Long-Term Outcome in a Phase II Study of Regional Hyperthermia Added to Preoperative Radiochemotherapy in Locally Advanced and Recurrent Rectal Adenocarcinomas

Abstract

Hyperthermia was added to standard preoperative chemoradiation for rectal adenocarcinomas in a phase II study. Patients with T3-4 N0-2 M0 rectal cancer or local recurrences were included. Radiation dose was 54 Gy combined with capecitabine 825 mg/m2 × 2 daily and once weekly oxaliplatin 55 mg/m2. Regional hyperthermia aimed at 41.5–42.5 °C for 60 min combined with oxaliplatin infusion. Radical surgery with total or extended TME technique, was scheduled at 6–8 weeks after radiation. From April 2003 to April 2008, a total of 49 eligible patients were recruited. Median number of hyperthermia sessions were 5.4. A total of 47 out of 49 patients (96%) had the scheduled surgery, which was clinically radical in 44 patients. Complete tumour regression occurred in 29.8% of the patients who also exhibited statistically significantly better RFS and CSS. Rate of local recurrence alone at 10 years was 9.1%, distant metastases alone occurred in 25.6%, including local recurrences 40.4%. RFS for all patients was 54.8% after 5 years and CSS was 73.5%. Patients with T50 temperatures in tumours above median 39.9 °C had better RFS, 66.7% vs. 31.3%, p = 0.047, indicating a role of hyperthermia. Toxicity was acceptable.

Oncologic Thermoradiotherapy: Need for Evidence, Harmonisation, and Innovation

“…In this special issue new evidence is presented. In a long term retrospective study of preoperative chemoradiation plus deep hyperthermia Schemm et al [1]. reports an encouraging level in five-year survival with better RFS for patients reaching T50 temperatures above 39.9 • C. The impact of a high thermal dose was also found in the retrospective study on RT+HT for prostate cancer by Nakahare et al [2]: CEM43T90 > 7 min.…”

Oncologic Thermoradiotherapy: Need for Evidence, Harmonisation, and Innovation

“…In this special issue new evidence is presented. In a long term retrospective study of preoperative chemoradiation plus deep hyperthermia Schemm et al [1]. reports an encouraging level in five-year survival with better RFS for patients reaching T50 temperatures above 39.9 • C. The impact of a high thermal dose was also found in the retrospective study on RT+HT for prostate cancer by Nakahare et al [2]: CEM43T90 > 7 min.…”

Neoadjuvant Radiochemotherapy Combined with Locoregional Hyperthermia in Locally Advanced Rectal Cancer: Feasibility and Tolerance of Short-Course Versus Long-Course Radiotherapy Schedules

“…The combination of RT with HT has demonstrated clinical evidence of synergistic effects in various tumor types, including rectal cancer [ 4 , 5 , 14 , 15 , 22 , 26 ]. HT improves tumor perfusion, increases oxygenation, and inhibits DNA repair, leading to enhanced radiosensitization and chemotherapy efficacy [ 4 , 5 ].…”

“…These observations are descriptive, and no formal statistical comparisons were performed. It is worth noting that, in the German experience reported previously [ 22 ], the treatment protocol anticipated the decline in patient tolerance over time and therefore started with two HT sessions per week during the initial phase of LCRT, aiming at completing approximately six sessions in total. This proactive approach was designed to complete the majority of HT treatments before cumulative toxicity compromised adherence.…”

Locoregional Hyperthermia in Cancer Treatment: A Narrative Review with Updates and Perspectives

“…HT and mEHT were used as neoadjuvant therapy in association with CRT in several studies regarding rectal cancer, resulting in significantly greater downstaging than CRT alone (80.7-82% vs. 62.7-67.2%; p < 0.05) [49][50][51][52][53][54][55]. Other beneficial effects of HT were observed in glioma, melanoma, and prostate cancer treatments [56,57,60].…”

Oncologic Thermoradiotherapy: Need for Evidence, Harmonisation, and Innovation

“…In this special issue new evidence is presented. In a long term retrospective study of preoperative chemoradiation plus deep hyperthermia Schemm et al [1]. reports an encouraging level in five-year survival with better RFS for patients reaching T50 temperatures above 39.9 • C. The impact of a high thermal dose was also found in the retrospective study on RT+HT for prostate cancer by Nakahare et al [2]: CEM43T90 > 7 min.…”

Neoadjuvant Radiochemotherapy Combined with Locoregional Hyperthermia in Locally Advanced Rectal Cancer: Feasibility and Tolerance of Short-Course Versus Long-Course Radiotherapy Schedules

“…The combination of RT with HT has demonstrated clinical evidence of synergistic effects in various tumor types, including rectal cancer [ 4 , 5 , 14 , 15 , 22 , 26 ]. HT improves tumor perfusion, increases oxygenation, and inhibits DNA repair, leading to enhanced radiosensitization and chemotherapy efficacy [ 4 , 5 ].…”

“…These observations are descriptive, and no formal statistical comparisons were performed. It is worth noting that, in the German experience reported previously [ 22 ], the treatment protocol anticipated the decline in patient tolerance over time and therefore started with two HT sessions per week during the initial phase of LCRT, aiming at completing approximately six sessions in total. This proactive approach was designed to complete the majority of HT treatments before cumulative toxicity compromised adherence.…”

Locoregional Hyperthermia in Cancer Treatment: A Narrative Review with Updates and Perspectives

“…HT and mEHT were used as neoadjuvant therapy in association with CRT in several studies regarding rectal cancer, resulting in significantly greater downstaging than CRT alone (80.7-82% vs. 62.7-67.2%; p < 0.05) [49][50][51][52][53][54][55]. Other beneficial effects of HT were observed in glioma, melanoma, and prostate cancer treatments [56,57,60].…”

Oncologic Thermoradiotherapy: Need for Evidence, Harmonisation, and Innovation

“…In this special issue new evidence is presented. In a long term retrospective study of preoperative chemoradiation plus deep hyperthermia Schemm et al [1]. reports an encouraging level in five-year survival with better RFS for patients reaching T50 temperatures above 39.9 • C. The impact of a high thermal dose was also found in the retrospective study on RT+HT for prostate cancer by Nakahare et al [2]: CEM43T90 > 7 min.…”

Neoadjuvant Radiochemotherapy Combined with Locoregional Hyperthermia in Locally Advanced Rectal Cancer: Feasibility and Tolerance of Short-Course Versus Long-Course Radiotherapy Schedules

“…The combination of RT with HT has demonstrated clinical evidence of synergistic effects in various tumor types, including rectal cancer [ 4 , 5 , 14 , 15 , 22 , 26 ]. HT improves tumor perfusion, increases oxygenation, and inhibits DNA repair, leading to enhanced radiosensitization and chemotherapy efficacy [ 4 , 5 ].…”

“…These observations are descriptive, and no formal statistical comparisons were performed. It is worth noting that, in the German experience reported previously [ 22 ], the treatment protocol anticipated the decline in patient tolerance over time and therefore started with two HT sessions per week during the initial phase of LCRT, aiming at completing approximately six sessions in total. This proactive approach was designed to complete the majority of HT treatments before cumulative toxicity compromised adherence.…”

Locoregional Hyperthermia in Cancer Treatment: A Narrative Review with Updates and Perspectives

“…HT and mEHT were used as neoadjuvant therapy in association with CRT in several studies regarding rectal cancer, resulting in significantly greater downstaging than CRT alone (80.7-82% vs. 62.7-67.2%; p < 0.05) [49][50][51][52][53][54][55]. Other beneficial effects of HT were observed in glioma, melanoma, and prostate cancer treatments [56,57,60].…”