Early clinical experience with a degraded 4 MeV electron beam in radiotherapy of superficial basal cell carcinoma.

The most common non-melanoma skin cancer is basal cell carcinoma (BCC). Surgery is the gold standard treatment but also non-surgical alternatives are needed. The purpose of this work was to present the early clinical experiences of degraded 4 MeV electron beam as a treatment method for superficial BCC. Twelve patients underwent two weeks radiation therapy treatment with either 5 × 7 Gy or 2 × 12 Gy. There were no significant differences in treatment outcome with different fractionations or lesion locations. The degraded beam method is a safe and valid non-surgical solution for suitable patients with superficial lesions.

Palliative intensity modulated radiotherapy of bone metastases based on diagnostic instead of planning computed tomography scans.

Background and purpose: Radiotherapy (RT) treatment planning is as a standard based on a computed tomography (CT) scan obtained at the planning stage (pCT), while most of the decisions whether to treat by RT are based on diagnostic CT scans (dCT). Bone metastases (BM) are the most common palliative RT target. The objective of this study was to investigate if a palliative RT treatment plan of BMs could be made based on a dCT with sufficient accuracy and safety, without sacrificing any treatment quality. Materials and methods: A retrospective study with 60 BMs of 8 anatomical sites was performed. RT planning was performed using intensity-modulated radiation therapy/volumetric modulated arc therapy techniques in dCT and transferred to pCT. The dose of clinical target volumes (CTVs), D(CTVV95%, V50%), were compared between plans for dCT and pCT. Patient setup was investigated in cone-beam CT scans. Results: The differences of D(CTVV95%, V50%) between dCT and pCT plans were the lowest in the pelvis (1.0%, 1.1%), lumbar spine (0.6%, 0.7%) and thoracic spine (0.7%, 2.1%), while the differences were higher in cervical spine (3.7%, 1.9%), long bones (2.3%, 0.8%), and costae (1.6%, 1.4%). The patient set-up was acceptable for 100% of the pelvic and lumbar, for 92% of thoracic spine cases, and for <80% of cases in other sites. Conclusion: This study showed the feasibility of using dCT images in palliative RT planning of BMs in thoracic, lumbar spine and pelvic sites, indicating the potential suitability of this strategy for clinical use.

Chemoradiation for oesophageal cancer: the choice of treatment modality.

BACKGROUND: Locally advanced oesophageal cancer can be treated with definitive chemoradiation (dCRT) or with neoadjuvant chemoradiation followed by surgery (nCRT + S), but treatment modality choice is not always clear. The aim of this study was to investigate the factors associated with the choice of treatment modality in locally advanced oesophageal cancer. METHODS: This was a retrospective cohort study of 149 patients treated with dCRT(n = 85) or nCRT + S (n = 64) for oesophageal cancer in Helsinki University Hospital in 2008-2018. Logistic regression was used to analyse factors associated with choice of treatment modality and to compare dosimetric factors with postoperative complications. Multivariate analyses identified factors associated with survival. RESULTS: Surgery was performed after chemoradiation as planned on 64/91 patients (70%). 28/64 had pathological complete response (44%). Probability of nCRT + S was higher in stages I-III versus IV (OR 3.62, 95% CI 1.53-8.53; P = .003), ECOG 0-1 versus 2 (OR 6.99, 95% CI 1.81-26.96; P = .005) or in the middle/lower vs upper oesophageal tumours (OR 5.61, 95% CI 1.83-17.16, P = .003). Probability for surgery was lower, if patient had lost > 10% of body weight (OR 0.46, 95% CI 0.21-0.98, P = 0.043). Patients in the nCRT + S group had significantly better median overall survival (mOS) and local control than the dCRT group (60 vs. 10 months, P < .001 and 53 vs. 6 months, P < 0.0001, respectively). 10/85 (12%) patients died within three months after dCRT. In multivariate analysis, nCRT + S was associated with improved mOS (HR 0.28, 95% CI 0.17-0.44, P < .001). Current smokers had worse mOS (HR 2.02, 95% CI 1.04-3.92, P = .037) compared to never-smokers. No significant dosimetric factor associated with postoperative complications was found. CONCLUSION: The overall clinical status of the patients and the stage of the cancer guide the choice of treatment modalities, leading to overtreatment. Patients with better prognoses were more likely operated after chemoradiation, although there is no evidence of OS benefit in previous randomized trials. On the other hand, the prognosis was poor for patients with poor general health and advanced cancers, despite the chemoradiation. Thus, there are signs of overtreatment. MDT practice should be recommended to optimise the choice of treatment modalities. Smoking status is an independent factor associated with survival.

Effect of palliative care decisions making on hospital service use at end-of-life in patients with malignant brain tumors: a retrospective study.

BACKGROUND: Palliative care (PC) improves Quality of life and reduces the symptom burden. Aggressive treatments at end of life (EOL) postpone PC. The aim of this single-center retrospective study was to evaluate the timing of the PC decision i.e., termination of cancer-specific treatments and focusing on symptom-centered PC, and its impact on the use of tertiary hospital services at the EOL. METHODS: A retrospective cohort study on brain tumor patients, who were treated at the Comprehensive Cancer Center of the Helsinki University Hospital from November 1993 to December 2014 and died between January 2013 and December 2014, were retrospectively reviewed. The analysis comprised 121 patients (76 glioblastoma multiforme, 74 males; mean age 62 years; range 26-89). The decision for PC, emergency department (ED) visits and hospitalizations were collected from hospital records. RESULTS: The PC decision was made for 78% of the patients. The median survival after diagnosis was 16 months (13 months patients with glioblastoma), and after the PC decision, it was 44 days (range 1-293). 31% of the patients received anticancer treatments within 30 days and 17% within the last 14 day before death. 22% of the patients visited an ED, and 17% were hospitalized during the last 30 days of life. Of the patients who had a PC decision made more than 30 days prior to death, only 4% visited an ED or were hospitalized in a tertiary hospital in the last 30 days of life compared to patients with a late (< 30 days prior to death) or no PC decision (25 patients, 36%). CONCLUSIONS: Every third patient with malignant brain tumors had anticancer treatments during the last month of life with a significant number of ED visits and hospitalizations. Postponing the PC decision to the last month of life increases the risk of tertiary hospital resource use at EOL.

From Nuclear Reactor-Based to Proton Accelerator-Based Therapy: The Finnish Boron Neutron Capture Therapy Experience.

The authors review the results of 249 patients treated with boron neutron capture therapy (BNCT) at the Helsinki University Hospital, Helsinki, Finland, from May 1999 to January 2012 with neutrons obtained from a nuclear reactor source (FiR 1) and using l-boronophenylalanine-fructose (l-BPA-F) as the boron delivery agent. They also describe a new hospital BNCT facility that hosts a proton accelerator-based neutron source for BNCT. Most of the patients treated with nuclear reactor-derived neutrons had either inoperable, locally recurrent head and neck cancer or malignant glioma. In general, l-BPA-F-mediated BNCT was relatively well tolerated with adverse events usually similar to those of conventional radiotherapy. Twenty-eight (96.6%) out of the evaluable 29 patients with head and neck cancer and treated within a clinical trial either responded to BNCT or had tumor growth stabilization for at least 5 months, suggesting efficacy of BNCT in the treatment of this patient population. The new accelerator-based BNCT facility houses a nuBeam neutron source that consists of an electrostatic Cockcroft-Walton-type proton accelerator and a lithium target that converts the proton beam to neutrons. The proton beam energy is 2.6 MeV operating with a current of 30 mA. Treatment planning is based on Monte Carlo simulation and the RayStation treatment planning system. Patient positioning is performed with a 6-axis robotic image-guided system, and in-room imaging is done with a rail-mounted computed tomography scanner. Under normal circumstances, the personnel can enter the treatment room almost immediately after shutting down the proton beam, which improves the unit capacity. ClinicalTrials.gov ID: NCT00114790.

Effect of Palliative Care Decision on Use of Hospital Services in Pancreatic Cancer Patients: A Retrospective Study.

BACKGROUND/AIM: Continuing chemotherapy or using hospital services near the end of life (EOL) and delaying the approach to palliative care (PC) services are factors impairing quality of life near the EOL. PATIENTS AND METHODS: Records of patients with pancreatic cancer treated at Helsinki University Hospital in 2013 and deceased by the end of 2014 were reviewed (N=221). The PC decision establishes the point when anticancer treatment is interrupted and the focus shifts to symptom-centered PC. The timing of the PC decision, referrals to specialized PC, use of hospital services at the EOL, and place of death were examined. RESULTS: The median overall survival was 13 months from diagnosis. The PC decision was made <30 days prior to death or not at all for 44% of patients. In addition, 68% of these patients used hospital service in the last month of life compared to 32% of patients with an earlier PC decision (p<0.001). A later or lacking PC decision correlated with a larger proportion of deaths in a secondary or tertiary hospital (64% vs. 36%), but the difference was not statistically significant (p=0.25). CONCLUSION: A late or lacking PC decision for patients with pancreatic cancer was found in almost half of the patients. There was a significant difference in the use of hospital services depending on the timing of the decision. An earlier PC decision might improve EOL care, since a late or lacking PC decision relates to a more abundant use of hospital services and an increased risk of hospital deaths.

End-of-life care of patients with esophageal or gastric cancer: decision making and the goal of care.

BACKGROUND: Overall survival (OS) with advanced esophageal or gastric cancer is poor. To avoid overly aggressive treatments at the end-of-life and assure adequate end-of-life quality, the decision to focus on symptom-centered palliative care (PC) and terminate anticancer treatments, i.e., the PC decision, should be made in time. MATERIAL AND METHODS: We reviewed the charts of patients (N = 160) with esophageal or gastric cancer treated at the Department of Oncology at Helsinki University Central Hospital in 2013 and deceased by December 2014. The use of acute services (Emergency department (ED) visits and hospitalizations) and places of death were compared according to the timing of the PC decision. Reasons for ED visits and hospitalizations were collected. RESULTS: The median OS from diagnosis of advanced cancer was 6 months. Anti-cancer treatments were never started for 34% of the patients. The PC decision was made early (>30 days before death) for 54% of the patients and late (≤30 days before death) or not at all for 46%. Patients with late or no PC decision died more often in tertiary/secondary hospital (29 versus 7%, p = 0.001) and had more ED visits (49 versus 29%, p < 0.001) and hospitalizations (53 versus 28%, p = 0.001) in their last month, and visited the PC unit less often (18 versus 69%, p < 0.001), than the patients with early PC decision. The ED visits were most commonly related to cancer progression, and clinical deterioration (17%), fever (16%), and dysphagia (15%) were the most common symptoms. CONCLUSION: The decision to focus on PC and terminate anticancer treatments, i.e., the PC decision, was made late or not at all in every other patient, leading to increased tertiary/secondary hospital service use and deaths at tertiary/secondary hospital. Early decision-making increased end-of-life care at specialized PC services or at home, implying better end-of-life care.

[Treatment of esophageal cancer]. / Ruokatorvisyövän hoito.

Treatment of choice for esophageal cancer requires multidisciplinary collaboration and requires careful assessment of the stage of the tumor and the patient's condition. When the cancer has extended or if the patient will not tolerate burdensome treatments, the possibilities of oncological therapies must be evaluated. The ability to eat must be secured and the quality of life optimized by using palliative means. Surgery still plays a central role in striving for curative treatment. Surgical techniques and results have improved, and the five-year life expectancy of patients having undergone surgery is over 40%.

[Treatment of dyspnea and other respiratory symptoms in palliative care]. / Hengenahdistuksen ja muiden hengitystieoireiden palliatiivinen hoito.

Respiratory symptoms cause much of suffering in palliative care. Opioids are the first-line drugs in symptomatic treatment, and a therapeutic intervention with benzodiazepines may also be justified. If the patient does not have hypoxia, oxygen and air stream have similar effects on dyspnea. Cough reflex is attenuated with opioids, and symptoms due to respiratory secretions are alleviated with anticholinergic drugs and mucolytics. Physical therapy and methods of respiratory management are profitable in the treatment of respiratory symptoms. Radiation therapy relieves cancer-induced hemoptysis, cough, chest pain and dyspnea.

Pretreatment serum syndecan-1 levels and outcome in small cell lung cancer patients treated with platinum-based chemotherapy.

Syndecan-1 is a multifunctional transmembrane heparan sulphate proteoglycan (HSPG) that is present on a variety of cell types. The extracellular syndecan domains can be shed from the cell surface in a highly regulated process called ectodomain shedding. We studied the influence of soluble syndecan-1 on outcome in 88 small cell lung cancer (SCLC) patients treated within the context of two randomised clinical trials with platinum-based therapy. Serum syndecan-1 concentrations were determined using enzyme-linked immunosorbent assay (ELISA) from sera taken prior to initiation of chemotherapy. Patients with the serum syndecan-1 level within the highest tertile (>212 microg/l) had only 38% 1-year and 3% 2-year survival, whereas 58% of those with a lower serum level survived for 1 year and 25% for 2 years following the diagnosis (P=0.0034). A high serum syndecan-1 level (>212 microg/l) was associated with a high pretreatment lactate dehydrogenase (LDH) level (P=0.0024) and a poor Karnofsky's performance status (P=0.021), but not with the clinical stage or the presence of distant metastases at diagnosis. A high serum syndecan-1 level had independent influence on survival also in a multivariate analysis (the relative risk, RR, 1.68; 95% CI, 1.02-2.77; P=0.044) together with the clinical stage (RR, 1.72; 95% CI, 1.05-2.82; P=0.032). We conclude that high pretreatment serum syndecan-1 level is associated with poor prognosis in SCLC treated with platinum-based chemotherapy.

Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic factors in lung cancer.

Syndecan-1 is a ubiquitous and multifunctional extracellular matrix proteoglycan,which mediates basic fibroblast growth factor (bFGF) binding and activity. Shedding of syndecan-1 ectodomain from the plasma membrane is highly regulated. We evaluated the influence of soluble syndecan-1 and serum bFGF determined by ELISA on outcome in 184 lung cancer patients (non-small cell lung cancer, n = 138; small cell lung cancer, n = 46). Serum syndecan-1 and bFGF levels were determined from sera taken before treatment. The median follow-up of the patients alive (n = 21) was 8.1 years (range, 6.6-8.9 years). High serum syndecan-1 and bFGF levels tended to occur in the same patients (P = 0.044). When the serum values corresponding to the highest tertile were used as the cutoff value, the median survival time of the patients with a high serum syndecan-1 level (>59 ng/ml) was 4 months [95% confidence interval (CI), 3-6 months] as compared with 11 months (9-16 months) among those with lower serum levels (P = 0.0001), and the median survival time of the patients with a high bFGF level (>3.4 pg/ml) was 5 months (3-8 months) versus 11 months (8-14 months) in those with a lower level (P = 0.023). In general, the prognostic influence of both factors was independent of the histological subtype. Both serum syndecan-1 level (relative risk, 1.8; 95% CI, 1.1-3.1) and serum bFGF level (relative risk, 1.6; 95% CI, 1.0-2.7) had independent influence on survival in a multivariate survival analysis in non-small cell lung cancer. We conclude that high serum syndecan-1 and bFGF levels at diagnosis are associated with poor outcome in lung cancer.