Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: Study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background: A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods: Thismulticentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2- week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged usingMRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8Gy in radiotherapy-naive patients, and 15 × 2.0Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-termoncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion: This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Lack of beneficial effects of low-dose radiation therapy on hand osteoarthritis symptoms and inflammation: a randomised, blinded, sham-controlled trial

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Coverage of lateral lymph nodes in rectal cancer patients with routine radiotherapy practice and associated locoregional recurrence rates

Background & purpose: Involved internal iliac and obturator lateral lymph nodes (LLNs) are a known risk factor for ipsi-lateral local recurrences (LLR) in rectal cancer. This study examined coverage of LLNs with routine radiotherapy practice in the Netherlands and associated LLR rates. Materials & methods: Patients with a primary tumor ≤8cm of the anorectal junction, cT3-4 stage and at least one internal iliac or obturator LLN with short-axis ≥5mm who received neoadjuvant (chemo)radiotherapy, were selected from a national, cross-sectional study of rectal cancer patients treated in the Netherlands in 2016. MR-images and radiotherapy treatment plans were reviewed regarding segmented LLNs as gross-tumor volume (GTV), location of LLNs within clinical target volume (CTV), and received proportion of the planned radiotherapy dose.  Results: A total of 223 out of 3057 patients with at least one LLN ≥5mm were selected. Of those, 180 (80.7%) LLNs were inside the CTV, of which 60 (33.3%) were segmented as GTV. Overall, 202 LLNs (90.6%) received >95% of the planned dose. Four-year LLR rates were not significantly higher for LLNs situated outside the CTV compared to inside (4.0% vs. 12.5%, p=.092) or when receiving 95% of the planned radiotherapy dose (7.1% vs. 11.3%, p=.843), respectively. Two of seven patients who received a dose-escalation of 60Gy developed a LLR (4-year LLR rate 28.6%). Conclusion: This evaluation of routine radiotherapy practice showed that adequate coverage of LLNs was still associated with considerable 4-year LLR rates. Techniques resulting in better local control for patients with involved LLNs need to be explored further. </p

Coverage of Lateral Lymph Nodes in Rectal Cancer Patients with Routine Radiation Therapy Practice and Associated Locoregional Recurrence Rates

Purpose: Involved internal iliac and obturator lateral lymph nodes (LLNs) are a known risk factor for the occurrence of ipsilateral local recurrences (LLR) in rectal cancer. This study examined coverage of LLNs with routine radiation therapy practice in the Netherlands and associated LLR rates. Methods and Materials: Patients with a primary tumor ≤8 cm of the anorectal junction, cT3-4 stage, and at least 1 internal iliac or obturator LLN with short axis ≥5 mm who received neoadjuvant (chemo)radiation therapy, were selected from a national, cross-sectional study of patients with rectal cancer treated in the Netherlands in 2016. Magnetic resonance images and radiation therapy treatment plans were reviewed regarding segmented LLNs as gross tumor volume (GTV), location of LLNs within clinical target volume (CTV), and received proportion of the planned radiation therapy dose. Results: A total of 223 out of 3057 patients with at least 1 LLN ≥5 mm were selected. Of those, 180 (80.7%) LLNs were inside the CTV, of which 60 (33.3%) were segmented as GTV. Overall, 202 LLNs (90.6%) received ≥95% of the planned dose. Four-year LLR rates were not significantly higher for LLNs situated outside the CTV compared with those inside (4.0% vs 12.5%, P =.092) or when receiving &lt;95% versus ≥95% of the planned radiation therapy dose (7.1% vs 11.3%, P =.843), respectively. Two of 7 patients who received a dose escalation of 60 Gy developed an LLR (4-year LLR rate of 28.6%). Conclusions: This evaluation of routine radiation therapy practice showed that adequate coverage of LLNs was still associated with considerable 4-year LLR rates. Techniques resulting in better local control for patients with involved LLNs need to be explored further.</p

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background: A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods: Thismulticentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2- week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged usingMRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 2.0 Gy or 28 1.8Gy in radiotherapy-naive patients, and 15 2.0Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-termoncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion: This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections