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Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial.

https://arctichealth.org/en/permalink/ahliterature16621
Source
J Clin Oncol. 2005 Dec 1;23(34):8697-705
Publication Type
Article
Date
Dec-1-2005
Author
Helgi Birgisson
Lars Påhlman
Ulf Gunnarsson
Bengt Glimelius
Author Affiliation
Department of Surgery, Akademiska Sjukhuset, S-751 85 Uppsala, Sweden. helgi.birgisson@akademiska.se
Source
J Clin Oncol. 2005 Dec 1;23(34):8697-705
Date
Dec-1-2005
Language
English
Publication Type
Article
Keywords
Abdominal Pain - etiology
Aged
Combined Modality Therapy
Comparative Study
Digestive System Surgical Procedures
Female
Follow-Up Studies
Fractures, Bone - etiology
Humans
Intestinal Obstruction - etiology
Male
Middle Aged
Nausea - etiology
Neoplasm Recurrence, Local
Preoperative Care
Radiotherapy, Adjuvant - adverse effects
Rectal Neoplasms - therapy
Research Support, Non-U.S. Gov't
Risk factors
Sweden
Time Factors
Treatment Outcome
Abstract
PURPOSE: To analyze the occurrence of subacute and late adverse effects in patients treated with preoperative irradiation for rectal cancer. PATIENTS AND METHODS: The study population included 1,147 patients randomly assigned to preoperative radiation therapy or surgery alone in the Swedish Rectal Cancer Trial conducted 1987 through 1990. Patient data were matched against the Swedish Hospital Discharge Register to identify patients admitted to hospital after the primary treatment of the rectal cancer. Patients with known residual disease were excluded, and patients with a recurrence were censored 3 months before the date of recurrence. Relative risks (RR) with 95% CIs were calculated. RESULTS: Irradiated patients were at increased risk of admissions during the first 6 months from the primary treatment (RR = 1.64; 95% CI, 1.21 to 2.22); these were mainly for gastrointestinal diagnoses. Overall, the two groups showed no difference in the risk of admissions more than 6 months from the primary treatment (RR = 0.95; 95% CI, 0.80 to 1.12). Regarding specific diagnoses, however, RRs were increased for admissions later than 6 months from the primary treatment in irradiated patients for unspecified infections, bowel obstruction, abdominal pain, and nausea. CONCLUSION: Gastrointestinal disorders, resulting in hospital admissions, seem to be the most common adverse effect of short-course preoperative radiation therapy in patients with rectal cancer. Bowel obstruction was the diagnosis of potentially greatest importance, which was more frequent in irradiated than in nonirradiated patients.
PubMed ID
16314629 View in PubMed
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Common variants in human CRC genes as low-risk alleles.

https://arctichealth.org/en/permalink/ahliterature98081
Source
Eur J Cancer. 2010 Apr;46(6):1041-8
Publication Type
Article
Date
Apr-2010
Author
Simone Picelli
Pawel Zajac
Xiao-Lei Zhou
David Edler
Claes Lenander
Johan Dalén
Fredrik Hjern
Nils Lundqvist
Ulrik Lindforss
Lars Påhlman
Kennet Smedh
Anders Törnqvist
Jörn Holm
Martin Janson
Magnus Andersson
Susanne Ekelund
Louise Olsson
Joakim Lundeberg
Annika Lindblom
Author Affiliation
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Source
Eur J Cancer. 2010 Apr;46(6):1041-8
Date
Apr-2010
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Alleles
Case-Control Studies
Colorectal Neoplasms - epidemiology - genetics
Female
Genetic Predisposition to Disease - epidemiology - genetics
Genome-Wide Association Study
Genotype
Germ-Line Mutation - genetics
Humans
Male
Middle Aged
Penetrance
Polymorphism, Genetic
Risk factors
Sweden - epidemiology
Young Adult
Abstract
The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.
PubMed ID
20149637 View in PubMed
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The effects of short-course preoperative irradiation on local recurrence rate and survival in rectal cancer: a population-based nationwide study.

https://arctichealth.org/en/permalink/ahliterature134697
Source
Dis Colon Rectum. 2011 Jun;54(6):672-80
Publication Type
Article
Date
Jun-2011
Author
Marit Tiefenthal
Per J Nilsson
Robert Johansson
Bengt Glimelius
Lars Påhlman
Author Affiliation
Department of Surgery, Ersta Hospital, Stockholm, Sweden. marit.tiefenthal@erstadiakoni.se
Source
Dis Colon Rectum. 2011 Jun;54(6):672-80
Date
Jun-2011
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Combined Modality Therapy
Female
Humans
Male
Middle Aged
Neoplasm Recurrence, Local - prevention & control
Neoplasm Staging
Preoperative Care
Proportional Hazards Models
Rectal Neoplasms - mortality - pathology - radiotherapy - surgery
Registries
Retrospective Studies
Risk factors
Survival Analysis
Sweden - epidemiology
Treatment Outcome
Abstract
Preoperative irradiation with 5 × 5 Gy in randomized trials reduces local recurrence rate and may improve survival in patients with resectable rectal cancer.
The aim of this study was to determine whether the same favorable effects could be observed in a population-based study.
This study was conducted via a retrospective analysis of prospectively collected data from the Swedish Rectal Cancer Registry.
This study examined population-based data from Sweden.
All newly diagnosed rectal cancers in Sweden are reported to the Swedish Rectal Cancer Registry.
Between 1995 and 2001, 6878 patients (stages I-III) were operated on with an anterior resection, an abdominoperineal resection, or a Hartmann's procedure. Short-course irradiation was given to 41% of patients preoperatively. To reduce bias, patients operated on with a Hartmann procedure or older than 75 years were excluded when 5-year survival was analyzed (n = 3466). Tumors were analyzed according to height (0-5 cm, 6-10 cm, 11-15 cm).
Five-year cumulative local recurrence and survival rates.
The 5-year cumulative local recurrence rate was 6.3% (95% CI 5.4-7.4) for patients receiving preoperative irradiation and 12.1% (95% CI 10.8-13.5) for patients not receiving preoperative irradiation. Multivariate analyses indicated the risk of local recurrence was 50% lower for patients receiving preoperative irradiation compared with patients not receiving irradiation (hazard ratio = 0.50; 95% CI 0.40-0.62). Among patients younger than 76 years and operated on with an anterior resection or abdominoperineal resection, the 5-year cumulative survival rate was 0.70 (95% CI 0.69-0.72). Disease-free and overall survivals were higher in irradiated patients, and the difference was statistically significant in low tumors.
In this population-based analysis, the favorable effect of preoperative short-course irradiation on local recurrence rates, seen in randomized trials, was confirmed for the entire Swedish population irrespective of tumor height and stage. Data also suggested an effect on 5-year survival, especially in patients with low tumors (0-5 cm).
PubMed ID
21552050 View in PubMed
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Occurrence of second cancers in patients treated with radiotherapy for rectal cancer.

https://arctichealth.org/en/permalink/ahliterature16805
Source
J Clin Oncol. 2005 Sep 1;23(25):6126-31
Publication Type
Article
Date
Sep-1-2005
Author
Helgi Birgisson
Lars Påhlman
Ulf Gunnarsson
Bengt Glimelius
Author Affiliation
Department of Surgery, Akademiska Sjukhuset, S-751 85 Uppsala, Sweden. helgi.birgisson@akademiska.se
Source
J Clin Oncol. 2005 Sep 1;23(25):6126-31
Date
Sep-1-2005
Language
English
Publication Type
Article
Keywords
Aged
Humans
Incidence
Neoplasms, Radiation-Induced - epidemiology - etiology
Randomized Controlled Trials
Rectal Neoplasms - radiotherapy
Registries - statistics & numerical data
Research Support, Non-U.S. Gov't
Risk factors
Sweden
Abstract
PURPOSE: To analyze the occurrence of second cancers in patients with rectal cancer treated with external radiotherapy (RT) in addition to surgery. PATIENTS AND METHODS: The analyses were based on the Uppsala Trial (completed in 1985), with patients randomly assigned to preoperative RT to all stages or postoperative RT for stage II and III cancers, and the Swedish Rectal Cancer Trial (completed in 1990), with patients randomly assigned to preoperative RT or surgery alone. Patients from the trials were matched against the Swedish Cancer Registry. RESULTS: A total of 115 (7%) of the 1,599 patients developed 122 second cancers. More patients treated with RT developed a second cancer (relative risk [RR], 1.85; 95% CI, 1.23 to 2.78). A significant increased risk for second cancers in the RT group was seen in organs within or adjacent to the irradiated volume (RR, 2.04; 95% CI, 1.10 to 3.79) but not outside the irradiated volume (RR, 1.78; 95% CI, 0.97 to 3.27). For the Swedish Rectal Cancer Trial, 20.3% of the RT patients got either a local recurrence or a second cancer, compared with 30.7% of the non-RT patients (RR, 0.55; 95% CI, 0.44 to 0.70). CONCLUSION: An increased risk of second cancers was found in patients treated with RT in addition to surgery for a rectal cancer, which was mainly explained by an increase in the risk of second cancers in organs within or adjacent to the irradiated volume. However, a favorable effect of radiation seemed to dominate, as shown by the reduced risk of the sum of local recurrences and second cancers.
PubMed ID
16135478 View in PubMed
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