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Optimising Radiotherapy in Rectal Cancer Patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rectal cancer is the eight most common cancer diagnosis in Sweden in both men and women, with almost 2000 new cases per year. Radiotherapy, which is an important treatment modality for rectal cancer, has evolved during the past decades. Diagnostic tools have also improved, allowing better staging and offering information used to make well-founded decisions in multidisciplinary team conferences.

In a retrospective study (n=46) with locally advanced rectal cancer (LARC) patients, unfit for chemoradiotherapy, patients were treated with short-course radiotherapy. Delayed surgery was done when possible. Radical surgery was possible in 89% of the patients who underwent surgery (80%). Grade IV diarrhoea affected three elderly patients. Target radiation volume should be reduced in elderly or metastatic patients.

In a prospective study (n=68) with LARC patients, magnetic resonance imaging (MRI) and 2-18F-fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) were used to determine if FDG-PET could provide extra treatment information. Information from FDG-PET changed the stage of 10 patients. Delineation with FDG-PET generally resulted in smaller target volumes than MRI only.

Seven of the most advanced LARC patients in the above cohort were used for a methodological study to determine if dose escalation to peripheral, non-resectable regions was feasible. Simultaneous integrated boost plans with photons and protons were evaluated. While toxicity was acceptable in five patients with both protons and photons, two patients with very large tumours had unacceptable risk for intestinal toxicity regardless of modality.

In the interim analysis of the Stockholm III Trial (n=303, studying radiotherapy-fractionation and timing of surgery in relation to radiotherapy) compliance was acceptable and severe acute toxicity was infrequent, irrespective of fractionation. Short-course radiotherapy with immediate surgery tended to give more postoperative complications, but only if surgery was delayed more than 10 days after the start of radiotherapy.

Quality-of-life in the Stockholm III Trial was studied before, during and shortly after treatment using the EORTC QLQ-C30 and CR38 questionnaires. Surgery accounted for more adverse effects than radiotherapy in all groups. Postoperatively, the poorest quality-of-life was seen in patients given short-course radiotherapy followed by immediate surgery. No postoperative differences were seen between the two groups with delayed surgery.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 775
Keyword [en]
Rectal cancer, locally advanced, radiotherapy, FDG-PET, peripheral boost, protons, quality-of-life
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:uu:diva-172531ISBN: 978-91-554-8367-8 (print)OAI: oai:DiVA.org:uu-172531DiVA: diva2:516752
Public defence
2012-06-11, Skoogsalen, Akademiska Sjukhuset, ingång 78, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2012-05-21 Created: 2012-04-11 Last updated: 2012-08-01Bibliographically approved
List of papers
1. Short-course preoperative radiotherapy with delayed surgery in rectal cancer: a retrospective study
Open this publication in new window or tab >>Short-course preoperative radiotherapy with delayed surgery in rectal cancer: a retrospective study
2008 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, Vol. 87, no 3, 343-9 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: In the most advanced, non-resectable primary rectal cancers, conventional long-course radiotherapy (RT) (1.8-2Gyx25-28), frequently combined with chemotherapy, has been used since tumour regression is needed in order to allow a radical (R0) resection. In Uppsala, short-course 5x5Gy with planned delayed surgery has been used in patients with contraindications to long-course RT (+/-chemotherapy). The aim is to describe our experience of using this approach in patients not eligible for standard treatment. PATIENTS AND METHODS: During 2002 and 2005, 46 patients with non-resectable rectal cancer (+/-synchronous distant metastases) were treated with 5x5Gy and delayed surgery if possible. The clinical records were retrospectively evaluated. The first group (A) had no metastases (T4NXM0), whereas the other two groups (B+C) had metastases (T4NXM1). In group (B), the patients had predominantly loco-regional disease and were not candidates for combination chemotherapy (high age, co-morbidities), and in group (C) up-front combination chemotherapy was given, with the intention to have surgery of both the primary and the secondaries if sufficient regression at both sites were seen. RESULTS: The patients in the first two groups (A+B) were old (median 79 and 76 years, respectively), and had several co-morbidities. In group (C), median age was 63 years. The 5x5Gy RT was well tolerated by most patients, but grade IV diarrhoea was recorded in three elderly patients. One patient in the group (C) died from neutropenic fever. Many patients were reported to have less local symptoms after the treatment given. Delayed surgery was performed in all but nine patients. Radical surgery (R0+R1) was performed in 22 (92%) (group A), 4 (44%) (group B), and 6 (46%) (group C) patients, respectively. A pCR was seen in four patients (two in group A and two in group C). No postoperative deaths occurred. CONCLUSIONS: Considering the very high age and presence of co-morbidity, the 5x5Gy schedule is well tolerated. Further, considering the very advanced local stage, the schedule has considerable anti-tumour activity and can result in radical surgery in a high proportion of patients.

Keyword
Rectal cancer, Radiotheraphy, Non-resectable, 5 ×5 Gy, Delay surgery
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-98972 (URN)10.1016/j.radonc.2007.11.025 (DOI)000257631700007 ()18093674 (PubMedID)
Available from: 2009-03-05 Created: 2009-03-05 Last updated: 2012-08-01Bibliographically approved
2. Delineation of gross tumor volume (GTV) for radiation treatment planning of locally advanced rectal cancer using information from MRI or FDG-PET/CT: a prospective study
Open this publication in new window or tab >>Delineation of gross tumor volume (GTV) for radiation treatment planning of locally advanced rectal cancer using information from MRI or FDG-PET/CT: a prospective study
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2011 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 81, no 4, e439-e445 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE:

Accurate delineation of target volumes is important to maximize radiation dose to the tumor and minimize it to nontumor tissue. Computed tomography (CT) and magnetic resonance imaging (MRI) are standard imaging modalities in rectal cancer. The aim was to explore whether functional imaging with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), combined with CT (FDG-PET/CT) gives additional information to standard pretreatment evaluation and changes the shape and size of the gross tumor volume (GTV).

METHODS AND MATERIALS:

From 2007 to 2009, 77 consecutive patients with locally advanced rectal cancer were prospectively screened for inclusion in the study at two university hospitals in Sweden, and 68 patients were eligible. Standard GTV was delineated using information from clinical examination, CT, and MRI (GTV-MRI). Thereafter, a GTV-PET was defined in the fused PET-CT, and the target volume delineations were compared for total volume, overlap, and mismatch. Pathologic uptake suspect of metastases was also registered.

RESULTS:

The median volume of GTV-MRI was larger than that of GTV-PET: 111 cm3 vs. 87 cm3 (p < 0.001). In many cases, the GTV-MRI contained the GTV defined on the PET/CT images as subvolumes, but when a GTV total was calculated after the addition of GTV-PET to GTV-MRI, the volume increased, with median 11% (range, 0.5–72%). New lesions were seen in 15% of the patients for whom PET/CT was used.

CONCLUSIONS:

FDG-PET/CT facilitates and adds important information to the standard delineation procedure of locally advanced rectal cancer, mostly resulting in a smaller GTV, but a larger total GTV using the union of GTV-MRI and GTV-PET. New lesions were sometimes seen, potentially changing the treatment strategy.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-169858 (URN)10.1016/j.ijrobp.2011.03.031 (DOI)000309412300031 ()21641122 (PubMedID)
Available from: 2012-03-06 Created: 2012-03-06 Last updated: 2017-12-07Bibliographically approved
3. Integrated peripheral boost in preoperative radiotherapy for the locally most advanced non-resectable rectal cancer patients
Open this publication in new window or tab >>Integrated peripheral boost in preoperative radiotherapy for the locally most advanced non-resectable rectal cancer patients
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-172407 (URN)
Available from: 2012-04-10 Created: 2012-04-10 Last updated: 2012-08-01
4. Health-related quality-of-life during treatment in the Stockholm III Trial, evaluating different preoperative radiotherapy regimens for rectal cancer
Open this publication in new window or tab >>Health-related quality-of-life during treatment in the Stockholm III Trial, evaluating different preoperative radiotherapy regimens for rectal cancer
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-172410 (URN)
Available from: 2012-04-10 Created: 2012-04-10 Last updated: 2012-08-01
5. Health-related quality-of-life during treatment in the Stockholm III Trial, evaluating different preoperative radiotherapy regimens for rectal cancer
Open this publication in new window or tab >>Health-related quality-of-life during treatment in the Stockholm III Trial, evaluating different preoperative radiotherapy regimens for rectal cancer
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-172410 (URN)
Available from: 2012-04-10 Created: 2012-04-10 Last updated: 2012-08-01

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