as Prognostic Factors in Soft Tissue Sarcoma: VEGFR-3 Is an Independent Predictor of Poor Prognosis

BACKGROUND: In non-gastrointestinal stromal tumor soft tissue sarcoma (non-GIST STS) optimal treatment is surgery with wide resection margins. Vascular endothelial growth factors (VEGFs) and receptors (VEGFRs) are known to be key players in the initiation of angiogenesis and lymphangiogenesis. This study investigates the prognostic impact of VEGFs and VEGFRs in non-GIST STS with wide and non-wide resection margins. METHODS: Tumor samples from 249 patients with non-GIST STS were obtained and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expressions of VEGF-A, -C and -D and VEGFR-1, -2 and -3. RESULTS: In the univariate analyses, VEGF-A (P=0.040) in the total material, and VEGF-A (P=0.018), VEGF-C (P=0.025) and VEGFR-3 (P=0.027) in the subgroup with wide resection margins, were significant negative prognostic indicators of disease-specific survival (DSS). In the multivariate analysis, high expression of VEGFR-3 (P=0.042, HR=1.907, 95% CI 1.024-3.549) was an independent significant negative prognostic marker for DSS among patients with wide resection margins. CONCLUSION: VEGFR-3 is a strong and independent negative prognostic marker for non-GIST STSs with wide resection margins

Platelet-Derived Growth Factors in Non-GIST Soft-Tissue Sarcomas Identify a Subgroup of Patients with Wide Resection Margins and Poor Disease-Specific Survival

Background. Optimal treatment of nongastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) is resection with wide margins. This study investigates the prognostic impact of the angiogenesis-associated platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in non-GIST STS patients with wide and nonwide resection margins. Method. Tumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expression of PDGF-A, -B, -C, and -D and PDGFR-α and -β. Results. In the multivariate analysis of patients with wide resection margins, high expression of PDGF-B (P = .013, HR = 2.954, and 95% CI = 1.255–6.956) and the coexpression of PDGF-B and PDGFR-α (overall; P = .016, high-low/low-high; P = .051, HR = 2.678, 95% CI = 0.996–7.200, high/high; P = .004, HR = 3.930, 95% CI = 1.542–10.015) were independent negative prognostic markers for disease-specific survival. Conclusion. PDGF-B and the coexpression of PDGF-B and PDGFR-α are strong and independent prognostic factors in non-GIST STSs with wide resection margins

Fibroblast growth factor 2 orchestrates angiogenic networking in non-GIST STS patients

<p>Abstract</p> <p>Background</p> <p>Non-gastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) constitute a heterogeneous group of tumors with poor prognosis. Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor-1 (FGFR-1), in close interplay with platelet-derived growth factor-B (PDGF-B) and vascular endothelial growth factor receptor-3 (VEGFR-3), are strongly involved in angiogenesis. This study investigates the prognostic impact of FGF2 and FGFR-1 and explores the impact of their co-expression with PDGF-B and VEGFR-3 in widely resected tumors from non-GIST STS patients.</p> <p>Methods</p> <p>Tumor samples from 108 non-GIST STS patients were obtained and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expressions of FGF-2, FGFR-1, PDGF-B and VEGFR-3.</p> <p>Results</p> <p>In the multivariate analysis, high expression of FGF2 (P = 0.024, HR = 2.2, 95% CI 1.1-4.4) and the co-expressions of FGF2 & PDGF-B (overall; P = 0.007, intermediate; P = 0.013, HR = 3.6, 95% CI = 1.3-9.7, high; P = 0.002, HR = 6.0, 95% CI = 2.0-18.1) and FGF2 & VEGFR-3 (overall; P = 0.050, intermediate; P = 0.058, HR = 2.0, 95% CI = 0.98-4.1, high; P = 0.028, HR = 2.6, 95% CI = 1.1-6.0) were significant independent prognostic indicators of poor disease-specific survival.</p> <p>Conclusion</p> <p>FGF2, alone or in co-expression with PDGF-B and VEGFR-3, is a significant independent negative prognosticator in widely resected non-GIST STS patients.</p

Prognostic Impacts of Hypoxic Markers in Soft Tissue Sarcoma

Background. We aimed to explore the prognostic impact of the hypoxia-induced factors (HIFαs) 1 and 2, the metabolic HIF-regulated glucose transporter GLUT-1, and carbonic anhydrase IX (CAIX) in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STS). Methods. Duplicate cores with viable tumor tissue from 206 patients with non-GIST STS were obtained and tissue microarrays were constructed. Immunohistochemistry (IHC) was used to evaluate expression of hypoxic markers. Results. In univariate analyses, GLUT-1 (P < 0.001) and HIF-2α (P = 0.032) expression correlated significantly with a poor disease-specific survival (DSS). In the multivariate analysis, however, only high expression of GLUT-1 (HR 1.7, CI 95% 1.1–2.7, P = 0.021) was a significant independent prognostic indicator of poor DSS. Conclusion. GLUT-1 is a significant independent negative prognostic factor in non-GIST STS

Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer

Publisher Copyright: © 2022 The Author(s)Background: The incidence of colorectal cancer (CRC) in individuals of fertile age is increasing. Oxaliplatin is a cornerstone treatment in the adjuvant setting for stage III and high-risk stage II CRC. Limited data exist on possible side effects of oxaliplatin on fertility and gonadal function. More data is needed to guide possible fertility preservation procedures and aid evidence-based fertility counselling. Patients and methods: The aim of this study (EudraCT2006-002832-10) was to prospectively investigate sex hormones and sperm parameters after oxaliplatin-based adjuvant chemotherapy to clarify the risk of infertility and hypogonadism. Twenty males aged ≤55 years and 16 females aged ≤40 years were recruited from five hospitals in the Nordic countries. All had undergone radical surgery due to CRC and were given adjuvant oxaliplatin in combination with 5-fluorouracil. Measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG) and semen analysis were done in males, while LH, FSH and oestradiol were measured in females. Measurements were done prior to chemotherapy, after completion of adjuvant treatment and at follow-up 1 and up to 5 years after end of treatment. Results: FSH and testosterone levels increased in males after chemotherapy treatment but were restored at follow-up. No patients developed hypogonadism. There was a trend towards a decrease in sperm concentration during treatment (p = 0.063). When comparing sperm concentration and rapid progressive motility of sperms prior to chemotherapy and at follow-up, there were no differences, and no patients became permanently azoospermic by treatment. No distinct altering of gonadal function could be observed in females. Conclusions: Oxaliplatin in combination with 5-fluorouracil seems to induce transient decrease in sperm concentration with recovery and a minor transient increase in FSH in males. No distinct altering of gonadal function was observed in females. The risk of infertility and hypogonadism in males and females after adjuvant oxaliplatin-based chemotherapy seems low.Peer reviewe