| 451. |
- Pettersson, D., et al.
(författare)
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Preoperative short-course radiotherapy with delayed surgery in primary rectal cancer
- 2012
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 99:4, s. 577-583
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short-course radiotherapy (SRT) with immediate surgery and long-course chemoradiotherapy (CRT) are currently the standard preoperative treatment options for rectal cancer. SRT with surgery delayed for 4-8 weeks (SRT-delay) is an option described for patients with locally advanced tumours who are not fit for CRT. This study examined early toxicity, response to radiotherapy (RT) and short-term outcomes of SRT-delay. Methods: Patients in the Stockholm region diagnosed with rectal cancer between January 2002 and December 2008, who received SRT (25 Gy over 5-7 days) and had surgery with resection of the primary tumour more than 4 weeks after the start of RT, were identified from a prospective register. Additional data were obtained by retrospective review of clinical records. Results: A total of 112 patients had SRT and delayed surgery. The reasons given for SRT included primary unresectable disease and co-morbidities. Severe RT-induced toxicity was noted in six patients (5.4 per cent). Signs of tumour regression were seen on magnetic resonance imaging in 74 per cent of patients reassessed after RT. Pathological stage (44.9 versus 60.7 per cent stage 0-II; P < 0.001), tumour category (11.9 versus 29.4 per cent T0-T2; P < 0.001) and node category (45.8 versus 63.6 per cent N0; P = 0.014) were significantly lower than those at initial assessment. Nine patients (8.0 per cent) had a complete pathological response. Conclusion: The SRT-delay schedule was a feasible alternative with low toxicity. The study indicated a downstaging effect of SRT if surgery was delayed.
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| 452. |
- Pettersson, D., et al.
(författare)
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Tumour regression in the randomized Stockholm III Trial ofradiotherapy regimens for rectal cancer
- 2015
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 102:8, s. 972-978
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Stockholm III Trial randomized patients with primary operable rectal cancers to either short-course radiotherapy (RT) with immediate surgery (SRT), short-course RT with surgery delayed 4-8 weeks (SRT-delay) or long-course RT with surgery delayed 4-8 weeks. This preplanned interim analysis examined the pathological outcome of delaying surgery. MethodsPatients randomized to the SRT and SRT-delay arms in the Stockholm III Trial between October 1998 and November 2010 were included, and data were collected in a prospective register. Additional data regarding tumour regression grade, according to Dworak, and circumferential margin were obtained by reassessment of histopathological slides. ResultsA total of 462 of 545 randomized patients had specimens available for reassessment. Patients randomized to SRT-delay had earlier ypT categories, and a higher rate of pathological complete responses (118 versus 17 per cent; P=0001) and Dworak grade 4 tumour regression (101 versus 17 per cent; P<0001) than patients randomized to SRT without delay. Positive circumferential resection margins were uncommon (63 per cent) and rates did not differ between the two treatment arms. ConclusionShort-course RT induces tumour downstaging if surgery is performed after an interval of 4-8 weeks.
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| 453. |
- Pfeiffer, Per, et al.
(författare)
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Calmangafodipir for Prevention of Oxaliplatin-Induced Peripheral Neuropathy : Two Placebo-Controlled, Randomized Phase 3 Studies (POLAR-A/POLAR-M)
- 2022
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Ingår i: JNCI CANCER SPECTRUM. - : OXFORD UNIV PRESS. - 2515-5091. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Calmangafodipir (CaM, PledOx) demonstrated efficacy in preventing patient-reported chemotherapy-induced peripheral neuropathy (CIPN) in a randomized phase 2 study in patients with metastatic colorectal cancer. The Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy (POLAR) program aimed to assess efficacy and safety of CaM in the prevention of CIPN in patients treated with oxaliplatin in adjuvant (POLAR-A, ClinicalTrials.gov.NCT04034355) or metastatic (POLAR-M, ClinicalTrials.gov.NCT03654729) settings. Methods Two randomized, placebo-controlled phase 3 trials investigated patient-reported, moderate-to-severe CIPN 9 months after beginning folinic acid, 5-fluorouracil, and oxaliplatin therapy with or without CaM. In POLAR-A, patients with stage III or high-risk stage II colorectal cancer were randomly assigned 1:1 to receive CaM 5 mu mol/kg or placebo. In POLAR-M, patients with metastatic colorectal cancer were randomly assigned 1:1:1 to receive CaM 5 mu mol/kg, CaM 2 mu mol/kg, or placebo. Results POLAR-A (n = 301) and POLAR-M (n = 291) were terminated early following unexpected hypersensitivity reactions in CaM-treated patients. In a combined analysis of month 9 CIPN (primary endpoint) data from both trials (CaM 5 mu mol/kg, n = 175; placebo, n = 176), 54.3% of patients in the CaM group had moderate-to-severe CIPN compared with 40.3% in the placebo group. The estimated relative risk for moderate-to-severe CIPN at month 9 was 1.37 (95% confidence interval = 1.01 to 1.86; P = .045). A higher proportion of patients experienced serious hypersensitivity reactions across both trials with CaM treatment (3.6%) than with placebo (0.8%). Conclusion The POLAR clinical studies failed to meet their primary endpoint. These results highlight the challenges of targeting oxidative stress for preventing CIPN in both the adjuvant and metastatic settings.
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| 454. |
- Pfeiffer, Per, et al.
(författare)
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Maintenance Therapy With Cetuximab Every Second Week in the First-Line Treatment of Metastatic Colorectal Cancer : The NORDIC-7.5 Study by the Nordic Colorectal Cancer Biomodulation Group
- 2015
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Ingår i: Clinical colorectal cancer. - : Elsevier BV. - 1533-0028 .- 1938-0674. ; 14:3, s. 170-176
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Tidskriftsartikel (refereegranskat)abstract
- In the NORDIC-7.5 trial, cetuximab administered every 2 weeks in 152 patients with Kirsten rat sarcoma viral oncogene homolog wild type metastatic colorectal cancer was investigated. After 4 months of induction therapy with Nordic FLOX (oxaliplatin, bolus 5-fluorouracil, and bolus folinic acid) and cetuximab, patients continued with cetuximab monotherapy. Cetuximab might have added to a longer chemotherapy-free interval, but needs to be validated in clinical trials. Background: In the NORDIC-7.5 trial, how cetuximab might safely and conveniently be added to an intermittent treatment strategy in patients with prospectively selected Kirsten rat sarcoma viral oncogene homolog wild type (KRASwt) metastatic colorectal cancer (mCRC) was investigated. Patients were treated in a multicenter phase II trial with cetuximab in combination with the Nordic bolus FLOX (oxaliplatin, 5-fluorouracil, and folinic acid) for 4 months followed by maintenance cetuximab. Patients and Methods: Patients had KRASwt, nonresectable mCRC, no previous chemotherapy, and Eastern Cooperative Group performance status of 0 to 2. Patients received 8 courses of Nordic FLOX (oxaliplatin 85 mg/m(2) over 1 hour on day 1, and 5-fluorouracil 500 mg/m(2) as a bolus injection, followed 30 minutes later with bolus folinic acid 60 mg/m(2) on days 1 and 2). Cetuximab was administered every 2 weeks at a dose of 500 mg/m(2) for 16 weeks followed by cetuximab as maintenance therapy until disease progression. Results: Between July 2008 and September 2010, 152 KRASwt patients were included. The response rate was 62% (95% confidence interval [CI], 54%-69%), median progression-free survival was 8.0 months (95% CI, 7.5-8.9) and median overall survival was 23.2 (95% CI, 18.1-27.4) months. Twenty-one patients (14%) had later R0-resection of metastasis. FLOX with cetuximab was reintroduced in 47 of 85 patients (55%). The most common Grade 3/4 nonhematologic adverse events were diarrhea in 14 patients (9%), skin rash in 13 patients (9%), infection without neutropenia in 11 patients (7%), and fatigue in 11 patients (7%). Conclusion: In a prospectively selected KRASwt population, biweekly cetuximab was safely integrated in an intermittent chemotherapy strategy and might have added to a longer chemotherapy-free interval. However, the combination of biweekly cetuximab with chemotherapy needs to be validated in trials using FOLFOX (oxaliplatin, fluorouracil, and leucovorin) or FOLFIRI (irinotecan, fluorouracil, and leucovorin).
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| 455. |
- Prata, Ilaria, et al.
(författare)
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Results of a diagnostic imaging audit in a randomised clinical trial in rectal cancer highlight the importance of careful planning and quality control
- 2023
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Ingår i: Insights into Imaging. - : Springer. - 1869-4101. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Background: Magnetic resonance (MR) imaging is the modality used for baseline assessment of locally advanced rectal cancer (LARC) and restaging after neoadjuvant treatment. The overall audited quality of MR imaging in large multicentre trials on rectal cancer is so far not routinely reported.Materials and methods: We collected MR images obtained within the Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation (RAPIDO) trial and performed an audit of the technical features of image acquisition. The required MR sequences and slice thickness stated in the RAPIDO protocol were used as a reference.Results: Out of 920 participants of the RAPIDO study, MR investigations of 668 and 623 patients in the baseline and restaging setting, respectively, were collected. Of these, 304/668 (45.5%) and 328/623 (52.6%) MR images, respectively, fulfilled the technical quality criteria. The main reason for non-compliance was exceeding slice thickness 238/668, 35.6% in the baseline setting and 162/623, 26.0% in the restaging setting. In 166/668, 24.9% and 168/623, 27.0% MR images in the baseline and restaging setting, respectively, one or more of the required pulse sequences were missing.Conclusion: Altogether, 49.0% of the MR images obtained within the RAPIDO trial fulfilled the image acquisition criteria required in the study protocol. High-quality MR imaging should be expected for the appropriate initial treatment and response evaluation of patients with LARC, and efforts should be made to maximise the quality of imaging in clinical trials and in clinical practice.
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| 456. |
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| 457. |
- Påhlman, Lars, et al.
(författare)
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Role of radiotherapy
- 2008
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Ingår i: International Handbook of colorectal cancer. - : Euromed Communications Ltd. ; , s. 57-70
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Bokkapitel (populärvet., debatt m.m.)
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| 458. |
- Quirke, Phil, et al.
(författare)
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Evidence-based medicine : the time has come to set standards for staging
- 2010
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 221:4, s. 357-360
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Tidskriftsartikel (refereegranskat)abstract
- For international communication in cancer, staging systems such as TNM are essential; however, the principles and processes used to decide about changes in every new edition of TNM need to be subject to debate. Changes with major impact for patient treatment are introduced without evidence. We think that TNM should be a continual reactive process, rather than a proactive process. Changes should only occur after extensive discussion within the community, and before the introduction of any changes these should be tested for reproducibility and compared to the currently used gold standard. TNM should not be used to test hypotheses. It should introduce established facts that are beneficial to predicting patient prognosis. TNM should thus be restructured on a basis equivalent to evidence-based guidelines. The strength of the evidence should be explicitly stated and the evidence base given. It is time for the principles of staging to be widely debated and new principles and processes to be introduced to ensure that we are not in the same situation in the future. The disparity between therapeutic decision making and TNM staging is marked and we would appeal for the radical overhaul of TNM staging to make it fit for the twenty-first century. TNM is central to the management of cancer patients and we must protect and enhance its reputation.
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| 459. |
- Qvortrup, Camilla, et al.
(författare)
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A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX(30) and chronomodulated XELOX(30) as first-line therapy in patients with advanced colorectal cancer
- 2010
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 21:1, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronotherapy is one of the several approaches to increase efficacy and reduce toxicity of chemotherapy. In a phase II study in the second-line in patients with metastatic colorectal cancer (mCRC), we found that chronomodulated XELOX (XELOX(30Chron)) was a well-tolerated regimen with potentially reduced toxicity. PATIENTS AND METHODS: One hundred and forty-one patients with unresectable mCRC were enrolled in a randomized study comparing standard XELOX (XELOX(30)), arm A, and XELOX(30Chron), arm B-both with short-time infusion of oxaliplatin-with the primary aim of reducing overall toxicity. RESULTS: Overall toxicity grade 2-4 was 90% versus 85%, P = 0.47 and grade 3-4 was 31% versus 37%, P = 0.6 in arm A and B, respectively. We found no significant differences in median overall survival (17.6 versus 15.5 months; P = 0.068) and median progression-free survival (8.9 versus 8.8 months; P = 0.7). The incidence of grade 3 neuropathy was 16% in arm A and 19% in arm B (P = 0.7) after a cumulative dose of oxaliplatin of 1000 mg/m(2). CONCLUSION: XELOX(30Chron) does not reduce toxicity or improve efficacy. A 30-min infusion of oxaliplatin is safe and does not increase the severity of chronic neuropathy.
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| 460. |
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