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Background Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan–Meier estimates of overall survival (OS). Results In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. Conclusions Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup., Highlights • Colorectal liver metastases respond to systemic therapy by shrinking but also by morphological and metabolic changes. • Advanced MRI technologies (DWI and 1H-MRS) might provide more detailed insight into cancer treatment-induced changes. • We compare changes seen in MRI with histology. • Reduction of ADC during chemotherapy was associated with improved survival after liver resection.

Background: Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure (TTF) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer. Patients and methods: Women diagnosed with advanced breast cancer were randomly allocated to receive 3-weekly docetaxel (group D) or 3-weekly docetaxel alternating with 3-weekly gemcitabine (group D/G) until treatment failure as first-line chemotherapy. The primary end point was TTF. Results: Two hundred and thirty-seven subjects were assigned to treatment (group D, 115; group D/G, 122). The median TTF was 5.6 and 6.2 months in groups D and D/G, respectively (hazard ratio 0.85, 95% confidence interval 0.63–1.16; P = 0.31). There was no significant difference in time-to-disease progression, survival, and response rate between the groups. When adverse events were evaluated for the worst toxicity encountered during treatment, there was little difference between the groups, but when they were assessed per cycle, alternating treatment was associated with fewer severe (grade 3 or 4) adverse effects (P = 0.013), and the difference was highly significant for cycles when gemcitabine was administered in group D/G (P < 0.001). Conclusion: The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles.

The objective of this retrospective follow-up study was to evaluate the outcome of patients with soft-tissue sarcoma treated by the authors' protocol, which consists of a selective combination of conservative surgery and radiotherapy. Patients who relapsed were especially evaluated to improve treatment results. The authors examined 80 patients with local soft-tissue sarcoma in the upper extremity referred to their multidisciplinary group. Fifteen patients were referred for first or subsequent local recurrence, and 65 patients were treated for primary tumor. The goal of treatment was local control and preservation of a functional limb. Wide excision was attempted. If the margin was less than 2.5 cm, postoperative radiotherapy was administered. Eighty-five percent of the patients were treated by limb salvage. Thirty patients needed reconstructive procedures such as pedicled (20 patients) or free flaps (10 patients). No free flaps were lost. The 5-year disease-specific overall survival rate was 75 percent, the local recurrence-free survival rate was 79 percent, and the metastasis-free survival rate was 68 percent. In univariate analysis, prognostic factors for local recurrence were extracompartmental site; for development of metastases, large size and extracompartmental site; and for decreased disease-specific overall survival, large size and extracompartmental site. Intramuscular, cutaneous, and subcutaneous tumors had a 5-year local control rate of 100 percent, and extracompartmental tumors had a local control rate of 69 percent. Extracompartmental tumors clearly have the worst prognosis and should be the main target for improving treatment strategies. After exclusion of patients with inadequate treatment according to the authors' protocol, the local control rate at 5 years was 90 percent. Strict adherence to treatment protocol should be practiced.

We compared oncologic and surgical outcome between minimally invasive esophagectomy (MIE) and the Ivor Lewis-type open approach (OE) in the treatment of locally advanced esophageal adenocarcinoma (EAC).Of 284 patients undergoing surgery for EAC between 2003 and 2013, the 153 selected with locally advanced EAC were 74 MIEs and 79 OEs [median age, 66 for MIE, 63 for OE (p = 0.009)]. Neoadjuvant therapy was given to 82% of MIEs and 78% of OEs. In the OE group, 86% was male, and in the MIE group, 78%. Data assessed were oncologic, intraoperative, and postoperative.Mortality at 30 days was 3% for MIE and 1% for OE; and 90-day mortality was 4% for MIE and 5% for OE. The complication rate for MIE was 50%, and 60% for OE (p = 0.181). The pneumonia rate was 18% for MIE and 19% for OE; leak rate was 7% for MIE and 6% for OE; conduit necrosis was 0 for MIE and 3% for OE; and rate of airway-conduit fistula was 3% for MIE and 1 % for OE. Median blood loss (MIE 300 vs. OE 800, p0.0001), overall stay (MIE 13 vs. OE 14, p = 0.040), and harvested lymph nodes (MIE 20 vs. OE 22, p = 0.021) all were in favor of MIE. Median ICU stay and operative time did not differ. Neither did overall (OS) nor recurrence-free (RFS) 3-year survival differs significantly (MIE 64% vs. OS OE 49%, MIE 57% vs. RFS OE 53%).In our institution, MIE appears to produce oncologic and survival results similar to those of OE. Shorter length of stay and less operative blood loss may reduce costs for MIE.

Patients with pseudomyxoma peritonei (PMP) benefit from cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Reports on this modality usually have included only patients with successful HIPEC treatment, which can potentially cause biased results. We report the survival of a PMP population treated by CRS and HIPEC, including patients who were not eligible for HIPEC. The outcome of the whole population of 87 patients with PMP treated by CRS and HIPEC in Helsinki University Central Hospital between 2008 and 2011 was evaluated. The results of treatment were compared with 33 patients treated by serial debulking in our unit between 1984 and 2008. Of the 87 patients in the HIPEC-era group, 56 received HIPEC, 12 were treated non-radically in an attempt at HIPEC, 9 were debulked and 10 were referred back or transferred to palliative care without surgery. The 5-year overall survival for the debulking-era group and the HIPEC-era group were 67 and 69 %, respectively. The number of patients with no evidence of disease was higher in the HIPEC-era group (47/87) than that in the debulking-era group (8/33) at the end of the follow-up. Overall survival for patients who underwent successful CRS and HIPEC at 2 and 5 years was 95 and 93 %, respectively. The improved survival from using the CRS and HIPEC was not apparent after 5-year follow-up, when the whole patient population was included in the analysis. Even so, patients successfully treated by CRS and HIPEC manage well.

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%.

In many malignant diseases the expression levels of CD44 and its splice variant v6 (CD44v6) have been associated with the prognosis. The purpose of this study was to investigate the clinical significance of CD44 in adult soft tissue sarcomas (STS). 133 STS patients with a limb or superficial trunk tumour treated at the Helsinki University Central Hospital in 1987–1993 with a median follow-up time of 68 months were included in this study. The expression of CD44 and CD44v6 was determined immunohistochemically on paraffin-embedded tumour samples. 95% of the tumours expressed CD44 and CD44v6 was detected in 57%. Strong CD44 expression was associated with low grade (P = 0.04) and small tumour size (P = 0.02). In diploid tumours the CD44 expression was correlated with low S-phase fraction (P = 0.001). High expression of both, CD44 in general as well as that of CD44v6, predicted a higher risk for local recurrence (CD44: P = 0.01 and CD44v6: P = 0.05). Low CD44v6 content of the primary tumour correlated with poor survival (P = 0.02). Determining the expression of CD44 or CD44v6 in a primary STS could be a valuable tool for selecting the group of patients who might benefit from intensified local tumour treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com

Aims The aims of this retrospective follow-up study were to evaluate the justification for limb-saving multi-disciplinary treatment of soft tissue sarcomas (STS) and to report the results achieved by our treatment protocol. Local control was studied, with emphasis on tumour depth, operation margin and need for post-operative radiotherapy. Methods We examined 130 patients with STS in the lower limb referred to the multi-disciplinary group of Helsinki University Central Hospital. For the survival analysis 106 patients with local disease remained. The goal of treatment was to preserve a functional limb. Wide excision was attempted. If the margin was less than 2.5 cm, post-operative radiotherapy (RT) was delivered to all except 20 patients. Results Ninety-two per cent of the patients were treated by limb salvage. The success rate of free flaps was 16 out of 18. The 5-year disease-specific overall survival was 76%, metastasis-free survival 72% and local control 79%. Prognostic factors for local recurrence were extracompartmental site and large size; for development of metastases high grade, extracompartmental site and large size; for decreased disease-specific overall survival high grade, large size and advanced age. Local control of intramuscular tumours ( n =6) was 100%, subcutaneous tumours ( n =38) 94% and tumours penetrating the deep or muscle fascia and those locating extracompartmentally ( n =62) 67%. Conclusions Limb salvage in patients with STS is possible with an acceptable outcome by selective combination of treatment modalities. Modern plastic surgical methods with free tissue transfers are successful and often needed. Subcutaneous and intramuscular tumours have good local control. The outcome is poorest for tumours penetrating the deep or muscle fascia and for those located extracompartmentally, and patients with such tumours might be a target for adjuvant therapy. Treatment should be coordinated by multidisciplinary teams.

A small but not insignificant number of patients experience a prolonged survival after treatment of metastatic soft tissue sarcoma. This must be weighed against the majority of the patients who benefit little from the therapy, but nevertheless experience its side-effects. It would therefore be of utmost importance to be able to screen for those patients who respond to the treatment. Since proliferating cells are more sensitive to chemotherapy than non-proliferative cells, we measured the proliferation rate of the primary tumour of 55 soft tissue sarcoma patients with locally advanced or metastatic disease by determining the flow cytometric S phase fraction and immunohistochemical Ki-67 and cyclin A scores. S phase fraction or Ki-67 score did not predict chemotherapy response or progression-free survival. A high cyclin A score, however, correlated with a better chemotherapy response (P = 0.02) and longer progression-free survival time (P = 0.04). Our results suggest that a high cyclin A score predicts chemotherapy sensitivity. © 1999 Cancer Research Campaign

The aims of the present study were to compare genetic aberrations in primary sarcomas and their pulmonary metastases and to explore the pathways associated with disease spreading. The primary tumor and its subsequent pulmonary metastasis of 22 patients were analyzed by comparative genomic hybridization. All samples were obtained before the initiation of chemo- or radiotherapy. The mean total number of aberrations per tumor was 7.6 (range, 0–17) in primary tumors and 7.5 (range, 0–19) in metastases. The mean numbers of high-level amplifications per tumor were similar (0.32 in primary tumors and 0.36 in metastases). The frequencies of the most common aberrations were relatively similar in primary tumors and metastases: the most frequent gain affected 1q (minimal common regions 1q21–q23 in 36% of primary tumors and 1q21 in 45% of metastases). The most frequent losses were detected at 9p (9p22–pter in 32% of primary tumors and 9p21–pter in 32% of metastases), 10p (10p11.2–p12 in 41% of primary tumors and 10p11.2–pter in 32% of metastases), 11q (11q23–qter in 36% of primary tumors and 32% of metastases), and 13q (13q14–q21 in 45% of primary tumors and 50% of metastases). No aberrations specific to metastases were detected. An increase in the total number of changes during progression was a predominant feature in a majority of these paired samples. Also, the number of differences in the genetic profile outnumbered common changes in a majority of the samples. However, despite the heterogeneous and numerous changes, all pairs with aberrations in both specimens had some shared alterations in both samples. Genes Chromosomes Cancer 25:323–331, 1999. © 1999 Wiley-Liss, Inc.

Immunohistochemically determined Ki-67 scores and flow cytometrically determined S-phase fractions were successfully evaluated from the primary tumours of 123 patients with soft-tissue sarcoma. All patients had either limb or superficial trunk tumours. Ki-67 score correlated strongly with ploidy, S-phase fraction and grade. Ki-67 did not correlate with the size of the primary tumour. When analysed as a continuous variable, Ki-67 was a stronger predictor of both metastasis-free survival and disease-specific overall survival (P= 0.003 and 0.04 respectively) than was the S-phase fraction (P= 0.06 and 0.07 respectively). We tested the relevance of different cut-point values by dividing the whole material into two parts at every 10% (e.g. 10% of patients vs. the remaining 90%, 20% vs. 80%, etc.). We counted the relative risk and confidence interval at all these cut-off points. Ki-67 had good prognostic discriminating power irrespective of the cut-point value, but S-phase fraction lost its prognostic power at higher cut-point values. In conclusion, we found that Ki-67 is a useful prognostic tool in the treatment of soft-tissue sarcoma patients irrespective of the cut-point value. S-phase fraction can be used at lower cut-point values. © 1999 Cancer Research Campaign

We used comparative genomic hybridization (CGH) to evaluate DNA sequence copy number changes in 67 synovial sarcomas of both monophasic and biphasic histological subtypes. Changes (mean among aberrant cases: 4.7 aberrations/tumor; range: 1–17), affecting most often entire chromosomes or chromosome arms, were detected in 37 sarcomas (55%). Gains and losses were distributed equally, but different chromosomes were affected with variable frequencies. The most frequent aberrations, each detected in 9–11 of 67 tumors, were gain of 8q and gain at 12q (12q14-15 and 12q23-qter), loss of 13q21-31, and loss of 3p. Other frequent changes (in 7 or 8 cases) included gains at 2p, 1q24-31, and 17q22-qter, and losses at 3cen-q23 and 10q21. High-level amplifications were seen in 7 cases. A total of 16 regions were detected. Two of them, 8p12-qter and 21q21-qter, seen in 4 and 2 tumors, respectively, were recurrent. No aberrations specific to histological subtype were identified. However, genetic changes in the monophasic tumors were more complex and numerous (mean among aberrant cases: 5.3 aberrations/tumor; range: 1–17) than in the biphasic tumors (mean: 2.5 aberrations/tumor; range: 1–5), and high-level amplifications occurred more frequently. All but 1 of the sarcomas showing high-level amplification were of the monophasic subtype. These findings may reflect differences in the pathogenesis and biological behavior of both histological subtypes of synovial sarcoma. Genes Chromosomes Cancer 23:213–219, 1998. © 1998 Wiley-Liss, Inc.

A significant correlation (r = -0.48) was found between the logarithm of the S-phase fraction of the primary tumour (SPF) and the logarithm of the doubling time of lung metastases (T2). The estimated median cell loss factor was 88% (range 35-99%).

Background The aim was to review a single-institution experience of a prospective treatment protocol for soft tissue sarcoma of the extremity and trunk wall, with particular focus on the smallest surgical margin leading to local control. Methods The study included 270 patients who had surgery for soft tissue sarcoma at Helsinki University Central Hospital between 1987 and 1997. Resection margins were measured prospectively from tumour specimens. Radiotherapy was administered if the smallest margin measured less than 2·5 cm, irrespective of tumour grade. Results With a median follow-up of 6·6 years, the 5-year local control rate was 76·4 per cent. On multivariable analysis, the smallest surgical margin around the sarcoma (after radiotherapy) was prognostic for local control. A margin of at least 2·5 cm was associated with a local recurrence-free rate of 89·2 per cent at 5 years. Tumour size, depth or grade and patient's age had no independent prognostic effect on local control. Conclusion Surgical margin had independent prognostic value for local control. A surgical margin of 2–3 cm provided reasonable local control of soft tissue sarcoma, even without radiotherapy. Radiotherapy is recommended for smaller margins, irrespective of tumour grade.

Cyclooxygenase-2 (Cox-2) is expressed by several types of epithelial malignancies, i.e., carcinomas, and inhibition of Cox-2 may have a therapeutic role in chemoprevention and treatment of cancer. The role of Cox-2 in non-epithelial malignancies, however, is unclear.We investigated, by immuno- histochemistry, the expression of Cox-2 in 103 human soft-tissue sarcomas.All 10 biphasic synovial sarcomas were positive for Cox-2, but positivity was observable only in the epithelial component of these tumours. Excluding sarcomas with epithelial differentation, uniform staining of the tumour was observed in only 2 samples. In addition, positivity for Cox-2 appeared in tumour cells in only 18 samples around necrotic areas.In human soft-tissue sarcomas, Cox-2 expression seems to be associated with epithelial differentation and, in some types of sarcomas, to be expressed in otherwise negative tumours at sites of necrosis.

1035 Background: Alternating use of single agents has not been compared with single-agent taxane as treatment of ABC. Methods: The key eligibility criteria for this open-label, prospective, randomized, multicenter, phase II trial were female gender, age

10064 Background: A single-institution experience using a prospective treatment protocol for soft tissue sarcoma (STS) of the extremity and trunk wall was reviewed. Special interest of smallest surgical margin on local control was taken. Methods: Between 1987 and 1997 361 patients with STS were treated by the STS Group at Helsinki University Central Hospital. Patients with borderline malignancies or metastatic disease were excluded leaving 270 patients to the present study. All patients included underwent surgery. Postoperative radiotherapy was administered if the smallest surgical margin was less than 2.5 cm when there was no natural barrier, irrespective of tumor grade. Results: With a median follow-up of 6.6 years, the 5-year local control for the whole study population was 76 %. On multivariate analysis, the smallest surgical margin in centimeters, adequacy of treatment according to protocol and postirradiation sarcoma were prognostic for local control. A margin of at least 2,5 cm yielded recurrence-free rate of 89 % at five years. Conclusions: Our findings show that size, depth and grade of the tumor, and patient`s age at diagnosis do not have independent prognostic effect on local control, nor has recurrent disease at referral. Instead, surgical margin in centimeters and adequacy of treatment according to protocol had independent prognostic value for local control. This is encouraging since these factors can be affected by aggressive local treatment. Soft tissue sarcomas should be referred to a specialized multimodality treatment group before biopsy or any surgery. A surgical margin of 2–3 cm yield a reasonable local control in STS even without radiotherapy. No significant financial relationships to disclose.