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1.
  • Dantonello, Tobias M., et al. (författare)
  • Initial patient characteristics can predict pattern and risk of relapse in localized rhabdomyosarcoma
  • 2008
  • Ingår i: Journal of Clinical Oncology. - American Society of Clinical Oncology. - 1527-7755. ; 26:3, s. 406-413
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Evaluation of primary tumor-, treatment-, and patient-related factors predicting relapse pattern, risk, and survival after relapse with the aim to design a risk-adapted, tumor- directed surveillance program for patients with localized rhabdomyosarcoma (RMS). Patients and Methods One thousand one hundred sixty-four patients with nonmetastatic RMS achieved complete remission at the end of multimodal therapy in the consecutive trials of the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, CWS-86, CWS-91, and CWS-96 between 1980 and 2002 ( median follow-up, 5 years). Three hundred thirty-seven of these individuals developed either locoregional, metastatic, or combined relapses. Predictive factors for relapse, its pattern, and postrelapse survival were analyzed. Results Age, histology, tumor size, tumor site, postsurgical stage, and omission of radiotherapy were identified as factors associated with an increased relapse risk in multivariate analyses. Relapse rates did not differ among the CWS trials. Median time to relapse was 1.43 years from first diagnosis ( range, 0.13 to 13.5 years). There were 217 locoregional, 72 metastatic, and 48 combined recurrences. Only two patients developed metastases more than 4 years after diagnosis, and both had combined recurrences. Five-year postrelapse survival was 24%. Patient subsets with consistent relapse pattern, risk, and postrelapse survival rates were identified on the basis of histologic subtype and tumor size. Conclusion Initial patient and tumor characteristics predict pattern and risk of relapse and also correlate with postrelapse survival probabilities. In localized RMS, tumor- directed follow-up should focus on the primary site. Screening for metastatic relapse may not be necessary more than 4 years after diagnosis. The identification of subgroups with distinctive pattern and risk of relapse may be used to develop risk-adapted, tumor- directed guidance for detection of recurrent disease in localized RMS.
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2.
  • Ferrari, S, et al. (författare)
  • Neoadjuvant chemotherapy with high-dose ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: A joint study by the Italian and Scandinavian Sarcoma Groups
  • 2005
  • Ingår i: Journal of Clinical Oncology. - American Society of Clinical Oncology. - 1527-7755. ; 23:34, s. 8845-8852
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose To explore the effect of high-dose ifosfamide in first-line treatment for patients <= 40 years of age with nonmetastatic osteosarcoma of the extremity. Patients and Methods From March 1997 to September 2000, 182 patients were evaluated. Primary treatment consisted of two blocks of high-dose ifosfamide (15 g/m(2)), methotrexate (12 g/m(2)), cisplatin (120 mg/m(2)), and doxorubicin (75 mg/m(2)). Postoperatively, patients received two cycles of doxorubicin (go mg/m(2)), and three cycles each of high-dose ifosfamide, methotrexate, and cisplatin (120 to 150 mg/m(2)). Granulocyte colony-stimulating factor support was mandatory after the high-dose ifosfamide/cisplatin/doxorubicin combination. Results No disease progression was recorded during primary chemotherapy, 164 patients (92%) underwent limb-salvage surgery, four patients (2%) underwent rotation plasty, and 11 patients (6%) had limbs amputated. Three (1.6%) patients died as a result of treatment-related toxicity, and one died as a result of pulmonary embolism after pathologic fracture. Grade 4 neutropenia and thrombocytopenia followed 52% and 31% of all courses, respectively, and mild to severe nephrotoxicity was recorded in 19 patients (10%). The median received dose-intensity compared with protocol was 0.82. With a median follow-up of 55 months, the 5-year probability of event-free survival was 64% (95% CI 57% to 71%) and overall survival was 77% (95% CI 67% to 81%), whereas seven patients (4%) experienced local recurrence. Conclusion The addition of high-dose ifosfamide to methotrexate, cisplatin, and doxorubicin in the preoperative phase is feasible, but with major renal and hematologic toxicities, and survival rates similar to those obtained with four-drug regimens using standard-dose ifosfamide. Italian Sarcoma Group/Scandinavian Sarcoma Group study I showed that in a multicenter setting, more than 90% of patients with osteosarcoma of the extremity can undergo conservative surgery.
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3.
  • Petersson-Ahrholt, Magnus, et al. (författare)
  • Development and Implementation of Survivorship Tools to Enable Medical Follow-Up After Childhood Cancer Treatment in Southern Sweden
  • 2019
  • Ingår i: JCO clinical cancer informatics. - American Society of Clinical Oncology. - 2473-4276. ; 3, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Survival rates after childhood cancer have increased from 20% to 80% since the 1970s. The increased number of survivors emphasizes the importance of late effects and their monitoring. Late effects may have a strong impact on quality of life in survivors. The purpose of this study was to make key data in a quality registry available for direct clinical use, enabling health care professionals to perform efficient and appropriate long-term medical follow-up after childhood cancer treatment.METHODS: The population-based quality registry upon which this study is centered contains data on all individuals diagnosed with childhood cancer (diagnosed at 18 years of age or younger) in southern Sweden since January 1, 1970, and treatment data on 5-year survivors. Web tools, which were developed and implemented in a health care setting, generate a personalized treatment summary for each patient and enable risk group stratification of survivors.RESULTS: Generation of a personalized treatment summary and risk group stratification of survivors led to identification of women at risk for developing breast cancer as a consequence of childhood cancer treatment. Three novel cases of previously undiagnosed breast cancer were identified.CONCLUSION: The registry, together with the developed tools, enabled health care professionals to perform medical follow-up in this at-risk patient population.
4.
  • Romerius, Patrik, et al. (författare)
  • Estrogen receptor alpha single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors
  • 2011
  • Ingår i: Pharmacogenetics & Genomics. - Lippincott Williams & Wilkins. - 1744-6872. ; 21:5, s. 263-269
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered. METHODS: Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER β genes were examined in 127 adult childhood cancer survivors. RESULTS: In ERα, markers of one specific haplotype block (rs2207396, rs9340958, rs9340978) were associated with an increased risk of azoospermia. Compared with those with the GG genotype, patients being heterozygous for the A allele in rs2207396 had a significantly increased risk of azoospermia [odds ratio (OR): 3.8; 95% confidence interval: 1.5-9.5; P=0.008], this OR being even higher in the subgroup treated with alkylating drugs (OR: 8.8; 95% confidence interval: 2.1-36; P=0.004). In this subgroup, 48% of the patients carried the A allele of rs2207396, this proportion being 70% among the azoospermic patients. CONCLUSION: Use of genetic markers of high risk of posttreatment azoospermia may, in the future, prove an important clinical tool in selection of boys to whom preservation of testicular tissue before cancer therapy should be offered.
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5.
  • Romerius, Patrik, et al. (författare)
  • Estrogen receptor α single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors
  • 2011
  • Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 21:5, s. 263-269
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>OBJECTIVE:</p> <p>Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered.</p> <p>METHODS:</p> <p>Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER β genes were examined in 127 adult childhood cancer survivors.</p> <p>RESULTS:</p> <p>In ERα, markers of one specific haplotype block (rs2207396, rs9340958, rs9340978) were associated with an increased risk of azoospermia. Compared with those with the GG genotype, patients being heterozygous for the A allele in rs2207396 had a significantly increased risk of azoospermia [odds ratio (OR): 3.8; 95% confidence interval: 1.5-9.5; P=0.008], this OR being even higher in the subgroup treated with alkylating drugs (OR: 8.8; 95% confidence interval: 2.1-36; P=0.004). In this subgroup, 48% of the patients carried the A allele of rs2207396, this proportion being 70% among the azoospermic patients.</p> <p>CONCLUSION:</p> <p>Use of genetic markers of high risk of posttreatment azoospermia may, in the future, prove an important clinical tool in selection of boys to whom preservation of testicular tissue before cancer therapy should be offered.</p>
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6.
  • Romerius, Patrik, et al. (författare)
  • High risk of azoospermia in men treated for childhood cancer.
  • 2011
  • Ingår i: International Journal of Andrology. - Wiley-Blackwell. - 1365-2605. ; 34, s. 69-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary Childhood cancer survivors (CCS) have an increased risk of impaired spermatogenesis, but data regarding the disease- and treatment-related risk factors of azoospermia are scarce. Such information is crucial both for counselling CCS and for selecting patients for testicular tissue cryopreservation. The proportion of azoospermic men in CCS was 18% [95% confidence interval (CI): 12-26], specifically for leukaemias (19%; 95% CI: 5.5-42), Hodgkin's disease (53%; 95% CI: 29-76), non-Hodgkin's lymphoma (11%; 95% CI: 0.28-48) and testicular cancer (11%; 95% CI: 0.28-48). In CCS treated with high doses of alkylating agents, the proportion of azoospermic men was 80% (95% CI: 28-99) and if radiotherapy was used additionally, the proportion was 64% (95% CI: 35-87). In CCS with subnormal Inhibin B levels, the proportion of azoospermic men was 66% (95% CI: 47-81) and for those with elevated follicle-stimulating hormone (FSH) levels, the proportion was 50% (95% CI: 35-67). Among CCS with subnormal testicular volume (</=24 mL), azoospermia was found in 61% (95% CI: 39-80) of the cases. Most childhood cancer diagnoses are associated with an increased risk of azoospermia, especially in CCS receiving testicular irradiation, high doses of alkylating drugs and other types of cytotoxic treatment, if combined with irradiation. Inhibin B, FSH and testicular volume can be used as predictors for the risk of azoospermia.
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7.
  • Romerius, Patrik, et al. (författare)
  • Hypogonadism Risk in Men Treated for Childhood Cancer.
  • 2009
  • Ingår i: The Journal of clinical endocrinology and metabolism. - Oxford University Press. - 1945-7197. ; 94, s. 4180-4186
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Pediatric cancer treatment may imply an increased risk of hypogonadism, leading to metabolic disorders and osteoporosis. Such complications are potentially preventable. Objective: The aim of this study was to assess diagnosis- and treatment-dependent risk of hypogonadism in male childhood cancer survivors (CCS). Design: Male CCS who were treated during the period 1970-2002 and who in 2004 were 18-45 yr of age were eligible. Setting: The study was conducted in a university hospital clinic. Patients: A consecutive group of CCS treated at Lund University Hospital was selected for the study, of whom 151 (38%) agreed to participate. Furthermore, 141 healthy fertile men served as controls. Interventions: We measured serum levels of free and total testosterone, SHBG, and LH. Main Outcome Measures: Odds ratios (OR) for biochemical hypogonadism, defined as total testosterone less than 10 nmol/liter and/or LH above 10 IU/liter, were calculated and related to type of cancer, treatment received, as well as testicular volume. Results: Hypogonadism was more commonly detected in CCS than in controls (OR, 6.7; 95% CI, 2.7, 17). The increased presence of hypogonadism was noted in the following treatment groups: brain surgery, chemotherapy (with and without radiotherapy), and testicular irradiation. Low total testicular volume (</=24 ml) was associated with a high risk of hypogonadism (OR, 31; 95% CI, 11, 92). Conclusion: Adult male survivors of childhood cancer are at risk of hypogonadism, which should be acknowledged in the long-term follow-up of these men.
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8.
  • Romerius, Patrik, et al. (författare)
  • Sperm DNA Integrity in Men Treated for Childhood Cancer.
  • 2010
  • Ingår i: Clinical Cancer Research. - American Association for Cancer Research. - 1078-0432. ; Jul 1, s. 3843-3850
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: It is unknown whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study was to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), treatment regimen taken into account.EXPERIMENTAL DESIGN: In 99 CCS and 193 age-matched healthy controls, the DFI was assessed by the use of Sperm Chromatin Structure Assay.RESULTS: In the whole group of CCS DFI was increased as compared to the controls with borderline statistical significance (mean difference=0.94%; 95%CI: -0.0088; 3.7%). Those treated with radiotherapy only (mean difference=6.0%; 95%CI: 1.6; 10%) or surgery only (mean difference=2.9%; 95%CI: 0.083; 3.7%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS as compared to the control group (OR=2.2, 95%CI: 1.1; 4.4). For the radiotherapy only group the OR was even higher (OR=4.9, 95%CI 1.3; 18). The DFI was not associated to the dose of scattered testicular irradiation or the type of chemotherapy given.CONCLUSIONS: The DFI is increased in CCS, those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment and may have negative consequences in terms of fertility and risk of transmission to the offspring.
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