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- Berndsen, Marta, 1986, et al.
(författare)
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Long-term outcome after surgical resection of non-high-risk gastrointestinal stromal tumours without adjuvant therapy
- 2023
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Ingår i: The British journal of surgery. - 1365-2168. ; 110:12, s. 1857-1862
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common intra-abdominal sarcoma. Risk classification systems, commonly the modified National Institutes of Health consensus criteria, identify tumour properties relating to patient outcomes. However, owing to limited long-term evidence, most guidelines recommend up to 10-year follow-up for all risk groups except very low-risk GIST. METHODS: This retrospective multicentre study included patients who had complete resection of primary, non-metastatic GIST from three Scandinavian sarcoma centres: Gothenburg (2004-2020), Stockholm (2000-2019), and Oslo (2000-2017). Medical records were reviewed for clinical details regarding diagnosis, treatment, and follow-up, and recurrence-free and disease-specific survival evaluated. RESULTS: The total cohort consisted of 1213 patients with GIST. High-risk patients and those treated with tyrosine kinase inhibitors were excluded. The remaining 649 patients were included in the present analysis: 118 with very low-, 381 with low-, and 150 with intermediate-risk GISTs. Five-year recurrence-free survival rates were 100, 98.5, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.246). Disease-specific survival rates 10 years after surgery were 100, 98.4, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.262). CONCLUSION: Patients with completely resected non-high-risk GISTs have an excellent long-term outcome, irrespective of risk group. Follow-up programmes to detect disease recurrences in these patients are probably not indicated.
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| 2. |
- Hübbert, Laila, et al.
(författare)
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Long-term and real-life incidence of cancer therapy-related cardiovascular toxicity in patients with breast cancer: a Swedish cohort study
- 2023
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Ingår i: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 44
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe administration of anticancer drugs in females with comorbidity increases the risk for cancer therapy-related cardiovascular toxicity (CTR-CVT), which in turn contributes to cardiovascular disease (CVD). Furthermore, a pathophysiological connection between cancer and cardiovascular disease may exist. ObjectiveTo assess the long-term risks and predictors of CTR-CVT, including clinical hypertension (HT), coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), as well as all-cause mortality in women diagnosed with early breast cancer (BC) and eligible for adjuvant chemotherapy in Sweden. MethodsData were extracted from Swedish registers and medical records on 433 women, 18-60 years of age, diagnosed 1998-2002 with lymph node-positive BC, and considered for adjuvant chemotherapy. CTR-CVT was defined as HT, CAD, HF, or AF after the diagnosis of BC. Follow-up was from the date of BC diagnosis until November 30, 2021, or death. Prevalence of CTR-CVT and all-cause mortality were calculated. Hazard ratios (HR) were determined for factors associated with CTR-CVT. ResultsThe median age was 50 (interquartile range (IQR) 32) years. 910 CTR-CVT events were diagnosed in 311 women with a median of 19.3 (IQR 15,3) years follow-up. The proportions of CTR-CVT events were: HT 281 (64%); CAD 198 (46%); HF 206 (47%); and AF 225 (51%). The cumulative incidence of CTR-CVT was 71.8%, and 50% of all 433 patients developed CTR-CVT within 11.7 years of BC diagnosis (standard deviation (SD) 0.57, 95% confidence interval (CI) 10.6-12.9). Age was a risk factor for CTR-CVT. Anthracycline increased the risk for HF (p=0,001; HR 2,0; 95%CI 1,4-2,8), CAD (p= 0,002; HR 1,7; 95% CI 1,2-2,4), and AF (p=0,013; HR 1,5; 95% CI 1,0-2,0). At the end of the 24-year study period, 227 of the 433 women were alive, and the total cumulative mortality was 47,6%. ConclusionThe prevalence of CTR-CVT and all-cause mortality is high after BC diagnosis and treatment, particularly in older patients and those receiving anthracyclines. These findings and the onset of CTR-CVT support cardio-oncology guidelines recommending initial risk stratification and cardiovascular monitoring during treatment, followed by long-term annual screening for cardiovascular risk factors and CTR-CVT among BC survivors.
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| 3. |
- Ofverholm, Ingegerd, et al.
(författare)
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Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma
- 2024
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research (AACR). - 1078-0432 .- 1557-3265. ; 30:12, s. 2647-2658
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Tumor classification is a key component in personalized cancer care. For soft-tissue and bone tumors, this classification is currently based primarily on morphology assessment and IHC staining. However, these standard-of-care methods can pose challenges for pathologists. We therefore assessed how whole-genome and whole-transcriptome sequencing (WGTS) impacted tumor classification and clinical management when interpreted together with histomorphology.Experimental Design: We prospectively evaluated WGTS in routine diagnostics of 200 soft-tissue and bone tumors suspicious for malignancy, including DNA and RNA isolation from the tumor, and DNA isolation from a peripheral blood sample or any non-tumor tissue.Results: On the basis of specific genomic alterations or absence of presumed findings, WGTS resulted in reclassification of 7% (13/197) of the histopathologic diagnoses. Four cases were downgraded from low-grade sarcomas to benign lesions, and two cases were reclassified as metastatic malignant melanomas. Fusion genes associated with specific tumor entities were found in 30 samples. For malignant soft-tissue and bone tumors, we identified treatment relevant variants in 15% of cases. Germline pathogenic variants associated with a hereditary cancer syndrome were found in 22 participants (11%).Conclusions: WGTS provides an important dimension of data that aids in the classification of soft-tissue and bone tumors, correcting a significant fraction of clinical diagnoses, and identifies molecular targets relevant for precision medicine. However, genetic findings need to be evaluated in their morphopathologic context, just as germline findings need to be evaluated in the context of patient phenotype and family history.
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| 4. |
- Papakonstantinou, Andri
(författare)
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Studies of side effects related to adjuvant breast cancer regimens with focus on chemotherapy
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Radiotherapy, endocrine therapy, chemotherapy and targeted therapy adjunct to surgery have a critical role in the management of early breast cancer for outcome improvement. Anthracycline containing chemotherapy reduces 10-year incidence of breast cancer mortality by an absolute 6.5% compared to no adjuvant chemotherapy and addition of taxanes to anthracycline regimes leads to additional gain of 2.8% in 8-years breast cancer mortality. Dose dense chemotherapy improves breast cancer mortality by an estimated relative reduction of 40%. Trastuzumab, the first anti-HER2 agent among plenty, administered for one year, led to a paradigm shift in the management of HER2 positive breast cancer and significantly altered prognosis. Adjuvant trastuzumab improves disease free survival by a relative risk reduction of 40%. Despite beneficial effect of chemotherapy and anti-HER2 targeted therapy, acute or late toxicity can be dose limiting and even influence patients’ quality of life during treatment and long time after it is completed. Given the good prognosis of breast cancer and the millions of breast cancer survivors, therapy related toxicity affects a considerable number of women. Efforts to escalate or de-escalate treatment are ongoing and potential trade-offs in safety are monitored, resulting at best to improved benefit-risk balance. The aim of the current thesis was to examine heart failure outcomes and management after breast cancer diagnosis compared to a population of women with heart failure and toxicity outcomes related to tailored dose dense chemotherapy namely, cardiotoxicity after combination with trastuzumab, neutropenia related events and premature ovarian insufficiency. The Swedish Registry for heart failure (SwedeHF) and the national health care registries were utilised for the purposes of Paper I. Patients enrolled in the SwedeHF registry between 2008 and 2013 were included and followed for a median period of two years. Patients with breast cancer history, identified through the National Cancer Registry, and age-matched controls (1:5) were investigated. Heart failure related baseline characteristics and outcomes did not differ amid presence of breast cancer history among women registered in the SwedeHF registry with incident heart failure. Differences in the history of myocardial infarction, administration of aspirin and device therapy were observed among women with prevalent heart failure, depending on previous breast cancer history. Breast cancer history did not alter heart failure outcomes but time from heart failure diagnosis did; women with prevalent heart failure had worse survival than those with incident heart failure. Papers II-IV investigated different toxicity aspects related to the population enrolled and treated in the PANTHER phase III study comparing tailored (protocol predefined dose escalation or de-escalation) and dose dense (every two weeks) chemotherapy to standard dose three weekly chemotherapy. Paper II, investigated if tailored dose dense chemotherapy can further improve trastuzumab efficacy, compared to combination with standard chemotherapy and whether this combination would jeopardise cardiac safety; both parts of the study were predefined. The trastuzumab and tailored dose dense group demonstrated a 32% relative improvement in risk for breast cancer relapse but the results did not reach formal statistical significance. Despite small reductions of left ventricular ejection fraction at four- and sixyears follow-up, no clinically meaningful difference in the risk for cardiotoxicity was demonstrated between tailored dose dense chemotherapy and standard chemotherapy compared as administration per HER2 treatment or as per chemotherapy group. Compliance to the planned chemotherapy schedule is related to better breast cancer outcomes, underscoring the value of prophylactic granulocyte-colony stimulating factor (GCSF). Efficacy of G-CSF in preventing neutropenic events and delays in the delivery of the planned chemotherapy dose were examined in a secondary analysis in Paper III. Administration of G-CSF reduced the risk for neutropenic events defined as febrile neutropenia or infection with low absolute neutrophil count. Although a comparison between the two treatment groups was not possible, within group investigation in the standard chemotherapy group revealed improved adherence to planned schedule by fewer dose delays when G-CSF was administered. Chemotherapy-induced amenorrhea is a therapy-related adverse event but it also improves breast cancer survival. Efficacy of dose dense chemotherapy has been assumed to derive from increased incidence of chemotherapy-induced amenorrhea. Thus, the exploratory, post hoc studies in Paper IV investigated the incidence of chemotherapy-induced amenorrhea and impact on treatment outcomes, excluding patients receiving gonadotropin releasing hormone agonists. Even though the delivered mean chemotherapy doses in the experimental treatment group were higher than in the standard chemotherapy group, amenorrhea incidence at two years of follow-up between the two treatment groups did not differ. Hence, benefit of dose dense chemotherapy is deemed to stem from chemotherapy effect per se and not aggravated gonadal toxicity. Breast cancer relapse events were too few to make any inference on the impact of amenorrhea on breast cancer relapse outcomes and longer follow-up is required. Menstruation status did not impact efficacy of allocated treatment although a non-significant benefit from tailored dose dense chemotherapy was demonstrated and persisted in most breast cancer subgroups. Sub-group analysis of the different breast cancer subtypes did not reveal any influence of the baseline menopause status on the efficacy of given chemotherapy schedule, except in triple negative breast cancer. There is no known biological plausibility to explain this interaction and the possibility of a chance finding cannot be excluded. In summary, at median follow-up of two years, having previously been diagnosed with breast cancer did not alter heart failure outcomes, compared to controls, although some limited discrepancies in existing comorbidities and heart failure treatment were observed. Moreover, increasing dose intensity did not relate to excess cardiotoxicity when combined with trastuzumab, did not increase the risk for neutropenic events, provided G-CSF prophylaxis is administered, and did not affect risk for premature ovarian insufficiency. Conclusively, patients with early breast cancer should be offered efficient breast cancer therapy related to their risk level, with proper supportive therapy and assessment of potential comorbidities such as cardiovascular risk factors.
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