Papers by Odd R. Schibsted Monge
Tumori, Jan 5, 2017
The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international s... more The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study. The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively.In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no...
Acta Orthopaedica Supplementum, 2009
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 23, 2006
Sarcoma, 2015
Purpose. A retrospective study of prognostic factors and treatment outcome of osteosarcoma (OS) d... more Purpose. A retrospective study of prognostic factors and treatment outcome of osteosarcoma (OS) during modern chemotherapy era with focus on patients with primary metastatic disease, nonextremity localisation, or age >40 years (nonclassical OS). Methods. A nationwide cohort, comprising 424 high-grade Norwegian bone OS patients, was based on registry sources supplemented with clinical records from hospitals involved in sarcoma management between 1975 and 2009. Results. Only 48% were younger patients with tumour in the extremities and without metastasis at diagnosis (classical OS). A considerable discrepancy in survival between classical and nonclassical OS was observed: 61% versus 26% 10-year sarcoma specific survival. Twice as many of the former received both adequate surgery and chemotherapy compared to the latter. This could only partly explain the differences in survival due to inherent chemoresistance in primary metastatic disease and a higher rate of local relapse among pati...
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Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 7, 2005
Gastrointestinal stromal tumour (GIST) is the most frequent mesenchymal tumour type of the digest... more Gastrointestinal stromal tumour (GIST) is the most frequent mesenchymal tumour type of the digestive tract. Between 30 and 40% of patients have high-risk, malignant GIST with poor prognosis after surgery. Imatinib mesylate is a recently introduced KIT tyrosine kinase inhibitor with effect on metastatic GIST. We report our experience with imatinib mesylate in the treatment of GIST. Nine patients diagnosed with GIST have received imatinib mesylate since August 2001. Eight patients had metastatic disease, one patient received adjuvant treatment. The patients were evaluated according to standard protocols for clinical performance, effect of treatment, and adverse effects. Tumour tissue was analysed for mutational status in KIT and PDGFRA. All patients with metastatic disease had palliative benefit; three had partial response and the remaining stable disease. The single patient receiving adjuvant treatment had no sign of recurrence. Side effects were mainly mild diarrhoea, nausea and vom...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 30, 1990
Tamoxifen was given as primary systemic treatment to 28 patients with locally advanced breast can... more Tamoxifen was given as primary systemic treatment to 28 patients with locally advanced breast cancer. In all tumours, receptors for estrogen (ER) and/or progesterone (PGR) were positive. All patients (15) with high levels of hormone receptors (ER greater than or equal to 100 mumols/g protein and/or PGR greater than or equal to 200 mumols/g protein) were alive after two years of observation as against 60% of the patients (13) with lower hormone receptor values.
Acta Oncologica, 2014
Currently there is no consensus on the use of adjuvant radiotherapy (RT) in retroperitoneal sarco... more Currently there is no consensus on the use of adjuvant radiotherapy (RT) in retroperitoneal sarcoma (RPS). We have analysed clinical outcomes in patients with localised RPS treated at two Scandinavian Sarcoma Group (SSG) centres: Haukeland University Hospital (HUH), Bergen, Norway and Skåne University Hospital (SUH), Lund, Sweden to clarify the effects of adjuvant RT on local control and overall survival (OS). Local databases and registers at HUH and SUH as well as the SSG central register were used to identify RPS patients. Patients with localised RPS who underwent surgery in Bergen between 1988 and 2009 and in Lund from 1998 to 2009 were included. Medical records were examined for clinical data, tumour characteristics, treatment factors and follow-up status. Archived tumour sections and tumour tissue were reviewed, and when necessary, restained and reclassified. Cox regression was used to analyse the association of potential prognostic factors with local recurrence-free survival (LRFS), metastasis-free survival (MFS) and OS. The study included 97 patients: 52 from Norway and 45 from Sweden. The proportion of high-grade tumours was 73%. The five-year LRFS, MFS and OS were 55%, 59% and 60%, respectively. RT was significantly associated with improved local control resulting in a five-year LRFS of 77% compared with 39% without (p < 0.001). Furthermore, five-year OS was 71% in the RT group in contrast to 52% with surgery alone (p = 0.019). In the adjusted analysis RT proved to be a significant factor also for MFS (HR = 0.42, 95% CI 0.20-0.88, p = 0.021). In addition, high-grade malignancy, large tumour and positive surgical margin were risk factors for local recurrence. High malignancy grade was the only significant adverse prognostic factor for metastasis. High age and high-grade malignancy were negative prognostic factors for OS. Adjuvant RT was significantly associated with an improved five-year LRFS and OS.
World Journal of Surgical Oncology, 2010
Background: We aimed to assess whether high-dose preoperative chemoradiotherapy (CRT) improves ou... more Background: We aimed to assess whether high-dose preoperative chemoradiotherapy (CRT) improves outcome in esophageal cancer patients compared to surgery alone and to define possible prognostic factors for overall survival. Methods: Hundred-and-seven patients with disease stage IIA -III were treated with either surgery alone (n = 45) or high-dose preoperative CRT (n = 62). The data were collected retrospectively. Sixty-seven patients had adenocarcinomas, 39 squamous cell carcinomas and one undifferentiated carcinoma. CRT was given as three intensive chemotherapy courses by cisplatin 100 mg/m 2 on day 1 and 5-fluorouracil 1000 mg/m 2 /day, from day 1 through day 5 as continuous infusion. One course was given every 21 days. The last two courses were given concurrent with highdose radiotherapy, 2 Gy/fraction and a median dose of 66 Gy. Kaplan-Meier survival analysis with log rank test was used to obtain survival data and Cox Regression multivariate analysis was used to define prognostic factors for overall survival. Results: Toxicity grade 3 of CRT occurred in 30 (48.4%) patients and grade 4 in 24 (38.7%) patients of 62 patients. One patient died of neutropenic infection (grade 5). Fifty percent (31 patients) in the CRT group did undergo the planned surgery. Postoperative mortality rate was 9% and 10% in the surgery alone and CRT+ surgery groups, respectively (p = 1.0). Median overall survival was 11.1 and 31.4 months in the surgery alone and CRT+ surgery groups, respectively (log rank test, p = 0.042). In the surgery alone group one, 3 and 5 year survival rates were 44%, 24% and 16%, respectively and in the CRT+ surgery group they were 68%, 44% and 29%, respectively. By multivariate analysis we found that age of patient, performance status, alcoholism and > = 4 pathological positive lymph nodes in resected specimen were significantly associated with overall survival, whereas high-dose preoperative CRT was not. We found no significant survival advantage in esophageal cancer stage IIA-III following preoperative highdose CRT compared to surgery alone. Patient's age, performance status, alcohol abuse and number of positive lymph nodes were prognostic factors for overall survival.
Radiotherapy and Oncology, 1991
Radiotherapy and Oncology, 1985
X-ray and heat survival curves were established for melanoma cells derived directly from surgical... more X-ray and heat survival curves were established for melanoma cells derived directly from surgical specimens of tumours in man by using the Courtenay soft agar colony assay. The plating efficiency for 11 of the 14 melanomas studied was sufficiently high (PE = 0.3-58%) to measure cell survival over at least two decades. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. The melanomas exhibited individual and characteristic survival curves whether exposed to radiation or heat (43.5 degrees C). The Do-values were in the ranges 0.63-1.66 Gy (X-rays) and 33-58 min (heat). The survival curves were similar to those reported previously for human melanoma xenografts. The radiation sensitivity of the cells was not correlated to the heat sensitivity. Since the melanomas appeared to be very heterogeneous in radiation response in vitro as melanomas are known to be clinically, it is suggested that melanomas may be suitable for prospective studies aimed at establishing whether clinical radioresponsiveness somehow is related to in vitro survival curve parameters.
Journal of Surgical Oncology, 1987
Laparotomy in a 41‐year‐old married man with non‐treated left cryptorchidism revealed female inte... more Laparotomy in a 41‐year‐old married man with non‐treated left cryptorchidism revealed female internal genitals on the left side, and an epithelial ovarian tumor of intermediate malignancy. Germinal malignancies are frequent in intersexes, but non‐germinal gonadal neoplasms are rare. This is the second reported case of epithelial ovarian tumor in intersexes, and the first case of epithelial ovarian tumor in an intersex registered as made.
International Journal of Radiation Oncology*Biology*Physics, 2013
There is limited evidence on dose fractionation issues in adjuvant radiation therapy (RT) of soft... more There is limited evidence on dose fractionation issues in adjuvant radiation therapy (RT) of soft tissue sarcoma. In this study of 426 patients from The Scandinavian Sarcoma Group Register, no doseeresponse effect of RT was demonstrated. After wide margin surgery, 50 Gy in 25 fractions seemed adequate. Accelerated RT Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant doseeresponse effect of adjuvant RTwas demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome.
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose: Adjuvant radiotherapy has during the past decades become increasingly used in the treatm... more Purpose: Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of localized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scandinavia between 1986 and 2005. Methods and Materials: A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian sarcoma centers were stratified according to the treatment period (1986-1991, 1992-1997, and 1998-2005). The use of adjuvant RT, quality of the surgical margin, interval between surgery and RT, and LRR were analyzed. The median follow-up was 5 years. Results: The use of RT (77% treated postoperatively) increased from 28% to 53%, and the 5-year LRR decreased from 27% to 15%. The rate of wide surgical margins did not increase. The risk factors for local recurrence were histologic high-grade malignancy (hazard ratio [HR], 5), an intralesional (HR, 6) or marginal (HR, 3) surgical margin, and no RT (HR, 3). The effect of RT on the LRR was also significant after a wide margin resection and in lowgrade malignant tumors. The LRR was the same after preoperative and postoperative RT. The median interval from surgery to the start of RT was 7 weeks, and 98% started RT within 4 months. The LRR was the same in patients who started treatment before and after 7 weeks. Conclusion: The results of our study have shown that adjuvant RT effectively prevents local recurrence in soft tissue sarcoma, irrespective of the tumor depth, malignancy grade, and surgical margin status. The effect was most pronounced in deep-seated, high-grade tumors, even when removed with a wide surgical margin.
International Journal of Radiation Oncology*Biology*Physics, 1993
Purpose: Nineteen patients with locally advanced breast carcinoma were subjected to computed tomo... more Purpose: Nineteen patients with locally advanced breast carcinoma were subjected to computed tomography exzns prior to thermoradiotherapy. Pre-and postcontrast computed tomography images were obtained, and tumor contrast enhancement was studied in relation to tissue perfusion, PERF, and steady state temperature, Ts, in an attempt to develop an assay for prediction of treatment temperatures in clinical hyperthermia of breast carcinoma. Methods and Materials: PERF and Ts were calculated from temperature data achieved during the first fraction of the heat treatment regimen. The computed tomography images were subjected to image analysis, and two parameters representing tumor contrast enhancement were calculated from the computed tomography numbers; the absolute increase in mean attenuation, AN, and the fraction of the postcontrast attenuation values that was higher than the mean precontrast attenuation value, F+c. Results: AN and F+, were clearly correlated to each other. The two parameters differed considerably among the patients, showing that the accumulation of contrast medium was higher in some tumors than in others. Tumor contrast enhancement increased with increasing PERF, suggesting that the accumulation of contrast medium in the tumors was determined mainly by the effective tissue perfusion. There was also a clear correlation between tumor contrast enhancement and Ts. The tumors showing a high accumulation of contrast medium were more difficult to heat than those showing a low accumulation. Conclusion: The results indicate that contrast enhanced computed tomography images may give information about the treatment temperatures that can be achieved in clinical hyperthermia of breast carcinoma. The computed tomography images may possibly be used to predict those tumors that can be heated to therapeutic temperatures.
International Journal of Radiation Oncology*Biology*Physics, 1991
Temperature distributions achieved during hyperthermic treatment of 16 patients with locally adva... more Temperature distributions achieved during hyperthermic treatment of 16 patients with locally advanced breast cancer were analyzed in relation to tissue perfusion, vascular density, and histology of treated volume. Temperatures were measured using multi-sensor thermistor probes inserted in the center and periphery of the treatment volume. A steady state temperature, Z',, and a perfusion related parameter, PERF, were determined for each probe location. Vascular density and tissue composition were determined by histologic analysis of biopsies taken from the temperature probe locations before treatment. Both malignant and normal tissue were found in the biopsies, reflecting a diffusive tumor growth pattern. The malignant and normal tissue compartments were analyzed separately using stereologic techniques. T,, PERF, vascular density, and tissue composition differed significantly between patients. There was a clear relationship between T, and PERF, showing that the local tissue perfusion was decisive for the temperatures achieved. T, and PERF showed a clear correlation with the normal tissue vascular density, but not with the malignant tissue vascular density; that is, the treatment temperatures achieved were mainly determined by the vascularization of the normal tissue compartment. Fraction of necrosis was the only tissue compartment parameter that showed a clear relationship to T, and PERF. T, increased and PERF decreased with increasing necrotic fraction. Invasive ductal breast carcinoma, Hyperthermia, Temperature distribution, Vascular density.
International Journal of Radiation Biology, 1991
It follows from the present work that the vascularization of the normal tissue present in the tre... more It follows from the present work that the vascularization of the normal tissue present in the treatment volume limits the temperatures achieved during heat treatment of invasive ductal breast carcinoma. The temperatures can often be increased by giving fractionated heat treatment because heat treatment may reduce the cooling capacity of the normal tissue vasculature. Significant damage to supplying vessels occurs at the heat doses necessary to cause necrosis in the tumour and surrounding normal tissue, indicating that secondary cell death is an important mechanism for cell inactivation following hyperthermic treatment of breast carcinoma.
International Journal of Hyperthermia, 1991
Seventeen patients with locally advanced breast cancer were given hyperthermic treatment, and cha... more Seventeen patients with locally advanced breast cancer were given hyperthermic treatment, and changes in temperatures and thermal doses with fraction number were studied. The changes were related to the vascular density of the treated volume before treatment. Multi-point thermistor probes were used for temperature measurements. Two parameters were determined for each probe location, a steady-state temperature, Ts, and a thermal dose, t43. To quantify changes in Ts and t43, linear curves were fitted to plots of these temperature parameters versus fraction number. The slopes of the curves, kTs and kt43, were used to represent the changes in Ts and t43, respectively. Vascular density was determined by histological analysis of biopsies taken from the temperature probe locations before the first heat treatment. Generally, Ts and t43 increased with increasing fraction number. kTs and kt43 were positively correlated to the vascular density of the normal tissue in the treatment volume, i.e. the increase in Ts and t43 was largest in the best-vascularized tissue. The cooling capacity of the normal tissue was probably reduced during the later heat fractions, either because of direct damage to the blood vessels or because of an impaired thermoregulative response. No relationship was found between the temperature parameters and the vascularization of the malignant tissue in the treatment volume. The present results show that the use of a fractionated schedule for heat treatment of locally advanced breast carcinoma may increase the temperatures and thermal doses achieved during treatment. A more uniform heating of the tumours can therefore be achieved by giving multiple heat fractions in the tumour areas that are difficult to heat adequately in one session.
International Journal of Hyperthermia, 1989
The ability of cyclophosphamide (CTX) and mitomycin C (MMC) to modify the expression of thermotol... more The ability of cyclophosphamide (CTX) and mitomycin C (MMC) to modify the expression of thermotolerance in vivo at 43.5 degrees C was investigated in a transplantable C3H mouse mammary carcinoma grown s.c. in feet of C3D2F1/Bom mice. Dose-effect curves subjected to linear regression analysis were constructed for single-fraction treatment and for a second treatment 24 h after a priming heat treatment of 43.5 degrees C for 30 min. Tumour volume doubling time during regrowth showed no significant variation among treatment groups, justifying the use of tumour growth time as effect parameter. Thermotolerance ratio for heat alone was 11.6 +/- 2.3. Drug enhancement ratio in thermotolerant tumours was 6.2 +/- 1.4 for CTX (100 mg/kg) and 3.5 +/- 0.9 for MMC (3 mg/kg). These values are about 4 and 3 times larger than the corresponding enhancement ratios found for previously untreated tumours. Thermotolerance ratio for thermochemotherapy was 2.6 +/- 0.3 for CTX and 4.4 +/- 0.7 for MMC, i.e. the degree of thermotolerance was substantially reduced by both drugs, but not completely overcome. Thermal enhancement ratio for CTX and MMC was about equally large in thermotolerant and previously untreated tumours. Thermotolerant tumours showed a tendency for increased resistance to drug treatment alone. Both CTX and MMC may be used clinically to reduce the expression of thermotolerance, particularly in situations with inhomogeneous heating and short fractionation intervals.
European Journal of Cancer, 1997
The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuo... more The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m2 as a 72 h infusion and ifosfamide 1500 mg/ m2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31-52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver metastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.
European Journal of Cancer, 2003
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Papers by Odd R. Schibsted Monge