Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. METHODS: This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. DISCUSSION: The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. TRIAL REGISTRATION: Clinical Trials: NCT04927780. Registered June 16, 2021.

Morbidity of immediate breast reconstruction (IBR) after mastectomy by a subpectorally placed silicone prosthesis: the adverse effect of radiotherapy.

AIMS: This study evaluates the incidence of local complications after immediate breast reconstruction (IBR) following mastectomy with a subpectorally placed silicone prosthesis, with emphasis on the effect of radiation treatment on IBR. METHODS: The medical records of 100 women, who underwent a mastectomy followed by IBR with a subpectorally placed silicone prosthesis at the University Hospital Rotterdam/Daniel den Hoed Cancer Center, between March 1990 and March 1995, were reviewed. Thirteen prostheses were implanted prior to radiation treatment, and 15 prostheses were implanted after irradiation of the chest wall. RESULTS: Early complications were seen in 15% of the IBR and were more often in irradiated women. At long-term follow-up, the most common complication was capsular contracture (21%). This occurred significantly more around prostheses placed in a previously irradiated area (P<0.0005), or which were irradiated after IBR (P=0.001). Loss of prosthesis was seen in 11 cases, and was significantly (P<0.005) more in irradiated women (n=5; 18%) compared to women who were not irradiated (n=6; 7%). CONCLUSIONS: Complications after IBR with a silicone prosthesis were more common in women who were treated with radiotherapy prior to or after IBR following mastectomy than in women who were not irradiated. In particular, capsular contracture around a prosthesis placed in a previously irradiated area was significantly increased. The use of musculocutaneous flaps, such as the transverse rectus abdominis muscle or latissimus dorsi flap, is preferable for reconstruction of previously irradiated breasts. There is no indication to remove the prosthesis before radiation therapy of the chest wall.

Reirradiation combined with hyperthermia in recurrent breast cancer results in a worthwhile local palliation.

Both experimental and clinical research have shown that hyperthermia (HT) gives valuable additional effects when applied in combination with radiotherapy (RT). The purpose of this study was evaluation of results in patients with recurrent breast cancer, treated at the Daniel den Hoed Cancer Center (DHCC) with reirradiation (re-RT; eight fractions of 4 Gy twice weekly) combined with HT. All 134 patients for whom such treatment was planned were included in the analysis. The complete response rate in 119 patients with macroscopic tumour was 71%. Including the 15 patients with microscopic disease, the local control rate was 73%. The median duration of local control was 32 months, and toxicity was acceptable. The complete response (CR) rate was higher, and the toxicity was less with the later developed 433-MHz HT technique compared with the 2450-MHz technique used initially. With this relatively well-tolerated treatment, palliation by local tumour control of a worthwhile duration is achieved in the majority of patients. The technique used for hyperthermia appeared to influence the achieved results. The value of HT in addition to this re-RT schedule has been confirmed by a prospective randomized trial in a similar patient group. In The Netherlands, this combined treatment is offered as standard to patients with breast cancer recurring in previously irradiated areas.