| 1. |
- Amin, Nadia Emad Lotfi, et al.
(författare)
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Randomized Phase II trial of combination chemotherapy with panitumumab or bevacizumab for patients with inoperable biliary tract cancer without KRAS exon 2 mutations
- 2021
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 149:1, s. 119-126
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Tidskriftsartikel (refereegranskat)abstract
- Biliary tract cancers (BTC) are rare and often diagnosed in late stages with advanced, nonresectable disease. The targeted agents panitumumab and bevacizumab have shown promising outcomes in combination with chemotherapy in other gastrointestinal (GI) cancers. We wanted to investigate if panitumumab or bevacizumab was the most promising drug to add to chemotherapy. Eighty-eight patients were randomized to combination chemotherapy supplemented by either panitumumab 6 mg/kg or bevacizumab 10 mg/kg on Day 1 in Arm A and Arm B, respectively. All patients received gemcitabine 1000 mg/m2 on Day 1, oxaliplatin 60 mg/m2 on Day 1 and capecitabine 1000 mg/m2 twice daily from Days 1 to 7. Treatment was repeated every 2 weeks until progression or for a maximum of 6 months. At progression, crossover was made to the other treatment arm. The primary endpoint was progression-free survival (PFS) at 6 months. With 19 of 45 in Arm A and 23 of 43 in Arm B PFS at 6 months, the primary endpoint was not met. The overall response rate (ORR) was 45% vs 20% (P =.03), median PFS was 6.1 months vs 8.2 months (P =.13) and median overall survival (OS) was 9.5 months vs 12.3 months (P =.47) in Arm A and Arm B, respectively. Our study showed no consistent differences between adding panitumumab or bevacizumab to chemotherapy in nonresectable BTC and none of the two regimens qualify for testing in Phase III. However, we found a higher response rate in the panitumumab arm with potential implication for future trials in the neoadjuvant setting.
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| 2. |
- Borg, David, et al.
(författare)
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Palliative short-course hypofractionated radiotherapy followed by chemotherapy in esophageal adenocarcinoma : the phase II PALAESTRA trial
- 2020
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Ingår i: Acta Oncologica. - 0284-186X. ; 59:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Background: The majority of patients with incurable esophageal adenocarcinoma suffer from dysphagia. We assessed a novel treatment strategy with initial short-course radiotherapy followed by chemotherapy with the primary aim to achieve long-term relief of dysphagia. Methods: This phase II trial included treatment-naîve patients with dysphagia due to esophageal adenocarcinoma not eligible for curative treatment. External beam radiotherapy with 20 Gy in five fractions to the primary tumor was followed by four cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a five-grade scale. Results: From October 2014 to May 2018 a total of 29 patients were enrolled. The rate of dysphagia improvement was 79%, median duration of improvement 6.7 months (12.2 months for responders) and median overall survival 9.9 months. In the pre-specified per protocol analysis (23 patients) the rate of dysphagia improvement was 91%, median duration of improvement 12.2 months (14.0 months for responders) and median overall survival 16.0 months. The most common grade 3–4 adverse events were neutropenia (29%), infection (25%), anorexia (11%), esophagitis (11%) and fatigue (11%). Conclusion: Initial palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma.
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| 3. |
- Ekedahl, Henrik, et al.
(författare)
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Low-grade inflammation in survivors of childhood cancer and testicular cancer and its association with hypogonadism and metabolic risk factors
- 2022
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 22, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In childhood (CCS) and testicular cancer (TCS) survivors, low-grade inflammation may represent a link between testosterone deficiency (hypogonadism) and risk of metabolic syndrome. We aimed to study levels of inflammatory markers in CCS and TCS and the association with hypogonadism and future cardio-metabolic risk factors.METHODS: Serum levels of inflammatory markers and testosterone were analyzed in CCS (n = 90), and TCS (n = 64, median time from diagnosis: 20 and 2.0 years, respectively), and in controls (n = 44). Differences in levels between patients and controls were calculated using univariate analysis of variance. T-test and logistic regression were applied to compare levels of cardio-metabolic risk factors and odds ratio (OR) of hypogonadism and metabolic syndrome in low and high inflammatory marker groups after 4-12 years of follow up. Adjustment for age, smoking, and active cancer was made.RESULTS: TCS and CCS, as compared to controls, had 1.44 (95%CI 1.06-1.96) and 1.25 (95 CI 1.02-1.53) times higher levels of IL-8, respectively. High IL-6 levels were associated with hypogonadism at baseline (OR 2.83, 95%CI 1.25-6.43) and the association was stronger for high IL-6 combined with low IL-10 levels (OR 3.10, 95%CI 1.37-7.01). High IL-6 levels were also associated with higher BMI, waist circumference, insulin, and HbA1c at follow up. High TNF-α was associated with higher diastolic blood pressure. No individual inflammatory marker was significantly associated with risk of metabolic syndrome at follow up. High IL-6 combined with low IL-10 levels were associated with risk of metabolic syndrome (OR 3.83, 95%CI 1.07-13.75), however not statistically significantly after adjustment.CONCLUSION: TCS and CCS present with low-grade inflammation. High IL-6 levels were associated with hypogonadism and cardio-metabolic risk factors. Low IL-10 levels might reinforce the IL-6 mediated risk of developing metabolic syndrome.
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| 4. |
- Ekström, Anders, et al.
(författare)
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Integration of Specialized Palliative Care with Oncological Treatment in Patients with Advanced Pancreatic Cancer
- 2022
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Ingår i: Journal of pancreatic cancer. - : Mary Ann Liebert Inc. - 2475-3246. ; 8:1, s. 2-8
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The incidence of pancreatic cancer is around 5 in 100,000, and the 5-year survival is poor. Pancreatic cancer patients have a high disease-specific burden of symptoms, and palliative chemotherapy has varying side effects. The American Society of Clinical Oncology (ASCO) suggests integrating specialized palliative care (SPC) with standard oncological treatment for pancreatic cancer patients at stage ≥III. This study investigated the effects of enrollment into SPC >30 days before death.MATERIALS AND METHODS: This retrospective study included 170 patients with histopathologically verified pancreatic adenocarcinoma who received palliative chemotherapy at Skåne University Hospital and died between February 1, 2015, and December 31, 2017.RESULTS: Of the 170 patients, 151 were enrolled within the SPC unit; 97 of them for >30 days before death (group A). The remainder (group B) received SPC for ≤30 days before death (n = 54) or not at all (n = 19). Patients in groups A and B lived a median of 73 and 44 days, respectively, after the last palliative chemotherapy treatment (p < 0.001), but did not differ in terms of median overall survival (11.2 months vs. 10.9 months). Death in the hospital occurred in 84% of patients never admitted to SPC and 2% of patients ever admitted to SPC.CONCLUSION: Enrollment in SPC for longer than 30 days may lower the risk of receiving futile palliative chemotherapy at the end of life, compared with patients enrolled in SPC for 30 days or less before death. Enrollment in SPC lowers the risk of dying in a hospital.
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| 5. |
- Ekström, Anders, et al.
(författare)
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Second-line palliative chemotherapy, survival, and prognostic factors in patients with advanced pancreatic cancer
- 2021
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Ingår i: Acta Oncologica. - 1651-226X. ; 60:12, s. 1580-1588
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Pancreatic cancer is a highly lethal disease with a close association between incidence and mortality. First-line (FL) palliative chemotherapy prolongs survival and alleviates cancer-related symptoms. However, the survival benefit of second-line (SL) treatment is uncertain, as studies fail to consistently show prolonged survival for any given SL treatment, and in the absence of prognostic factors patients will receive a futile treatment. The aim of this study was to examine prognostic factors and survival in patients with pancreatic cancer, with special reference to SL therapy. Material and methods: This retrospective study included all patients with histopathologically verified pancreatic adenocarcinoma who received palliative chemotherapy at Skåne University Hospital and died between 1 Feb 2015 and 31 Dec 2017. Results: During the study period, a total of 170 patients with pancreatic cancer died after receiving palliative chemotherapy. Of these, 72 had received SL treatment after progression on FL treatment. Median overall survival (OS) from the start of SL treatment was 5.0 months (95% CI: 4.0–6.1). Median OS was 2.9 months for patients with performance status 2 at start of SL treatment compared to 5.3 months for patients with performance status 0–1 (p =.03), and 3.5 months (95% CI: 3.0–5.4) in patients with hypoalbuminemia (<36 g/L) at the start of SL therapy compared to 8.0 months (95% CI: 5.3–11.1) for patients with normal albumin levels (p =.009). Weight loss during FL therapy, a doubling of CA 19-9 after FL therapy, and length of progression-free survival during FL treatment were not associated with survival following SL therapy. Conclusion: Poor performance status and hypoalbuminemia are negative prognostic factors for survival on SL palliative treatment in patients with advanced pancreatic cancer. Possible gain in survival should be carefully considered before initiating SL chemotherapy.
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| 6. |
- Hau, Sofie Olsson, et al.
(författare)
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Chemotherapy, host response and molecular dynamics in periampullary cancer : The CHAMP study
- 2020
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the "Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)" study aims to monitor these processes to gain new insight into this perplexing disease. Methods: The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. Discussion: Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. Trial registration: This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.
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| 7. |
- Hau, Sofie Olsson, et al.
(författare)
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Trajectories of immune-related serum proteins and quality of life in patients with pancreatic and other periampullary cancer : the CHAMP study
- 2023
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Ingår i: BMC Cancer. - 1471-2407. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP).METHODS: Proximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts.RESULTS: In total nine proteins; chemokine (C-C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman's Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19-9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain.CONCLUSIONS: This is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as "chemo brain". It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition.TRIAL REGISTRATION: Clinical Trial Registration: NCT03724994.
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| 8. |
- Heby, Margareta, et al.
(författare)
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Additive clinical impact of epidermal growth factor receptor and podocalyxin-like protein expression in pancreatic and periampullary adenocarcinomas
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n = 175) and (Cohort 2, n = 189). The effect of TGF-β-induced expression and siRNA-mediated knockdown of PODXL and EGFR, were investigated in pancreatic cancer cells (PANC-1) in vitro. We found a correlation between PODXL and EGFR in these cancers, and a synergistic adverse effect on survival. Furthermore, silencing PODXL in pancreatic cancer cells resulted in the down-regulation of EGFR, but not vice versa. Consequently, these findings suggest a functional link between PODXL and EGFR, and the potential combined utility as biomarkers possibly improving patient stratification. Further studies examining the mechanistic basis underlying these observations may open new avenues of targeted treatment options for subsets of patients affected by these particularly aggressive cancers.
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| 9. |
- Masulli, P., et al.
(författare)
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Data-driven analysis of gaze patterns in face perception: Methodological and clinical contributions
- 2022
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Ingår i: Cortex. - : Elsevier BV. - 0010-9452. ; 147, s. 9-23
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Tidskriftsartikel (refereegranskat)abstract
- Gaze patterns during face perception have been shown to relate to psychiatric symptoms. Standard analysis of gaze behavior includes calculating fixations within arbitrarily predetermined areas of interest. In contrast to this approach, we present an objective, data-driven method for the analysis of gaze patterns and their relation to diagnostic test scores. This method was applied to data acquired in an adult sample (N = 111) of psychiatry outpatients while they freely looked at images of human faces. Dimensional symptom scores of autism, attention deficit, and depression were collected. A linear regression model based on Principal Component Analysis coefficients computed for each participant was used to model symptom scores. We found that specific components of gaze patterns predicted autistic traits as well as depression symptoms. Gaze patterns shifted away from the eyes with increasing autism traits, a well-known effect. Additionally, the model revealed a lateralization component, with a reduction of the left visual field bias increasing with both autistic traits and depression symptoms independently. Taken together, our model provides a data-driven alternative for gaze data analysis, which can be applied to dimensionally-, rather than categorically-defined clinical subgroups within a variety of contexts. Methodological and clinical contribution of this approach are discussed. © 2021 The Author(s)
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