• Long-Term quality of life after (chemo)radiotherapy for high-risk endometrial cancer in PORTEC-3

      Post, C.; De Boer, S. M.; Powell, M. E.; Mileshkin, L.; Katsaros, D.; Bessette, P.; Haie-Meder, C.; Ottevanger, P. B.; Ledermann, J. A.; Khaw, P.; et al. (2020)
      Purpose or Objective The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiotherapy versus radiotherapy alone. The present analysis was performed to establish long-term adverse events and health related quality of life (HRQOL). Material and Methods The PORTEC-3 trial is an international randomized phase 3 trial. Women with high-risk endometrial cancer (stage I grade 3 with deep myometrial invasion or lymph-vascular space invasion; stage II/III endometrioid cancer; or stage I-III serous or clear cell cancer) were randomly assigned to receive pelvic radiotherapy alone (RT) or chemoradiotherapy (CTRT, concurrent 2 cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel). Adverse events (AE) were graded using CTCAE v3.0. HRQOL was measured using the EORTC QLQ-C30 and CX24 and OV28 symptom scales at baseline, after radiotherapy, and at 6, 12, 18, 24, 36 and 60 months. Symptoms rated as “quite a bit” or “very much” were considered as severe. Toxicity and HRQOL were analyzed according to treatment received. HRQOL scores were compared to an agematched European norm-population. Clinical trial information: NCT00411138. Results Between 2006 and 2013, 660 women were randomized, of whom 579 (88%) responded for HRQOL assessment at baseline, 355 at 3 years and 237 at 5 years. Median follow up was 74.6 months. At 5 years, AE grade ≥2 were scored for 80 (39%) patients who had received CTRT vs 50 (26%) who had received RT (p=0.007). Grade 3 AE did not differ significantly between the two groups (8% vs 5%, p=0.24) at 5 years and only one grade 4 AE was reported (ileus/obstruction after CTRT). Sensory neuropathy AE persisted at long-term after CTRT in 7% (vs 0% after RT, p<0.001 at 3 and 5 years). At 3 and 5 years, more women who had CTRT reported severe tingling or numbness at HRQOL (27% vs 8%, p<0.001 at 3 years; 24% vs 9%, p=0.002 at 5 years). At 3 years, more women reported severe weakness of arms/legs (21% vs 5%, p<0.001) and lower physical (79.4 vs 86.6, p<0.001, Fig 1) and role functioning (78.3 vs 88.0, p<0.001) scores. Additionally, a trend towards more reported severe muscle or joint pain was seen (28% vs 16%, p=0.037). At 5 years, no significant differences in these HRQOL symptoms or functioning scales were seen, with scores within range of the norm population scores; however, trends towards a lower global health/QOL score (74.4 vs 79.3, p=0.045), a higher fatigue score (24.1 vs 18.7, p=0.036) and more severe hearing problems (12% vs 4%, p=0.044) were observed after CTRT. Conclusion Chemoradiotherapy causes significantly higher rates of grade >2 AE, worse physical functioning and higher symptom scores as compared with RT, but with clear recovery within 2 years and stable scores from then onwards. The most important long-term AE and QOL impairment after CTRT was sensory neuropathy. These long-term data are essential for patient information and shared decision-making regarding adjuvant chemotherapy for high-risk endometrial cancer.
    • Long-term toxicity and health-related quality of life after adjuvant chemoradiotherapy or radiotherapy alone for high-risk endometrial cancer in the randomised PORTEC-3 trial

      Post, C. C. B.; de Boer, S. M.; Powell, M. E.; Mileshkin, L.; Katsaros, D.; Bessette, P.; Haie-Meder, C.; Ottevanger, N. P. B.; Ledermann, J. A.; Khaw, P.; et al. (2020)
      Background: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiotherapy versus pelvic radiotherapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL). Patients and methods: 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiotherapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiotherapy alone. Toxicity was graded using CTCAE v3.0. HRQOL was measured using EORTC QLQ-C30 and CX24/OV28-subscales and compared to normative-data. An as-treated analysis was performed. Results: Median follow up was 74.6 months; 574 (87%) patients were evaluable for HRQOL. At 5 years, grade ≥2 AE were scored for 78 (38%) patients who had received chemoradiotherapy versus 46 (24%) who had received radiotherapy (p=0.008). Grade 3 AE did not differ significantly between the groups (8% vs 5%, p=0.18) at 5 years, and only one new late grade 4 toxicity had been reported. At 3 and 5 years, sensory neuropathy toxicity grade ≥2 persisted after chemoradiotherapy in 6% (vs 0% after radiotherapy, p<0.001) and more patients reported significant tingling or numbness at HRQOL (27% vs 8%, p<0.001 at 3 years; 24% vs 9%, p=0.002 at 5 years). Until 3 years, more patients who had chemoradiotherapy reported limb weakness (21% vs 5%, p<0.001) and lower physical (79 vs 87, p<0.001) and role functioning (78 vs 88, p<0.001) scores. Both treatment groups reported similar long-term global health/QOL scores, which were better than those of the normative-population. Conclusion: This study shows a long-lasting, clinically relevant, negative impact of chemoradiotherapy on toxicity and HRQOL, most importantly persistent peripheral sensory neuropathy. Physical and role functioning impairments were seen until 3 years. These long-term data are essential for patient information and shared decision-making regarding adjuvant chemotherapy for high-risk endometrial cancer.