In total, 127 PET/CT scans were analyzed. Forty-one patients (75%) of 55 had FDG-avid sdLNs (N = 136) in preoperative FDG-PET/CT. The responders group consisted of 29 patients with 97 FDG-avid sdLNs prior to therapy and the non-responders group included 12 patients with 39 FDG-avid sdLNs. One to nine sdLNs per patient (mean 3.3) were analyzed.
FDG-avid sdLNs in preoperative PET/CT
Of the 136 FDG-avid sdLNs, 16% (22/136) sdLNs were enlarged (short axis ≥ 10 mm). The size, SUVmax values and distribution of FDG-avid sdLNs in preoperative PET/CT is presented in Fig. 2. There was no statistically significant difference in the average size and SUVmax values of FDG-avid sdLNs in preoperative imaging between the responders and non-responders (p = 0.84 and 0.29).
Of the 41 patients, 31 (76%) had metabolically active sdLNs in multiple anatomical sites (Table 2, Fig. 2). 76% (31/41) had preoperatively FDG-avid LNs in the cardiophrenic area, that could potentially be resected in surgery. Notably, in 6 patients this was the only FDG-avid sdLN station.
The behavior of FDG-avid sdLNs in response to the primary treatment
The behavior of sdLNs during primary therapy reflected the patients’ overall chemotherapy response.
The metabolic response of 97 preoperatively detected FDG-avid sdLNs in responders and 39 in non-responders group were evaluated. After the completion of the first line chemotherapy, 96% (93/97) of the FDG-avid sdLNs in responders group responded metabolically to the treatment, 82.5% (80/97) with complete and 13.4% (13/17) partial metabolic response. In the non-responders group, despite the disease progression elsewhere, 22 (56%) of the preoperatively FDG-avid 39 sdLNs showed complete metabolic response, whereas 21% (8/39) showed partial metabolic response.
The sdLNs in the responders group more frequently showed a complete metabolic resolution after primary treatment compared to the non-responders group, hazard ratio 1.46 (95%CI: 1.09–1.96) (p = 0.002).
Of the sdLNs that were still metabolically active in the response evaluation PET/CT, there had been a mean decline in the SUV max values of 42% in the responders group compared to only 20% in the non-responders group (p = 0.02).
The same tendency, although not statistically significant, was detected when analyzed at the level of the individual patients: the 35% (10/29) of patients in the responders group and 71% (7/12) in the non-responders group had FDG avid sdLNs in the response evaluation scan (p = 0.18) (Table 2).
Similar to retroperitoneal LNM, the metabolic response to chemotherapy in FDG-avid sdLNs was already detectable after NACT (Table 3).
The FDG-avid sdLNs profile at the first disease relapse
The FDG-avid sdLNs which responded to first line chemotherapy often reactivated during disease recurrence. Disease recurrence in the thorax alone was rare. Figure 3 presents the behavior of preoperatively detected FDG-avid sdLNs of our study patient in FDG-PET/CT during primary treatment until the first recurrence.
The responders (n = 29) had regular follow-up visits after completion of primary therapy. Within the median follow-up time of 35.8 months (95% Cl: 31.7–41.0), 90% (26/29) responders experienced disease recurrence and 69% (20/29) died. The median PFS of responders was 14 months (95% Cl: 1.1–18.4). There was no difference in median PFS of patients with complete and partial metabolic response in FDG-avid sdLNs (13,6 vs 14.9 months), respectively (p = 0.59).
The overall distribution of the disease when relapse occurred is presented in Additional file 1: Table S1. In 50% (11/22) of first line responders the same sdLNs activated when recurrence was detected.
Biopsies from FDG-avid sdLNs were pre-operatively taken from five patients and malignant histology was confirmed in all 5 cases (4 axillary and 1 subclavicular LNM). Two of the confirmed sdLN metastases were enlarged (≥10 mm) and 3 normal (< 10 mm) in size. The mean preoperative SUV max of the confirmed sdLN metastases was 3.3 and their metabolic response to first line chemotherapy was complete. The size and preoperative SUVmax values of the confirmed sdLN metastases did not differ statistically that from the not biopsied FDG-avid sdLNs.