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1.
Clin Oncol (R Coll Radiol) ; 28(8): 532-9, 2016 08.
Article in English | MEDLINE | ID: mdl-26888115

ABSTRACT

AIMS: This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. MATERIALS AND METHODS: Ninety-seven patients (57 T2-3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m(2) day 1 and bolus 5-fluorouracil 500 mg/m(2) and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. RESULTS: Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. CONCLUSIONS: In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.


Subject(s)
Neoadjuvant Therapy/methods , Organoplatinum Compounds/administration & dosage , Rectal Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/administration & dosage , Capecitabine/adverse effects , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Disease Progression , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoplasm Staging , Organoplatinum Compounds/adverse effects , Oxaliplatin , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Treatment Outcome
2.
Br J Radiol ; 88(1051): 20150097, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25899892

ABSTRACT

OBJECTIVE: To investigate if MRI-assessed tumour volumetry correlates with histological tumour response to neoadjuvant chemotherapy (NACT) and subsequent chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). METHODS: Data from 69 prospectively enrolled patients with LARC receiving NACT followed by CRT and radical surgery were analysed. Whole-tumour volumes were contoured in T2 weighted MR images obtained pre-treatment (VPRE), after NACT (VNACT) and after the full course of NACT followed by CRT (VCRT). VPRE, VNACT and tumour volume changes relative to VPRE, ΔVNACT and ΔVCRT were calculated and correlated to histological tumour regression grade (TRG). RESULTS: 61% of good histological responders (TRG 1-2) to NACT followed by CRT were correctly predicted by combining VPRE < 10.5 cm(3), ΔVNACT > -78.2% and VNACT < 3.3 cm(3). The highest accuracy was found for VNACT, with 55.1% sensitivity given 100% specificity. The volume regression after completed NACT and CRT (VCRT) was not significantly different between good and poor responders (TRG 1-2 vs TRG 3-5). CONCLUSION: MRI-assessed small tumour volumes after NACT correlated with good histological tumour response (TRG 1-2) to the completed course of NACT and CRT. Furthermore, by combining tumour volume measurements before, during and after NACT, more good responders were identified. ADVANCES IN KNOWLEDGE: MRI volumetry may be a tool for early identification of good and poor responders to NACT followed by CRT and surgery in LARC in order to aid more individualized, multimodal treatment.


Subject(s)
Chemoradiotherapy , Chemotherapy, Adjuvant , Magnetic Resonance Imaging , Neoadjuvant Therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Neoplasm Grading , Prospective Studies , Tumor Burden , Young Adult
3.
Clin Oncol (R Coll Radiol) ; 27(4): 213-21, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25624156

ABSTRACT

AIMS: To evaluate potential prognostic factors for predicting survival after radiotherapy in patients with painful spinal metastases and normal neurological function. MATERIALS AND METHODS: In total, 173 patients were included. The following prognostic factors were assessed: primary cancer site, age, gender, albumin and haemoglobin levels, Karnofsky performance status (KPS), analgesic use, pain intensity, number of extraspinal bone metastases and visceral metastases, presence of tumour-conditioned spinal canal stenosis and metastatic spinal cord compression, and extension of spinal metastatic disease on magnetic resonance imaging (MRI). Ongoing systemic treatment, use of bisphosphonates and response to radiotherapy were also evaluated. A simple scoring system for predicting survival was used. RESULTS: The following predictive factors were found to be significant in multivariate analysis: primary cancer site, KPS, albumin level, number of visceral metastases and analgesic use. Three survival groups were proposed. The overall survival probabilities for groups 1-3 were 13, 46 and 94% at 6 months; 4, 28 and 79% at 12 months, respectively. The median survival times for groups 1-3 were 2.1, 5.5 and 24.9 months, respectively (P < 0.001). CONCLUSION: The pretreatment albumin level was a significant prognostic indicator for survival. Similarly, the primary cancer site, KPS and number of visceral metastases were associated with survival; these findings were consistent with the results of previous studies. The pretreatment analgesic use was significant using the univariate and multivariate analyses and this factor can be verified in future trials. Self-reported pain intensity, pain response to radiotherapy and MRI findings did not influence survival times.


Subject(s)
Spinal Neoplasms/radiotherapy , Spinal Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Spinal Neoplasms/physiopathology , Survival Analysis
4.
Br J Cancer ; 112(2): 382-90, 2015 Jan 20.
Article in English | MEDLINE | ID: mdl-25461803

ABSTRACT

BACKGROUND: The hypoxia marker pimonidazole is a candidate biomarker of cancer aggressiveness. We investigated the transcriptional programme associated with pimonidazole staining in prostate cancer. METHODS: Index tumour biopsies were taken by image guidance from an investigation cohort of 52 patients, where 43 patients received pimonidazole before prostatectomy. Biopsy location within the index tumour was verified for 46 (88%) patients, who were included for gene expression profiling and immunohistochemistry. Two independent cohorts of 59 and 281 patients were used for validation. RESULTS: Expression of genes in proliferation, DNA repair and hypoxia response was a major part of the transcriptional programme associated with pimonidazole staining. A signature of 32 essential genes was constructed and showed positive correlation to Ki67 staining, confirming the increased proliferation in hypoxic tumours as suggested from the gene data. Positive correlations were also found to tumour stage and lymph node status, but not to blood prostate-specific antigen level, consistent with the findings for pimonidazole staining. The association with aggressiveness was confirmed in validation cohorts, where the signature correlated with Gleason score and had independent prognostic impact, respectively. CONCLUSIONS: Pimonidazole staining reflects an aggressive hypoxic phenotype of prostate cancer characterised by upregulation of proliferation, DNA repair and hypoxia response genes.


Subject(s)
Nitroimidazoles , Prostatic Neoplasms/pathology , Transcriptome , Cell Hypoxia , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Nitroimidazoles/pharmacokinetics , Proportional Hazards Models , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/mortality , Staining and Labeling , Tissue Distribution
5.
Acta Radiol ; 53(10): 1164-72, 2012 Dec 01.
Article in English | MEDLINE | ID: mdl-23047848

ABSTRACT

BACKGROUND: Magnetic resonance imaging (MRI) is the recommended primary investigation method for metastatic spinal cord compression (MSCC). Initiating treatment before the development of motor deficits is essential to preserve neurological function. However, the relationship between MRI-assessed grades of spinal metastatic disease and neurological status has not been widely investigated. PURPOSE: To analyze the association between neurological function and MRI-based assessment of the extent of spinal metastases using two different grading systems. MATERIAL AND METHODS: A total of 284 patients admitted to our institution for initial radiotherapy or surgery for symptomatic spinal metastases were included in the study. Motor and sensory deficits were categorized according to the Frankel classification system. Pre-treatment MRI evaluations of the entire spine were scored for the extent of spinal metastases, presence and severity of spinal cord compression, and nerve root compression. Two MRI-based scales were used to evaluate the degree of cord compression and spinal canal narrowing and relate these findings to neurological function. RESULTS: Of the patients included in the study, 28 were non-ambulatory, 49 were ambulatory with minor motor deficits, and 207 had normal motor function. Spinal cord compression was present in all patients with Frankel scores of B or C, 23 of 35 patients with a Frankel score of D (66%), and 48 of 152 patients with a Frankel score of E (32%). The percentage of patients with severe spinal canal narrowing increased with increasing Frankel grades. The grading according to the scales showed a significant association with the symptoms according to the Frankel scale (P < 0.001). CONCLUSION: In patients with neurological dysfunction, the presence and severity of impairment was associated with the epidural tumor burden. A significant number of patients had radiological spinal cord compression and normal motor function (occult MSCC).


Subject(s)
Magnetic Resonance Imaging/methods , Motor Activity , Spinal Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Epidural Space/pathology , Female , Humans , Male , Middle Aged , Neurologic Examination/methods , Neurologic Examination/statistics & numerical data , Prospective Studies , Severity of Illness Index , Spinal Canal/pathology , Spinal Cord Compression/pathology , Spinal Neoplasms/secondary , Spine/pathology , Young Adult
6.
Ann Oncol ; 23(5): 1254-1259, 2012 May.
Article in English | MEDLINE | ID: mdl-21926399

ABSTRACT

BACKGROUND: From 1999, Norwegian guidelines recommend two escalated (esc) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) followed by six standard (s) BEACOPP for patients with advanced-stage classical Hodgkin lymphoma (HL) with an international prognostic score (IPS) ≥ 4. We evaluated retrospectively the experience with this recommendation at the Norwegian Radium Hospital, also including all IPS 3 patients treated with the same regimen. PATIENTS AND METHODS: Forty-seven patients were treated between June 1999 and December 2008. IPS was 3 in 10 patients and ≥ 4 in 37. RESULTS: Thirty-five patients received eight cycles of BEACOPP, 12 patients received one to six cycles only, mainly due to toxicity. Sixty percent of patients had dose reductions. With median follow-up of survivors of 89 months, 5-year progression-free and overall survival are 84% [95% confidence interval (CI) 73% to 95%] and 91% (95% CI 82% to 100%), respectively. Toxicity was considerable with grade 3 or more infections/febrile neutropenia in 66% of patients, including one death and three cases of Pneumocystis jiroveci pneumonia. Of note, 10 patients (21%) experienced symptomatic aseptic osteonecrosis, of whom 3 have had hip replacement surgery after treatment. CONCLUSION: Two escBEACOPP plus six sBEACOPP is efficacious in advanced-stage high-risk HL. We document a high incidence of aseptic bone necrosis, possibly related to prednisolone.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Hodgkin Disease/drug therapy , Osteonecrosis/chemically induced , Adolescent , Adult , Bleomycin/administration & dosage , Bleomycin/adverse effects , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Disease Progression , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Administration Schedule , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Follow-Up Studies , Hodgkin Disease/diagnosis , Hodgkin Disease/mortality , Hodgkin Disease/pathology , Humans , Male , Middle Aged , Neoplasm Staging , Osteonecrosis/diagnosis , Osteonecrosis/etiology , Osteonecrosis/mortality , Practice Guidelines as Topic/standards , Prednisone/administration & dosage , Prednisone/adverse effects , Procarbazine/administration & dosage , Procarbazine/adverse effects , Retrospective Studies , Risk , Survival Analysis , Vincristine/administration & dosage , Vincristine/adverse effects , Young Adult
7.
Eur Radiol ; 21(6): 1188-99, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21127880

ABSTRACT

OBJECTIVE: To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not. METHODS: Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37-72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated. RESULTS: Before NAC, HER2 overexpression was the single significant predictor of pCR (p = 0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42 × 10(-3) mm(2)/s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%. CONCLUSION: ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Diffusion Magnetic Resonance Imaging/methods , Gadolinium DTPA , Adult , Aged , Contrast Media , Female , Humans , Middle Aged , Neoadjuvant Therapy/methods , Prognosis , Reproducibility of Results , Sensitivity and Specificity , Treatment Outcome
8.
Colorectal Dis ; 11(7): 759-67, 2009 Sep.
Article in English | MEDLINE | ID: mdl-18662240

ABSTRACT

OBJECTIVE: To compare the clinical ability of MRl taken before and after neo-adjuvant treatment in locally advanced rectal cancer (LARC) to predict the necessary extension of TME (ETME) and the possibility to achieve a R0 resection. METHOD: Prospective registration of 92 MRI evaluated T4a cancers undergoing elective surgery between 2002 and 2007 in a tertiary referral centre for multimodal treatment of rectal cancer. RESULTS: MRI identified patients in need of neo-adjuvant treatment and predicted T-downstaging in 10% and N-downstaging in 59%. Seventy-nine percent R0 resections, 18% R1 and 3% R2 were obtained after ETME in 95% of the patients and TME in the rest. Higher tumour regression grade (TRG) was achieved in higher ypT-stage (P < 0.01). Preoperative chemo radiotherapy resulted in that more patients obtained TRG1-3 compared to those receiving radiotherapy (79% vs. 57%, P = 0.02). The pelvic wall was the area of failure in 70% of the R1 resections. Tumour cells outside the mesorectal fascia scattered within fibrosis was found in 18 TRG2-3 among 33 ypT4 tumours (55%). CONCLUSION: MRl cannot discriminate tumour within fibrosis. Therefore, if a R0 resection is the goal, we advocate optimal surgery in accordance with the pre-treatment MRI. Post treatment MRI is a poor predictor of final histology and should not be relied upon to guide the extent of surgical resection. The study has initiated a new approach to histopathological classification of the removed specimen where we introduce a MRI assisted technique for investigating the areas at risk outside the mesorectal fascia in the specimen.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/surgery , Magnetic Resonance Imaging , Neoadjuvant Therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Chemotherapy, Adjuvant , Female , Fibrosis/complications , Fibrosis/pathology , Humans , Male , Neoplasm Staging/methods , Prospective Studies , Radiotherapy, Adjuvant
9.
Tidsskr Nor Laegeforen ; 119(26): 3892-5, 1999 Oct 30.
Article in Norwegian | MEDLINE | ID: mdl-10592747

ABSTRACT

Ileal pouch-anal anastomosis is an alternative to ileostomy for patients with ulcerative colitis. Results of a questionnaire survey answered by 155 patients organised in a support group are presented. Consequences of the operation were mainly faecal incontinence, experienced by half of the group in the daytime, and frequent defaecations (5-7 per day, 1-2 per night). One half of the patients used medication every day to decrease the number of defaecations. 64% had changed their diet, while social and physical activities were reduced for 43% of the patients. Changes in lifestyle after the operation lead to increased expenses for 70% of the group. Women were more often incontinent than men and experienced it as a serious problem, and more women than men had changed their dietary habits. The quality of sleep was inferior to that of the preoperative period for 47% of the patients. 50% felt restricted in daily life activities due to frequent defaecations. These patients are living with a concealed disability. In spite of this, their assessments of self-esteem, health and quality of life were mainly positive.


Subject(s)
Proctocolectomy, Restorative/psychology , Adolescent , Adult , Child , Fecal Incontinence/etiology , Fecal Incontinence/psychology , Feeding Behavior , Female , Humans , Male , Middle Aged , Proctocolectomy, Restorative/adverse effects , Quality of Life , Self Concept , Socioeconomic Factors , Surveys and Questionnaires
10.
Tidsskr Nor Laegeforen ; 112(4): 518-23, 1992 Feb 10.
Article in Norwegian | MEDLINE | ID: mdl-1553709

ABSTRACT

During winter 1991, 60% of medical and nursing administrators in Telemark county made an extensive evaluation of their own jobs. Head of Department physicians spent 60% of their working time on medical tasks, 10% on budgets and accounting, and 30% on care of the staff. Direct work in connection with patients took 48% of time. 19% of the working time was spent on secretarial functions which could preferably be delegated to others. Head of Department doctors have too little education in budgeting and accounting. Head of Section doctors spent 77% of their working time on medical tasks. This is a group of contented and productive physicians. Head of Department nurses spent 74% of their time on administrative tasks and 11% on work directly connected to patients. 25% of the time was spent on individual care of colleagues in addition to professional instruction, and the group would like to have even more time for this task. Head of Ward nurses spent 38% of their working time on patients and 58% on tasks connected to the staff. 26% of their time is mere secretarial work. Individual care of colleagues required 21% of their time, and they would like to have even more time for this purpose. All groups of administrators would like to receive more feedback from the top management of their hospital.


Subject(s)
Hospital Administrators , Leadership , Nurse Administrators , Physicians , Attitude of Health Personnel , Evaluation Studies as Topic , Financial Management, Hospital , Hospital Administrators/standards , Hospital Administrators/statistics & numerical data , Norway , Nurse Administrators/standards , Nurse Administrators/statistics & numerical data , Personnel Administration, Hospital , Physicians/standards , Physicians/statistics & numerical data , Workload/statistics & numerical data
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