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After primary treatment, patients with early breast cancer (EBC) are followed-up for at least 5 years. At the Helsinki University Hospital (HUS) surveillance includes appointments at 1, 3 and 5 years, and between pre-planned visits a phone call service operated by a nurse practitioner for counseling about symptoms related to side-effects or potential recurrence. In 2015 HUS launched a digital solution for cancer patients. This study was designed to find out patient preference, Health related (HR) quality of life (QOL) and satisfaction with a digital solution compared to a phone call service during the first year of follow-up. Patients with EBC were randomized at the final visit of radiotherapy to surveillance by phone calls or by the digital Noona solution during the first year outside pre-planned visits. After six months the groups were crossed over to the other arm. Primary endpoint was patient preference for either follow-up method among those who had contacted the study nurse at least once by both phone service and digital solution. Out of the 765 patients randomized, 142 had contacted the hospital with both methods and were eligible for inclusion in the analyses of the present study. Out of the 142 patients, 56 preferred phone calls, 43 the digital solution while 43 considered both modalities equal. Preference for the digital solution was higher among patients aged 65 or less. There were no differences in HR QoL or overall satisfaction between the modalities. However, the patients rated the timeliness of response better while using the digital solution. Of the patients 30% preferred the digital solution, 40% phone calls while 30% found them equal as the primary follow-up method for EBC during the first year outside pre-planned visits. There is a need to include also digital solutions in surveillance of EBC. NCT04980989

Background Metaplastic breast cancer (MpBC) is a heterogeneous subtype of invasive mammary carcinoma associated with epithelial-mesenchymal transition (EMT) and cancer stem cell characteristics. Data regarding prognostic markers and potentially actionable targets for therapy are still limited. The present study aimed to characterize the immunohistochemical landscape of this rare malignancy and to identify potential prognostic factors and targets for therapy. Material and methods A total of 75 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for Ki-67 (MIB-1), epidermal growth factor receptor (EGFR), cytokeratin 5/6, vimentin, CD44, and androgen receptor (AR) and correlated their expression with clinicopathologic features and clinical outcomes. The p-values for survival analyses were corrected for multiple testing (threshold 0.01). Results Most tumors expressed CK5/6 (73%), EGFR (59%), CD44 (81%), and vimentin (87%). Eighty-nine percent had a high Ki-67 index. Eighty-four percent were classified as basal-like (CK 5/6 or EGFR positive). AR was expressed in 21% of the tumors. The basal-like phenotype was significantly (p = 0.009) associated with inferior disease-free (DFS) and breast-cancer-specific overall survival (BCOS) with borderline significance (p = 0.01). In addition, a low Ki-67 index was associated with improved DFS (p = 0.033) and BCOS (p = 0.03). Conclusion Most MpBCs express basal markers (CK5/6, EGFR), epithelial-mesenchymal transition marker vimentin, and the stem cell marker CD44. Expression of basal-like markers was significantly related to inferior DFS. All the 11 patients with a lack of expression of basal markers survived without relapse.

Introduction: To minimize the radiation exposure of mostly young testicular cancer patients, it is essential to find out whether CT could be replaced by magnetic resonance imaging (MRI) in the stag...

Desmoid tumors (DT) are nonmalignant mesenchymal neoplasms with a high recurrence rate. Tumors concentrate into the small bowel mesentery and the abdominal wall when associated with familial adenom...

Women irradiated for left-sided breast cancer (BC) have an increased risk of coronary artery disease compared to women with right-sided BC. We describe the distribution of radiation dose in segments of coronary arteries in women receiving adjuvant radiotherapy (RT) for left- or right-sided BC.Fifteen women with BC, seven left-sided and eight right-sided, who had received three-dimensional conformal radiotherapy (3DCRT), constituted the study base. The heart and the segments of the coronary arteries were defined as separate organs at risk (OAR), and the mean and maximum radiation doses were calculated for each OAR.In women with left-sided BC, irrespective of if regional lymph node RT was given or not, maximum dose in mid and distal left anterior descending artery (mdLAD) was approximately 50 Gy in 6/7 patients, whereas women with right-sided BC mainly received low doses of radiation. In women with left-sided BC, 6/7 patients had substantially higher mean dose to the distal LAD than to the heart, ranging from 30 to 55 Gy and 3 to13 Gy, respectively.We found a pronounced difference of radiation dose distribution in the coronary arteries between women with left- and right-sided BC. Women with left-sided BC had almost full treatment dose in parts of mdLAD, regardless of if regional lymph node irradiation was given or not, while women with right-sided BC mainly received low doses to the coronary arteries.

Premenopausal patients treated with adjuvant chemotherapy often develop early menopause and thus, may encounter significant bone loss. We studied the long-term effects of chemotherapy-induced ovarian dysfunction on bone mineral density in breast cancer patients.The effect of menstrual status after adjuvant chemotherapy on bone mineral density (BMD) was examined in 29 premenopausal breast cancer patients.During 10 years of follow-up, nearly 90% of women developed menstrual irregularities or amenorrhea. The total bone loss at the lumbar spine was -5.4% in women with preserved menstruation, -15.3% in those with irregular menses and -13.2% in amenorrheic women 10 years after adjuvant chemotherapy. The changes in lumbar spine BMD correlated significantly with menstrual function. Both amenorrhea and menstrual irregularities shortly after chemotherapy increased the risk of osteoporosis later on: one third of women with ovarian dysfunction developed osteoporosis of the lumbar spine during the follow-up. Osteopenia before adjuvant therapy predicted an increased risk for osteoporosis.The present study with a unique follow-up period of 10 years shows that ovarian dysfunction leads to long-term deleterious BMD changes and predisposes breast cancer survivors to osteoporosis.

The aim of this study was to study the relationship between physician-assessed quality of life parameters, i.e., toxicity and physical performance, and patients' self-reports of their quality of life (QoL). QoL was assessed at baseline and before each treatment, using the EORTC QLQ-C30. The WHO performance score (PS) and toxicity were assessed in physician interviews. The correlations between the WHO PS and the QLQ-C30 functioning scale scores varied from weak to moderate, depending on the scale. Strongest associations were found in physical-, social-, and role functioning, and in the global QoL. The QLQ-C30 nausea/vomiting and diarrhea scales correlated moderately to corresponding WHO scores. A multiple linear regression analysis was used to analyze the contribution of WHO PS and toxicity variables to the global QoL. The best model explained only 16% of the variance of the global QoL score. The present findings highlight the importance of independent QoL assessments focused on those aspects of QoL not captured in clinical interviews with the physician.

A prospective diagnostics and treatment protocol for extremity and trunk wall soft tissue sarcoma (STS) was introduced by the Scandinavian Sarcoma Group in 1986 and it was also widely adopted in Finland. We have updated the protocol and made it more detailed at the Helsinki University Central Hospital. We retrospectively compared diagnostics and treatment of STS in a nationwide population-based material to this protocol with special emphasis on local control.Data for 219 patients with an STS of extremity or trunk wall diagnosed during 1998-2001 was retrieved from the nationwide Finnish Cancer Registry. Histologic review was performed. Treatment centres were divided into high-, intermediate- and low-volume centres based on the number of patients with final surgery during the study period.Significantly more patients were operated with a preoperative histological or cytological diagnosis at high-volume centres. No preoperative diagnosis was a strong predictor for the patient to undergo more than one operation (p0.0001). Wide surgical margin was achieved more often at high-volume centres, but in all centre categories a considerable percentage of patients with inadequate surgical margin did not receive adjuvant radiation therapy. Local control at five years was 82% at high-volume centres, 61% at intermediate-volume centres treating highest percentage of deep tumours and 69% at low-volume centres (p = 0.046). Local control improved as the number of patients operated (surgical volume of the centre) increased.The present quality-control study is the first nationwide population-based study to assess diagnostics and treatment of STS. When referred to a specialised sarcoma centre even patients with inadequate surgery can achieve good local control. STS is a rare cancer and its treatment should be centralised in Finland, which has 5.4 million inhabitants and approximately 100 new STSs of extremities and trunk wall annually.

The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer.After a first standard dosed FEC course (5-fluorouracil 600 mg/m(2), epirubicin 60 mg/mg(2) and cyclophosphamide 600 mg/m(2)), patients who did not reach leukopenia grade III or IV were randomised to standard doses (group standard) or doses tailored to achieve grade III leukopenia (group tailored) at courses 2-7. Patients who achieved leukopenia grade III or more after the first course were not randomised but continued on standard doses (group registered).Both planned and actually delivered number of courses (seven) were the same in all three arms. The relative dose intensity was increased by a factor of 1.31 (E 1.22, C 1.43) for patients in the tailored arm compared to the expected on standard dose. Ninety percent of the patients in the tailored arm achieved leukopenia grade III-IV compared with 29% among patients randomised to standard dosed therapy. Dose tailoring was associated with acceptable acute non-haematological toxicity with more total alopecia, nausea, vomiting and fatigue.Dose tailoring according to leukopenia was feasible. It led to an increased dose intensity and was associated with acceptable excess of acute non-haematological toxicity.

Response Evaluation Criteria In Solid Tumors (RECIST) and WHO-criteria are used to evaluate treatment effects in clinical trials. The purpose of this study was to examine interobserver and intraobserver variations in radiological response assessment using these criteria.Thirty-nine patients were eligible. Each patient's series of CT images were reviewed. Each patient was classified into one of four categories according RECIST and WHO-criteria. To examine interobserver variation, response classifications were independently obtained by two radiologists. One radiologist repeated the procedure on two additional different occasions to examine intraobserver variation. Kappa statistics was applied to examine agreement.Interobserver variation using RECIST and WHO-criteria were 0.53 (95% CI 0.33-0.72) and 0.60 (0.39-0.80), respectively. Response rates (RR) according to RECIST obtained by reader A and reader B were 33% and 21%, respectively. RR according to WHO-criteria obtained by reader A and reader B were 33% and 23% respectively. Intraobserver variation using RECIST and WHO-criteria ranged between 0.76-0.96 and 0.86-0.91, respectively.Radiological tumor response evaluation according to RECIST and WHO-criteria are subject to considerable inter- and intraobserver variability. Efforts are necessary to reduce inconsistencies from current response evaluation criteria.

Some decades ago, patients with a newly diagnosed rectal cancer were locally staged clinically, using the finger and a rectoscope. If the tumour was judged resectable, patients were operated upon w...

A phase II study was conducted to assess the toxicity and response rate of vinorelbine (NavelbineR) combined with epirubicin and fluorouracil (NEF) in metastatic breast cancer. Vinorelbine was delivered at a dose of 25 mg/m2 on days 1 and 8, epirubicin at 60 mg/m2 on day 1 and fluorouracil at 600 mg/m2 on day 1, at 3-week intervals. Forty consecutive ambulant patients with breast cancer with measurable metastases were treated with a total of 310 cycles (median 8) as first-line therapy. The objective response rate was 83% (95% CI 71-95) (6/40 CR 15%, 27140 PR 68%). In 3 patients, CNS metastases were detected during NEF therapy those who had a partial response in their visceral metastases. Median time to progression was 13 months (95% CI 7-19) and estimated median survival time was 32 months. The main dose-limiting adverse effect, grade III-IV haematological toxicity, was reported in 92% of patients. One patient died of neutropenic sepsis. Grade III infections requiring hospitalization were observed in 8 patients (20%). Half of the patients complained of mild constipation, nausea or stomatitis, which were easily managed. Almost all patients had grade III alopecia. One patient with previous adjuvant anthracycline therapy (CEF x 9 two years earlier) developed fatal grade IV cardiac failure associated with pulmonary emboli 2 months after completion of NEF therapy (PR with 6 cycles). In line with the observations of others conducting phase II first-line trials combining vinorelbine and epirubicin, it is concluded that the NEF regimen is effective in metastatic breast cancer. Haematological toxicity, however, requires dose reductions in many patients. Furthermore, careful monitoring of cardiac function is necessary, particularly in patients who received prior adjuvant anthracycline therapy.

Chemotherapy doses are sometimes reduced because of obesity in patients. This study examines the effect of parameters reflecting the body size, body weight and height, body mass index (BMI), and body surface area (BSA) on the depth of the blood leukocyte nadir in breast cancer patients receiving adjuvant chemotherapy, when drug dosing was based on the BSA. Three hundred and forty patients with node positive breast cancer without distant metastases were treated with 6 cycles of adjuvant postoperative CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 i.v. every 3 weeks). Patients within the highest BMI had the highest leukocyte nadir values (Spearman correlation coefficient 0.3, p < 0.001). A high body weight and a large BSA were also associated with high leukocyte nadirs. We conclude that when the blood leukocyte nadir is used as a surrogate marker for the drug effect, obese patients receiving intravenous CMF have higher leukocyte nadirs than the lean ones. Therefore, the drug doses should not be reduced because of obesity, and even when obese patients are treated according to the scheduled doses they may remain slightly underdosed.

The feasibility of mobilizing peripheral blood stem cells (PBSC) using anthracycline containing polychemotherapy and G-CSF on the first 50 patients randomized to the high-dose arm in the adjuvant SBG 9401 is investigated. The patients were treated with standard FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2) for two courses followed by a modified third FEC course with a C dose of 1200 mg/m2 supported with subcutaneous G-CSF (filgrastim) at 5 mg/kg followed by harvest around day 11. The mean yield of CD34+

Ever since the earliest observations over 50 years ago of tumour volume reduction following treatment with alkylating drugs, the paradigm in medical anti-cancer treatment has been to find drugs wit...

For as long as cytotoxic treatment has been used in cancer the question has been asked: Why do some patients respond to therapy and others do not? The identification and better understanding of factors predicting response to chemotherapy might also help toward understanding the basic mechanisms behind response to cytotoxic agents in malignant disease. It would also assist the clinician in selecting the right candidates for chemotherapy and spare the others from unnecessary toxicity

Prostatic carcinoma is one of the leading causes of male cancer deaths. However, the routine diagnostic and therapeutic strategies have not yet been established. Although the outcome of surgical and radiotherapeutical approaches has frequently been reported to be comparable, the profile of side effects is different. This could offer the basis for selecting the treatment of choice in individual cases. During the last decade the radiotherapeutical technique has markedly improved, in part due to the achievements in the field of computer assisted tomography planning and conformal technique; the outcome of side-effects has decreased with concurrent increase in the rate of local control. The prescribing, recording and reporting of irradiation have also recently developed, as well as the staging of the disease. Therefore we consider it timely to review progress in this subject and to emphasize the role of radiotherapy in the treatment of localized prostatic cancer.

Clodronate, one of the most investigated bisphosphonates, has been clinically utilised for over 10 years in malignancy. It is the most used, most effective and safest drug in the treatment of hypercalcaemia. It inhibits lytic bone destruction, prevents bone fractures and relieves bone pain. Supportive clodronate therapy may even reduce hypercalcaemia mortality and the morbidity caused by osteolysis. These results have stimulated studies on the patients' quality of life. New methods for the measurement of bone resorption, such as the degradation product of type I collagen (ICTP), may improve the possibility of monitoring the effect of clodronate. Comparative studies with different bisphosphonates in hypercalcaemia and long-term controlled trials using bisphosphonates as supportive therapy in osteolysis due to malignancy are reviewed.

The estrogen receptor content of primary breast cancer is predictive for the outcome and response to hormonal manipulation ( I ) . Most data on the prognostic implication of estrogen receptor determinations have been generated with biochemical receptor determinations utilising the dextran-coated charcoal (DCC) method and more recently the RIA assay (2). During the last decade immunohistochemical (IH) receptor determinations have gained in popularity due to their lower costs and the lower requirements for sample size as well as the possibility to perform the determination on archival tumour material. A large number of publications have demonstrated a good correlation between IH and biochemical receptor determinations, but also clearly discrepant findings have been reported (for a review see (2)). Few studies have assessed the clinical utility of IH. A number of studies have shown that the predictive value of IH receptor determinations for endocrine treatment response are at least as good as those of biochemical assays for estrogen receptor binding (2). Only a few studies have compared the prognostic value of IH and biochemical estrogen receptor determinations (3-5). The purpose of the present investigation was to study the correlation between IH and DCC estrogen receptor determination as well as their prognostic value for recurrence and death. Material und Methods. A total of 142 consecutive cases of invasive breast cancer analysed at the Department of Pathology, University of Helsinki, during the years 1987-1988, were included in the study. The distribution of TNM-classes and the proportion of estrogen receptor positivity are shown in the Table. In 9 cases the determination was performed on a local recurrence. These patients are excluded from the analysis on the prognostic value of receptor determinations. One patient with previous metastatic contralateral breast cancer was excluded from analysis of survival and disease-free survival. Other patients with synchronous or metachronous bilateral breast cancer (n = 18) were included in all the analyses. In 5 cases TN-status was not known, all were cases with receptor determinations from a local recurrence. The turnour samples were sent to the laboratory on ice and arrived unfixed to the histological laboratory for diagnosis and estrogen receptor (ER) staining. Immunohistochemical staining for ER was performed on frozen sections using the ER-ICA kit (Abbott Laboratories, Chicago, IL, USA). The sections were fixed and stained for ER following the manufacturer’s directions, counterstained lightly in Mayer’s hematoxylin and mounted. The percentage of positively stained turnour cell nuclei was estimated by counting 5001 000 morphologically malignant cells in multiple random fields in every sample. The turnours were divided into four categories according to the number of positive nuclei found: 0-9% = negative, 10-39% = weakly positive (+), 40-69% moderately positive (+ +) and 70% or more = strongly positive ( + + +). Only nuclear immunohistochemical staining was regarded as positive. A sample of each tumour was taken by the surgeon, immediately frozen in liquid nitrogen and analysed at the Department of Clinical Chemistry for cytosol ER by the dextran-coated charcoal method (6) . Cause-specific disease-free survival (DFS) and cause-specific overall survival (0s) were estimated by the Kaplan-Meier method, and the statistical significance of differences tested by the log-rank test. For analysis of both 0s and DFS only breast cancer-related deaths were classified as events, i.e., patients dying from other causes without breast cancer recurrences were classified as censored at the time of death. Follow-up times ranged from 7 to 9 years with a median of 8 years. Fifty-eight patients (42%) had TI tumours, 62 (45%) T2, 12 (9%) T3 and 4 (4%) T4 tumours. Sixty-two patients (45%)) had axillary metastases. Only one patient had distant metastases at diagnosis. Fifty-four patients have died, 13 from causes other than breast cancer without evidence of recurrence. Results. The correlation between IH ER score and ER positivity by DCC assay was studied using a cut-off point of 10 fmol/rng protein (Table). In 44 cases (31%) the result was discrepant. Thirty-three cases (23%) were IH positive and DCC negative, whereas 11 cases (8%) were IH negative and DCC positive. The