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- Hallqvist, Andreas, 1973, et al.
(författare)
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Dose escalation to 84 Gy with concurrent chemotherapy in stage III NSCLC appears excessively toxic: Results from a prematurely terminated randomized phase II trial
- 2018
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 122, s. 180-186
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. Materials and Methods: NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. Results: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).
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- Nyman, J., et al.
(författare)
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Dose Escalated Chemo-RT to 84 Gy in Stage III NSCLC Appears Excessively Toxic : Results from a Randomized Phase II Trial
- 2018
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 13:10, s. S373-S373
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease, however, with a rather high probability of locoregional and metastatic recurrence further treatment optimization is warranted. Based on previous one-armed trials with dose escalated radiotherapy, showing feasibility, the Swedish Lung Cancer Study Group aimed to investigate whether dose escalation based on individual normal tissue constraints could improve outcome in this randomized phase II trial.Method: NSCLC patients with stage III disease, good performance status (0-1), adequate lung function (FEV1 > 1.0 L and CO diff. > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. The radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to a total dose of 68 Gy (standard arm A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week while keeping the total treatment time constant at seven weeks with the same dose to involved nodes and primary tumor.Result: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in the dose escalated group compared to 28 and 45 months in the standard group. The 1-, 3- and 5-year survival rates were 56%, 33% and 17% in the escalated arm and 72%, 61% and 34% in the standard arm. There were four toxicity-related deaths due to esophageal perforations (one in arm A and three in arm B) and three deaths due to pneumonitis (one in arm A and two in arm B).Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 5-year survival of 34%. A possible step forward will be to improve systemic therapy, but future approaches with escalated radiotherapy may include boost techniques to remaining PET positive areas or different escalation schedules to the primary tumor and mediastinal nodes.
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- Klevebro, F., et al.
(författare)
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Morbidity and mortality after surgery for cancer of the oesophagus and astro-oesophageal junction : a randomized clinical trial of neoadjuvant hemotherapy vs. neoadjuvant chemoradiation
- 2015
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 41:7, s. 920-926
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the incidence and severity of postoperative omplications after oesophagectomy for carcinoma of the oesophagus and astro-oesophageal junction (GOJ) after randomized accrual to eoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). ackground: Neoadjuvant therapy improves long-term survival after esophagectomy. To date, evidence is insufficient to determine whether ombined nCT, or nCRT alone, is the most beneficial. ethods: Patients with carcinoma of the oesophagus or GOJ, resectable ith a curative intention, were enrolled in this multicenter trial onducted at seven centres in Sweden and Norway. Study participants re andomized to nCT or nCRT followed by surgery with two-field ymphadenectomy. Three cycles of cisplatin/5-fluorouracil was dministered in all patients, while 40 Gy of concomitant radiotherapy as administered in the nCRT group. esults: Of the randomized 181 patients, 91 were assigned to nCT and 90 o nCRT. One-hundred-and-fifty-five patients, 78 nCT and 77 nCRT, nderwent resection. There was no statistically significant difference etween the groups in the incidence of surgical or nonsurgical omplications (P-value = 0.69 and 0.13, respectively). There was no 0-day mortality, while the 90-day mortality was 3% (2/78) in the nCT roup and 6% (5/77) in the nCRT group (P = 0.24). The median lavien-Dindo complication severity grade was significantly higher in he nCRT. group (P = 0.001). onclusion: There was no significant difference in the incidence of omplications between patients randomized to nCT and nCRT. However, omplications were significantly more severe after nCRT. Registration rial database: The trial was registered in the Clinical Trials tabase registration number NCT01362127).
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