A Retrospective Analysis of Systemic Oncologic Treatment in Older Patients With Advanced Soft-tissue Sarcoma.

BACKGROUND/AIM: Almost half of all patients with soft-tissue sarcoma are over 65 years of age, and the proportion of older patients is increasing. Despite this, they have been underrepresented in clinical trials and only limited data are available to guide treatment decisions. The aim of this study was to investigate treatment patterns and outcomes in older patients with soft-tissue sarcoma. PATIENTS AND METHODS: Patients over 50 years old treated for advanced soft-tissue sarcoma at the Helsinki University Hospital between January 2000 and July 2020 were included. Data on patient and tumor characteristics, treatment, and survival were retrospectively collected. A total of 152 patients were included: 14.5% (n=22) were over 75 years old, 34.2% (n=52) were 65-74 and 51.3% (n=78) were 50-64 years old. RESULTS: The outcomes of the oldest group differed from those of younger patients; they were more likely to receive single-agent treatment as first-line therapy (90.9% vs. 28.8% and 24.4%, p<0.001) and had the lowest relative dose-intensity (70% vs. 88% and 95%, p<0.05). They experienced grade three to four hematological adverse events less frequently (38.1%, 56.9% and 72.7%, respectively, p=0.031), and received fewer lines of treatment (median of 1, 2 and 2, respectively, p=0.01). In patients aged ≥75 years, there was no association between further lines of therapy and improved survival. Compared to the youngest group, the oldest patients had a greater risk of dying (hazard ratio=1.7, 95% confidence interval=1.0-2.8, p=0.041) and their median overall survival was only 7.4 months, compared to 14.3 and 12.9 months in the two younger groups. CONCLUSION: These findings suggest that older patients tolerate chemotherapy when treatment is tailored to their needs but may not benefit as much as younger patients.

Ultra-low-dose computed tomography and chest X-ray in follow-up of high-grade soft tissue sarcoma-a prospective comparative study.

Ultra-low-dose computed tomography (ULD-CT) may combine the high sensitivity of conventional computed tomography (CT) in detecting sarcoma pulmonary metastasis, with a radiation dose in the same magnitude as chest X-ray (CXR). Fifty patients with non-metastatic high-grade soft tissue sarcoma treated with curative intention were recruited. Their follow-up involved both CXR and ULD-CT to evaluate their different sensitivity. Suspected findings were confirmed by conventional CT if necessary. Patients with isolated pulmonary metastases were treated with surgery or stereotactic body radiation therapy (SBRT) with curative intent if possible. The median effective dose from a single ULD-CT study was 0.27 mSv (range 0.12 to 0.89 mSv). Nine patients were diagnosed with asymptomatic lung metastases during the follow-up. Only three of them were visible in CXR and all nine in ULD-CT. CXR had therefore only a 33% sensitivity compared to ULD-CT. Four patients were operated, and one had SBRT to all pulmonary lesions. Eight of them, however, died of the disease. Two patients developed symptomatic metastatic recurrence involving extrapulmonary sites+/-the lungs between two imaging rounds. ULD-CT has higher sensitivity for the detection of sarcoma pulmonary metastasis than CXR, with a radiation dose considerably lower than conventional CT.Clinical trial registration: NCT05813808. 04-14-2023.

A pilot study about methods to reduce prescription errors in a chemotherapy day unit - Aspects to consider in pharmacist verification process.

INTRODUCTION: Prescribing errors can happen unintentionally during the prescribing process, or when choosing a treatment therapy. Prescribing errors have the highest prevalence amongst common error types related to chemotherapy medication in outpatient settings. According to the Joint Commission International (JCI), prescriptions should be reviewed for appropriateness by someone else than the prescriber or practitioner to prevent medication errors. AIM: The study was aimed to map out the existing type and amount of occurring deviations in prescribing and to clarify the current chemotherapy prescribing practices at the Comprehensive Cancer Center at Helsinki University Hospital. Similar research has not been published in Finland before. METHODS AND PATIENTS: The researcher selected patients randomly from the daily outpatient attendance list following a predetermined numerical order. Data was collected by conducting a medication verification review in line with the JCI guidance by a clinical pharmacist the day before the patient's clinic appointment using the available medical documentation. A clinical pharmacist evaluated findings from prescriptions and contacted an oncologist if the findings were considered clinically significant. RESULTS: A clinical pharmacist verified prescriptions from 101 patients for appropriateness and found discrepancies in four percent of the prescriptions (n = 4/101). The oncologist approved 50 percent of the suggested amendments by the pharmacist as clinically significant (n = 2/4). The study revealed that patient's regular home medications were not always correctly recorded into the database, so verification of medicine interactions could not be trusted as completely accurate. It took on average 16 min per patient to perform a medication verification review. The process was slowed down by the lack of detailed enough protocols for this purpose and the current patient care record system not having structural formatting of data entry. CONCLUSIONS: Verification of prescriptions provides a tool to identify prescribing discrepancies and to prevent unintended medication errors affecting patients. The development of detailed protocols and guidelines, as well as an appropriate training program, would support pharmacists in compiling clinical medication reviews for chemotherapy patients. More research is needed to further develop the operating model in Finland. Information gathered from this study can be used for identifying training requirements.

Lung metastases and subsequent malignant transformation of a fumarate hydratase -deficient uterine leiomyoma.

Uterine leiomyomas, or fibroids, are very common smooth muscle tumors. Their potential to metastasize or transform into leiomyosarcomas is extremely low. Here, we report a patient who underwent hysterectomy due to a large leiomyoma and who was diagnosed with pulmonary tumors seven and nine years later. Histopathological re-evaluation confirmed the cellular leiomyoma diagnosis for the uterine tumor, whereas the pulmonary tumors met the diagnostic criteria of a leiomyosarcoma. Whole-exome sequencing revealed very similar mutational profiles in all three tumors, including a somatic homozygous deletion in a rare, but well-established leiomyoma driver gene FH. Tumor evolution analysis confirmed the clonal origin of all three tumors. In addition to mutations shared by all three tumors, pulmonary tumors harbored additional alterations affecting e.g. the cancer-associated genes NRG1 and MYOCD. The second pulmonary leiomyosarcoma harbored additional changes, including a mutation in FGFR1. In global gene expression profiling, the uterine tumor showed similar expression patterns as other FH-deficient leiomyomas. Taken together, this comprehensive molecular data supports the occasional metastatic capability and malignant transformation of uterine leiomyomas. Further studies are required to confirm whether FH-deficient tumors and/or tumors with cellular histopathology have higher malignant potential than other uterine leiomyomas.

Serum Concentration of Thymidine Kinase 1 (TK1) as a Tumor Marker in Soft Tissue Sarcomas.

BACKGROUND/AIM: The aim of this prospective study was to determine whether serum Thymidine kinase -1 (TK1) could serve as a tumor marker in soft tissue sarcomas (STS). PATIENTS AND METHODS: A total of 48 patients diagnosed with localized STS were included. None had received preoperative oncological treatment. Samples were collected before and after surgery and TK1 levels measured with the AroCell TK210 ELISA. RESULTS: Mean preoperative TK1 was 0.32 µg/l, range=0.11-1.47, and 18 cases (38%) had values above the reference limit (0.41 µg/l). Mean postoperative TK1 was 0.35 µg/l (0.06-0.86). In patients with preoperative values above the reference limit, TK1 decreased significantly after surgery (n=13, p=0.001). We found no association between increased preoperative TK1 and age, sex, tumor size, grade, and the presence of vascular invasion or necrosis. CONCLUSION: TK1 has limited use as a tumor marker in localized STS.

(Neo)adjuvant chemotherapy and interdigitated split-course hyperfractionated radiation in high risk soft tissue sarcoma - Results from a large single-institution series.

A single-institution series using a (neo)adjuvant chemotherapy and interdigitated hyperfractionated split-course radiation therapy (CRT) treatment protocol for soft tissue sarcoma was reviewed. Our specific aims were to study recurrence rates and long-term toxicity. Between 1998 and 2016, 89 patients with non-metastatic soft tissue sarcoma were treated with surgery combined with six courses of doxorubicin and ifosfamide and hyperfractionated radiation therapy (42-60 Gy/1.5 Gy twice daily). Patients were considered being at high risk if tumour malignancy grade was high and the tumour fulfilled at least two of the following criteria: size >8 cm, presence of necrosis or vascular invasion. The mean age of the patients was 50.7 years. With a median follow-up of 5.4 years for survivors, the local control rate was 81.4%. Six (7%) patients progressed during neoadjuvant CRT. Seven (8%) patients discontinued the treatment due to toxicity. Eighty-six patients were operated and three (3%) of these developed a long-term complication. The estimated metastasis-free survival was 47.6% and overall survival 53.0% at five years. The limb-salvage rate was 93%. The limb-salvage rate, local control and complication rates were good in these patients with high risk soft tissue sarcoma. Metastases-free survival and overall survival rates were less satisfactory, reflecting the aggressive nature of these tumours.

Long-term results of surgical resection of lung metastases from soft tissue sarcoma: A single center experience.

BACKGROUND: A single-institution experience of pulmonary metastasectomy in soft tissue sarcoma (STS) was retrospectively reviewed. Our specific aim was to examine, whether the resection of pulmonary metastases could be curative. We also compared overall survival (OS) of patients after complete or incomplete pulmonary resection and nonsurgical treatment. METHODS: Between 1987 and 2016, 1580 patients were treated for STS with curative intent by Soft Tissue Sarcoma Group at Helsinki University Hospital, Finland. Three hundred forty-seven patients (22%) developed advanced disease and 130 STS patients (9%) developed pulmonary metastases as first systemic relapse. Seventy four patients (5%) were operated for lung metastases. RESULTS: Fifty-five patients (42%) had a complete and 19 (15%) incomplete resection. Fifty-six (43%) were unoperated. Median OS after complete or incomplete metastasectomy, chemotherapy, or best supportive care was 22, 18, 8, and 5 months, respectively. Twelve patients (9%) developed no further metastases and are alive with no evidence of disease. Disease-free survival (DFS) for completely resected patients was 17% at 5 years. All long-term survivors had oligometastatic disease and they underwent one to three complete metastasectomies. CONCLUSIONS: Complete pulmonary metastasectomy in STS results in 5 years DFS in nearly one-fifth of patients. Most of these patients are probably cured.

Single-Institution, Multidisciplinary Experience of Soft Tissue Sarcomas in the Chest Wall.

INTRODUCTION: We report our single-institution, multidisciplinary experience of nearly 20 years of working on chest wall soft tissue sarcoma cases. The aim of this study was to evaluate clinical outcomes in patients with chest wall soft tissue sarcoma. MATERIALS AND METHODS: A retrospective review of 49 surgically treated patients with chest wall soft tissue sarcoma was conducted from 1997 to 2015. RESULTS: The median age of the patients was 57.0 years. There were 19 full-thickness and 30 partial-thickness resections. Reconstruction was warranted in 37 cases. Sarcomas were high grade in 31 (63.3%) and low grade in 18 (36.7%) cases. Local recurrence developed in 8 and metastasis in 9 patients. No 30-day mortality occurred. By the end of the study period, 35 patients were alive and 14 had died. The 1-, 5-, and 10-year survival rates were 93.8%, 76.0%, and 71.6%, whereas the overall recurrence-free rates were 84.4%, 70.7%, and 70.7% respectively. Favorable prognostic variables for survival included age <50 years and radical treatment (resection with wide margin or resection with marginal margin and adjuvant radiotherapy). Patients who had undergone nonradical treatment had a 3.1-fold lower chance of survival than did those who had undergone radical treatment (95% confidence interval, 0.96-10.12; P = 0.06). CONCLUSIONS: Our study suggests that surgical resection with wide margins should continue to be the mainstay for patients with chest wall sarcoma. Even extensive chest wall resections and reconstructions are safe. If wide margins are not achieved, (neo)adjuvant radiotherapy should be considered to improve local control.

[Hypersensitivity reactions caused by intravenously administered anticancer drugs]. / Suoneen annosteltavien syöpälääkkeiden aiheuttamat yliherkkyysreaktiot ja niiden hoito.

Intravenously administered cytotoxic drugs and biological antibodies may cause infusion reactions, the majority of which are mild. Severe, even fatal reactions occur as well. Adrenaline is invariably the most important treatment of a severe reaction. When contemplating whether the patient should again be subjected to a drug having caused a reaction, aspects to be considered include the degree of severity of the reaction, pathogenetic mechanism, the patient's general condition and cancer stage as well as the possibility to change the anticancer drug that caused reaction to another drug having a similar action on the patient's disease.

[How to treat an elderly person's cancer?]. / Miten ikääntyneen syöpää tulisi hoitaa?

Among the elderly having cancer, many are in good condition and wish for active treatment. Although elderly people have been shown to benefit from oncological treatments, they are more susceptible than the young to the adverse effects of treatment. Comprehensive geriatric assessment has been utilized in predicting the capability of an elderly patient to tolerate treatment. A functional status questionnaire completed by the patient her/himself has been used in the oncological unit of Helsinki University Hospital in support of a cancer drug therapy assessment. The consultations with an oncologist have been centralized and the patients have had a possibility to meet a geriatrist.

In school-aged children a combination of galacto-oligosaccharides and Lactobacillus GG increases bifidobacteria more than Lactobacillus GG on its own.

The aim of this study was to compare a combination of Lactobacillus GG (LGG) and galacto-oligosaccharides (GOS) with LGG on its own, and their effects on the intestinal microbiota in school-aged children. The randomized, double-blinded, crossover study comprised 30 healthy children. There were two 3-week study periods with a 4-week wash-out period in between. The children ingested daily 65 ml of milk-based fruit juice containing either LGG alone (6.5 x 10(9) CFU) or LGG plus 2 g of GOS. Symptom diaries were filled during the study periods. Fecal samples were collected at the beginning and end of both study periods. At the end of both study periods, the amount of bifidobacteria was significantly greater after the ingestion of LGG + GOS compared with LGG alone (geometric mean 9.33 x 10(9) vs. 4.28 x 10(9) CFU/g, p < 0.001). No significant differences were seen in the amount of lactobacilli or LGG, nor did gastrointestinal symptoms, defecation frequency, consistency of stools or ease of defecation differ between the two study periods. Ingestion of LGG combined with 2 g of GOS increased the bifidobacteria more than LGG on its own and thus GOS clearly has a prebiotic effect in children. The children tolerated well a daily intake of 2 g of GOS.

Plant stanol esters in low-fat milk products lower serum total and LDL cholesterol.

BACKGROUND: Oil-based matrices enriched with plant stanol esters lower serum LDL cholesterol. The effects of low-fat milk products have been less thoroughly examined. AIM OF THE STUDY: To evaluate the effect of three less explored low-fat milk products enriched with plant stanol esters on serum lipid concentrations in subjects with mild or moderate hypercholesterolemia. METHODS: A meta-analysis of four unpublished sub-studies (yoghurt, yoghurt single-shot drink: Studies I and II, or milk). All the substudies were randomized, placebo-controlled, double-blind and had a parallel-group design. They were carried out in order to evaluate the effect of low-fat milk products enriched with plant stanol esters on serum lipid concentration. Each stanol-ester-enriched milk product provided 2 g of stanols per day, and in each study the intervention period was 5 weeks. A total of 199 hypercholesterolemic subjects completed the studies. RESULTS: The pooled treatment difference in total cholesterol was -3.8% (95% CI -6.0 to -1.7, p < 0.001) when stanol was compared to placebo. In LDL cholesterol, the pooled treatment difference was -4.9% (95% CI -7.8 to -1.8, p = 0.002). There were no significant differences between the groups in pooled HDL cholesterol or triacylglycerol concentrations. The results tended to be more pronounced when we were certain that the yoghurt single-shot drink was ingested with lunch, and when the baseline LDL-cholesterol concentration was > or = 3.5 mmol/l. CONCLUSIONS: These results imply that low-fat milk products enriched with plant stanol esters lower both total cholesterol and LDL cholesterol statistically significantly in subjects with mild or moderate hypercholesterolemia. The changes tended to relate to the baseline LDL-cholesterol concentration.

The effect of Lactobacillus helveticus fermented milk on acute changes in calcium metabolism in postmenopausal women.

BACKGROUND: Milk fermented with Lactobacillus helveticus ( L. helveticus) has been shown to lower blood pressure and to increase bone mineral content in spontaneously hypertensive rats. The effect of L.helveticus may be due to better calcium availability. AIM OF THE STUDY: In the present study the effect of milk fermented with L. helveticus on acute changes in calcium metabolism and bone resorption in postmenopausal women was studied. METHODS: The study was performed as a randomised double-blind crossover study of 20 postmenopausal women (mean age 65, range 50-78). The study was carried out in two parts. Firstly, L. helveticus fermented milk was compared to a control milk. Secondly, juice containing peptides formed with L. helveticus bacteria was compared to a control juice. The acute effect on calcium metabolism was measured during the study day by serum ionised calcium (iCa), parathyroid hormone (PTH), calcium (Ca), phosphate (P), and urinary calcium. A direct marker of bone turnover, carboxyterminal telopeptide of type I collagen (ICTP), was measured from the serum. RESULTS: L. helveticus fermented milk reduced serum PTH (405.3 +/- 37 ng/l vs. 454.9 +/- 37, p = 0.012) and increased serum calcium (19.1 +/- 0.2 mmol/l vs. 18.8 +/- 0.2, p = 0.031) compared to the control milk. L. helveticus derived peptides had no significant acute effect on calcium metabolism, in fact, ionised calcium was lower and PTH higher after the juice containing peptides compared to the control juice. CONCLUSIONS: Fermentation of milk with Lactobacillus helveticus had a positive acute effect on calcium metabolism. This effect was not explained by the small peptides formed by L. helveticus.

Genistein treatment reduces arterial contractions by inhibiting tyrosine kinases in ovariectomized hypertensive rats.

The aim of the present study was to evaluate the vascular effects of genistein in a short-term study. The ovariectomized spontaneously hypertensive rats (SHR) were divided into four groups (n = 8 in each), which received the following subcutaneous treatments either for 2 days or for 2 weeks: (1) solvent control (96% dimethylsulphoxide (DMSO) 1 ml/kg), (2) estradiol-17beta (25 microg/kg), (3) genistein (2.5 mg/kg; low-dose), and (4) genistein (25 mg/kg; high-dose). The renal arterial rings were studied using organ bath system. The renal artery contractions were attenuated by the 2-day low-dose genistein treatment as follows: angiotensin II (46%), noradrenaline (42%) KCl (36%), and endothelin-1 (34%). Only the angiotensin II-induced contractions were reduced by the 2-week treatment with estradiol-17beta (38%) and with the low-dose of genistein (31%). The 2-day genistein treatment reduced tyrosine phosphorylation, while the other treatments or treatment times had no effect. The 2-day low-dose genistein treatment had no estrogenic effect on the uterine morphology. The mechanism for attenuated contractility in the renal arteries after the 2-day low-dose genistein treatment is independent of the estrogenic effect of genistein, but is due to the tyrosine kinase inhibitory property of genistein.