[Show abstract][Hide abstract] ABSTRACT: Background: Many patients with rectal cancer receive radiotherapy as a component of primary multimodality treatment. Although local recurrence is infrequent, reirradiation may be needed to improve resectability and outcomes. This systematic review investigated the effects of reirradiation in terms of feasibility, toxicity, and long-term outcomes. Methods: A Medline, Embase and Cochrane search resulted in 353 titles/abstracts. Ten publications describing seven prospective or retrospective studies were included, presenting results of 375 patients reirradiated for rectal cancer. Results: Median initial radiation dose was 50.4 Gy, median 8–30 months before reirradiation. Reirradiation was mostly administered using hyperfractionated (1.2–1.5 Gy twice-daily) or 1.8 Gy once-daily chemoradiotherapy. Median total dose was 30–40 Gy to the gross tumour volume with 2–4 cm margins. Median survival was 39–60 months in resected patients and 12–16 months in palliative patients. Good symptomatic relief was reported in 82–100%. Acute toxicity with diarrhoea was reported in 9–20%, late toxicity was insufficiently reported. Conclusions: Reirradiation of rectal cancer to limited volumes is feasible. When curative resection is possible, the goal is radical resection and long-term survival, and hyperfractionated chemoradiotherapy should be preferred to limit late toxicity. Reirradiation yielded good symptomatic relief in palliative treatment.
Radiotherapy and Oncology 11/2014; · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose. Few studies have explored the potential clinical advantages of dose escalation and integrated boosts for patients with non-resectable locally advanced rectal cancer. The possibility of escalating dose to non-resectable regions in these patients was the aim of this study. Patients and methods. Seven patients with locally very advanced rectal tumours (sacrum overgrowth or growth into pelvic side walls) were evaluated. Intensity modulated photon and pencil beam scanning proton plans with simultaneously integrated boosts (45 Gy to elective lymph nodes, 50 Gy to tumour and 62.5 Gy to boost area in 25 fractions) were compared. Results. Target coverage was achieved with both photon and proton plans. Estimated risks of acute side effects put the two patients with the largest tumours at unacceptable risk for intestinal toxicity, regardless of modality. The remaining five patients had beneficial sparing of dose to the small intestine with protons. Conclusions. Adding boost to areas where rectal tumours infiltrate adjacent non-resectable organs is an attractive option which appears possible using both photon and proton irradiation. Proton plans reduced dose to organs at risk. Integrated peripheral boosts should be considered more frequently in these very advanced tumours.
[Show abstract][Hide abstract] ABSTRACT: A randomised study in non-resectable rectal cancer showed that preoperative chemoradiotherapy (CRT) resulted in better local control and disease-specific survival, but not overall survival than radiotherapy alone. The present paper presents long-term (>4 years) health-related quality of life (HRQoL) and a comparison between the results and reference values from the Norwegian general population.
A total of 207 patients with primarily non-resectable rectal cancer were randomised to preoperative CRT (2Gyx25+5FU/leucovorin) or RT (2Gyx25) before surgery. HRQoL was assessed using EORTC QLQ-C30, completed at baseline and sent to all patients alive in Norway and Sweden (n=105) after a minimum of 4 years post treatment. A difference of ≥5 points on the 0-100 scales was considered clinically significant.
Seventy-six (72%) patients answered at follow-up. No statistically significant differences between the CRT and RT groups appeared at follow-up, although clinically significant differences in social functioning, dyspnoea and diarrhoea were found. Over time, a clinically significant reduction in physical functioning was found in both groups. Moreover, reduced social functioning and less diarrhoea in the CRT group and better role functioning and more diarrhoea in the RT group were found. Comparisons between the study group and age and gender matched reference values indicate impaired social functioning and more diarrhoea among the patients.
There were no statistically significant differences in HRQoL between the randomisation groups. In general, despite having impaired social functioning and more diarrhoea, patients reported HRQoL comparable with the reference population several years after treatment.
European journal of cancer (Oxford, England: 1990) 07/2011; 48(6):813-9. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
The median volume of GTV-MRI was larger than that of GTV-PET: 111 cm(3) vs. 87 cm(3) (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.
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.
International journal of radiation oncology, biology, physics 06/2011; 81(4):e439-45. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preoperative chemoradiotherapy (CRT) is superior to radiotherapy (RT) in locally advanced rectal cancer, but the survival gain is limited. Late toxicity is, therefore, important. The aim was to compare late bowel, urinary, and sexual functions after CRT or RT.
Patients (N = 207) with nonresectable rectal cancer were randomized to preoperative CRT or RT (2 Gy × 25 ± 5-fluorouracil/leucovorin). Extended surgery was often required. Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), International Index of Erectile Function (IIEF), and sexual function-vaginal changes questionnaire (SVQ).
Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up, 78 (74%) responded. More patients in the CRT group had received a stoma (73% vs. 52%, p = 0.09). Most patients without a stoma (7 of 12 in CRT group and 9 of 16 in RT group) had incontinence for liquid stools or gas. No stoma and good anal function were seen in 5 patients (11%) in the CRT group and in 11 (30%) in the RT group (p = 0.046). Of 44 patients in the CRT group, 12 (28%) had had bowel obstruction compared with 5 of 33 (15%) in the RT group (p = 0.27). One-quarter of the patients reported urinary incontinence. The majority of men had severe erectile dysfunction. Few women reported sexual activity during the previous month. However, the majority did not have concerns about their sex life.
Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer. There was a clear tendency for the problems to be more common after CRT than after RT.
International journal of radiation oncology, biology, physics 10/2010; 81(4):1017-24. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate.
The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109).
The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity.
CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.
Journal of Clinical Oncology 09/2008; 26(22):3687-94. · 17.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are 3 450 new cases of colorectal cancer in Norway annually. In half of the patients, metastatic disease will evolve with time. Palliative chemo- or radiotherapy can prolong disease- and symptom control when cure is not feasible.
This paper is based on publications retrieved from a PubMed search, the authors' knowledge of the field and on recent conference abstracts.
Patients with metastatic colorectal cancer should initially be considered for surgery, and judged if secondary surgery is a possibility. Palliative chemotherapy is used to increase survival and maintain quality of life. 5-FU/calsiumfolinat combined with oxaliplatin or irinotecan is usually given as first line treatment for patients below 75 years--and most of them respond. Median survival is close to two years. Bevacizumab combined with an irinotecan regimen is an alternative first line treatment. Elderly patients are judged on an individual basis. Half of the patients will receive second line therapy with the alternative chemotherapy schedule. Cetuximab combined with irinotecan is a possible third line treatment. Palliative radiotherapy is most often used for inoperable rectal cancer, local recurrences, and bone or brain metastases.
Tidsskrift for den Norske laegeforening 02/2008; 128(2):194-7.
[Show abstract][Hide abstract] ABSTRACT: This Nordic multicenter phase II study evaluated the efficacy and safety of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer.
Eighty-five patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1, followed by a 3-minute bolus injection with FU 500 mg/m(2) and, 30 minutes later, by a bolus injection with FA 60 mg/m(2) every second week. The same doses of FU and FA were also given on day 2.
Fifty-one of 82 assessable patients achieved a complete (n = 4) or partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to 72%). Nineteen patients showed stable disease, and 12 patients had progressive disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to-treat population. Neutropenia was the main adverse event, with grade 3 to 4 toxicity in 58% of patients. Febrile neutropenia developed in seven patients. Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients and grade 2 in another 27 patients).
Oxaliplatin combined with the bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and feasible bolus schedule as first-line treatment of metastatic colorectal cancer that yields comparable results compared with more complex schedules.
Journal of Clinical Oncology 02/2004; 22(1):31-8. · 17.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Three papers including five patients have described en bloc radical prostatectomy for locally advanced rectal cancer.
Six patients (median age 63 years) underwent en bloc radical prostatectomy for locally advanced (3) or recurrent (3) rectal cancer involving the prostate. Quality of life questionnaires were answered postoperatively and the data prospectively entered in a database.
One primary case had low anterior resection (LAR), the others abdominoperineal resections (APR) of R0 stage. Two recurrent cases had APRs and one tumour resection-all R1 stage. Anastomotic leakage led to construction of an ileal conduit in one patient and in two healed on conservative treatment. Follow up was 10-50 months. One patient died from distant metastases at 29 months postoperatively, one was operated for a single lung metastasis and one has disseminated lung metastases. None has developed local recurrence. Four of the five with anastomoses had good quality of life and none wanted an ileal conduit.
In spite of a relatively high urinary leak rate the total complication rate seems to be lower than after pelvic exenteration. En bloc radical prostatectomy seems an option in selected patients otherwise needing pelvic exenteration for locally advanced or recurrent rectal cancer.
European Journal of Surgical Oncology 07/2003; 29(5):455-8. · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the complication rate, local recurrence rate, and survival after total pelvic exenteration for primary advanced and recurrent rectal cancer.
Tertiary referral university hospital, Norway.
25 patients who were operated on for primary advanced and 22 for recurrent rectal cancer since 1991; 42 men and 5 women, mean age 64 years (range 44-78). All had preoperative irradiation of 46-50 Gy.
Incidence of major complications, and actuarial 5-year survival and local recurrence rate.
Twenty patients had RO resection in the primary group versus seven in the recurrent group. No R2 resections were done in the primary group compared with four in the recurrent group. Half the primary cases (n = 13) had abdominoperineal resections. Hartmann's procedures were common in both groups (n = 8 in each). Postoperative mortality at 30 days was 4% (n = 2) and in-hospital 13% (n = 6). 18 patients had major complications and 12 were reoperated on. Overall 5-year actuarial survival for 43 patients without distant metastases was 28%-those with primary tumours 36%, and those with recurrent tumours 18%-similar to the figures for RO and R1 resections. Actuarial local recurrence at 5 years for primary cancers was 18% compared with 68% for recurrent cancers, again nearly identical to the figures for R0/R1 operations (p = 0.008 and p = 0.03).
Some patients with advanced rectal cancer either primary or recurrent may benefit from simultaneous en-bloc cystectomy. The higher postoperative morbidity and mortality indicate the need for well-defined indications for this procedure and the necessity for thorough preoperative staging.
The European Journal of Surgery 02/2002; 168(1):42-8.
[Show abstract][Hide abstract] ABSTRACT: All patients with rectal cancer should undergo an accurate preoperative staging, including local staging for tumour extension and reliable staging for synchronous distant metastases. Imaging is of utmost importance as a basis for selecting the optimal treatment strategies and as an aid for precise target delineation. Anatomical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) have been the most commonly used pretreatment staging modalities, whereas endorectal ultrasonography may be useful for staging of smaller tumours (T2 or lower). MRI is the most accurate imaging technique for staging of T3 and T4 tumours. The role of fluorodeoxyglucose positron emission tomography (PET)/CT is under investigation, and diffusion-weighted MRI seems promising for prediction of pathological complete response. For target delineation, planning CT, preferably contrast-enhanced, is the most used imaging technique. For locally advanced tumours, coregistration with MRI or PET/CT may prove to be useful. In this article, the literature published on target delineation in rectal cancer radiotherapy is evaluated, with focus on the best imaging modality for volume definition and radiotherapy planning.